Marijuana for Medical Purposes - Queen's University€¦ · Cannabis (Sativa, Indica, or Hybrid) Marijuana (dried leaves and flowering heads) Isolated pure compounds Non-cannabinoids

MarijuanaforMedicalPurposes

Howtosuccessfullyintegrateherbalcannabisandcannabinoidsintoclinicalprac9ce

Faculty/PresenterDisclosure•  Faculty:DanialSchecter,MDCCFP•  Rela*onshipswithcommercialandnon-commercialinterests:–  Grants/ResearchSupport:N/A–  SpeakersBureau/Honoraria:Tweed,Tilray,Cannimed,CannTrust,MeErum

–  Consul*ngFees:MDBriefcase,Tilray,CannTrust,Tweed–  Other:Co-founderandExecu9veDirectoroftheCannabinoidMedicalClinic(CMClinic).

ThisprogramhasreceivedfinancialsupportfromTweedintheformofaneduca*onalgrant.

•  ThisprogramhasreceivedfinancialsupportfromTweedintheformofaneduca*onalgrant.

•  Poten*alforconflict(s)ofinterest:–  BedrocanandTweedbenefitfromthesaleofaproductthatwillbediscussed

inthisprogram:DriedMarijuana–  ValeantCanadabenefitsfromthesaleofaproductthatwillbediscussedin

thisprogram:Cesamet®–  BayerCanadabenefitsfromthesaleofaproductthatwillbediscussedinthis

program:Sa9vex®

DisclosureofCommercialSupport

Biashasbeenmi*gatedbythefollowing:•  Allprogramcontentwasdevelopedandpeer-reviewedbyanindependentphysicianssteeringgroup.

•  Nocommercialornon-commercialorganiza9onhashadanyinputtothecontentofthisprogram.

Mi9ga9ngPoten9alBias

Objec9vesAtthecomple9onofthisprogram,par9cipantswill:•  BeabletofollowtheCollegeofFamilyPhysiciansofCanada

PreliminaryGuidancefortheuseofMedicalMarijuana•  Conceptualizetheendocannabinoidsystemandfunc9on•  Knowtheexis9ngevidenceregardingtheuseofinhaled

marijuanaformedicalpurposes•  Recognizethepoten9alsideeffectsandcontraindica9ons

ofinhaledmarijuana•  UnderstandtheCanadianregula9onsregardingtheuseof

marijuanaformedicalpurposes•  Knowhowtominimizetheriskofabuse,diversionand

inappropriateprescribingofmedicalmarijuana

THEENDOCANNABINOIDSYSTEM

CannabinoidsCannabinoidsareaclassofdiversechemicalcompoundsthatactoncannabinoidreceptorsoncellsthatrepressneurotransmi5errelease

•  Endocannabinoids–Naturallyoccurring

–  Anandamide(AEA),2-arachidonoylglycerol(2-AG),andothers

•  Phytocannabinoids–Derivedfromcannabisplants–  70differentphytocannabinoids

•  delta-9-tetrahydrocannabinol(i.e.Δ9-THC,THC)•  cannabinol(CBN)•  cannabidiol(CBD)

•  Synthe9cCannabinoids

–  Nabilone(Cesamet®)–  Dronabinal(Marinol®)chemicallyiden9caltoΔ9-THC–  Nabiximols(Sa9vex®)mixtureofcannabinoidsderivedfromcannabis

plants•  1:1ra9oofCBDtoTHC

TheEndocannabinoidSystem

–  Immunefunc9on–  Inflamma9on– Appe9te– Metabolismandenergyhomeostasis

–  Cardiovascularfunc9on

– Diges9on–  Bonedevelopmentandbonedensity

–  Pain–  Reproduc9on–  Psychiatricdisease–  Psychomotorbehavior– Memory– Wake/sleepcycles–  Regula9onofstressandemo9onalstate

– Learning

Whatdoesitdo?Evidenceexiststosupporttheroleofthe

endocannabinoidsystemin:


AudienceInterac9onQues9on

Theendocannabinoidsystemis:A. FoundinvirtuallyeveryorganinthebodyB. Limitedtothecentralandperipheralnervoussystem

C. Clearlydefinedinitsfunc9onD. Affectedbyendocannabinoidsfoundininhaledmarijuana

E. Wellrepresentedinthebrainstem

WhatisinMarijuana?

WhatisinMarijuana?Cannabis (Sativa, Indica, or Hybrid)

Marijuana (dried leaves and flowering heads)

Isolated pure compounds

Non-cannabinoids Cannabinoids

Psychoactive •  Δ9-THC •  Δ8-THC •  cannabinol (weak)

Active but not psychoactive •  cannabidiol (CBD)

Inactive •  more than 60 compounds

More than 400 chemical

compounds More than 70

types of cannabinoids

Kalant 2001

CannabinoidAvailabilityinCanada

• TwoClassesofCannabinoidsavailableforpa9ents:

•  D.I.N.:– Nabilone(Cesamet)– Marinol(Dronabinol)–  Sa9vex(Nabiximols)

•  NON-D.I.N.:– HerbalCannabis,extractsandderiva9ves

Nabilone(Cesamet)•  Asynthe*ccannabinoidthatisastrongCB1/2

receptoragonist

•  Coveredbymostpublicandprivateinsuranceplans(ODB/ODSP/WSIB)withnoLUcodeneeded

•  Posologyof0.25mg,0.5mgand1mg(0.25notusuallycovered)

•  Maxrecommendeddailydosageis6mg

•  Indica9ons:Managementofseverenausea/vomi9ngassociatedwithchemotherapy

•  Usuallyused“offlabel”andneedtoinformpa9ents

Sa9vex(Nabiximols)•  Extractfromtheherbalcannabisplantinanoral-mucosalspray

•  HasstandardizeddoseofTHCandCBD;2.7mgTHCand2.5mgCBDperspray

•  Indicatedasadjunc9vetherapyforsymptoma9creliefofspas9cityand/orneuropathicpaininadultswithMS,andforanalgesiainpa9entswithcanceronhighdosesofopioidtreatment.

•  Actsasa9ncture,morerapidonsetofac9onthanNabilone,easyto9trate

•  $$$

HerbalCannabis

•  Noapprovedclinicalindica9onsinCanada•  Notapprovedasa“medica9on”byHealthCanada(NoD.I.N.)

•  Nostandardizeddosing•  VarietyofstrengthsTHC<1%to>29%CBD<1%to>20%

Whatarethedifferencesbetweensynthe9candnatural?

Entourageeffect:Atheorythatallofthevariouscompoundspresentintheplantworktogetherinacoopera9vemanneryieldingthebestresults

Nabilone-Singlemolecule

-Standardizeddosing

-Longeronsetofac9on

-Longerdura9onofac9on

HerbalCannabis-Over80cannabinoids

-Over350terpenes/flavonoids

-Shorteronsetofac9on(inhaled)

-Shorterdura9onofac9on(inhaled)

-Easily9trated

AudienceInterac9onQues9on

TheclinicalevidenceforInhaledMarijuanais:A. VirtuallyavoidB. Limitedtoextrapola9onfromdataonsynthe9ccannabinoids

C. Includesplacebocontrolled,randomizedtrialspublishedinwellrecognized,peerreviewedjournals

D. Includesthousandsofrandomizedsubjects

CLINICALEVIDENCEFORTHEUSEOFINHALEDMARIJUANA

WhatistheEvidenceforInhaledDriedCannabisinDiseaseManagement?

•  NeuropathicandotherPain•  Spas9cityinMul9pleSclerosis•  Anorexiaandwas9nginHIV•  Crohn’sDisease•  Other

DoesitReallyWork?

•  SelfreporteduserssayYES!-  97%useforchronicpain-  50%useforanxiety-  45%useforinsomnia• Systema9cReview(JAMA2015)-  Moderatequalityevidence(QE):

chronicpain&spas9city-  LowQE:CINV,WtgaininHIV,sleep

disorders,ToureEes

N=1

NeuropathicPain

•  Neuropathicpainofatleastthreemonthsindura*oncausedbytraumaorsurgery,withallodyniaorhyperalgesia

•  23cannabisnaïvesubjects•  Randomized,DoubleBlind,PlaceboCross-OverDesign•  2.5%,6%,9.4%THCorplacebo•  Deliveredasasinglesmokedinhala*on3*mesdaily

•  4–14dayperiod–5daysac*ve,9dayswashout

WareMAetal.CMAJ.2010Oct5;182(14):E694-701

Wareetal–Results

Pre-specifiedSecondaryOutcomes

•  Significantimprovementinsleepquality•  Significantimprovementinanxiety

PrimaryOutcome11itemnumericra*ngscale

WareMAetal.CMAJ.2010Oct5;182(14):E694-701

NeuropathicPain

•  Neuropathicpain(ComplexRegionalPainSyndrometype1)•  38cannabisnon-naïvesubjects•  Randomized,DoubleBlind,PlaceboCross-OverDesign•  0,3.5%,7%THCcigarehes•  Deliveredas2puffsfollowedby3puffsfollowedby4puffsat1hour

intervals

WilseyBetal.JPain.2008Jun;9(6):506-21

Wilseyetal-Results

P=0.016ac9vevsplacebo

Pre-specifiedSecondaryOutcomes•  Significantimprovementinpainunpleasantness,andmul9dimensionaldescriptors

•  Nochangenotedinallodyniaorresponsetoheats9muli•  WorseningofaEen9on,learningandmemorywithac9vetreatment

WilseyBetal.JPain.2008Jun;9(6):506-21

Design•  Chronicpain–MSK,posttrauma*c,arthri*c,cancer,fibromyalgia,MS,

sicklecell•  Cannabisnon-naïvesubjectsonsustainedreleasemorphineoroxycodone•  Randomized,DoubleBlind,PlaceboCross-OverDesign•  Inhaledvaporizedcannabis•  Delivered3x/dayfor5days

AbramsDIetal.Clin.Pharmacol.Ther.90:844-851.

•  Sta*s*callysignificant27%[95%CI9–46]reduc*oninpainscore•  Nosignificanteffectonopiatemetabolism•  Limitedby:

•  Smallsamplesize•  Shortdura*on•  Nonrandomized•  Noplaceboarm

AbramsDIetal.Clin.Pharmacol.Ther.90:844-851.

Abramsetal-Results

Baseline PostCannabis

HIVAssociatedNeuropathicPain

•  Double-blind,placebo-controlled,crossoverdesign•  34HIV-associateddistalsensorypredominantpolyneuropathy(DSPN)•  Refractorytoatleasttwopreviousanalgesicclasses•  1%-8%THCdoseescala*onQIDx5daysfollowedby2weekwashout•  Primaryoutcomewaschangeinpainintensityasmeasuredbythe

DescriptorDifferen*alScale(DDS)

Neuropsychopharmacology.2009Feb;34(3):672-80

Ellisetal-Results

•  DDSchange3.3pointsp=0.016vsplacebo•  SimilarresultsforVASpainscale•  46%ofsubjectsreceivedatleast30%reduc*oninpain

Neuropsychopharmacology.2009Feb;34(3):672-80

•  RecentstudyonopiateabuselookingathealthdatareportedbylargeinsuredU.S.employers1

•  AccordingtoCDC,2MAmericansabuseopiates2

•  16,000dieeveryyearfromRxopiateOD3

•  SalesofopiateRxinU.S.∧4xfrom1999–20104

•  259MopiateRxwriEenin2012–enoughforeveryAmericanadulttohavetheirownboEle5

1.  Castlight Health commissioned report. “The Opiate Crisis in America’s Workforce”. 2016 2.  Centers for Disease Control and Prevention (CDC); Prescription Opiate Data http://www.cdc.gov/drugoverdose/data/overdose.html 3.  CDC. Opioid Data Analysis (2013). http://www.cdc.gov/drugoverdose/data/analysis.html 4.  CDC. Morbidity and Mortality Weekly Report. http://www.cdc.gov/mmwr/preview/mmwrhtml/6043a4.htm?s_cid=mm6043a4_w#fig2 5.  CDC. Opioid Painkiller Prescribing. http://www.cdc.gov.vitalsigns/opioid-prescribing/

OpioidSparingEffectsofCannabis

•  OpiateabusecoststheU.S.economynearly$56B1

•  Opiateabusecostsemployers$10Bfromabsenteeism-alone2

Simplyput–theopioidprescrip9oncrisisisgeyngworse,notbeEer

1.  American Society of Addiction Medicine (ASAM). Cited in: Workforce. “Pain Points”. http://www.workforce.com/articles/21855-pain-points 2.  Ibid

OpioidSparingEffectsofCannabis

Costs

WhyAreThereNotMoreStudiesonMedicalCannabis?

•  Studyofendocannabinoidsystems9llininfancy•  Un9lrecentlynolegalaccess,difficul9eswith

standardiza9on•  Ethicalissueswithregardstostandardofcare•  DifficultywithblindingforRCTs•  Therearemanybasicscienceandpre-clinicalstudies•  Numerouspopula9onbasedstudies

PainResManag2014;19(6):328

Mul9pleSclerosis

•  Randomized,double-blind,placebocontrolledcrossoverdesign•  37cannabisnaïveorexposedMSpa*entswithmoderate+spas*city•  Averageof4puffsof4%THCorplacebocigarehes

Corey-BloometalCMAJ.2012Jul10;184(10):1143-50

Cory-Bloometal-Results

•  Significantlyimprovedspas*city(p<0.001)–Primaryoutcome•  Significantlyimprovedpain(p<0.01)•  Significantreduc*onincogni*vefunc*on(p=0.003)•  Nosignificantchangeinphysicalfunc*on

Corey-BloometalCMAJ.2012Jul10;184(10):1143-50

Crohn’sDisease

•  21pa*ents(meanage,40–14y;13men)withCrohn’sDiseaseAc*vityIndex(CDAI)scoresgreaterthan200whodidnotrespondtotherapywithsteroids,immunomodulators,oran*TNF

•  Random,doubleblindcigarehescontaining115mgofΔ9(THC)orplaceboBIDfor8weeks

Na{aliT,etal.ClinGastroenterolHepatol.2013;11:1276–1280

Na{alietal-Results

•  Clinicalresponsenotein10/11subjectsincannabisgroupvs4/10inplacebogroupp=0.028

•  Threepa*entsinthecannabisgroupwereweanedfromsteroiddependency

•  Subjectsreceivingcannabisreportedimprovedappe*teandsleepNa{aliT,etal.ClinGastroenterolHepatol.2013;11:1276–1280

SummaryofEvidenceforUseofDriedCannabisNauseaandvomi*ngMusty,RandRossi,R.(2001).JournalofCannabisTherapeu9cs.1:29-42.Soderpalm,A.H.,Schuster,A.,andde,WitH.(2001)..Pharmacol.Biochem.Behav.69:343-350.Pallia*veCareSuEon,I.R.andDaeninck,P.(2006).J.Support.Oncol.4:531-535.Pisan9,S.,Malfitano,A.M.,Grimaldi,C.,Santoro,A.andothers.(2009).Best.Pract.Res.Clin.Endocrinol.Metab.23:117-131.Mul*pleSclerosisCorey-Bloom,J.,Wolfson,T.,Gamst,A.,Jin,S.andothers.(2012).CMAJ.184:1143-1150.SpinalCordInjuryJoy,J.E.,Watson,S.J.,andBenson,J.A.Washington,DC:Na9onalAcademyPress,1999.Malec,J.,Harvey,R.F.,andCayner,J.J.(1982).Arch.Phys.Med.Rehabil.63:116-118.Was*ngSyndromeHaney,M.,Rabkin,J.,Gunderson,E.,andFol9n,R.W.(2005).Psychopharmacology(Berl).181:170-178.Haney,M.,Gunderson,E.W.,Rabkin,J.,Hart,C.L.andothers.(2007).J.Acquir.Immune.Defic.Syndr.45:545-554.PainMilstein,S.L.,MacCannell,K.,Karr,G.,andClark,S.(1975).Int.Pharmacopsychiatry.10:177-182.Greenwald,M.K.andS9tzer,M.L.(2000)..DrugAlcoholDepend.59:261-275.Wallace,M.,Schulteis,G.,Atkinson,J.H.,Wolfson,T.andothers.(2007).Anesthesiology.107:785-796.Wilsey,B.,MarcoEe,T.,Tsodikov,A.,Millman,J.andothers.(2008).J.Pain.9:506-521.Abrams,D.I.,Jay,C.A.,Shade,S.B.,Vizoso,H.andothers.(2007).Neurology.68:515-521.Ellis,R.J.,Toperoff,W.,Vaida,F.,vandenBrande,G.andothers.(2009).Neuropsychopharmacology.34:672-680.Abrams,D.I.,Couey,P.,Shade,S.B.,Kelly,M.E.andothers.(2011).Clin.Pharmacol.Ther.90:844-851.Ware,M.A.,Wang,T.,Shapiro,S.,Robinson,A.andothers.(2010).Wilsey,B.,MarcoEe,T.,Deutsch,R.,Gouaux,B.andothers.(2012).J.Pain.14:136-148.FibromyalgiaFiz,J.,Duran,M.,Capella,D.,Carbonell,J.andothers.(2011).PLoS.One.6:e18440.InsomniaHaney,M.,Gunderson,E.W.,Rabkin,J.,Hart,C.L.andothers.(2007).J.Acquir.Immune.Defic.Syndr.45:545-554.Ware,M.A.,Wang,T.,Shapiro,S.,Robinson,A.andothers.(2010).CMAJ.182:E694-E701.InflammatoryBowelDiseaseNa{aliT,Bar-LevSchleiderL,DotanIandothers.ClinGastroenterolHepatol.11:1276–1280Na{ali,T.,Lev,L.B.,Yablecovitch,D.,Half,E.andothers.(2011).Isr.Med.Assoc.J.13:455-458.

REFERENCE:hEp://www.cfpc.ca/uploadedFiles/Resources/_PDFs/Authorizing%20Dried%20Cannabis%20for%20Chronic%20Pain%20or%20Anxiety.pdf

SideEffects

Cardiovascular•  Heartrate/rhythm Tachycardiawithacutedosage

–  Prematureventricularcontrac9ons,atrialfibrilla9on•  Peripheralcircula*onVasodilata9on,conjunc9valredness–  Supinehypertension,posturalhypotension

•  Myocardialinfarc*on–  Increasedriskofacutemyocardialinfarc9onwithin1ha{ersmokingcannabisespeciallyinindividualswithexis9ngcardiovasculardisease

•  Stroke–  Increasedriskofexperiencingstrokea{eranacuteepisodeofsmokingcannabis

Respiratory•  Increasedcough,sputumwithchronicsmokingPsychiatric•  Acutepsychosis•  Worseningofpre-exis9nganxietyanddepression•  Possibleearlieronsetofschizophreniainyouth

Neurocogni*ve•  Shorttermreduc9onsofaEen9on,problemsolving,judgment,decision

making•  Typicallyresolvewithin6hours,butmaypersistupto3weeksorlong

las9nginthose<18yo•  DrivingcollisionriskincreaseswithserumTHCconcentra9on

Carcinogenesis

•  Cannabissmokecontainsmanyofthesamechemicalsastobaccosmoke,andcannabissmokecondensatesaremorecytotoxicandmutagenicthancondensatesfromtobaccosmoke

SideEffects

CannabisandYouth•  Increasedriskofaddic9on

– Unlikeothersubstancesthecommonesttoseektreatmentis<20yearsold1

–  35%ofyoungcannabisuseshave>1criteriaoffordependance2

•  Inthoseatrisk,youngerageoffirstcannabisuseisassociatedwithyoungerageofschizophrenia3

•  Regularusers<18increasedriskofpersistentcogni9veeffects4

•  Regularuseinyouthassociatedwithincreasedsocialdysfunc9on,anxietyanddepression5

1.  UrbanoskiKAetal.EurAddictRes2005;11(3):115-232.  NoconA,etal.JPsychiatrRes2006;40(5):394-4033.  DragtS,etal.ActaPsychiatrScand2012;125(1):45-534.  CreanRDetal.JAdddictMed2011;5(1):1-85.  FergussonDMetal.Addic9on2001;97(9):1123-35

Driving•  4.6%ofCanadianusersreportdrivingundertheinfluenceatleastonce

•  Cannabisintoxica9onincreasestheriskofcollisionrelatedmorbidityandmortalityupto3fold

•  Usersshouldnotdrive:–  Foratleast4hoursa{erinhala9on–  For8hoursfollowinguseifeuphoriaexperienced

•  Theabilitytodriveorperformac9vi9esrequiringalertnessmaybeimpairedforupto24hoursfollowingasingleconsump9on

WhoNOTtoPrescribe•  Underage25[CFPC/CPSO]]•  Historyofvasculardisease•  Respiratorydisease(smokedorvaporized)•  SchizophreniaorBipolarDisorder•  MoodorAnxietyDisorder•  Historyofsubstanceabuse•  Concomitantuseofhypno9cs,orotherpsychoac9vedrugs

•  Occupa9onalhazard•  Pregnancyandlacta9on

The“Prescrip9on”A.K .A “med ica l document”

blood pressure pills S: try some different ones, increase gradually, and see how it goes…

M: How much do you think you need?...

XSmoking•  Rapidabsorp9on•  Preferredmethodformany• Wehaveanobliga9ontodiscouragethesmokingofallplantsubstances

HowCanMarijuanabeConsumed?

Vaporiza*on•  Resultsinsmallerquan9tyoftoxicby-productssuchascarbonmonoxide,polycyclicaroma9chydrocarbons(PAHs),andtar

• Moreefficientextrac9onofTHCv.smoking

• Morerapidabsorp9on•  Longtermeffectsunknown



Ingested(oils/baked)• Muchsloweronsetofac9on,longT1/2,lowerpeakbloodlevels

•  Longerdura9onofeffect•  ‘Cleaner’&moreprecisedosing•  Easierto9trate•  Lesss9gmaandbarrierstouse


Brewedtea•  Bioavailabilitylowdueto

poorwatersolubilityofTHC•  Noreliabledataavailablewith

regardtoachievedTHCserumlevels

HarmReduc9on

REGULATIONSANDPRESCRIBINGOFMEDICALMARIJUANA

MMPRMarihuanaforMedicalPurposesRegula9ons

•  HealthCanadaoverhauledtheregula9onsbywhichpa9entswereabletoaccessherbalcannabisin2013.Theregula9onsarenowsimplifiedbutitnowmakesphysiciansthe“gatekeepers”.

•  NolongerformstofilloutthatgotoHealthCanada•  UndertheMMPRpa9entsareabletogetaccessto

herbalcannabis,witha“medicaldocument”(a.k.aprescrip9on)fromtheirdoctor

•  Onlywaytolegallyobtainmedicalcannabisisthroughlicensedproducers(LPs)

•  LPsareauthorizedbyHealthCanadatoproduceandsellherbalcannabisandcannabisoil

•  LPshavetodemonstratecompliancewithregulatoryrequirements(qualitycontrol,records,security)

•  Dispensariesandcompassionclubsare(s9ll)notlegal

MMPRMarihuanaforMedicalPurposesRegula9ons

TheProcess

Pt=pa9entHCP=healthcareproviderLP=licensedproducer

Ptconsultsauthorized

HCP

HCPprovidesmedicaldocument

PtregisterswithLPand

placesorder

LPsendsmedical

cannabistopt

MedicalDocument

Dosing•  Widevaria9oninpainandeuphoriaresponse

–  Painreliefmaybeachievedbylowerdruglevelsthaneuphoria

•  Experiencedvsnaïveimportantconsidera9on•  Pa9entsini9a9ngcannabisRxshouldstartwithverylowdosesandobserveresponse

•  1marijuanacigareEeorvaporizerbowl=300–750mgdriedcannabis–  Toconverttoorallyconsumedmarijuanamul9plyby2.5*

*hEp://www.hc-sc.gc.ca/dhp-mps/marihuana/med/infoprof-eng.php#tbl4

Dosing•  Establishmaintenancedosebyslowescala9onto

bestefficacywithleasteuphoriafromastar9ngdoseof:•  Naïve:0.5g/day5-7%THC1puffTID•  Experienced:1g/day9%THC3puffsTID

•  Upperlevelforuseofmedicaldriedcannabislikely~3.0gperday,andshouldbeconsideredonlyinverycircumscribedanddocumentedcondi7ons

•  CFPCadvisestospecifylowTHCconcentra9ons(≤9%)becausethesearebeststudied

ABUSEANDDIVERSION

IsMarijuanaAddic9ve?

Joy,JEetal.MarijuanaandMedicine:AssessingtheScienceBase,Na9onalAcademyPress,1999

CannabisUseDisorder(DMV-V)DSM-V:Aproblema9cpaEernofcannabisuseleadingtoclinicallysignificantimpairmentordistress

ClinicalFeatures

SocialNetworkExpressingConcern Withdrawal

Symptoms,EG:Anxiety/Insomnia/GIdisturbance

UseInterferes

withProduc9veAc9vi9es

DifficultyDecreasing

UseOtherSubstanceAbuse

Mood,AnxietyorPsycho9cIllness

DemandingRx

PoorSchool,Social

Func9oning

Addic9onRiskTool

BrownRLetal.WisMedJ1995;94:135-140

Diversion

•  Unlikeprescrip9onnarco9csmedicalmarijuanaispricedatorabovestreetlevels

•  Howevers9llsoughtfornon-medicalreasonsbecause:– Avoidsriskofcriminality– Knownhighqualityproduct– Availability– Highcostinremotecommuni9es

•  Urinedrugtes9ngshouldbeconducted

PainAssessment•  Avalidatedpaintooltoassesspainatbaselineandresponseshouldbeused

PainAssessment•  Avalidatedinterferencetooltoassesspainatbaselineandresponseshouldbeused

CleelendCSetal.AnnAcadMed.1994;23(20):129-138

AdaptedMMTreatmentAgreement•  IunderstandthatIamreceivingMedicalMarijuana(MM)

fromDr.__________totreat__________•  Iagreetothefollowing:•  IwillnotseekMMfromanotherphysician.OnlyDr.

_____________willprescribeMMforme.•  IwillnottakeMMinlargeramountsthanisprescribedby

Dr.___________•  Iwillnotgiveorsellmymedica9ontoanyoneelse,

includingfamilymembers;norwillIacceptanyMMfromanyone

•  Iwillstoremymedica9oninasecuredloca9on•  IunderstandthatifIbreakthesecondi9ons,Dr.

___________maychoosetoceasewri9ngMMprescrip9onsforme.

Alterna9vetreatmentagreementavailableintheCFPCPreliminaryGuidanceDocument

Pa9entReferrals

•  Beforereferringpa9ent,ensuretheclinic:– Hasexper9seinthepa9ent’smedical/psychiatriccondi9on

–  Conductsacarefulpa9entassessmentpriortorecommendinganytherapeu9cinterven9on

–  Providesanexplicitstatementonpoliciesontheindica9ons,contraindica9ons,anddosingfordriedcannabis

– Doesnothaveanyfinancialconflictsofinterest,suchaschargingpa9entsfees,orfinancialinvolvementwithlicensedcannabisproducers

CASESTUDY

Mr.JP•  57yearolddisabledformertaxidriver•  InvolvedinMVA7yearspreviouslyresul9ngincomminutedfractureofLhumerus

•  Acutelytreatedwithopenreduc9onandinternalfixa9on

•  Hassufferedregionalpainsince–  DescribedasburningconstantdiscomfortaboutLarm,shoulderandhand

–  Associatedallodynia–  Causedsignificantreduc9oninqualityoflifewithpain,insomniaanddepression

–  Disabledfromworkforpast5years

Mr.JP•  Physicalexam

–  SurgicalscaroverLdorsalhumerus–  Lshoulderrangeofmo9on~50%ofnormalwithstresspainonflexion

andabduc9on–  HyperalgesiaoverLarmfrommidhumerustodorsalhand–  Noapparentmusclewas9ng

•  Currentmanagement

–  NoimprovementnotedwithNSAID,tricyclics,SNRIorphysiotherapy–  Currentlyhasinsufficientreliefwith

•  Pregabalin225mgbid•  Hydromorphcon9n12mgbid

–  Hasbeenobtainingstreetmarijuanaandreportsimprovementinpain,moodandsleepwith1cigareEetwicedaily

•  Presentsreques9ngmedicalmarijuanaauthoriza9on

Mr.JP

Isthisanappropriatepa9entformedicalmarijuana?

A. YESB. NOC. Maybe

Mr.JPIfyouareconsideringprovidingamedical

document,whatwillyoudonext?

A. Providethedocumentauthorizing1.5gramsdaily

B. DourinedrugscreenC. CompleteopiaterisktoolD. CompletetreatmentagreementE. AlloftheaboveF. (B),(C),(D)only

Mr.JPWhichofthefollowingurinedrugscreenresults

wouldstopyoufromprovidingamedicaldocument?

A. Nega9veforalldrugsofabuseB. Posi9veforcannabisandopiatesC. Posi9veforcannabis,opiatesandcocaineD. AlloftheaboveE. (A)and(C)only

Mr.JPIfyouelecttoprescribeacannabinoidforthis

pa9ent,whatfactorswouldinfluenceyourchoiceoforal/sublingualversusinhaled

A. Pa9entpreferenceB. Insistenceofsmokedversusvaporizeduseofinhaledcannabis

C. PrevioususeofinhaledcannabisD. Alloftheabove

Summary•  Theendocannabinoidsystemisubiquitousinhumans•  Limitedevidencesupportstheuseofinhaledcannabisin:

–  Neuropathicandotherformsofpain–  Musclespasminmul9plesclerosis–  Was9ngsyndromeinHIV

•  Physiciansshouldexercisecau9oninprovidingmedicaldocumentsauthorizingpurchaseofmarijuanatoavoid–  Abuse–  Non-supportedindica9ons–  Diversion–  Useinyouth,psychosis,hazardoussitua9onsegdriving

•  LikeitornotphysicianshavebecomethelegislatedgatekeepersofmedicalmarijuanainCanada

Resources•  HealthCanadaInforma9onforHealthCareProfessionalsCannabis(marihuana,marijuana)andthecannabinoidshEp://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/marihuana/med/infoprof-eng.pdf

•  CollegeofPhysiciansandSurgeonsofOntarioPolicyStatement:MarijuanaforMedicalPurposeshEp://www.cpso.on.ca/policies-publica9ons/policy/medical-marijuana

•  CollegeofFamilyPhysiciansofCanadaAuthorizingDriedCannabisforChronicPainorAnxiety-preliminaryguidancehEp://www.cfpc.ca/Dried_Cannabis_Prelim_Guidance/

Date of preparation: December 2012 86

QUESTIONS?

Thankyouforyourpar9cipa9on!

SupplementarySlides

TheEndocannabinoidSystemComponents

Receptors•  CB1

–  AmongthemostcommonG-proteincoupledreceptorsinthecentralandperipheralnervoussystem,butrareinthebrainstem

–  alsoexpressedinmanyotherorgansand9ssuesincluding:»  Adipocytes,leukocytes,spleen,heart,lung,thegastrointes9naltract,kidney,bladder,reproduc9veorgans,skeletalmuscle,bone,joints,andskin

•  CB2–  mosthighlyconcentratedinthe9ssuesandcellsoftheimmunesystem

–  alsobefoundinboneandtoalesserdegreeinnervecellsincludingastrocytes,oligodendrocytesandmicroglia


ComponentsLigands

•  N-arachidonoylethanolamine(i.e."anandamide"orAEA)

•  2-arachidonoylglycerol(2-AG)Degradingenzymes

•  amidehydrolase(FAAH)•  monoacylglycerollipase(MAGL)

ComparisonofCannabisandPrescrip9onCannabinoidsinCanada

Spas9cityinMS,neuropathicpain,cancerpain

Hasbeendiscon9nuedbymanufacturer

MetabolismandDrugInterac9ons•  Primarilyhepa9cthrough2C9,2C19,and3A4•  CYPisozymepolymorphismsaffectthepharmacokine9csofTHC–  CYP2C9*3acommonlossoffunc7onallelesignificantlyincreasesserumconcentra7ons

•  Althoughknowntoinhibitandinducevariouscytochromesnoformaldruginterac9onstudieshavebeendone

•  Exis9ngstudieshavenotdemonstratedsignificanttoxicityorlossofeffectofconcomitantmedica9onsinstudies–  ...butremainawarethatthepossibilityremains

Gastrointes*nal•  Drymouth•  Decreasedgastric/colonicemptying•  Increasedriskofhepa9csteatosis/fibrosis,especiallyinpa9ents

withHepa99sC•  Acuteriskofpancrea99swithchronic,heavy,dailyuse

Reproduc*ve•  An9-androgenic•  Decreasedspermcountandspermmo9lity•  NeurodevelopmentalharmsincludingADD•  Possibleassocia9onwithincreasedfetalloss,lowbirthweight,

prematurity

OtherSideEffects

Medical Marijuana Authorization in Canada

Health Canada www.hc-sc.gc.ca

•  As of Apr 1, 2014 Marihuana for Medical Purposes Regulations (MMPR) replaced Medical Marijuana Access Regulations (MMAR) •  Under MMPR, legal obtainment of medical marihuana is through licensed producers authorized to produce and sell • Patients are no longer allowed to grow or designate a grower • The producers need to demonstrate compliance with regulatory requirements •  Medical marijuana is not prescribed, but its use is authorized

DrasPolicyHighlights•  Physiciansmustweightheavailableevidenceinsupportofdried

marijuanaagainstotheravailabletreatmentop9ons,includingtheoralpharmaceu9calformofcannabinoids.

•  Physiciansmustalsoconsidertherisksassociatedwiththeuseofdriedmarijuana,whichmayinclude,amongothers–  Addic9on–  Symptomsofchronicbronchi9s–  Onsetorexacerba9onofmentalillness

•  Assessmentriskofaddic9onandsubstancediversion•  Physicianswhoprescribedriedmarijuanamustadvisepa9ents

aboutthematerialrisksincluding:–  mustcau9onallpa9entswhoengageinac9vi9esthatrequiremental

alertnessthattheymaybecomeimpairedwhileusingdriedmarijuana

hEp://policyconsult.cpso.on.ca/wp-content/uploads/2014/09/Marijuana-for-Medical-Purposes-Dra{.pdf

Considerothertreatmentop*ons

Considersideeffects

Consideraddic*onanddiversion

Educatepa*entregardingrisks

DrasPolicyHighlights•  Physiciansmustexplaintothepa9enttheextentandquality

oftheevidencefortheirclinicalcondi9on•  Physiciansareadvisedtofollowtheguidelinesformanaging

theriskofabuse,misuseanddiversionofnarco9cs•  Recommendsthatphysicianswhoprescribedriedmarijuana

firstrequirepa9entstosignawriEentreatmentagreement•  Physiciansmustnotchargepa9entsforcomple9ngthe

medicaldocument,orforanyac9vi9esassociatedwithcomple9ngthemedicaldocument

hEp://policyconsult.cpso.on.ca/wp-content/uploads/2014/09/Marijuana-for-Medical-Purposes-Dra{.pdf

Advisepa*entsaboutexis*ngevidence

Documentstepstakentoavoidmisuse

Documentwrihenpa*entagreement

Donotchargeforanyservicesrelatedtoauthoriza*onofmedicalmarijuana

•  Theuseofdriedcannabisformedicalpurposesisnotarecognizedtreatment.•  Anunrecognizedtreatmentcanonlybeusedwithinaresearchframework.•  AsofApril1,2014andun9lfurtherno9ce,onlycertainindica9onswillhavetobe

considered.•  Beforeconsideringtheuseofdriedcannabistotreatamedicalcondi9onprovidedforinthe

previousregula9ons,othertherapeu9cop9onsmustbeconsidered,inpar9cularotherformsofcannabinoidsauthorizedforprescrip9onbyHealthCanada.

•  Aphysicianwhoisaskedtoprescribedriedcannabismustreadthemedicalliteratureandinformhispa9entthatdriedcannabiscanonlybeprescribedwithintheframeworkofaresearchproject.

•  Beforeprescribingdriedcannabis,thephysicianmustobtainthewriEenconsentofthepa9entpar9cipa9nginaresearchproject(consentform)andcarryoutacompletemedicalassessment(assessmentandfollow-upform).

•  Whenaphysicianprescribesdriedcannabis,hemustplanthepa9ent’sfollow-upinaccordancewiththeassessmentandfollow-upformandkeeparegisterofallpa9entsforwhomhehasprescribeddriedcannabis.

•  Aphysicianmaynotsupplythepa9entdirectlywithdriedcannabisordealincannabisorcannabinoids.

•  Aphysicianmaynotbecomeorapplytobecomeacannabisproducer.•  TheprescribingphysicianmustcollaboratewiththeCollègeanditspartnersinthecollec9on

ofscien9ficdatainordertoimproveknowledgeandprac9ceswithrespecttotheuseofcannabisformedicalpurposesandtoensurepa9entsafety.

• Notarecognizedtreatment• Canonlybeusedwithinaresearchframework

• MustobtainthewriEenconsentofthepa9entpar9cipa9nginaresearchproject

• Keeparegisterofallpa9ents• CollaboratewiththeCollègeanditspartnersinthecollec9onofscien9ficdata

Mul9pleSclerosis

•  SurveyofcannabisuseinMSpa*entsinNovaSco*a

•  14%reportedcon*nuinguseofcannabisforsymptomtreatment

ClarkAJetal.Neurology2004;62:2098–2100

Pahernsofcannabisuseamongpa*entswithmul*plesclerosis

ClarkAJ,WareMA,YazerE,MurrayTJ,LynchME.

DoesLongTermMarijuanaSmokingCauseLossofPulmonaryFunc9on

•  Measurementsofpulmonaryfunc*onandsmokingover20years•  5115blackandwhitemenandwomenrecruitedatage18–30

year•  Pulmonaryfunc*ontes*ngperformedatyears0,2,5,10and20

PletcherMJetalJAMA.2012January11;307(2)

DoesLongTermMarijuanaSmokingCauseLossofPulmonaryFunc9on

PletcherMJetalJAMA.2012January11;307(2) 1joint-yearofexposureis1jointorpipebowl/dayx1year

DoesMarijuanaSmokingCauseCancer?

Marijuanauseandriskoflungcancer:a40-yearcohortstudy.•  Cohortstudy49,321menassessedforcannabisuseandotherrelevantvariables

•  10.5%reportedlife9meuseofmarijuanaand1.7%useofmorethan509mes,designatedas"heavy"use

•  A{ercorrec9onforconfounders"heavy"cannabissmokingwassignificantlyassociatedwithhazardra9o2.12,95%CI1.08-4.14ofdevelopinglungcanceroverthe40-yearfollow-upperiod

CallaghanRCetal.CancerCausesControl.2013Oct;24(10):1811-20

COMMONPERCEPTIONSREGARDINGMARIJUANA

DoesMedicalMarijuanaLegaliza9onAffectCrimeRates?

•  RelyingonU.S.statepaneldata,weanalyzedtheassocia*onbetweenstateMMLandstatecrimeratesforallPartIoffensescollectedbytheFBI.

PLoSONE9(3):e92816.

DoesMarijuanaUseAffectCrimeRates?

PLoSONE9(3):e92816.

DoesMarijuanaUseCauseAmo9va9onalSyndrome?

SubstanceAbuseTreatment,Preven9on,andPolicy2006,1:2

•  243dailycannabisuserscomparedto244cannabisnon-users•  EvaluatedwithApathyEvalua9onScale(validatedmeasureofAmo9va9onal

Syndrome)

DoesMarijuanaUseCauseAmo9va9onalSyndrome?

SubstanceAbuseTreatment,Preven9on,andPolicy2006,1:2

•Insistsonamedicaldocumentfordriedcannabisratherthantryingothertreatmentsknowntobeeffec9veforhisorhercondi9on•Usescannabisdailyoralmostdaily,spendingconsiderablenon-produc9ve9meonthisac9vity•Haspoorschool,work,andsocialfunc9oning•Iscurrentlyaddictedtoormisusingothersubstances(otherthantobacco)•Hasriskfactorsforcannabisusedisorder:isyoung,hascurrentmoodoranxietydisorderorahistoryofaddic9onormisuse•Reportshavingdifficultystoppingorreducinguse•Reportscannabiswithdrawalsymptomsa{eradayormoreofabs9nence:intenseanxiety,fa9gue•Hasfriendsorfamilymembersconcernedabouthisorhercannabisuse

Clinicalfeaturesofcannabisusedisorder

Discon9nueAuthoriza9onifPa9ent:

•  Runsoutearlyorusescannabisfromothersources

•  Beginstousealcohol,opioids,orotherdrugsproblema9cally

•  Beginstoshowsignsofacannabisusedisorder

HIVAssociatedWeightLoss

•  Doubleblindcomparisonbetweensmokedmarijuana2%and3.9%anddronabinol5and10mg

•  10HIVposi*vecannabisnon-naïvesubjectsonatleast2an*-retrovirals•  4xdailyfor4daysfollowedby5daywashoutbetweenagents

Haneyetal.JAcquirImmuneDeficSyndr2007;45:545–554

HaneyMetal-Results

(*P,0.01;**P,0.005)

•  Sta*s*callysignificant,dosedependentincreaseincaloricintakenotedforbothac*vetreatments,nodifferencebetweenac*vetreatments

•  Higherdosemarijuanaincreasedsubjec*vera*ngsofsleep•  Allac*vetreatmentsincreasedra*ngsof“gooddrugeffect”,“mellow”

and“high”,onlymarijuanaincreasefeelingsof“s*mulated”,“friendly”and“self-confident”

•  Nochangesnotedincogni*veperformancetes*ng

Haneyetal.JAcquirImmuneDeficSyndr2007;45:545–554