David Casarett MD MA Professor of Medicine Duke …...David Casarett MD MA Professor of Medicine...
Transcript of David Casarett MD MA Professor of Medicine Duke …...David Casarett MD MA Professor of Medicine...
DavidCasarettMDMAProfessorofMedicineChiefofPalliativeCare
DukeUniversity
Conflictsofinterest
• SAB,CurioWellnessandPalliatech• Noconsultingorspeakingforthe
pharmaceuticalindustry
ViewsdonotreflecttheopinionsofDukeUniversityorDukeHealth
Marijuana:Medicationorweed?
IwroteStoned forJudith…
3Surprises• There’sascienceofhow
cannabisworks• Cannabishasrealpotential
benefits(andrisks)• There’sawidegap
betweenenthusiasmformedicalcannabisandtheevidencesupportingit
Surprise#1:Thereisascienceofhowmarijuanaworks
Surprise#1:There’sascienceofhowcannabisworks
• Tetrahydrocannabinol (THC)• Cannabidiol (CBD)• (Andmanyother
cannabinoids)
Ms.Sativa:Upcloseandpersonal
Cannabissativa/indica:what’sthedifference?
Sativa strains:OftenhigherTHCconcentrationsIndica strains:GenerallylowerTHCandhigherCBDBUT:Speciesdon’treallypredictTHC/CBDlevels
Thescienceofcannabinoidreceptors
THC:CB1andCB2receptors,mostlyinthebrain,plusreproductivesystem
CBD:Otherreceptors,mostlyintheimmunesystem,plusmicroglialcellsinthebrain
Othercannabinoids…Otherreceptors…
Cannabisisnature’swayofhackingtheendocannabinoidsystem
• Anandamide,the“BlissMolecule”
• 2-AG• Manymore
Surprise#1BThere’sascienceofhowtouse
marijuana
Absorptionandmetabolism• Concentration(THC)– flower=2-10%– hash>30%– shatter>80%
• Bioavailability– PO=10-20%;Inhaled=30-50%– BUT:Wide(10-fold)inter-individualvariability(inhaled)
Advantageofsmoking:fastuptake
WilliamO’Shaughnessy,goats,andtinctures
Edibles
Thescienceofedibles
• Cannabinoidsaresolubleinalcoholandlipids:
• Alcohol-based(infusedgrainEtOH)
• Lipid-based(Brownies)
Thefutureofcannabisdeliverysystems?
Surprise#2:Cannabisdoeshaverealmedicalbenefits(andrisks)
“Thebestmedicinethedrugcompaniesdon’twantyoutoknow
about.”-DispensaryownerinSanDiego
Potentialusesinstatelaws:
• Nausea• Chronicpain• Anxiety• PTSD• Anorexia/weightloss• Insomnia• Pediatricepilepsy• Andmanymore…
Howmuchevidenceisthereofmedicalbenefit?
Answer:Notasmuchaswe’dlike
• Moderate evidence:– Neuropathicpain– Spasticity
• Weak evidence:– Nausea–Weightgaininthesettingofchronic,seriousillness(AIDS,cancer)
– Sleep
Neuropathicpain
• GoodRCTdata*• Evidenceofeffectivenessasadjuvanttoopioids(Abrams,2011,ClinPharmTher)
*Abrams,Neurology,2007;Lynch,BrJClin Pharm,2011(Systematicreview);Wilsey,JPain,2008)
• Strengths– RCT– Placebocontrol– Blinded– Low- andhigh-dosegroupstoexaminedoseeffects
• Weaknesses– 39subjects– Imperfectblinding
vImperfectblindingandsmallsizemadethisa“lowquality”study
Blinding:TheAchillesheelofmedicalcannabisresearch
• Amongpatientsassignedfirstto“active”marijuana,14/15(93%)guessedcorrectly
Curescancer?
“Risks?Marijuanadoesn’thaveanyrisks—it’saflower.Notlike
morphine.”
-DispensaryownerinDenver
Risks?
Knownrisks• Drivingimpairment*• Addiction*• Hyperemesissyndrome
Possiblerisks• Myocardialinfarction• Stroke• Schizophrenia• (Psychoticepisodes)• Long-termcognitivedysfunction
• NOT:Cancer,lungdisease
(Pulmonaryrisks)
• VeryminorPFTchanges– IncreasedFVC– DecreasedFEV1andFEV1/FVCforveryheavyusers
– Nocancerrisk(Tashkin,AnnalsATS,2013)
Contaminants
Cardiovascularrisks
• Theoreticalrisk:– IncreasedHR– Orthostasis– Increasedclotting(invitro)
– Hx studies(Aronow andCassidy,NEJM,1974)
• ButnoevidenceofincreasedriskofstrokeorMI
N=3882;Mittleman,Circulation,2001
Weedandwheels
• Slowreactiontimes• Distraction• Lackoffocus• Poorsaliencedetection• Fieldsobrietytestnothelpful
Addiction
Addiction
Compton,JAMA,2003
“Other”
• Infertility• Gynecomastia• Recurrentherpes• Koro• Pneumothorax• Etc
Risks
• Afewrisksareknown• Manyarespeculative• Everyonehasanaxetogrind
• Casereportsarecommonandcanbemisleading
So…Medicationorweed?
• Significantbenefits• Realrisks
“Whatisaweed?Aplantwhosevirtueshaveneverbeendiscovered.”
-RalphWaldoEmerson
Themedicalmarijuanaenthusiasm-evidencegap
Howmuchevidenceofbenefitandsafetyisenough?
Forpatientsandphysicians:• Oneortwosmallstudies
• Ideallyacontrolledtrial• Anecdote
Forresearchersandpolicymakers:• Multiplelargecontrolledtrials
• Placebocontrols• Rigorousblinding• Large-scalesafetystudies
Ifenthusiasmformedicalmarijuanahasoutstrippedtheevidencesupportingitsuse,that’softenbecausepeoplearedissatisfiedwiththemedicalcarethey’rereceiving.
Thanks• ZachKlein,HeatherDespres,
NathanPollack,BobMelamede,JohnMorley,OrrinDevinsky,DonaldTashkin, BarthWilsey,JonathanGavrin,SteveLankenau,TeriFranklin,MarinaGoldman,ChristineRabinak,DonaldAbrams,RaphaelMechoulam,ClintWerner,LarryGidaley…andSashatheWonderDog