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Cannabis Vaporizer CombinesEfficient Delivery of THCwith Effective Suppressionof Pyrolytic Compounds
Dale GieringerJoseph St Laurent
Scott Goodrich
ABSTRACT Cannabis vaporization is a technology designed to deliverinhaled cannabinoids while avoiding the respiratory hazards of smokingby heating cannabis to a temperature where therapeutically active canna-binoid vapors are produced but below the point of combustion wherenoxious pyrolytic byproducts are formed
This study was designed to evaluate the efficacy of an herbal vapor-izer known as the Volcanoreg produced by Storz amp Bickel GmbHampCoKG Tuttlingen Germany (httpwwwstorz-bickelcom) Three 200 mgsamples of standard NIDA cannabis were vaporized at temperatures of155deg-218degC For comparison smoke from combusted samples was alsotested
The study consisted of two phases (1) a quantitative analysis of thesolid phase of the vapor using HPLC-DAD-MS (High Performance Liq-
Dale Gieringer is affiliated with California NORML 2215-R Market Street 278San Francisco CA 94114
Joseph St Laurent and Scott Goodrich are affiliated with Chemic Labs 480Neponset Street Building 7C Canton MA 02021
The authors offer thanks for insight and technical support to Jeff Jones ElvyMusikka Irvin Rosenfeld and Aidan Hampson
This research was supported by a grant from the Marijuana Policy Project Addi-tional support provided by the NORML Foundation the Multidisciplinary Associationfor Psychedelic Studies and Storz amp Bickel GmbHampCo
Journal of Cannabis Therapeutics Vol 4(1) 2004httpwwwhaworthpresscomwebJCANT
2004 by The Haworth Press Inc All rights reservedDigital Object Identifier 101300J175v04n01_02 7
uid Chromatograph-Diode Array-Mass Spectrometry) to determine theamount of cannabinoids delivered (2) a GCMS (Gas ChromatographMass Spectrometer) analysis of the gas phase to analyze the vapor for awide range of toxins focusing on pyrene and other polynuculear aro-matic hydrocarbons (PAHs)
The HPLC analysis of the vapor found that the Volcano delivered36-61 of the THC in the sample a delivery efficiency that comparesfavorably to that of marijuana cigarettes
The GCMS analysis showed that the gas phase of the vapor consistedoverwhelmingly of cannabinoids with trace amounts of three other com-pounds In contrast over 111 compounds were identified in the combustedsmoke including several known PAHs
The results indicate that vaporization can deliver therapeutic doses ofcannabinoids with a drastic reduction in pyrolytic smoke compoundsVaporization therefore appears to be an attractive alternative to smokedmarijuana for future medical cannabis studies [Article copies available fora fee from The Haworth Document Delivery Service 1-800-HAWORTH E-mailaddress ltdocdeliveryhaworthpresscomgt Website lthttpwwwHaworthPresscomgt 2004 by The Haworth Press Inc All rights reserved]
KEYWORDS Marijuana cannabis vaporization smoking harm re-duction
INTRODUCTION
Concern about the respiratory hazards of smoking has spurred the de-velopment of vaporization as an alternative method of medical cannabisadministration Cannabis vaporization is a relatively new technologyaimed at suppressing respiratory toxins by heating cannabis to a tem-perature where cannabinoid vapors form (typically around 180-190degC)but below the point of combustion where smoke and associated toxinsare produced (near 230degC) The purpose of this is to permit the inhala-tion of medically active cannabinoids while avoiding noxious smokecompounds that pose respiratory hazards Of particular concern arethe carcinogenic polynuclear (or ldquopolycyclicrdquo) aromatic hydrocarbons(PAHs) known byproducts of combustion that are thought to be a majorculprit in smoking-related cancers While there exists no epidemiologi-cal evidence that marijuana smokers face a higher risk of smoking-re-lated cancers studies have found that they do face a higher risk ofbronchitis and respiratory infections (Polen et al 1993 Tashkin 1993)This risk is not thought to be due to cannabinoids but rather to extrane-ous byproducts of pyrolysis in the smoke
8 JOURNAL OF CANNABIS THERAPEUTICS
In principle vaporization offers medical cannabis patients the advan-tages of inhaled routes of administration rapid onset direct deliveryinto the bloodstream ease of self-titration and concomitant avoidanceof over- and under-dosage while avoiding the respiratory disadvan-tages of smoking Compared to other proposed non-smoked deliverysystems using pharmaceutical extracts and synthetics vaporization alsooffers the economic advantage of allowing patients to use inexpensivehomegrown cannabis
In practice the major question concerning vaporization comes downto feasibility How well can one design a vaporizer that reliably pro-duces ldquosmokelessrdquo toxin-free cannabinoid vapors from crude canna-bis To address this question we tested a device known as the Volcanoregan herbal vaporizer produced by Storz amp Bickel GmbHampCo KGTuttlingen Germany (httpwwwstorz-bickelcom) The study was de-signed to measure how efficiently the device delivered delta-9-tetra-hydrocannabinol (THC) and other cannabinoids and how effectively itsuppressed other non-cannabinoid compounds from the vapor
The study consisted of two phases (1) a quantitative analysis of thesolid phase of the vapor using HPLC-DAD-MS (High PerformanceLiquid Chromatograph-Diode Array-Mass Spectrometry) to determinethe amount of cannabinoids delivered (2) a GCMS (Gas Chroma-tographMass Spectrometry) analysis of the gas phase to analyze thevapor for a wide range of toxins focusing on pyrene and other poly-nuculear aromatic hydocarbons Vapor was generated by loading theVolcano with 200 mg samples of NIDA cannabis For comparison acombusted control using 200 mg of cannabis burned in a glass pipebowl was also tested
Upon analysis the Volcano vapors were found to consist over-whelmingly of cannabinoids while the combusted control containedover one hundred additional chemicals including several known PAHsThe results which are discussed below provide encouraging confirma-tion of the feasibility and efficacy of vaporization
This study was the third in a series of cannabis smoke harm reductionstudies sponsored by California NORML (National Organization for theReform of Marijuana Laws wwwcanormlorg) and MAPS (Multidisci-plinary Association for Psychedelic Studies wwwmapsorg) (Gieringer2001) The first study tested a variety of smoking devices including twocrude homemade vaporizers along with several waterpipes and other de-vices specifically examining THC and solid smoke tars (Gieringer1996) It indicated that only vaporizers were capable of achieving re-ductions in tar relative to THC The second study (Chemic 2000) was a
Gieringer St Laurent and Goodrich 9
ldquoproof of conceptrdquo study of an electric radiant heat vaporizer known asthe M-1 Volatizerreg (httpwwwvolatizercom) The M-1 was found todeliver THC while completely eliminating three specific toxins (naph-thalene benzene and toluene) in the solid phase of the vapor The studyalso detected a 56 reduction in tars and a qualitative reduction incarbon monoxide but did not test for any other chemicals (Gieringer2001) The present study (Chemic 2003) is the first to use a GCMS toanalyze the gas phase of vaporized cannabis for a wide range of toxinsconcentrating on the highly carcinogenic PAHs
DESCRIPTION OF THE VOLCANOreg
The Volcano as its name suggests consists of a conical body con-taining a ceramic heater with a heat vent on top (Figure 1) Above thevent sits a removable chamber that is loaded with sample material Hotair is blown from below through the sample to produce vapor which iscollected in a detachable plastic balloon After the balloon has beenfilled it can be removed and fitted with a mouthpiece through whichthe vapors can be inhaled The balloon is a unique feature of the Vol-cano It has the advantages of preventing loss of sidestream vapor andproviding a uniform consistent dosage volume This renders it an idealinstrument for controlled dosage studies
The temperature control ranges from 1 to 9 corresponding to temper-atures of 130deg to 226degC The manufacturer suggests using a temperaturesetting of 7 corresponding to a nominal 202degC Our previous study us-ing the M-1reg found that sample temperatures around 185degC were opti-mal for vaporization with toxins beginning to appear above 200degC(Chemic 2000 Gieringer 2001) As a worst-case test of the Volcanorsquossafety we set it at its highest setting to ascertain whether pyrolytic by-products might result Two thermocouples were placed in the vaporizerabove and below the sample to determine the actual operating tempera-ture The temperature was found to be stable measuring 155degC on thetop surface of the sample and 218degC on the screen closest to the heater
THE SAMPLE
The sample consisted of standard NIDA cannabis supplied throughan independent laboratory Portions were prepared in 17 gram batchesby gently sifting through a 2 mm sieve screen and mixing
The baseline concentrations of cannabinoids in the sample were ana-
10 JOURNAL OF CANNABIS THERAPEUTICS
lyzed by Soxhlet extraction for THC cannabidiol (CBD) and canna-binol (CBN) Three separate samples of 200 mg were extracted in 250ml ethanol under heat for 2 hours concentrated by rotary evaporationand analyzed by HPLC-DAD-MS The mean concentration of THCwas 415 (range 40-43) consistent with NIDA standards CBDand CBN were detected in only trace amounts with the CBD showing awide range of variance 00428-0128 (mean 0075) CBN rangedmore tightly from 0086 to 010 (mean 0094)
The water content of the sample was measured by heating a prepared056 gram sample for 30 minutes at 140degC and measuring the weightloss The water content was found to be 119 by weight
PHASE ONE CANNABINOID RECOVERY ANALYSIS
Vapor from the Volcano was analyzed to determine the cannabinoiddelivery efficiency of the vaporizer A 200 mg sample was loaded into
Gieringer St Laurent and Goodrich 11
FIGURE 1 The Volcanoreg Vaporizer
Photograph courtesy of Storz amp Bickel
the Volcano and exposed to heat for 45 seconds enough to fill the col-lection balloon The vapor was then transferred from the balloon over aperiod of approximately 15 minutes by a vacuum pump into a solventreservoir containing 50 ml of methanol
Three balloons were collected from each sample The three balloonquota was based on preliminary tests which found that most of thecannabinoids were delivered in the first two balloons with just traceamounts in the third The vapor is typically visible as a light gray wispyhaze and has a distinct cannabis terpene odor In practice Volcano usersreport inhaling anywhere from two to six balloons from a given sampleHowever most load the chamber with a half gram or more over twicethe sample size in our tests The more cannabis that is loaded the moreballoons of vapor that can be drawn According to the manufacturer upto ten balloons can be drawn from a one-gram sample (Russo 2003) Inorder to facilitate maximal vaporization the manufacturer recommendsstirring the sample around after inhaling a few balloons then repeatingHowever this procedure was not followed in our tests since we usedrelatively small amounts of sieved material
The dissolved vapor from the Volcano was subjected to quantitativeanalysis on the HPLC-DAD Two separate samples of 15 ml weretested from each dissolved sample as a consistency check The entireprocess was repeated for three different 200 mg samples of cannabisResults are shown in Table 1 On average the recovered THC amountedto 195 of the original weight of the sample or 47 of the originalTHC in the crude sample There was a large variance in the percentageof THC recovered in the three different vaporizer test runs rangingfrom 36 to 61 This suggests that the efficiency of vaporization ishighly sensitive to variations in the sample and micro-conditions in itsenvironment
These results compare favorably to the delivery efficiencies of mari-juana cigarettes as measured in other studies THC efficiencies of 34to 61 were reported in studies of marijuana cigarettes smoked via asmoking machine under varying conditions of puff duration and airspeed (Fehr and Kalant 1971) Efficiencies of 50 were obtained usinga machine designed to mimic human marijuana cigarette smoking(Manno 1970) and in an unpublished study at Battelle by Foltz et al(cited in Truitt 1971) It has been estimated that 23-30 of the THC incombusted cannabis is destroyed by pyrolysis while as much as 40-50can be lost in sidestream smoke (Perez-Reyes 1990) Efficiencies aslow as 16-19 were reported in tests of cigarettes smoked intermit-
12 JOURNAL OF CANNABIS THERAPEUTICS
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
uid Chromatograph-Diode Array-Mass Spectrometry) to determine theamount of cannabinoids delivered (2) a GCMS (Gas ChromatographMass Spectrometer) analysis of the gas phase to analyze the vapor for awide range of toxins focusing on pyrene and other polynuculear aro-matic hydrocarbons (PAHs)
The HPLC analysis of the vapor found that the Volcano delivered36-61 of the THC in the sample a delivery efficiency that comparesfavorably to that of marijuana cigarettes
The GCMS analysis showed that the gas phase of the vapor consistedoverwhelmingly of cannabinoids with trace amounts of three other com-pounds In contrast over 111 compounds were identified in the combustedsmoke including several known PAHs
The results indicate that vaporization can deliver therapeutic doses ofcannabinoids with a drastic reduction in pyrolytic smoke compoundsVaporization therefore appears to be an attractive alternative to smokedmarijuana for future medical cannabis studies [Article copies available fora fee from The Haworth Document Delivery Service 1-800-HAWORTH E-mailaddress ltdocdeliveryhaworthpresscomgt Website lthttpwwwHaworthPresscomgt 2004 by The Haworth Press Inc All rights reserved]
KEYWORDS Marijuana cannabis vaporization smoking harm re-duction
INTRODUCTION
Concern about the respiratory hazards of smoking has spurred the de-velopment of vaporization as an alternative method of medical cannabisadministration Cannabis vaporization is a relatively new technologyaimed at suppressing respiratory toxins by heating cannabis to a tem-perature where cannabinoid vapors form (typically around 180-190degC)but below the point of combustion where smoke and associated toxinsare produced (near 230degC) The purpose of this is to permit the inhala-tion of medically active cannabinoids while avoiding noxious smokecompounds that pose respiratory hazards Of particular concern arethe carcinogenic polynuclear (or ldquopolycyclicrdquo) aromatic hydrocarbons(PAHs) known byproducts of combustion that are thought to be a majorculprit in smoking-related cancers While there exists no epidemiologi-cal evidence that marijuana smokers face a higher risk of smoking-re-lated cancers studies have found that they do face a higher risk ofbronchitis and respiratory infections (Polen et al 1993 Tashkin 1993)This risk is not thought to be due to cannabinoids but rather to extrane-ous byproducts of pyrolysis in the smoke
8 JOURNAL OF CANNABIS THERAPEUTICS
In principle vaporization offers medical cannabis patients the advan-tages of inhaled routes of administration rapid onset direct deliveryinto the bloodstream ease of self-titration and concomitant avoidanceof over- and under-dosage while avoiding the respiratory disadvan-tages of smoking Compared to other proposed non-smoked deliverysystems using pharmaceutical extracts and synthetics vaporization alsooffers the economic advantage of allowing patients to use inexpensivehomegrown cannabis
In practice the major question concerning vaporization comes downto feasibility How well can one design a vaporizer that reliably pro-duces ldquosmokelessrdquo toxin-free cannabinoid vapors from crude canna-bis To address this question we tested a device known as the Volcanoregan herbal vaporizer produced by Storz amp Bickel GmbHampCo KGTuttlingen Germany (httpwwwstorz-bickelcom) The study was de-signed to measure how efficiently the device delivered delta-9-tetra-hydrocannabinol (THC) and other cannabinoids and how effectively itsuppressed other non-cannabinoid compounds from the vapor
The study consisted of two phases (1) a quantitative analysis of thesolid phase of the vapor using HPLC-DAD-MS (High PerformanceLiquid Chromatograph-Diode Array-Mass Spectrometry) to determinethe amount of cannabinoids delivered (2) a GCMS (Gas Chroma-tographMass Spectrometry) analysis of the gas phase to analyze thevapor for a wide range of toxins focusing on pyrene and other poly-nuculear aromatic hydocarbons Vapor was generated by loading theVolcano with 200 mg samples of NIDA cannabis For comparison acombusted control using 200 mg of cannabis burned in a glass pipebowl was also tested
Upon analysis the Volcano vapors were found to consist over-whelmingly of cannabinoids while the combusted control containedover one hundred additional chemicals including several known PAHsThe results which are discussed below provide encouraging confirma-tion of the feasibility and efficacy of vaporization
This study was the third in a series of cannabis smoke harm reductionstudies sponsored by California NORML (National Organization for theReform of Marijuana Laws wwwcanormlorg) and MAPS (Multidisci-plinary Association for Psychedelic Studies wwwmapsorg) (Gieringer2001) The first study tested a variety of smoking devices including twocrude homemade vaporizers along with several waterpipes and other de-vices specifically examining THC and solid smoke tars (Gieringer1996) It indicated that only vaporizers were capable of achieving re-ductions in tar relative to THC The second study (Chemic 2000) was a
Gieringer St Laurent and Goodrich 9
ldquoproof of conceptrdquo study of an electric radiant heat vaporizer known asthe M-1 Volatizerreg (httpwwwvolatizercom) The M-1 was found todeliver THC while completely eliminating three specific toxins (naph-thalene benzene and toluene) in the solid phase of the vapor The studyalso detected a 56 reduction in tars and a qualitative reduction incarbon monoxide but did not test for any other chemicals (Gieringer2001) The present study (Chemic 2003) is the first to use a GCMS toanalyze the gas phase of vaporized cannabis for a wide range of toxinsconcentrating on the highly carcinogenic PAHs
DESCRIPTION OF THE VOLCANOreg
The Volcano as its name suggests consists of a conical body con-taining a ceramic heater with a heat vent on top (Figure 1) Above thevent sits a removable chamber that is loaded with sample material Hotair is blown from below through the sample to produce vapor which iscollected in a detachable plastic balloon After the balloon has beenfilled it can be removed and fitted with a mouthpiece through whichthe vapors can be inhaled The balloon is a unique feature of the Vol-cano It has the advantages of preventing loss of sidestream vapor andproviding a uniform consistent dosage volume This renders it an idealinstrument for controlled dosage studies
The temperature control ranges from 1 to 9 corresponding to temper-atures of 130deg to 226degC The manufacturer suggests using a temperaturesetting of 7 corresponding to a nominal 202degC Our previous study us-ing the M-1reg found that sample temperatures around 185degC were opti-mal for vaporization with toxins beginning to appear above 200degC(Chemic 2000 Gieringer 2001) As a worst-case test of the Volcanorsquossafety we set it at its highest setting to ascertain whether pyrolytic by-products might result Two thermocouples were placed in the vaporizerabove and below the sample to determine the actual operating tempera-ture The temperature was found to be stable measuring 155degC on thetop surface of the sample and 218degC on the screen closest to the heater
THE SAMPLE
The sample consisted of standard NIDA cannabis supplied throughan independent laboratory Portions were prepared in 17 gram batchesby gently sifting through a 2 mm sieve screen and mixing
The baseline concentrations of cannabinoids in the sample were ana-
10 JOURNAL OF CANNABIS THERAPEUTICS
lyzed by Soxhlet extraction for THC cannabidiol (CBD) and canna-binol (CBN) Three separate samples of 200 mg were extracted in 250ml ethanol under heat for 2 hours concentrated by rotary evaporationand analyzed by HPLC-DAD-MS The mean concentration of THCwas 415 (range 40-43) consistent with NIDA standards CBDand CBN were detected in only trace amounts with the CBD showing awide range of variance 00428-0128 (mean 0075) CBN rangedmore tightly from 0086 to 010 (mean 0094)
The water content of the sample was measured by heating a prepared056 gram sample for 30 minutes at 140degC and measuring the weightloss The water content was found to be 119 by weight
PHASE ONE CANNABINOID RECOVERY ANALYSIS
Vapor from the Volcano was analyzed to determine the cannabinoiddelivery efficiency of the vaporizer A 200 mg sample was loaded into
Gieringer St Laurent and Goodrich 11
FIGURE 1 The Volcanoreg Vaporizer
Photograph courtesy of Storz amp Bickel
the Volcano and exposed to heat for 45 seconds enough to fill the col-lection balloon The vapor was then transferred from the balloon over aperiod of approximately 15 minutes by a vacuum pump into a solventreservoir containing 50 ml of methanol
Three balloons were collected from each sample The three balloonquota was based on preliminary tests which found that most of thecannabinoids were delivered in the first two balloons with just traceamounts in the third The vapor is typically visible as a light gray wispyhaze and has a distinct cannabis terpene odor In practice Volcano usersreport inhaling anywhere from two to six balloons from a given sampleHowever most load the chamber with a half gram or more over twicethe sample size in our tests The more cannabis that is loaded the moreballoons of vapor that can be drawn According to the manufacturer upto ten balloons can be drawn from a one-gram sample (Russo 2003) Inorder to facilitate maximal vaporization the manufacturer recommendsstirring the sample around after inhaling a few balloons then repeatingHowever this procedure was not followed in our tests since we usedrelatively small amounts of sieved material
The dissolved vapor from the Volcano was subjected to quantitativeanalysis on the HPLC-DAD Two separate samples of 15 ml weretested from each dissolved sample as a consistency check The entireprocess was repeated for three different 200 mg samples of cannabisResults are shown in Table 1 On average the recovered THC amountedto 195 of the original weight of the sample or 47 of the originalTHC in the crude sample There was a large variance in the percentageof THC recovered in the three different vaporizer test runs rangingfrom 36 to 61 This suggests that the efficiency of vaporization ishighly sensitive to variations in the sample and micro-conditions in itsenvironment
These results compare favorably to the delivery efficiencies of mari-juana cigarettes as measured in other studies THC efficiencies of 34to 61 were reported in studies of marijuana cigarettes smoked via asmoking machine under varying conditions of puff duration and airspeed (Fehr and Kalant 1971) Efficiencies of 50 were obtained usinga machine designed to mimic human marijuana cigarette smoking(Manno 1970) and in an unpublished study at Battelle by Foltz et al(cited in Truitt 1971) It has been estimated that 23-30 of the THC incombusted cannabis is destroyed by pyrolysis while as much as 40-50can be lost in sidestream smoke (Perez-Reyes 1990) Efficiencies aslow as 16-19 were reported in tests of cigarettes smoked intermit-
12 JOURNAL OF CANNABIS THERAPEUTICS
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
In principle vaporization offers medical cannabis patients the advan-tages of inhaled routes of administration rapid onset direct deliveryinto the bloodstream ease of self-titration and concomitant avoidanceof over- and under-dosage while avoiding the respiratory disadvan-tages of smoking Compared to other proposed non-smoked deliverysystems using pharmaceutical extracts and synthetics vaporization alsooffers the economic advantage of allowing patients to use inexpensivehomegrown cannabis
In practice the major question concerning vaporization comes downto feasibility How well can one design a vaporizer that reliably pro-duces ldquosmokelessrdquo toxin-free cannabinoid vapors from crude canna-bis To address this question we tested a device known as the Volcanoregan herbal vaporizer produced by Storz amp Bickel GmbHampCo KGTuttlingen Germany (httpwwwstorz-bickelcom) The study was de-signed to measure how efficiently the device delivered delta-9-tetra-hydrocannabinol (THC) and other cannabinoids and how effectively itsuppressed other non-cannabinoid compounds from the vapor
The study consisted of two phases (1) a quantitative analysis of thesolid phase of the vapor using HPLC-DAD-MS (High PerformanceLiquid Chromatograph-Diode Array-Mass Spectrometry) to determinethe amount of cannabinoids delivered (2) a GCMS (Gas Chroma-tographMass Spectrometry) analysis of the gas phase to analyze thevapor for a wide range of toxins focusing on pyrene and other poly-nuculear aromatic hydocarbons Vapor was generated by loading theVolcano with 200 mg samples of NIDA cannabis For comparison acombusted control using 200 mg of cannabis burned in a glass pipebowl was also tested
Upon analysis the Volcano vapors were found to consist over-whelmingly of cannabinoids while the combusted control containedover one hundred additional chemicals including several known PAHsThe results which are discussed below provide encouraging confirma-tion of the feasibility and efficacy of vaporization
This study was the third in a series of cannabis smoke harm reductionstudies sponsored by California NORML (National Organization for theReform of Marijuana Laws wwwcanormlorg) and MAPS (Multidisci-plinary Association for Psychedelic Studies wwwmapsorg) (Gieringer2001) The first study tested a variety of smoking devices including twocrude homemade vaporizers along with several waterpipes and other de-vices specifically examining THC and solid smoke tars (Gieringer1996) It indicated that only vaporizers were capable of achieving re-ductions in tar relative to THC The second study (Chemic 2000) was a
Gieringer St Laurent and Goodrich 9
ldquoproof of conceptrdquo study of an electric radiant heat vaporizer known asthe M-1 Volatizerreg (httpwwwvolatizercom) The M-1 was found todeliver THC while completely eliminating three specific toxins (naph-thalene benzene and toluene) in the solid phase of the vapor The studyalso detected a 56 reduction in tars and a qualitative reduction incarbon monoxide but did not test for any other chemicals (Gieringer2001) The present study (Chemic 2003) is the first to use a GCMS toanalyze the gas phase of vaporized cannabis for a wide range of toxinsconcentrating on the highly carcinogenic PAHs
DESCRIPTION OF THE VOLCANOreg
The Volcano as its name suggests consists of a conical body con-taining a ceramic heater with a heat vent on top (Figure 1) Above thevent sits a removable chamber that is loaded with sample material Hotair is blown from below through the sample to produce vapor which iscollected in a detachable plastic balloon After the balloon has beenfilled it can be removed and fitted with a mouthpiece through whichthe vapors can be inhaled The balloon is a unique feature of the Vol-cano It has the advantages of preventing loss of sidestream vapor andproviding a uniform consistent dosage volume This renders it an idealinstrument for controlled dosage studies
The temperature control ranges from 1 to 9 corresponding to temper-atures of 130deg to 226degC The manufacturer suggests using a temperaturesetting of 7 corresponding to a nominal 202degC Our previous study us-ing the M-1reg found that sample temperatures around 185degC were opti-mal for vaporization with toxins beginning to appear above 200degC(Chemic 2000 Gieringer 2001) As a worst-case test of the Volcanorsquossafety we set it at its highest setting to ascertain whether pyrolytic by-products might result Two thermocouples were placed in the vaporizerabove and below the sample to determine the actual operating tempera-ture The temperature was found to be stable measuring 155degC on thetop surface of the sample and 218degC on the screen closest to the heater
THE SAMPLE
The sample consisted of standard NIDA cannabis supplied throughan independent laboratory Portions were prepared in 17 gram batchesby gently sifting through a 2 mm sieve screen and mixing
The baseline concentrations of cannabinoids in the sample were ana-
10 JOURNAL OF CANNABIS THERAPEUTICS
lyzed by Soxhlet extraction for THC cannabidiol (CBD) and canna-binol (CBN) Three separate samples of 200 mg were extracted in 250ml ethanol under heat for 2 hours concentrated by rotary evaporationand analyzed by HPLC-DAD-MS The mean concentration of THCwas 415 (range 40-43) consistent with NIDA standards CBDand CBN were detected in only trace amounts with the CBD showing awide range of variance 00428-0128 (mean 0075) CBN rangedmore tightly from 0086 to 010 (mean 0094)
The water content of the sample was measured by heating a prepared056 gram sample for 30 minutes at 140degC and measuring the weightloss The water content was found to be 119 by weight
PHASE ONE CANNABINOID RECOVERY ANALYSIS
Vapor from the Volcano was analyzed to determine the cannabinoiddelivery efficiency of the vaporizer A 200 mg sample was loaded into
Gieringer St Laurent and Goodrich 11
FIGURE 1 The Volcanoreg Vaporizer
Photograph courtesy of Storz amp Bickel
the Volcano and exposed to heat for 45 seconds enough to fill the col-lection balloon The vapor was then transferred from the balloon over aperiod of approximately 15 minutes by a vacuum pump into a solventreservoir containing 50 ml of methanol
Three balloons were collected from each sample The three balloonquota was based on preliminary tests which found that most of thecannabinoids were delivered in the first two balloons with just traceamounts in the third The vapor is typically visible as a light gray wispyhaze and has a distinct cannabis terpene odor In practice Volcano usersreport inhaling anywhere from two to six balloons from a given sampleHowever most load the chamber with a half gram or more over twicethe sample size in our tests The more cannabis that is loaded the moreballoons of vapor that can be drawn According to the manufacturer upto ten balloons can be drawn from a one-gram sample (Russo 2003) Inorder to facilitate maximal vaporization the manufacturer recommendsstirring the sample around after inhaling a few balloons then repeatingHowever this procedure was not followed in our tests since we usedrelatively small amounts of sieved material
The dissolved vapor from the Volcano was subjected to quantitativeanalysis on the HPLC-DAD Two separate samples of 15 ml weretested from each dissolved sample as a consistency check The entireprocess was repeated for three different 200 mg samples of cannabisResults are shown in Table 1 On average the recovered THC amountedto 195 of the original weight of the sample or 47 of the originalTHC in the crude sample There was a large variance in the percentageof THC recovered in the three different vaporizer test runs rangingfrom 36 to 61 This suggests that the efficiency of vaporization ishighly sensitive to variations in the sample and micro-conditions in itsenvironment
These results compare favorably to the delivery efficiencies of mari-juana cigarettes as measured in other studies THC efficiencies of 34to 61 were reported in studies of marijuana cigarettes smoked via asmoking machine under varying conditions of puff duration and airspeed (Fehr and Kalant 1971) Efficiencies of 50 were obtained usinga machine designed to mimic human marijuana cigarette smoking(Manno 1970) and in an unpublished study at Battelle by Foltz et al(cited in Truitt 1971) It has been estimated that 23-30 of the THC incombusted cannabis is destroyed by pyrolysis while as much as 40-50can be lost in sidestream smoke (Perez-Reyes 1990) Efficiencies aslow as 16-19 were reported in tests of cigarettes smoked intermit-
12 JOURNAL OF CANNABIS THERAPEUTICS
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
ldquoproof of conceptrdquo study of an electric radiant heat vaporizer known asthe M-1 Volatizerreg (httpwwwvolatizercom) The M-1 was found todeliver THC while completely eliminating three specific toxins (naph-thalene benzene and toluene) in the solid phase of the vapor The studyalso detected a 56 reduction in tars and a qualitative reduction incarbon monoxide but did not test for any other chemicals (Gieringer2001) The present study (Chemic 2003) is the first to use a GCMS toanalyze the gas phase of vaporized cannabis for a wide range of toxinsconcentrating on the highly carcinogenic PAHs
DESCRIPTION OF THE VOLCANOreg
The Volcano as its name suggests consists of a conical body con-taining a ceramic heater with a heat vent on top (Figure 1) Above thevent sits a removable chamber that is loaded with sample material Hotair is blown from below through the sample to produce vapor which iscollected in a detachable plastic balloon After the balloon has beenfilled it can be removed and fitted with a mouthpiece through whichthe vapors can be inhaled The balloon is a unique feature of the Vol-cano It has the advantages of preventing loss of sidestream vapor andproviding a uniform consistent dosage volume This renders it an idealinstrument for controlled dosage studies
The temperature control ranges from 1 to 9 corresponding to temper-atures of 130deg to 226degC The manufacturer suggests using a temperaturesetting of 7 corresponding to a nominal 202degC Our previous study us-ing the M-1reg found that sample temperatures around 185degC were opti-mal for vaporization with toxins beginning to appear above 200degC(Chemic 2000 Gieringer 2001) As a worst-case test of the Volcanorsquossafety we set it at its highest setting to ascertain whether pyrolytic by-products might result Two thermocouples were placed in the vaporizerabove and below the sample to determine the actual operating tempera-ture The temperature was found to be stable measuring 155degC on thetop surface of the sample and 218degC on the screen closest to the heater
THE SAMPLE
The sample consisted of standard NIDA cannabis supplied throughan independent laboratory Portions were prepared in 17 gram batchesby gently sifting through a 2 mm sieve screen and mixing
The baseline concentrations of cannabinoids in the sample were ana-
10 JOURNAL OF CANNABIS THERAPEUTICS
lyzed by Soxhlet extraction for THC cannabidiol (CBD) and canna-binol (CBN) Three separate samples of 200 mg were extracted in 250ml ethanol under heat for 2 hours concentrated by rotary evaporationand analyzed by HPLC-DAD-MS The mean concentration of THCwas 415 (range 40-43) consistent with NIDA standards CBDand CBN were detected in only trace amounts with the CBD showing awide range of variance 00428-0128 (mean 0075) CBN rangedmore tightly from 0086 to 010 (mean 0094)
The water content of the sample was measured by heating a prepared056 gram sample for 30 minutes at 140degC and measuring the weightloss The water content was found to be 119 by weight
PHASE ONE CANNABINOID RECOVERY ANALYSIS
Vapor from the Volcano was analyzed to determine the cannabinoiddelivery efficiency of the vaporizer A 200 mg sample was loaded into
Gieringer St Laurent and Goodrich 11
FIGURE 1 The Volcanoreg Vaporizer
Photograph courtesy of Storz amp Bickel
the Volcano and exposed to heat for 45 seconds enough to fill the col-lection balloon The vapor was then transferred from the balloon over aperiod of approximately 15 minutes by a vacuum pump into a solventreservoir containing 50 ml of methanol
Three balloons were collected from each sample The three balloonquota was based on preliminary tests which found that most of thecannabinoids were delivered in the first two balloons with just traceamounts in the third The vapor is typically visible as a light gray wispyhaze and has a distinct cannabis terpene odor In practice Volcano usersreport inhaling anywhere from two to six balloons from a given sampleHowever most load the chamber with a half gram or more over twicethe sample size in our tests The more cannabis that is loaded the moreballoons of vapor that can be drawn According to the manufacturer upto ten balloons can be drawn from a one-gram sample (Russo 2003) Inorder to facilitate maximal vaporization the manufacturer recommendsstirring the sample around after inhaling a few balloons then repeatingHowever this procedure was not followed in our tests since we usedrelatively small amounts of sieved material
The dissolved vapor from the Volcano was subjected to quantitativeanalysis on the HPLC-DAD Two separate samples of 15 ml weretested from each dissolved sample as a consistency check The entireprocess was repeated for three different 200 mg samples of cannabisResults are shown in Table 1 On average the recovered THC amountedto 195 of the original weight of the sample or 47 of the originalTHC in the crude sample There was a large variance in the percentageof THC recovered in the three different vaporizer test runs rangingfrom 36 to 61 This suggests that the efficiency of vaporization ishighly sensitive to variations in the sample and micro-conditions in itsenvironment
These results compare favorably to the delivery efficiencies of mari-juana cigarettes as measured in other studies THC efficiencies of 34to 61 were reported in studies of marijuana cigarettes smoked via asmoking machine under varying conditions of puff duration and airspeed (Fehr and Kalant 1971) Efficiencies of 50 were obtained usinga machine designed to mimic human marijuana cigarette smoking(Manno 1970) and in an unpublished study at Battelle by Foltz et al(cited in Truitt 1971) It has been estimated that 23-30 of the THC incombusted cannabis is destroyed by pyrolysis while as much as 40-50can be lost in sidestream smoke (Perez-Reyes 1990) Efficiencies aslow as 16-19 were reported in tests of cigarettes smoked intermit-
12 JOURNAL OF CANNABIS THERAPEUTICS
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
lyzed by Soxhlet extraction for THC cannabidiol (CBD) and canna-binol (CBN) Three separate samples of 200 mg were extracted in 250ml ethanol under heat for 2 hours concentrated by rotary evaporationand analyzed by HPLC-DAD-MS The mean concentration of THCwas 415 (range 40-43) consistent with NIDA standards CBDand CBN were detected in only trace amounts with the CBD showing awide range of variance 00428-0128 (mean 0075) CBN rangedmore tightly from 0086 to 010 (mean 0094)
The water content of the sample was measured by heating a prepared056 gram sample for 30 minutes at 140degC and measuring the weightloss The water content was found to be 119 by weight
PHASE ONE CANNABINOID RECOVERY ANALYSIS
Vapor from the Volcano was analyzed to determine the cannabinoiddelivery efficiency of the vaporizer A 200 mg sample was loaded into
Gieringer St Laurent and Goodrich 11
FIGURE 1 The Volcanoreg Vaporizer
Photograph courtesy of Storz amp Bickel
the Volcano and exposed to heat for 45 seconds enough to fill the col-lection balloon The vapor was then transferred from the balloon over aperiod of approximately 15 minutes by a vacuum pump into a solventreservoir containing 50 ml of methanol
Three balloons were collected from each sample The three balloonquota was based on preliminary tests which found that most of thecannabinoids were delivered in the first two balloons with just traceamounts in the third The vapor is typically visible as a light gray wispyhaze and has a distinct cannabis terpene odor In practice Volcano usersreport inhaling anywhere from two to six balloons from a given sampleHowever most load the chamber with a half gram or more over twicethe sample size in our tests The more cannabis that is loaded the moreballoons of vapor that can be drawn According to the manufacturer upto ten balloons can be drawn from a one-gram sample (Russo 2003) Inorder to facilitate maximal vaporization the manufacturer recommendsstirring the sample around after inhaling a few balloons then repeatingHowever this procedure was not followed in our tests since we usedrelatively small amounts of sieved material
The dissolved vapor from the Volcano was subjected to quantitativeanalysis on the HPLC-DAD Two separate samples of 15 ml weretested from each dissolved sample as a consistency check The entireprocess was repeated for three different 200 mg samples of cannabisResults are shown in Table 1 On average the recovered THC amountedto 195 of the original weight of the sample or 47 of the originalTHC in the crude sample There was a large variance in the percentageof THC recovered in the three different vaporizer test runs rangingfrom 36 to 61 This suggests that the efficiency of vaporization ishighly sensitive to variations in the sample and micro-conditions in itsenvironment
These results compare favorably to the delivery efficiencies of mari-juana cigarettes as measured in other studies THC efficiencies of 34to 61 were reported in studies of marijuana cigarettes smoked via asmoking machine under varying conditions of puff duration and airspeed (Fehr and Kalant 1971) Efficiencies of 50 were obtained usinga machine designed to mimic human marijuana cigarette smoking(Manno 1970) and in an unpublished study at Battelle by Foltz et al(cited in Truitt 1971) It has been estimated that 23-30 of the THC incombusted cannabis is destroyed by pyrolysis while as much as 40-50can be lost in sidestream smoke (Perez-Reyes 1990) Efficiencies aslow as 16-19 were reported in tests of cigarettes smoked intermit-
12 JOURNAL OF CANNABIS THERAPEUTICS
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
the Volcano and exposed to heat for 45 seconds enough to fill the col-lection balloon The vapor was then transferred from the balloon over aperiod of approximately 15 minutes by a vacuum pump into a solventreservoir containing 50 ml of methanol
Three balloons were collected from each sample The three balloonquota was based on preliminary tests which found that most of thecannabinoids were delivered in the first two balloons with just traceamounts in the third The vapor is typically visible as a light gray wispyhaze and has a distinct cannabis terpene odor In practice Volcano usersreport inhaling anywhere from two to six balloons from a given sampleHowever most load the chamber with a half gram or more over twicethe sample size in our tests The more cannabis that is loaded the moreballoons of vapor that can be drawn According to the manufacturer upto ten balloons can be drawn from a one-gram sample (Russo 2003) Inorder to facilitate maximal vaporization the manufacturer recommendsstirring the sample around after inhaling a few balloons then repeatingHowever this procedure was not followed in our tests since we usedrelatively small amounts of sieved material
The dissolved vapor from the Volcano was subjected to quantitativeanalysis on the HPLC-DAD Two separate samples of 15 ml weretested from each dissolved sample as a consistency check The entireprocess was repeated for three different 200 mg samples of cannabisResults are shown in Table 1 On average the recovered THC amountedto 195 of the original weight of the sample or 47 of the originalTHC in the crude sample There was a large variance in the percentageof THC recovered in the three different vaporizer test runs rangingfrom 36 to 61 This suggests that the efficiency of vaporization ishighly sensitive to variations in the sample and micro-conditions in itsenvironment
These results compare favorably to the delivery efficiencies of mari-juana cigarettes as measured in other studies THC efficiencies of 34to 61 were reported in studies of marijuana cigarettes smoked via asmoking machine under varying conditions of puff duration and airspeed (Fehr and Kalant 1971) Efficiencies of 50 were obtained usinga machine designed to mimic human marijuana cigarette smoking(Manno 1970) and in an unpublished study at Battelle by Foltz et al(cited in Truitt 1971) It has been estimated that 23-30 of the THC incombusted cannabis is destroyed by pyrolysis while as much as 40-50can be lost in sidestream smoke (Perez-Reyes 1990) Efficiencies aslow as 16-19 were reported in tests of cigarettes smoked intermit-
12 JOURNAL OF CANNABIS THERAPEUTICS
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
tently on smoking machines (Davis et al 1984) In contrast continuoussmoking on a smoking machine yielded efficiencies of 69
The THC delivery of combusted cannabis was measured in our studyby repeating the experiment with three more 200 mg samples The sam-ples were not rolled into cigarettes but combusted in a glass pipe bowllike that of a marijuana bong Each sample was ignited by exposure toan electric radiant heater placed over the bowl and the smoke wasdrawn through a tube directly into the methanol (Figure 2) The dis-solved smoke was assayed for cannabinoids as previously described
The combusted sample registered a relatively high THC delivery ef-ficiency of 78 The variance was low for the three different test runsThe high efficiency may be explained by the fact that the laboratoryconditions minimized loss of sidestream smoke the sample was com-pletely consumed with no ldquobuttrdquo remaining and the pipestem led di-rectly into the solvent so as not to cause excessive loss by adhesion to
Gieringer St Laurent and Goodrich 13
TABLE 1 Cannabinoid Recovery Efficiencies
(A) CRUDE CANNABIS (Soxhlet Extraction)
Sample THC () CBD () CBN ()
Crude 1 43 0044 010
Crude 2 41 0055 00925
Crude 3 40 0127 00975
Mean (StdDev) 415 (017) 0075 (0044) 0094 (0007)
(B) VOLCANO VAPOR
Sample THC () CBD () CBN ()
Volcano 1 255 012 011
Volcano 2 150 0068 00595
Volcano 3 180 0081 0070
Mean 195 (049) 0091 (0026) 0081 (0025)
(C) COMBUSTED SMOKE
Sample THC () CBD () CBN ()
Combustion 1 34 0155 019
Combustion 2 32 016 0185
Combustion 3 31 013 018
Mean 324 (011) 015 (0016) 019 (0005)
Note Each sample was tested twice in each case results were consistent within 3 Data above reflectthe average of the two test results
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
the walls The amount of THC lost (22) in combustion was consistentwith the losses attributed to pyrolysis in other studies
Theoretically the vaporizer might have been expected to realize ahigher THC delivery efficiency than combustion since it should haveavoided loss of THC by pyrolysis That this was not observed indicatesthat there were other inefficiencies in the vaporization process Themost likely explanation would seem to be incomplete vaporization dueto lack of uniform thorough heating and ventilation of the sample It iscertainly possible that higher efficiencies might have been achieved bystirring the sample and drawing another balloon from the vaporizer asrecommended by the manufacturer
All of the vaporized and combusted samples were also assayed forCBD and CBN The amount of CBD delivered was unexpectedly some-what higher for both the vaporized and combusted samples At firstglance this result is not easy to explain However given the unusuallyhigh variance of CBD measured in the crude samples and the minimallevels of CBD detected the results do not seem to be significant
14 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 2 Combustion Setup Electric heater (MI) radiates down into bowl ig-niting sample below Smoke is drawn by vacuum through tube to solvent reser-voir (below not shown)
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
For CBN there was no significant change under vaporization Incontrast the level of CBN was twice as high in all three combusted sam-ples with little variance This result may be explained by the oxidationof THC under heat (El Sohly 2002) However it should be noted thatthe amounts of CBN observed were still quite low (019) two ordersof magnitude less than the loss of THC observed under combustion
PHASE 2 GAS PHASE GCMS ANALYSIS
The second phase of the study analyzed the gas phase of the vapor fora broad spectrum of compounds via GCMS The GCMS was outfittedwith a DB-XLB analytical separation column (DB-xtra low bleed30 M 025 mm 025 microm film) which is especially suited for the de-tection of polynuclear aromatic hydrocarbons
A PAH reference stock solution was used that included analytes fornaphthalene acenaphthalene anthracene chrysense benzo(a)pyrenebenzo(k)fluoranthene 112-benzoperylene indeno(123-cd)pyreneancenaphthylene fluorene phenanthrene pyrene 12-benzanthracenebenzo(b)fluroanthene and 1246-dibenzanthrancene Pyrene was usedas a reference standard
The evolved vapor from the Volcano was transferred from the collec-tion balloon via vacuum directly to a 250 ml volatile gas trap A 20 mlportion of the gaseous sample was then transferred using a headspacesyringe directly onto the chromatographic system and assayed In addi-tion the condensed residue that had adhered to the gas trap was analyzedby adding 20 ml of methanol to the trap to dissolve it Subsequently1 microl of the solution was injected directly into the GCMS This processwas repeated for three samples with three balloons from each samplemaking a total of nine runs with gas samples and nine more with thecondensed residue
The gas was analyzed qualitatively and semi-quantitatively for poly-nuclear aromatic hydrocarbons at sample concentrations of 225-125microgml The GCMS operated at a thermal gradient of 110deg-320degC over53 min Different compounds were qualitatively identified by compar-ing their response peaks with an NBS reference library Compoundsthat demonstrated greater than 70 match quality in comparison to theNBS mass spectral standard were reported as identified isolated com-pounds Their mass concentrations were estimated from the responsepeak area in terms of the calibrated reference standard for pyrene Thisyielded approximate semi-quantitative mass determinations
Gieringer St Laurent and Goodrich 15
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
A review of the data showed that the Volcano vapor was overwhelm-ingly dominated by THC with trace amounts of a handful of other com-pounds
Representative data for the vapor gas and solvated condensate areshown in Tables 2 and 3 (from the first balloon of one of the samples)
Aside from THC one other cannabinoid CBN was detected NoCBD was detected This was not unexpected since the GCMS analysiswas much less sensitive to cannabinoids than to PAHs In general the
16 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 2 GC-MS Semi-Quantitative Results Gaseous Headspace AnalysisVaporized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
933 1221726 Caryophyllene1 78 00010 13
3062 2417494 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 00020 25
3256 85295887 Dronabinol (THC) 99 0070 891
3362 5487650 Cannabinol (CBN) 81 00045 57
4297 1289703 5-[(Acetyl benz [e] azulene-38-dione 86 00011 13
Total recovered massas Pyrene (mg) 0079Weight extracted (mg) 200 recovered 004 (Nominal semi-quantitative figures)
1 ldquoSesquiterpinoid essential oil commonly found in cannabisrdquo Ethan Russo MD Montana NeurobehavioralSpecialists Missoula MT 59802
TABLE 3 GCMS Semi-Quantitative Results Solvated Extract Analysis Va-porized Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3062 4961669 2-Methyl-2 4 (2H-1-benzopyran-5-ol) 81 0065 190
3255 246510987 Dronabinol (THC) 99 32 943
3362 9875017 Cannabinol (CBN) 94 013 378
Total recovered massas Pyrene (mg) 34Weight extracted (mg) 200 recovered 17 (Nominal semi-quantitative figures)
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
GCMS analysis was intended to measure PAHs but did not provide anaccurate measure of cannabinoids For the latter it was necessary to usethe HPLC
Aside from the cannabinoids only three other compounds were ten-tatively identified in the vapor gas and one in the solvated condensateThe three were caryophyllene (an aromatic terpene found in cannabisand other plants) plus two other compounds of undetermined originone of which also appeared in the condensate
An estimated 17 of the weight of the 200 mg sample was recov-ered in the solvated condensate as approximately quantified in terms ofthe pyrene standard THC accounted for a nominal 943 of the in-ferred estimated mass That the apparent concentration of THC inferredin the GCMS analysis (32 mggm) was much lower than in the HPLC(195 mggm) was partly an artifact of the mathematical representationof THC in terms of pyrene and partly due to the lack of applicability ofthe GCMS system to THC due to low volatility and to sorbation char-acteristics of the analytic column
The gaseous headspace was more tenuous yielding an estimated re-covered mass of just 004 of the sample weight Once again the sam-ple was overwhelmingly dominated by THC
A striking result in both analyses was a lack of significant quantitiesof pyrolytic-induced analytes in the vapor
Comparison runs using combusted cannabis presented a strikinglydifferent picture As in the previous experiment smoke produced by200 mg of cannabis combusted under the M-1 was drawn into a 250 mlvolatile gas trap A 2 ml gaseous sample was injected into the GCMS20 ml of methanol was added to the trap to dissolve the condensed andanother 1 microl sample was injected into the GCMS for a second analysisThis process was repeated for three separate samples
Representative results for the gas and solvated condensate are pre-sented in Tables 4 and 5 respectively (data taken from first run)
Review of the data from the gaseous headspace detected 111 tenta-tively identified compounds including THC and CBN Included werefive known PAHs Cannabinoids represented only 12 of the inferredrecovered mass the remaining 88 consisted of extraneous products ofcombustion
The solvated extract yielded 37 tentatively identified compounds in-cluding five known PAHs THC and CBN constituted 90 of the esti-mated recovered mass (When combusted the product saturated thechromatographic system producing a distorted response hence the ap-parently elevated concentration of THC (579 mggm) as noted above
Gieringer St Laurent and Goodrich 17
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
18 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 GCMS Semi-Quantitative Results Gaseous Headspace AnalysisCombusted Sample
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
430 32935726 Benzeneacetonitrile 91 0027 016
460 2310571 1-Chloro-octadecane 91 0002 001
499 18390657 Naphthalene 90 0015 009
518 69332076 23-Dihydro-benzofuran 86 0057 034
621 4465468 261014-Tetramethyl-hexadecane 90 0004 002
691 86166759 Indole 90 0071 042
712 7925421 1-Methyl-naphthalene 93 0007 004
852 35115397 11-Oxybis-octane 83 0029 017
869 12256513 2610-Trimethyl-tetradecane 83 0010 006
900 23982131 3-Methyl-1H-indole 81 0020 012
932 116897251 Caryophyllene 98 0096 057
1015 313228545 Cyclododecane 97 0257 152
1074 4799627 Pentadecane 97 0004 002
1085 146804387 Heptadecane 98 0120 071
1135 950013208 Nonadecene 86 0780 460
1195 90056152 22-Diethyl-11-biphenyl 94 0074 044
1263 154063760 Hexadecanal 76 0126 075
1310 2964842 Hexadecane 90 0002 001
1350 35308265 Caryophyllene oxide 95 0029 017
1413 33918891 22-Diethyl-11-biphenyl 80 0028 016
1482 296612752 Tetradecanoic acid 99 0243 144
1512 42131403 (Z)-3-Hexadecene 98 0035 020
1547 295232200 Octadecane 98 0242 143
1618 4653356 2-Dodecen-1-yl () succinic anhydride 89 0004 002
1628 3384476 2-Methyl-1-hexadecanol 78 0003 002
1632 5094990 1-Pentadecene 92 0004 002
1733 34270249 2-Heptadecanol 78 0028 017
1752 34215482 2-(Tetradecyloxy)-ethanol 81 0028 017
1774 13953740 Hexadecane 90 0011 007
1787 18906884 Heneicosane 87 0016 009
1808 85618813 Pentadecanoic acid 97 0070 041
1819 151994108 12-Benzenedicarboxylic acid bis (2) 86 0125 074
1850 2213315118 Cyclohaxadecane 99 1816 1071
1865 45837144 Nonadecane 96 0038 022
1877 42293352 1-Nonadecene 90 0035 020
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
Gieringer St Laurent and Goodrich 19
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1900 199692334 2-Hexadecanol 90 0164 097
1917 76550515 2-Heptadecanone 87 0063 037
1937 103194224 Caffeine 94 0085 050
1977 14872741 Docosane 86 0012 007
2002 102125171 1-Octadecene 97 0084 049
2020 96794873 1-Hexadecanol 86 0079 047
2039 57493519 3-Eicosene 97 0047 028
2091 2933718734 Dibutyl phthalate 83 2407 1420
2124 114002736 Nonadecane 90 0094 055
2149 9672077 1-Nonadecene 86 0008 005
2176 122401077 1-Octadecene 99 0100 059
2243 51345191 3567-Tetrah-s-indacen-1(2H)-one 81 0042 025
2254 4913720 Octadecane 95 0004 002
2263 33563860 1-Nonadecene 86 0028 016
2303 32829703 N-Methyl-N-[4-[4-methoxy-acetamide 90 0027 016
2315 82313597 2356-Tetra-s-indacene-17-dione 76 0068 040
2348 857664501 5-Octadecene 97 0704 415
2401 15554319 Octadecane 90 0013 008
2435 140996042 16-Methyl- met heptadecanoic acid 96 0116 068
2452 95037913 5-Dodecyldihydro-2 (3H)-furanone 83 0078 046
2466 32387060 1-Henricosyl formate 90 0027 016
2501 14710926 (Z)-9-Tricosene 91 0012 007
2579 32371423 2-Hexyl-1-decanol 86 0027 016
2586 200623444 Hexadecanamide 93 0165 097
2600 32616620 1-Nonadecene 99 0027 016
2633 53218271 2-Dodecen-1-yl () succinic anhydride 86 0044 026
2665 7339051 2-Dodecen-1-yl () succinic anhydride 89 0006022 004
2709 56583135 Cis-11-Hexadecen-1-yl acetate 81 0046430 027
2721 129242826 1-Phenantthrenecarboxylic acid 7-et 96 0106053 063
2736 10625426 1-Phenantthrenecarboxylic acid 7-et 92 0008719 005
2751 17570838 Tricosane 98 0014418 009
2758 156887637 1-Nonadecene 98 0128737 076
2837 69739203 121-Phenanthrenecarboxylic acid 92 0057226 034
2873 20887801 Hexanedioic acid dioctyl ester 90 0017140 010
2895 98593890 1-Phenantthrenecarboxylic acid 7-et 86 0080903 048
2910 627678209 121-Phenanthrenecarboxylic acid 99 0515053 304
2926 380114163 2-[(2-bu Cyclopropanenanoic acid 92 0311910 184
3065 70574444 2H-1-Benzopyran-5-ol 2-methyl-2-(4 94 0057911 034
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
20 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 4 (continued)
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
3075 85939990 Resocinol 2-p-mentha-18-dien-3-y 98 00705 042
3107 125006268 Tricosane 93 0103 061
3166 21935407 Acetamide N-methyl-N-[4-[4-4methoxy 91 00180 011
3183 432784246 Hexadecanoic acid 23-dihyroxypro 74 0355 210
3246 10236345 Cyclotetradecane1711-trimethyl- 91 000840 005
3258 2219980004 Dronabinol (THC) 99 182 1075
3272 63820716 Hexacosane 96 00524 031
3323 27548366 13-Benzenediol2-(37-dimethyl-2 90 00226 013
3343 33550885 Acetamide N-methyl-N-[4-[4-4methoxy 94 00275 016
3363 240628731 Cannabinol (CBN) 95 0197 116
3409 13044163 Cyclohexane 1-(15-dimethylhexyl)- 86 00107 006
3432 125757721 Heptacosane 99 0103 061
3452 197356583 1-Octdecanethiol 87 0162 096
3517 243624195 Octadecanoic acid 23-dihydroxypro 86 0200 118
3586 69273621 Tricosane 92 00568 034
3615 1676695684 Squalene 94 138 812
3729 34686159 3-Eicosene (E)- 91 00285 017
3734 71189968 Heneicosane 96 00584 034
3877 62069103 Heptacosane 95 00509 030
3910 20150673 2-Dodecen-1-yl () succinic anhydride 94 00165 010
4016 67270687 Heptacosane 97 00552 033
4096 109391601 9-Hexadecenoic acid eicosyl ester 76 00898 053
4104 9230053 Cyclotetradecane 1711-trimethyl- 83 000757 004
4150 30676052 Eicosane 91 00252 015
4179 1169213328 Cholesterol1 99 0959 566
4227 45017056 9-Hexadecenoic acid eicosyl ester 72 00369 022
4261 16741293 Cholesteryl acetate 97 00137 008
4269 4624026 Heneicosane 3-methyl- 91 000379 002
4280 36515665 Eicosane 90 00300 018
4300 4896647 Heneicosane 3-methyl- 91 000402 002
4322 61362365 Cholesta-35-dien-7-one 96 00504 030
4332 28641892 Cholesteryl acetate 99 00235 014
4358 130345192 9-Hexadecenoic acid eicosyl ester 91 0107 063
4386 206844252 Hexadecanoicacid hexadecyl ester 95 0170 100
4415 31783685 Eicosane 83 00261 015
4670 150517876 9-Hexadecenoic acid eicosyl ester 83 0124 073
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
Gieringer St Laurent and Goodrich 21
Retentiontime (min)
Response(area)
Best match1 NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
4702 108047194 1-Octadecanethiol 84 00887 052
5091 86165775 9-Hexadecenoic acid eicosyl 83 00707 042
Total recovered (mg) 170Weight extracted (mg) 200 recovered 85 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons
1 ldquoBest matchrdquo compounds were determined by comparing the GCMS output to the NBS standard refer-ence library They do not necessarily correspond to the true compound present in every case For instancethe entry identified as ldquocholesterolrdquo at retention time 4179 is presumably something else since cholesterolis not produced in plants Most likely it is a wax-like fatty acid of similar molecular weight
TABLE 5 GCMS Semi-Quantitative Results Solvated Extract Analysis Com-busted Sample
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
427 5371404 Phenol 4-ethyl- 91 0071 010
446 4820930 1H-Indene 1-methyl- 91 0063 009
462 11975267 12-Benzennediol 74 0157 023
501 28398562 Naphthalene 91 0373 053
517 33292637 Benzofuran 23-dihydro- 72 0437 063
691 21443444 Indole 87 0282 040
714 5635171 Naphthalene 2-methyl- 95 0074 011
745 5932574 Naphthalene 2-methyl- 93 0078 011
772 4757806 14-Benzenedoil 2-methyl- 91 0062 009
899 11013411 1H-Indole 4-methyl- 90 0145 021
932 60797737 Caryophyllene 99 0798 115
971 4674849 1610-Dodetatriene 711-dimethyl- 96 0061 009
997 2209752 Naphthalene 12356788a-octah 89 0029 004
1020 18874442 4710-Cycloundecatriene 99 0248 036
1112 2060913 1H-3a7-Methanoazuleneoctahydro-1 90 0027 004
1120 2094526 Cylohexene 1-methyl-4-(5-methyl-1 86 0027 004
1214 13696523 Naphthalene decahydro-4a-methyl-1- 92 0180 026
1233 16059454 Naphthalene 12356788a-octah 98 0211 030
1350 17021514 Caryophyllene oxide 96 0223 032
1359 4347127 1H-Cyclopropa [a]naphthalene1a23 98 0057 008
1475 2271757 1010-Dimethylenebicyc 89 0030 004
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
the GCMS did not provide an accurate measurement of cannabinoids)Altogether eight different PAHs were identified in the solvated extractand the gaseous headspace
DISCUSSION
The major finding of this study was a drastic quantitative reduction innon-cannabinoid compounds in the vapor from the Volcano This stronglysuggests that vaporization is an effective method for delivering medi-cally active cannabinoids while effectively suppressing other poten-tially deleterious compounds that are a byproduct of combustion
Numerous outstanding questions about vaporization remain to be re-
22 JOURNAL OF CANNABIS THERAPEUTICS
TABLE 5 (continued)
Retentiontime (min)
Response(area)
Best match NBSLibrarymatchquality
Recoveredconc aspyrene(mgg)
Recovered of total
1533 2173568 5-Azulenemethanol 1233a4567 86 0029 004
1567 26178775 alpha-Bisabolol 87 0344 049
1585 9580620 1-Decene 90 0126 018
1837 32298240 6-Octen-1-ol 37-domethyl- acetate 78 0424 061
1870 2422132 Diphenylethyne 90 0032 005
2124 4388527 Hexadecanoic acid 92 0058 008
2916 3509363 Glaucyl alcohol 86 0046 007
3063 69664748 2H-1-Benzopyran-5-ol 2-methyl-2-(4 95 0915 131
3073 75367485 Resorcinol 2-pmemtha-18-dien-3-y 98 0990 142
3184 4625532 Delta8-Tetrahydrocannabinol 91 0061 009
32591 4408666746 Dronabinol (THC)1 98 579 8304
33071 2029605 Dronabinol (THC)1 91 0027 004
3363 334263844 Cannabinol (CBN) 97 4389 630
3734 3583356 Docosane 96 0047 007
4122 25609584 Vitamine E 89 0336 048
4539 28142178 beta-Amyrin 95 0369 053
Total recovered (mg) 697Weight extracted (mg) 200 recovered 35 (Nominal semi-quantitative figures)
Polynuclear aromatic hydrocarbons1 Significantly increased response resulting in peak splitting thus two consecutive retention times
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
searched This study was not designed to measure the presence of toxicgases with low molecular weight such as ammonia hydrogen cyanideand carbon monoxide which are known to be produced by marijuanacigarettes (Huber 1991 Institute of Medicine 1982) Previous studieshave indicated a qualitative decrease in CO with vaporization but thisremains to be quantitatively measured Neither did this study analyzethe solid tar phase of the vapor for non-cannabinoids However there issound reason to believe that the total amount of tar was drastically re-duced given the absence of detectable combustion Unlike the combustedmarijuana which turned to ash the vaporized sample remained green-ish-brown and intact though clearly dessicated
Numerous unexplored variables could conceivably affect the effi-ciency and output of vaporization Included are variations in tempera-ture differences in the density weight and consistency of material inthe chamber differences in the variety and potency of cannabis usedand use of different preparations such as hashish hash oil etc Furtherresearch is needed to determine the extent of such effects
The effects of vaporization are illustrated in Figure 3 from the manu-facturer The vaporized cannabis does not turn to ash but retains itsoriginal shape as discussed above A microscopic examination revealsthe physical nature of the process The cannabinoids in cannabis areborne in droplets of resin known as glandular trichomes which coat theexterior structures of the flowering tops and the leaves to a lesser ex-tent The trichomes resemble small stalks or protuberances appearinglike dewy-capped mushrooms under a microscope After vaporizationthe resin has evaporated and trichomes have withered while the under-lying vegetative matter remains intact This confirms that vaporizationis essentially a different physical process than combustion
The efficacy of vaporization is further attested by the growing num-ber of patients who have taken up vaporizers instead of smoking Manyusers say they have ceased smoking marijuana altogether because theyfind it unduly irritating to their throat and lungs Instead they say va-porization gives them the same therapeutic effects without any unto-ward irritation or sore throat On the other hand a few refractoryindividuals say they prefer the savor of smoke or claim not to feel thesame impact from vapor It should be noted that vaporizers do not en-tirely eliminate respiratory irritation A puff of strong vaporized canna-bis will occasionally elicit a cough This could be entirely due to THCitself which is known to irritate the bronchial tract (Tashkin 1977)
In summary there is good reason to believe that vaporization is ahighly effective method of smoke harm reduction Nonetheless at pres-
Gieringer St Laurent and Goodrich 23
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
24 JOURNAL OF CANNABIS THERAPEUTICS
FIGURE 3 Cannabis before and after vaporization
(A) Macrophoto of cannabis sample prior to vaporization showing trichomes withresin
(B) Macrophoto after the first passage of hot air flow from the Volcano Part of theresin has vaporized but the majority appears to be intact
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
ent smoked cigarettes from NIDA remain the only FDA approvedmethod of administering cannabis to human subjects The shortcomingsof smoked marijuana have been widely viewed as an obstacle to ap-proval of natural cannabis as a medicine This view was expressed bythe Institute of Medicine in its report on medical marijuana (IOM 1999Executive Summary p 8)
Because of the health risks associated with smoking smokedmarijuana should generally not be recommended for long-termuse
The goal of clinical trials of smoked marijuana would not be todevelop marijuana as a licensed drug but rather as a first step to-wards the possible development of non-smoked rapid-onset de-livery systems However it will likely be many years before a safeand effective cannabinoid delivery system such as an inhaler willbe available for patients
The IOM report failed to note that vaporizers appear to offer a feasi-ble ldquonon-smoked rapid-onset delivery systemrdquo
Gieringer St Laurent and Goodrich 25
(C) Macrophoto after several passages of hot air from the Volcano The resin hasdisappeared and trichomes have withered but non-incinerated fibrous material re-mains
Figure 3 macrophotos reprinted with permission of Storz amp Bickel lthttpwwwvapormeddeen_anwndghtmgt 72403
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
SUBMITTED 070903ACCEPTED IN REVISED FORM 080203
Gieringer St Laurent and Goodrich 27
A major goal of this study was to pave the way for vaporizers to be in-troduced into human studies in particular studies of medical cannabisthat are now normally conducted using NIDA cigarettes Data from thisstudy have been submitted to the FDA in support of an application for aninvestigational device exemption (IDE) to permit the Volcano to be usedin a study by Dr Donald Abrams of the University of California SanFrancisco The study which is being supported by Californiarsquos Center forMedicinal Cannabis Research is essentially a Phase I study of vaporiza-tion The protocol calls for testing inhaled cannabis of three different po-tencies in healthy test subjects The study will compare subjective effectscannabinoid blood levels and carbon monoxide levels in exhaled breathin subjects on six different days three days smoking 400 mgs of NIDAmarijuana of either 17 THC 35 THC or 7 THC and three daysvaporizing identical amounts and strengths of NIDA marijuana
The FDA currently has no criteria for evaluating vaporization de-vices The only device now approved for administering marijuana tohumans is NIDA pre-rolled cigarettes which were approved beforemodern medical device regulations were enacted in 1976 At that timethere was no need for data on toxicity dosage delivery or the chemicalcontent of the smoke delivered Based on the evidence of this study theVolcano should compare favorably in every respect It remains to beseen whether the FDA will require additional pre-clinical tests beforeallowing the Volcano to be used in human subjects
In any case however our research indicates that vaporization is apromising technology for smoke harm reduction A growing number ofvaporizers are now available through the internet (for a list see httpwwwcanormlorghealthfactsvaporizershtml) They range from high-technology devices with medical grade components to simple hand-held glass pipes to be heated over a flame Despite their obvious useful-ness for medical cannabis patients they have to be marketed as herbalvaporizers in order not to run afoul of federal drug paraphernalia lawsWhile usage of vaporizers is rapidly spreading further testing and re-search are clearly needed to optimize vaporization technology
REFERENCES
Chemic Laboratories 2000 Proof of concept release of chemical constituents in can-nabis sativa at 170-185deg versus combustion Unpublished report to CaliforniaNORML and MAPS Nov 17th 2000
Chemic Laboratories 2003 Evaluation of Volcanoreg vaporizer for the efficient emis-sion of THC CBD CBN and the significant reduction andor elimination of
26 JOURNAL OF CANNABIS THERAPEUTICS
polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
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polynuclear-aromatic (PNA) analytes resultant of pyrolysis Unpublished report toCalifornia NORML and MAPS Apr 8th 2003
Davis KH et al 1984 Some smoking characteristics of marijuana cigarettes InAgurell S Dewey WL and Willette RE eds The Cannabinoids ChemicalPharmacologic and Therapeutic Aspects NY Academic Press
ElSohly M 2002 Chemical constituents of cannabis In Grotenhermen F and RussoE eds Cannabis and Cannabinoids Pharmacology Toxicology and TherapeuticPotential NY The Haworth Press
Fehr KO and Kalant H 1972 Analysis of cannabis smoke obtained under differentcombustion conditions Can J Physiol Pharmacol 50 761-7
Gieringer D 1996 Marijuana research waterpipe study MAPS (MultidisciplinaryAssociation for Psychedelic Studies) Bul 6(3) 59-66
Gieringer D 2001 Cannabis vaporization a promising strategy for smoke harm re-duction J Cannabis Therap 1(3-4) 153-70
Huber G M First and O Grubner 1991 Marijuana and tobacco smoke gas-phasecytotoxins Pharmacol Biochem Behav 40(3) 629-36
Institute of Medicine 1982 Marijuana and Health Washington DC National Acad-emy Press
Institute of Medicine 1999 Marijuana and Medicine Assessing the Science BaseWashington DC National Academy Press
Manno JE et al 1970 Comparative effects of smoking marihuana or placebo on hu-man motor performance Clin Pharmacol Ther 11 808-15
Perez-Reyes M 1990 Marijuana smoking factors that influence the bioavailability oftetrahydrocannabinol In CN Chiang and RL Hawks eds Research Findings onSmoking of Abused Substances NIDA Research Monograph 9942-62
Polen M et al 1993 Health care use by frequent marijuana smokers who do notsmoke tobacco West J Med 158(6) 596-601
Russo E 2003 An interview with Markus Storz June 19 2002 J Cannabis Therap3(1) 67-78
Tashkin DP et al 1977 Bronchial effects of aerolized delta-9-tetrahydrocannabinolin healthy and asthmatics subjects Amer Rev Resp Dis 11557-65
Tashkin D 1993 Is frequent marijuana smoking hazardous to health West J Med158(6) 635-7
Truitt E 1971 Biological disposition of tetrahydrocannabinols Pharmacol Rev23(4) 273-8
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Gieringer St Laurent and Goodrich 27
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