Cannabis in Medicine & Society: A New Paradigm? · Cannabis in Medicine & Society: A New...

CannabisinMedicine&Society:ANewParadigm?DrMarkA.WareMBBSMSc

AnesthesiaandFamilyMedicine,McGillUniversityAlanEdwardsPainManagementUnit

MUHC

14November2017

LearningObjectives

1. Appreciatethecomponentsofthecannabinoidsysteminplantandhuman

2. Discussthechallengesfacingthehealthprofessionalinachangingcannabisregulatorylandscape

DrMarkA.WareMcGillUniversity2017

Whydohealthprofessionalsneedtoknowaboutcannabis?

AccesstoherbalcannabisInformeddecisionmakingDevelopcannabisresearch

ChangingregulatoryenvironmentInternationalinterest

DrMarkA.WareMcGillUniversity2017

WHO2016DrMarkA.WareMcGillUniversity2017

DrMarkA.WareMcGillUniversity2017

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’

DrMarkA.WareMcGillUniversity2017

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

• …

DrMarkA.WareMcGillUniversity2017

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

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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