CannabisinMedicine&Society:ANewParadigm?DrMarkA.WareMBBSMSc
AnesthesiaandFamilyMedicine,McGillUniversityAlanEdwardsPainManagementUnit
MUHC
14November2017
LearningObjectives
1. Appreciatethecomponentsofthecannabinoidsysteminplantandhuman
2. Discussthechallengesfacingthehealthprofessionalinachangingcannabisregulatorylandscape
DrMarkA.WareMcGillUniversity2017
Whydohealthprofessionalsneedtoknowaboutcannabis?
AccesstoherbalcannabisInformeddecisionmakingDevelopcannabisresearch
ChangingregulatoryenvironmentInternationalinterest
DrMarkA.WareMcGillUniversity2017
WHO2016DrMarkA.WareMcGillUniversity2017
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Ware et al. Pain Res Manage 2002;7(2):95-99
DrMarkA.WareMcGillUniversity2017
Epidemiologyofmedicalcannabisuse
Disease Prevalence Author(s)
HIV/AIDS 15-40% Sidney 2001, Braitstein 2002, Ware 2002, Woolridge 2005, Prentiss 2006
Epilepsy 21% Gross 2004
Chronic noncancer pain (CNCP) 15% Ware 2003
Multiple sclerosis (MS) 10-12% Page 2005, Clark 2006, Chong 2006
DrMarkA.WareMcGillUniversity2017
CanadianMedicalAssociation2013• E=panelsurvey(n=607;27%)
• concernthatpatientswhorequestmedicalmarijuanamayactuallywantitforrecreationalpurposes(64%)
• insufficientinformationontherisksandbenefitsofmarijuanawhenusedformedicalpurposes(57%)
• insufficientinformationregardingtheappropriateuseofmarijuanaformedicalpurposes(56%)
http://www.cma.ca/advocacy/epanel-medicinal-marijuanaDrMarkA.WareMcGillUniversity2017
Paradigmelements
1. Drugofabusetotherapeuticuse
DrMarkA.WareMcGillUniversity2017
DrMarkA.WareMcGillUniversity2017
Non-psychoactivephytocannabinoids
Cannabis‘strains’
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THCandCBDlevelsincannabisstrains(2015)• DatafromMarch2015
• ~210strainsavailablefor15MMPRLPs
0
2
4
6
8
10
12
14
16
18
20
0 5 10 15 20 25 30 35
CB
D (%
dry
wei
ght)
THC (% dry weight)
Average17.5%THC0.3%CBD
SlidecourtesyofJonPageDrMarkA.WareMcGillUniversity2017
Paradigmelements
1. Drugofabusetotherapeuticuse2. Cannabisisacomplexbotanicalpharmacologicalconstruct
DrMarkA.WareMcGillUniversity2017
©CanadianConsortium for the Investigationof CannabinoidsDrMarkA.WareMcGillUniversity2017
Cannabinoidsas
‘synapticcircuit-
breakers’
NatMed2008;14(9):923-30
DrMarkA.WareMcGillUniversity2017
• Endocannabinoidlevelsincreasedafter:• 30minuterunning(AEA)• Biking• Strenuoushiking• Massage• Osteopathicmanipulation
• Dietaryomega-3sarerequiredforproperendocannabinoidsignalling
DrMarkA.WareMcGillUniversity2017
Syntheticpharmaceuticalapproaches
• FAAHinhibition• PfizercompoundfailedinOAkneetrial(Huggins2012)
• PeripherallyrestrictedCB1agonist• AstraZenecacompoundstatusunknown(Yu2010)
• CB2agonists• GSKcompoundfailedin3rd molarextractiontrial(Ostenfeld 2011)
• CB1antagonists• Rimonabant approvedinEuropeforobesityandsmokingcessation• Withdrawnin2014forsafetyconcerns(depressionandsuicidality)
Paradigmelements
1. Drugofabusetotherapeuticuse2. Cannabisisacomplexbotanicalpharmacologicalconstruct3. Theendocannabinoidsystemisaubiquitousandimportant
physiologicalsubstratefortherapeutictargetidentification
DrMarkA.WareMcGillUniversity2017
CannabinoidsareeffectiveinperipheralneuropathicpainmodelsNerveinjury
• Chronicconstrictioninjury• Sciaticnerveligation• Brachialplexusavulsion• Trigeminalneuralgia
Diabetes• Streptozotocin
Chemotherapy• Paclitaxel• Cisplatin• Vincristine
HIVneuropathyPharmacology&TherapeuticsVolume109,Issues1–2,January2006,Pages57–77
DrMarkA.WareMcGillUniversity2017
WareMA.Cannabinoids.InToth &Moulin(eds)NeuropathicPain.Cambridge,2013
DrMarkA.WareMcGillUniversity2017
15mgherbalcannabis;19%THCSingleinhalationusinginhalerN=10neuropathicpainpatients
25mgherbalcannabis;0,2.5,6,9.4%THCSingleinhalationusingpipe,3timesdailyN=23neuropathicpainpatients
DrMarkA.WareMcGillUniversity2017
The Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for Research
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: Current state of evidence and recommendations for research. Washington, DC: The National Academies Press.
DrMarkA.WareMcGillUniversity2017
MarkA.WareMcGIllUniversity2017
Paradigmelements
1. Drugofabusetotherapeuticuse2. Cannabisisacomplexbotanicalpharmacologicalconstruct3. Theendocannabinoidsystemisaubiquitousandimportant
physiologicalsubstratefortherapeutictargetidentification4. Drugdevelopmentpathwaysforcannabinoidsarechallenging
fromanIPperspectiveanddonotfollowconventionalregulatorychannels
DrMarkA.WareMcGillUniversity2017
Safetyconcerns
• Braindevelopment• Psychosis• Cannabisusedisorder• Cognitivefunction• Driving• Druginteractions• Anxiety/depression• Cardiovasculareffects
• Pregnancy/lactation• Bronchitis• Cannabinoidhyperemesissyndrome
• …
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Uncertaintyinunderstandingcannabis
DrMarkA.WareMcGillUniversity2017
DrMarkA.WareMcGillUniversity2017
DrMarkA.WareMcGillUniversity2017
Incidencerateofnon-seriousAEs
4.62
4.02
6.185.65
2.85 2.93 2.81
0
1
2
3
4
5
6
7
8
Overall Currentcannabis user
Ex cannabisusers
Naïve users
Inci
denc
e ra
te (e
vent
s/pe
rson
-yea
r)
CannabisControl
DrMarkA.WareMcGillUniversity2017
Causality
• Non-serious AEs “certainly/very likely” related to cannabis
• Somnolence: 5• Amnesia: 4• Cough: 4• Nausea: 4• Dizziness: 3
DrMarkA.WareMcGillUniversity2017
“Overthepastyear,Ihaveputalmost40patientsonmedicalcannabis,usuallyoil,almostallwithneuropathicpain…Iamveryimpressedwithitsefficacyandutilityasanopioid-sparingmedication. Itellpatientsthatoncethey areonthecannabisoil,Iwillhelpthemslowlybringdowntheiropioids…a veryfewhavesaiditdidnothingforthem,but90-95%havebeenhelpedtremendously.”
DrMarkA.WareMcGillUniversity2017
MarkA.WareMcGIllUniversity2017
DrMarkA.WareMcGillUniversity2017
DrMarkA.WareMcGillUniversity2017
Prescription cannabinoids
Dronabinol (Δ-9 tetrahydrocannabinol – THC) (2.5 - 10mg)• Oral capsule• Approved for chemotherapy-induced nausea and vomiting and anorexia associated with HIV/AIDS
Nabilone (0.25 - 1.0mg)• Oral capsule• Approved for chemotherapy-induced nausea and vomiting
Nabiximols (2.7mg THC + 2.5mg CBD)• Oromucosal spray• Approved in Canada for multiple sclerosis-associated neuropathic pain, spasticity and advanced
cancer pain
DrMarkA.WareMcGillUniversity2017
Precautionsandcontraindications• Contraindications:
• psychosis• unstableheartdisease• pregnancy
• Precautions• screenforcannabisusedisorder
Paradigmelements
1. Drugofabusetotherapeuticuse2. Cannabisisacomplexbotanicalpharmacologicalconstruct3. Theendocannabinoidsystemisaubiquitousandimportant
physiologicalsubstratefortherapeutictargetidentification4. Drugdevelopmentpathwaysforcannabinoidsarechallengingfrom
anIPperspectiveanddonotfollowconventionalregulatorychannels
5. Withlimiteddataonsafetyandefficacy,howdowemakeclinicaldecisions?
DrMarkA.WareMcGillUniversity2017
Cannabis for Medical Purposes Market Data
FOR OFFICIAL USE ONLY
44
AsofJune30,2017,therewere:
• 201,398 activeclientregistrationswithLPs(↑20%sincelastquarter)
• 6,880individualsregisteredtoproducealimitedamountforpersonalmedicalpurposes(↑101%sincelastquarter)
Cannabis for Medical Purposes Market Data (cont.)
FOR OFFICIAL USE ONLY
45
• Clientdemandforcannabisoilcontinuestorise.
• Q12017-18markedthefirstquarterinwhichsalesofcannabisoilbyweightexceededsalesofdriedmarijuana(6,194kgofcannabisoilvs.5,895kgofdriedmarijuana)
Cannabis for Medical Purposes Market Data (cont.)
FOR OFFICIAL USE ONLY
46
www.registrecannabisquebec.com
DrMarkA.WareMcGillUniversity2017
Paradigmelements
1. Drugofabusetotherapeuticuse2. Cannabisisacomplexbotanicalpharmacologicalconstruct3. Theendocannabinoidsystemisaubiquitousandimportant
physiologicalsubstratefortherapeutictargetidentification4. Drugdevelopmentpathwaysforcannabinoidsarechallengingfrom
anIPperspectiveanddonotfollowconventionalregulatorychannels
5. Withlimiteddataonsafetyandefficacy,howdowemakeclinicaldecisions?
6. Emergingroleof‘realworld’datainevidence-basedmedicine
DrMarkA.WareMcGillUniversity2017
MarkA.WareMcGill2017
Cannabisregulatorydimensions
• Minimizeharms• Age,marketing,labelling,potency,tax&pricing,education,preventionandtreatment,workplacesafety
• Supplyanddistribution• Production,extraction,distributionandsale,derivatives,co-salewithalcohol,personalcultivation
• Publicsafety• Possessionlimits,placeofuse,saletominors,impaireddriving
• Medicalaccess• Researchanddevelopment,cost,access
MarkA.WareMcGill2017
• 43 documents including five systematic reviews, six non-systematic literature reviews, one program evaluation, and 31 primary studies to inform this rapid synthesis.
• Generally, authors found a reduction in the perception of risk of epidemiological harms, and an increase in the adult use of cannabis.
• Mixed effects were found with regards to the impact of cannabis on using other substances, with findings indicating a substitutive or additive effect for the use of alcohol, largely depending on the construction of the cannabis legislation.
• Reduction in mortality from opioid overdoses among states in the U.S. that have legalized medicinal cannabis,
• Reduction in the rates of suicide following legalization of medicinal cannabis.• Increased cannabis-induced visits to the emergency room• Greater number of telephone calls to poison control centres following
children’s accidental ingestion of cannabis
Waddell K, Wilson MG. Rapid synthesis: Examining the impact of decriminalizing or legalizing cannabisfor recreational use. Hamilton, Canada: McMaster Health Forum/Michael G. DeGroote Centre for Medicinal
Cannabis Research, 31 July 2017.
A newparadigm?
• Targetingtheendocannabinoidsystemforhealthanddisease• Understanding‘entourage’effectsofacomplexbotanicalsubstance• Balancingpatient/consumerdemandwithappropriatepolicyresponseandcommunications
• Scienceisslowlyvalidatingpatient’sstories• Arewereadytotalkabout‘safeandresponsiblecannabisuse’?• Withevolvingregulations,wemaybebetterinformedtobeabletomaximizethebenefitandminimizetheharmsofcannabisuseformedicalandnon-medicalpurposes
DrMarkA.WareMcGillUniversity2017