201764 Cannabisuseanddisorder:Epidemiology,comorbidity,healthconsequences,andmedicolegalstatusUpToDate

OfficialreprintfromUpToDate
www.uptodate.com2017UpToDate

Cannabisuseanddisorder:Epidemiology,comorbidity,healthconsequences,andmedicolegalstatus

Author: DavidAGorelick,MD,PhD
SectionEditor: AndrewJSaxon,MD
DeputyEditor: RichardHermann,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2017.|Thistopiclastupdated:Oct28,2016.

INTRODUCTIONCannabis(alsocalledmarijuana)isthemostcommonlyusedillegalpsychoactivesubstance
worldwide[1].Itspsychoactivepropertiesareprimarilyduetoonecannabinoid:delta9tetrahydrocannabinol
(THC)THCconcentrationiscommonlyusedasameasureofcannabispotency[2].

Thelegalstatusofcannabisuse,formedicalaswellasrecreationalpurposes,variesinternationallyaswellas
acrosstheUnitedStates.Thepotencyofcannabishasincreasedsignificantlyaroundtheworldinrecent
decades,whichmayhavecontributedtoincreasedratesofcannabisrelatedadverseeffects.Cannabisuse
disorderdevelopsinapproximately10percentofregularcannabisusers,andmaybeassociatedwithcognitive
impairment,poorschoolorworkperformance,andpsychiatriccomorbiditysuchasmooddisordersand
psychosis.

Themedicolegalcontext,epidemiology,comorbidity,andhealthconsequencesofcannabisuseandcannabis
usedisorderinadultsarereviewedhere.Thepathogenesis,pharmacology,clinicalmanifestations,course,
assessment,diagnosis,andtreatmentofcannabisusedisorderarereviewedseparately.Acutecannabis
intoxicationisalsoreviewedseparately.(See"Cannabisuseanddisorder:Pathogenesisandpharmacology"and
"Cannabisuseanddisorder:Clinicalmanifestations,course,assessment,anddiagnosis"and"Treatmentof
cannabisusedisorder"and"Cannabis(marijuana):Acuteintoxication".)

EPIDEMIOLOGYCannabisgrowsinnearlyeverycountryintheworld.

CannabisuseCannabiswasusedbyanestimated182millionpeople(range128to234million)worldwidein
2014,approximately3.8percent(range2.7to4.9percent)oftheglobalpopulationage15to64years[1].
CannabisuseismostprevalentinWestandCentralAfrica(12.4percent,30.6millionusers),NorthAmerica
(12.1percent,38.5millionusers),andOceania(10.2percent,2.6millionusers),andleastprevalentinEastand
SouthEastAsia(0.6percent,10.2millionusers),EasternandSouthEasternEurope(2.4percent,5.5million
users),theCaribbean(2.5percent,700thousandusers),andCentralAmerica(2.9percent,810thousandusers)
[1].

Alarge,nationallyrepresentative,communitybased,epidemiologicsurveyestimatedthe2015prevalencerateof
pastyearcannabisuseinthegeneralUnitedStatespopulation(12yearsorolder)at13.5percent(estimated36
millionusers)andpastmonthuseof8.3percent(estimated22.2millionusers)[3].Cannabisuseduringthepast
monthincreasedfrom6.2percent(estimated14.5millionusers)in2003.Twopointsixmillionindividualsinitiated
cannabisusein2015,almosthalf(45percent)12to17yearsold[3].

Riskandprotectivefactorsforcannabisuseinclude:

AgeCannabisusevarieswithage.Thehighestpastyearprevalenceisamongyoungadults(18to25
yearsold)(32.2percent)thelowestprevalenceisamongearlyadolescents(0.8percentamong12year

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oldsand2.6percentamong13yearolds)pastyearprevalenceis10.4percentamongthose26yearsor
older(6.5percent)[3].Cannabisuseisrareinthose65yearsorolder(2.4percent).In2015,themeanage
offirsttimecannabisuserswas21.1years[3].

SexMenarealmosttwiceaslikelyaswomentohaveusedcannabisoverthepastmonth,10.6versus6.2
percent,respectively[3].Menandwomeninitiatecannabisuseinroughlycomparablenumbersandat
roughlycomparablemeanages[3],suggestingthatwomenmaystopcannabisuseathigherrates.Pregnant
womenareonethirdaslikelyasnonpregnantwomentohaveusedcannabisinthepastmonth,withrates
somewhatlowerduringthethirdtrimester(2.7percent)thanthefirsttrimester(4.0percent)[3].

RaceandethnicityCannabisuseoverthepastmonthismoreprevalentamongthoseofmixedrace(13.4
percent),PacificIslanders(9.2percent),blacksorAfricanAmericans(10.7percent),andNativeAmericans
(11.2percent)comparedwithamongthegeneralnonHispanicUnitedStatespopulation(8.5percent),and
lessprevalentamongAsians(3.0percent)[3].Cannabisuseamongwhites(8.4percent)andHispanics(7.2
percent)iscomparabletothatofthegeneralpopulation.

EducationCollegegraduateshavealowerprevalenceofcannabisuseduringthepastmonth(5.9percent)
thandothosewithlesseducation(8.2to10.5percent)[3].Fulltimecollegestudentshavethesamerateof
currentuseasdotheirnonstudentpeers.

Theschoolexperiencestronglyinfluencesriskofcannabisuse.Amongadolescentsenrolledinschool,two
threefoldgreaterprevalenceofcannabisuseduringthepastmonthisseenamongadolescentswith
(comparedwithwithout)thefollowingcharacteristics[4]:

Failinggrades
Nonparticipationinextracurricularactivities
Dislikeofschool
Othersingradewhousecannabis,alcohol,orcigarettes

EmploymentstatusThoseemployedfulltimeornotinthelaborforce(eg,students,retired,disabled)have
lowerprevalenceofcannabisuseduringthepastmonththandothoseworkingparttime(11.6percent)or
unemployed(7.5and4.8versus15percent)[4].

IncomeAdultswithincomelessthan$20,000USDannuallyhave2.5timeshigherratesofcannabisuse
duringthepastyearthanadultswithincomeofatleast$70,000USDannually(15.6versus5.9percent)[5].

MaritalstatusUnmarriedadultsaremorelikelytohaveusedcannabisduringthepastyearthanare
marriedadultsorthosewidowed/separated(21.0versus5.5versus8.3percent)[5].

LegalstatusAdultsonparole,probation,orsupervisedreleasestatusareapproximatelythreetimesmore
likelytohaveusedcannabisinthepastmonththanareindividualsnotinsuchlegalstatus[4].Adolescents
withviolentorillegalbehaviorinthepastyearareatleasttwiceaslikelyasthosewithoutsuchbehavior[4].

SocialnetworkAmongadolescents,apositiverelationshipwithparentsandhavingparents,friends,or
peerswhodisapproveofcannabisuseareallassociatedwithatleasttwofoldlowerprevalenceofcannabis
useoverthepastmonth[4].

ReligionAdolescentswithfrequentattendanceatreligiousservicesorstrongreligiousbeliefsaretwoto
threetimeslesslikelytohaveusedcannabisoverthepastmonththanthosewithoutsuchprotectivefactors
[4].

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OthersubstanceuseCigarettesmokersandalcoholdrinkersareeachfivetosixtimesmorelikelythan
nonsmokersandnondrinkerstousecannabis[4].

GeographyPrevalenceofcannabisuseoverthepastmonthintheUnitedStatesvariessomewhatby
geographiccharacteristics[3].HighestratesarefoundinNewEngland(11.0percent)andtheWest(10.3
percent)andinlarge(>1millionpopulation)metropolitanareas(8.7percent).Lowestratesarefoundinthe
SouthCentralregion(5.9percent)andinruralareas(4.5percent).

PatternsofuseFrequencyofcannabisusevarieswidelyamongthosenotintreatment[4].Approximatelya
quarterofcurrentusersuseonlyonetotwodayspermonth,whileapproximatelytwofifthsuseatleast20days
monthly.Prospectivelongitudinalstudiessuggestseveraldistinctpatternsofuseovertime[6]:

Earlyonsetwithpersistingchronicuse
Lateonsetwithincreasinguseovertime
Uselimitedtoadolescence
Occasionalusewhichneverincreases

Twomodelshavebeenproposedtoexplainthesequenceofcannabisuseinrelationshiptootherpsychoactive
substanceuse:thesequentialgatewaymodelandthecommonliabilitymodel:

SequentialgatewaymodelTheclassicalgatewaymodelholdsthatthereisatypicalsequenceof
initiationofuseofpsychoactivesubstances:firstuse(usuallyinadolescence)oflegalsubstances(alcohol,
tobacco),followedbycannabisuse,andthenuseofmoreharmfulillegaldrugssuchasstimulants,opiates,
orhallucinogens.Themodelassumesacausalrelationshipacrossthesequence,sothatpreventionof
cannabisusewouldlikelypreventlateruseofotherillegaldrugs[7,8].

CommonliabilitymodelPreexistingenvironmentalandgeneticfactorscontributetoallsubstanceuse
andsubstanceusedisorders,sothatuseofaspecificsubstanceatonetimeisnotamajorfactorin
determiningwhatsubstanceisusedatalatertime[8].

Datafromlarge,wellcontrolled,communitybasedepidemiologicstudiesandtwinstudiesaregenerallynot
consistentwiththesequentialgatewaymodel,butareoftensuggestiveofthecommonliabilitymodel[8,9].Cross
nationalstudiessuggestthattheunderlyingprevalenceofsubstanceuseinthepopulationalsoinfluencesthe
sequenceofsubstanceuse[10].

CannabisusedisorderAnestimated13.1millionindividualsworldwidehadmoderateseverecannabisuse
disorderin2010,apointprevalenceof0.19percent[11].Prevalencewasgreatestinyoungadult(20to24years
old)maleslivinginhighincomeregions.

Anestimated4.0millioncommunitydwellingresidentshadcurrent(useduringpastyear)cannabisusedisorder
intheUnitedStatesin2015,aprevalencerateof1.5percent[3],whichhadnotchangedsubstantiallyoverthe
previousdecade(1.8percentin2002)[4].Approximatelyoneineightcannabisusershadacannabisuse
disorder(12.7percent).Asmaller,moredetailedcommunitybasedepidemiologicsurveyfoundadoublingofthe
cannabisusedisorderrateamongadultsoveracomparableperiod,from1.5percent(standarderror0.08)in
2001to2002to2.9percent(standarderror0.13)in2012to2013[5].

Usersofcannabisoverthepastyearare7.6(95%CI4.812.0)timesmorelikelythannonuserstodevelop
cannabisusedisorderoverthenextthreeyears,aftercontrollingforpotentialconfounders[12].Riskof
developingcannabisusedisorderincreasessignificantlywithgreaterintensityofcannabisuse.

Therearesubstantialdifferencesinpopulationratesofcannabisusedisorderoverthepastyearamongdifferent
sociodemographicgroups.Theriskofcannabisusedisorderoverthepastyearamongcannabisusers(socalled

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conditionalcannabisusedisorder)variesmuchless,suggestingthatmuchofthevariationincannabisuse
disorderratesismoreduetodifferencesinratesofcannabisusethantodifferencesindevelopmentofcannabis
usedisorder.

AgePrevalenceofcannabisusedisorderdeclinessubstantiallywithageinadults:7.5percentamong
youngadults(18to29yearsold),1.3percentamongthemiddleaged(45to64yearsold),and0.3percent
amongolderadults65yearsorolder[5].Adolescents(12to17yearsold)haveanintermediateprevalence
(2.9percent)[4].

SexAdultmenaremorethantwiceaslikelyasadultwomentohavecannabisusedisorderoverthepast
year(4.2versus1.7percent,respectively)[5].

EducationAdultswithatleastsomecollegeeducationarelesslikelytohavecannabisusedisorderover
thepastyear(2.5percent)thanarehighschooldropouts(3.3percent)andhighschoolgraduates(3.7
percent)[5].

RaceandethnicityNativeAmericans(5.5percent)andblacks(4.6percent)havehighercannabisuse
disorderratesoverthepastyearthanwhites(2.7percent)andAsians(1.3percent)[5].Hispanicshavea
rate(2.8percent)comparabletothegeneralpopulation(2.9percent).

IncomeCannabisusedisorderratesdeclinesignificantlywithincreasingincomefromlessthan$20,000
USDannuallytoatleast$70,000USDannually[5].

UrbanresidenceThecannabisusedisorderrateoverthepastyearisgreaterinurban(3.1percent)than
inrural(2.3percent)areas[5].

PSYCHIATRICCOMORBIDITYCannabisuseandusedisorderhavehighratesofcomorbidity,inboth
directions,withseveralpsychiatricdisorders,includingothersubstanceusedisorders.Itisoftenuncleartowhat
extentthisisduetoadirectcausalrelationship,thechancecooccurrenceoftwocommonconditions,orthe
presenceofriskfactorscommontobothconditions.(See"Cooccurringschizophreniaandsubstanceuse
disorder:Epidemiology,pathogenesis,clinicalmanifestations,course,assessmentanddiagnosis",sectionon
'Etiologictheories'.)

Themostrigorousinformationcomesfromlarge,representativecommunitybasedstudies,preferably
prospectivelongitudinalstudies,ratherthancrosssectional.Caseseriesofpatientsintreatmentareless
informative,andsubjecttoselectionbias.

AlcoholThereissubstantialbidirectionalcomorbiditybetweencannabisuseorcannabisusedisorderand
alcoholuseoralcoholusedisorder.Prospectivelongitudinalsurveyssuggestthatcannabisusersare2.0(95%
CI1.42.7)[12]to5.43(95%CI4.546.49)[13]timesmorelikelytodevelopalcoholusedisorderoverthenext
threeyearsthanarenonusers.Amongadultswithahistoryofalcoholusedisorder,cannabisuseisassociated
withincreasedlikelihoodofpersistentalcoholusedisorderoverthenextthreeyearscomparedwiththosewithout
cannabisuse(oddsratio1.74,95%CI1.561.95)[13].Amajorityofdailyrecreationalcannabisusersalsobinge
drinkalcohol[14].

TobaccoThereissubstantialbidirectionalcomorbiditybetweencannabisuseorcannabisusedisorderand
cigarettesmoking[15].Alargerepresentative,communitybasedsurveyofUnitedStatesadultsfoundthat
lifetimecannabisusersweremorelikelytoreportlifetimecigarettesmokingcomparedwithrespondentswho
reportednocannabisuse(90versus46.8percent).Peoplewithactivecannabisusedisorderweremorelikelyto
reportcurrentmoderateseveretobaccousedisordercomparedwiththosewithoutcannabisusedisorder(37.5
versus12.9percent).Aprospectivelongitudinalstudyof34,653UnitedStatesadultsfoundthatcannabisusers

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were1.8(95%CI1.22.7)timesaslikelytodevelopamoderatetoseveretobaccousedisorderoverthenext
threeyearsaswerenonusers,aftercontrollingforpotentialconfounders[12].

OpiatesIndividualswithcurrentcannabisusedisorderare2.6timesmorelikelytohaveacurrentheroinuse
disordercomparedwiththosewithoutasubstanceusedisorder[16].

MooddisordersThereissubstantialcomorbiditybetweencannabisuse/cannabisusedisorderandmood
disorders(depression,bipolardisorder).Secondaryanalysesofdatafromarepresentativesampleof43,093
communitybasedadultsintheUnitedStatesfoundthatindividualswithalifetimemooddisorderweretwoto
threetimesmorelikelytohaveusedcannabisduringtheirlifetimecomparedwiththosewithoutanypsychiatric
disorder[17]andtodevelopacannabisusedisorderafterstartingcannabisuse[17,18].Crosssectionalstudies
havefoundlifetimeratesofcannabisuseofapproximately70percentandcannabisusedisorderof
approximately30percentamongpatientswithbipolardisorder[19].

Schizophrenia(nonaffectivepsychosis)Thereissubstantialcomorbiditybetweencannabisuseand
schizophreniasomeexpertsbelievethatearlycannabisuseisacausalfactorindevelopingschizophrenia.(See
'Psychoticdisorders'below.)

Crosssectionalstudiesindicatethatcannabisusershavetwotothreefoldincreasedprevalenceofschizophrenia
comparedwithnonusers[20].Thisassociationisstrongerwithearlierageofonsetofuse(eg,early
adolescence),moreintensecannabisuse,anduseofcannabiswithhighdelta9tetrahydrocannabinol(THC)
contentandTHC:cannabidiolratio[21].Secondaryanalysesofdatafromarepresentativesampleof43,093
communitylivingadultsintheUnitedStatesfoundthatindividualswithlifetimeschizophreniaweretwotothree
timesmorelikelytohavelifetimecannabisusethanthosewithoutanypsychiatricdisorder[17]andtodevelop
cannabisusedisorder[17,18].

Asystematicreviewof53publishedstudiesfoundthatpatientswithschizophreniaspectrumdisordershada23.1
percentprevalence(range4.5to81.1percent)ofcannabisuseoverthepast6monthsanda42.2percent
(range19.2to89.1percent)prevalenceoflifetimeuse[22].Asystematicreviewof35publishedstudiesfound
thatpatientswithschizophreniaspectrumdisordershada16.0percent(8.6to28.6percentinterquartilerange)
prevalenceofcurrentcannabisusedisorderanda27.1percent(12.2to38.5percentinterquartilerange)
prevalenceoflifetimecannabisusedisorder[23].

AnxietydisordersThereissubstantialcomorbiditybetweenanxietydisordersandcannabisuse.Ameta
analysisof31studiesinvolving112,000individualsin10countriesfoundassociationsbetweenanxietydisorder
andcannabisuse(oddsratio=1.24,95%CI1.061.45)orcannabisusedisorder(oddsratio=1.68,95%CI
1.232.31)[24].

Secondaryanalysesofarepresentativesurveyof43,093communitybasedadultsintheUnitedStatesfoundthat
individualswithalifetimeanxietydisorderweretwotothreetimesmorelikelytohavelifetimecannabisusethan
thosewithoutanypsychiatricdisorder[17]andtodevelopacannabisusedisorderafterstartingcannabisuse
[17,18].

Acommunitybased,nationallyrepresentativesurveyofapproximately43,000adultsintheUnitedStatesfound
approximatelyonequarter(24.1percent)ofrespondentswithcurrentcannabisusedisorderhadananxiety
disorder,includingaspecificphobia(14.3percent),generalizedanxietydisorder(7.8percent),socialphobia(7.4
percent),orpanicdisorder(7.3percent)[25].

PersonalitydisordersThereissubstantialcomorbiditybetweencannabisusedisorderandseveral
personalitydisorders,especiallyantisocialandobsessivecompulsivepersonalitydisorders.Acommunitybased,
nationallyrepresentativestudyofapproximately43,000adultsintheUnitedStatesfoundhighratesoflifetime

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personalitydisorderinrespondentswithcurrent(48.4percent)orlifetime(35.9percent)cannabisusedisorder
[25].Lifetimeprevalenceofspecificpersonalitydisordersincluded:

30.2percentforantisocialpersonalitydisorder
18.9percentforobsessivecompulsivepersonalitydisorder
9.1percentforavoidantpersonalitydisorder
4.8percentfordependentpersonalitydisorder

Prospectivefollowupofthecohortfoundthatcannabisuserswithanypersonalitydisorderweremorethantwice
aslikelytodevelopcannabisusedisorderthanthosewithoutanydisorder(adjustedoddsratio2.36,95%CI
2.052.71)[18].

Respondentswithcannabisusedisorderwere10foldmorelikely(oddsratio10.2,95%CI8.7711.88)tohave
antisocialpersonalitydisorderthanthosewithoutcannabisusedisorder[26].Respondentswithcannabisuse
disorderwerealsotwiceaslikelytohavechildhoodconductdisorder(2.2,95%CI1.653.03)andseventimes
morelikelytohaveadultantisocialbehavior(7.1,95%CI6.477.88).Womenshowthisincreasedprevalenceof
personalitydisorderstwothreetimesmorethanmen.

ADVERSEEFFECTSOFCANNABISUSECannabisusedisorderconstitutesasmallproportionoftheglobal
burdenofdiseaserelativetoothersubstanceusedisorders.Oftheapproximatelytwomilliontotaldisability
adjustedlifeyearslosttosubstanceusedisorders(notincludingtobacco),individualsubstanceusedisorders
were[11]:

Alcohol47percent
Opioids24.3percent
Amphetamines7.0percent
Cannabis5.5percent
Cocaine2.9percent
Otherillicitdrugs13.4percent

Largescalecrosssectionalepidemiologicalstudiesandsmallerprospectivelongitudinalstudieshavenotfound
cannabisusetobesignificantlyassociatedwithseriousorchronicmedicalconditionsordeathfrommedical
conditions[11,27].Cannabisusemaybeassociatedwithdeathfrommotorvehicleaccidents.Asexamples:

Asystematicreviewof19publishedstudiesfoundnoevidenceofanassociationbetweenheavycannabis
useandadversehealthoutcomes,exceptforfatalmotorvehiclecrashes[27].

A201640yearlongitudinalcohortstudyof50,373Swedishmalemilitaryconscriptsfoundasignificant,
albeitsmall,associationbetweenheavycannabisuse(>50times)atbaseline(age18to19years)and
overallmortality(hazardratio1.4,95%CI1.11.8)[28].Theassociationwassimilarinthosewithandwithout
ahistoryofpsychoticdisorder,suggestingthatschizophreniawasnotamajorfactordrivingtheincreased
mortality.Theonlyspecificcausesofdeathsignificantlyassociatedwithheavycannabisusewereinfections,
cardiovascular,andinjuriesofunknowncause,allofwhichshowedapositivedoseresponserelationship
withintensityofbaselinecannabisuse.

A13yearprospectivelongitudinalstudyof3124randomlyrecruitedUnitedStatesyoungadultsfoundno
associationbetweenbaselinecannabisuseatleastfourtimespermonthandsubsequentdeclineinself
reportedgeneralhealth[29].

A20yearprospectivelongitudinalstudyofarepresentativebirthcohortof1037individualsborninDunedin,
NewZealandin1972to1973andrecruitedatage18yearsfoundnosignificantassociationbetween

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cannabisuseorcannabisusedisorderandselfreportedphysicalhealth[30].

PsychosocialfunctioningandhealthAdolescentcannabisuseisstronglyassociatedwithlowereducational
attainmentandincreaseduseofotherdrugs,butnotwithschoolperformanceorpsychologicalhealtheventhe
strongassociationsarenotclearlycausal:

Asystematicreviewof16higherqualityprospectivelongitudinalstudiesfoundconsistentassociationsfor
cannabisusewithlowereducationalattainment,andwithincreaseduseofotherillegaldrugs[31].
Inconsistentassociationswerefoundforcannabisusewithpoorpsychologicalhealth,andwithproblematic
orcriminalbehavior.Noneoftheassociationswasdefinitelycausal,withthepossibilitiesofreverse
causation,potentialbias,orconfoundingfactors.

Two2015prospectivelongitudinalstudiesfoundnoassociationforadolescentcannabisusewithhighschool
academicperformanceormentalhealthproblems,aftercontrollingforconcurrentalcoholandtobaccouse
[6,32].

NeuropsychologicaleffectsCannabisacutelyimpairsavarietyofneuropsychologicalfunctionsinadose
dependentmanner,especiallyattention,concentration,episodicmemory,andassociativelearning[33,34].
However,evidenceofanassociationbetweencannabisuseandlongtermneurocognitivedeficitsismixed
[34,35].

Whilemetaanalysesandsystematicreviewsofstudiesoncannabisassociatedneuropsychologicalfunctionin
cannabisusersgenerallyshowimpairment[3335],ametaanalysisof13studiesincludingcannabisuserswithat
leastonemonthofabstinencefoundnodifferencesfromnonusersonneuropsychologicaltestperformance[36].
Thisfindingsuggeststhatcannabisassociatedimpairmentresolvesoverthetimeperiodneededtoeliminate
bodystoresoflipidsolublecannabinoids.

Areviewofthreelongtermprospectivelongitudinalstudiessuggestedthatgreatercumulativeintensityof
cannabisexposureandearlierageofonsetofcannabisusewereassociatedwithgreaterpersistenceof
cannabisassociatedimpairment[37].Amorerecentprospectivelongitudinalstudyof5115adults(aged18to30
yearsatbaseline)foundthat84.3percentwerelifetimecannabisusersat25yearfollowup,whileonly11.6
percentwerecurrentusers[38].Currentcannabisusewasassociatedwithimpairedverbalmemoryandslower
cognitiveprocessingspeed.Alinearregressionanalysisthatexcludedcurrentcannabisusersandcontrolledfor
age,useoftobacco,alcohol,andotherillegaldrugs,andbaselinecognitivefunctionfoundcumulativelifetime
cannabisusesignificantlyassociatedwithimpairedverbalmemory,butnotwithprocessingspeedorexecutive
function.

PsychoticdisordersThereissubstantialevidencethatchroniccannabisuse,especiallyduringadolescence,
isassociatedwithlaterdevelopmentofschizophrenia.Themechanismsresponsiblefortheassociationbetween
cannabisuseandschizophreniaremainunclear.Someexpertsbelievethatearlycannabisuseisacausalfactor
indevelopingschizophrenia.

Asystematicreviewof35longitudinalstudiesfoundanincreasedriskofpsychosisforthosewhoeverused
cannabiscomparedwiththosewhodidnot(adjustedoddsratio1.41,95%CI1.201.65)[39].Therewasa
significantdoseresponserelationship,withatwofoldincreaseinriskamongthosewhousedcannabismost
frequently(oddsratio2.09,95%CI1.542.84).Thereviewadjustedforseveralknownconfoundingfactorsand
excludedcohortswithidentifiedmentalillnessorsubstanceuseproblemsatbaseline.

Cannabisusecausestransientacutepsychosisinsomeusers.Itisnotknownwhetherthisacuteeffectisrelated
tothedevelopmentofschizophreniaassociatedwithchroniccannabisuse.(See"Cannabis(marijuana):Acute
intoxication",sectionon'Toxiceffects'.)

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Cannabisuseexacerbatessymptomsinpatientswithestablishedpsychoticdisorderssuchasschizophrenia.A
systematicreviewandmetaanalysisof24publishedlongitudinalstudies(involving16,565participants)found
thatcannabisusewasassociatedwithincreasedrelapse,rehospitalization,andpositivesymptoms(butnot
negativesymptoms),andpoorerleveloffunctioning[40].Atwoyear,prospectivelongitudinalstudyof220adults
withfirstepisodepsychosisfoundasignificantlyincreasedriskofrelapsewithhospitalizationduringperiodsof
cannabisuse(oddsratio1.1395%CI1.021.24)[41].(See"Cooccurringschizophreniaandsubstanceuse
disorder:Epidemiology,pathogenesis,clinicalmanifestations,course,assessmentanddiagnosis".)

MooddisordersMost,butnotall,prospectivelongitudinalstudieshavefoundthatcannabisuseorcannabis
usedisorderisassociatedwithsubsequentdevelopmentofdepressionorbipolardisorder:

DepressionA2014metaanalysisof14prospectivelongitudinalstudiesthatcontrolledfordepressionat
baselinefoundthatheavycannabisusershada1.62oddsratio(95%CI1.212.16)fordevelopingclinically
diagnosedmajordepressionordepressivesymptoms,comparedwithlightornonusers[42].Asanexample,
athreeyearprospectivelongitudinalstudyofarepresentativesampleofalmost35,000communityliving
UnitedStatesadultsfoundabidirectionalcomorbiditybetweencannabisusedisorderandmajordepressive
disorder[43].Individualswithcannabisusedisorderatbaselinehadanadjustedoddsratio=6.61(95%CI
1.6726.21)formajordepressivedisorderatfollowup,aftercontrollingforlikelyconfounding
sociodemographicvariables.However,aprospectivelongitudinalcommunitybasedstudyof34,653adults
foundcannabisusersatnoincreasedriskofdevelopingamooddisorder(oddsratio1.2,95%CI0.81.6)
[12].

Atwinstudyconcludedthatcomorbidityofcannabisdependenceandmajordepressivedisorderisprobably
duetogeneticandenvironmentalfactorsthatpredisposetobothoutcomes,ratherthanadirectcausal
relationshipbetweencannabisuseanddepression[44].

BipolardisorderAmetaanalysisoftwostudiesofindividualswithbipolardisorderfoundcannabisuse
associatedwithathreefoldincreasedrisk(oddsratio=2.97,95%CI1.804.90)fornewonsetofmanic
symptoms[45].Asanexample,athreeyearprospectivelongitudinalstudyofcommunitylivingUnitedStates
individualsfoundthatinitiationofweeklytoalmostdailycannabisusewasassociatedwithincreased
incidenceofbipolardisorder(adjustedoddsratio=2.47[1.035.9295%CI]),whiledailyusewasnot
associatedwithincreasedincidence(0.61[0.361.04])[46].

Cannabisusehasbeenfoundtobeassociatedwithearlierageofonsetoffirstmanicepisodeandmore
frequentmoodepisodes[19].

AnxietydisordersCannabisintakecausestransientacuteanxietyinmanyusers.Twoprospective
longitudinalstudieshadconflictingfindingsregardingtheassociationbetweenlongtermcannabisuseand
anxietydisorders:

Aprospectivelongitudinalcommunitybasedstudyof34,653UnitedStatesadultsfoundcannabisusersatno
increasedriskofdevelopingananxietydisorder(oddsratio1.0,95%CI0.81.3)[12].

A15yearprospectivelongitudinalstudyof1943Australianadolescentsfounddailycannabisuseduring
adolescenceassociatedwitha2.5foldincreasedriskofanxietydisorderatage29years[47].

PulmonaryCannabissmokecontainsmanyofthesamerespiratoryirritantsandcarcinogensastobacco
smoke[48],althoughtheireffectsmaybemoderatedbytheabsenceofnicotine[49].Cannabissmokingacutely
irritatestheairwaysandisassociatedwithtransientcough,sputumproduction,wheezing,chesttightness,and
airwayinflammation,aswellasbronchodilatation,whichmayaccountforpastuseofcannabistotreatasthma
[48,50].

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Cannabissmokingproducesacute,transitoryrespiratorysymptoms,butchroniccannabisuseisnotassociated
withimpairedpulmonaryfunction:

Asystematicreviewof12studiesthatevaluatedtheeffectofasmokedcannabischallengeonlungfunction
foundan8to48percentdecreaseinairwayresistancelastinguptoonehour(eightstudies),a0.15to0.25
Lincreaseinforcedexpiratoryvolumeone(FEV1)(fivestudies),a10percentincreaseinpeakairflow(one
study),andimmediatereversalofmethacholineinducedorexerciseinducedbronchospasminasthma
patients(onestudy)[50].

Asubacutestudyinwhich28healthy,youngadultmalecannabisuserssmokedcannabiscigarettes(2.2
percentdelta9tetrahydrocannabinol)adlibfor47to59days(meanof5.2cigarettes/day)foundsignificant
decreases,comparedwithbaseline,inFEV1(31percent),maximalmidexpiratoryflowrate(112percent),
plethysmographicspecificairwayconductance(162percent),anddiffusingcapacity(82percent)[51].
Thesefindingssuggestthatregularcannabissmokingforsixtoeightweekscausesmildairwayobstruction.

Asystematicreviewof14studies(9crosssectional,4longitudinal,1casecontrol)comparinglongterm
cannabissmokerswithnonsmokersfoundincreasesinchroniccough,sputumproduction,wheezing,
dyspnea,bronchitis,andpharyngitis,butnosignificantabnormalitiesinpulmonaryfunction[50].

Acrosssectionalsurvey(2007to2010)of6723UnitedStatescommunitylivingadults(18to59yearsold)
foundnosignificantassociationbetweencumulativecannabisuseupto20jointyearsandperformanceon
standardspirometrytests(forcedvitalcapacity[FVC],forcedexpiratoryvolume[FEV],orFEV/FVC)[52].
Greatercumulativeusewasassociatedwithanoddsratioof2.1(95%CI1.1,3.9)foranabnormallylow
(<70percent)FEV/FVC,whichwasduetoincreasedFVC,ratherthandecreasedFEV(unlikeobstructive
lungdisease,whichistypicallyassociatedwithdecreasedFEV).

Aprospectivelongitudinalstudyof5115UnitedStatesadultsfollowedfor20yearsfoundanonlinear
associationbetweencannabisuseandperformanceonstandardspirometrytests[53].Occasionalandlow
intensitycumulativecannabisuse(<7jointyears)wasassociatedwithnochangefrombaselineoreven
improvementinFVCandFEVgreatercumulativecannabisusewaslinearlyassociatedwithworselung
function.

A20yearprospectivelongitudinalstudyofarepresentativebirthcohortof1037individualsborninDunedin,
NewZealandin1972to1973andrecruitedatage18yearsfoundnosignificantassociationbetween
cannabisuseorcannabisusedisorderandimpairedlungfunction[30].

Limitedevidencefromsmallcaseseriesandcasecontrolstudiessuggeststhatinhalationofcannabisvapor
generatedbyelectronicdevicesmaybelessirritatingtothelungsthaninhalationofcannabissmoke[5456].This
suggestionhassomebiologicalplausibility,inthatcannabisvaporhaslesshotgasesandlesstoxicpyrolytic
breakdownproducts,butremainstobeconfirmedbylargersystematicstudies.

CancerMolecular,cellular,andhistopathologicalevidence,bothinvivoandinvitro,plausiblysuggeststhat
cannabissmokingmaycausecancer[57,58]however,epidemiologicstudiesdonotconsistentlyshowa
significantassociation.Thefailuretoobserveasignificantassociationmaybedue,inpart,tosubstantial
methodologiclimitationsinmanystudies,suchasthedifficultycontrollingforimportantconfoundingfactors,
especiallycigarettesmoking,theassessmentofcannabisusebyretrospectiveselfreport,andthesmallsample
sizesforheavycannabisusers.

LungcancerA2006systematicreviewof19studiesevaluatingtheassociationbetweencannabis
smokingandlungcancerfoundassociationswithalveolarmacrophagedysfunction,oxidativestress,and
bronchialmucosalabnormalities,butnoassociationwithlungcancerafteradjustingfortobaccouse[58].A

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morerecentreviewofsixepidemiologicstudiesalsofoundnosignificantassociation[57].(See"Cigarette
smokingandotherpossibleriskfactorsforlungcancer",sectionon'Marijuanaandcocaine'.)

HeadandneckcancerAreviewof11studiesfoundsomeincreasedriskandsomedecreasedrisk
associatedwithcannabissmoking,possiblydueinparttodifferencesinhumanpapillomavirusstatus(a
knowncausalfactorinsuchcancers)[57].Apooledanalysisoffivecasecontrolstudiesincluding4029
casesand5015controlsdidnotfindanassociationbetweencannabisuseandcanceroftheheadandneck
[59].(See"Epidemiologyandriskfactorsforheadandneckcancer",sectionon'Tobaccoproducts'.)

TesticularcancerAmetaanalysisofthreecasecontrolstudiesfoundcannabisuseatleastweekly
associatedwithanincreasedrisk(oddsratioof2.59[95%CI1.60,4.19])fornonseminomatesticularcancer
comparedwithneverusers[60].Therewasinconsistentevidenceregardinganassociationwithseminoma
tumors.

CardiovascularCannabisintakeacutelyincreasessympatheticactivityanddecreasesparasympathetic
activity,resultinginreleaseofcatecholamines,tachycardia,vasodilation,andanincreaseincardiacoutputand
myocardialoxygendemandwithlittleornoincreaseinbloodpressure[61,62].Theseacutechangesprobably
accountfortheorthostatichypotensionassociatedwithcannabisuse[63]andtheassociationbetweencannabis
smokingandacutemyocardialinfarction(althoughtheabsoluteriskappearstobesmall).Furtherinformation
approximatelyassociationsbetweencannabisuseandcardiovasculardiseaseisasfollows:

MyocardialinfarctionCannabissmokingmaybeassociatedwithamodest,shortlivedincreaseinriskof
acutemyocardialinfarction,eveninindividualswithoutahistoryofanginaorhypertension.Aprospective
studyfollowed3886adultinpatientswithanacutemyocardialinfarction,3.2percentofwhomhadsmoked
cannabiswithintheprioryear[64].Cannabissmokerswerelesslikelythannonsmokerstohaveahistoryof
angina(12versus25percent)orhypertension(30versus44percent)attheirindexhospitalization.Acase
crossoveranalysisfounda4.8fold(95%CI2.4,9.5)increasedriskofmyocardialinfarctioninthefirst60
minutesaftercannabisuse,whichbecamenonsignificantbythesecondhour[64].Afteramedian3.8years
offollowup(1913subjects),weeklycannabisusershadahazardratioof4.2(95%CI1.214.3)for
subsequentmortality,comparedwithnonusers[65].Afterupto18yearsoffollowupoftheentirecohort,
therewasnolongeranysignificantdifferenceinmortalityratebetweencannabissmokersandnonsmokers
(29percenthigherrate,95%CI0.81,2.05)[66].

StrokeCannabisusehasbeenassociatedwithstroke,althoughtheabsoluteriskappearstobesmall.A
reviewof64publishedcasesofstrokeassociatedwithcannabisusefoundthatthemajorityhad
characteristicssuggestingcausality,ie,aclosetemporalrelationship,exclusionofotherlikelycauses,and
anotherstrokeafterreuseofcannabis[67].Acrosssectionalnationalsurveyofpatientshospitalizedfor
acuteischemicstrokefoundthatcannabisusershada17percentincreasedlikelihoodofacuteischemic
strokecomparedwithnonusers(oddsratio1.17,95%CI1.15,1.20)[68].

AtrialfibrillationCannabisusehasbeenassociatedwithatrialfibrillationinagrowingnumberofcase
reports,althoughtheabsoluteriskappearstobesmall[69,70].

ArteritisA2013reviewidentified80publishedcases(91percentmen,meanage28.4years)ofcannabis
associatedlimbarteritis,themajorityaffectingthelowerlimbs[61].

HyperemesissyndromeCannabinoidhyperemesissyndromeisawelldefinedbutapparentlyrelativelyrare
syndromeinvolvingepisodicseverenauseaandvomitingandabdominalpainwhichisrelievedbyexposureto
hotwater(showerorbath)[71].Thepathophysiologyremainsunknown,butpatientsarealmostalwaysdaily
cannabisusersforatleastoneyearandsymptomsresolvewithinonetotwodaysofcessationofcannabisuse.
(See"Cyclicvomitingsyndrome",sectionon'Chroniccannabisuse'.)

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ReproductiveCannabisusehasbeenfoundtobeassociatedwithseveralreproductiveprocesses:

SpermatogenesisTheendocannabinoidsystemisinvolvedinregulationofthemalereproductivesystem.
Invitroandinvivostudiessuggestthatcannabisdisruptsthehypothalamicpituitaryadrenalaxis,reduces
spermatogenesis,andimpairsseveralspermfunctions,includingmotility,capacitation,andtheacrosome
reaction[72].Acrosssectionalstudyof1215Danishmalemilitaryrecruitswhohadsmokedcannabiswithin
thepriorthreemonthsfoundthatweeklyormorefrequentusershada28percent(95%CI48,1)lower
spermconcentrationanda29percent(95%CI46,1)lowertotalspermcountcomparedwithlessfrequent
users[73].

ProlactinAcutecannabisuseprobablyhasnosignificanteffectonplasmaprolactinlevels,althoughsome
earlier,smallstudiesshowedeitherincreasesordecreases[74].Chroniccannabisusershaveapproximately
20percentlowerplasmaprolactinlevelsthanhealthynonusers[74].

NeonataloutcomesCannabisusebypregnantwomendoesnotappeartosignificantlyaffectfetalhealth
orneonataloutcome[75].Almostallstudiesarelimitedbyrelyingonselfreporttoassesscannabisuse.A
metaanalysisof10studiesoftheassociationbetweencannabisuseduringpregnancyandbirthweightfound
apooledoddsratioof1.09(95%CI0.941.27)forlowbirthweightwithanycannabisuse[76].Womenwho
usedcannabismorethanfourtimesaweekhadbabieswithbirthweightsameanof131glighterthan
womenwhodidnotuseanycannabis.

Tworetrospectivecohortstudiesfrom2015and2016,oneincluding8138women,680(8.4percent)of
whomusedcannabisduringpregnancy[77],andoneincluding12,069women,106(0.88percent)ofwhom
reportedcannabisuseduringpregnancy[78],foundnosignificantadverseneonataloutcomesassociated
withcannabisuse,aftercontrollingforknownconfounderssuchascigarettesmokingandotherdruguse.
Thelatterstudyfoundthatconcurrentuseofcannabisandtobaccowasassociatedwithsignificantly
increasedrisksovertobaccousealone:pretermbirth(adjustedoddsratio2.6,95%CI1.3,4.9),lowbirth
weight(adjustedoddsratio2.8,95%CI1.6,5.0),andincreasedratesofpreeclampsia(adjustedoddsratio
2.5,95%CI1.4,5.0)[78].(See"Substancemisuseinpregnantwomen",sectionon'Marijuana'.)

BreastmilkCannabinoidsappearinbreastmilk,atlevelsestimatedat0.8percentofthoseingestedby
themother[75].Limitedpreclinicalevidencesuggeststhatcannabisusemayreducelactationbyinhibiting
prolactinsecretion[79].

LiverCannabisuseisnotassociatedwithacutehepatotoxicity[80].Dailycannabisuseworsensthe
progressionofchronicviralhepatitisCinfection.Twocrosssectionalstudieswithacombined585consecutive
patientswithchronichepatitisCinfectionundergoingliverbiopsy(approximatelyhalfcannabisusers)founddaily
cannabissmokingassociatedwithmoreseverefibrosis(oddsratio3.4,95%CI1.57.4)[81]andmoresevere
steatosis(oddsratio2.1,95%CI1.014.5)[82].

DentalCannabissmokingisassociatedacutelywithdrymouthandirritatedoralmucosa,chronicallywith
leukoplakia,inflamedoralmucosa(cannabisstomatitis),increasedriskofperiodontaldisease(gingivitis),andoral
candidiasis[83].A20yearprospectivelongitudinalstudyofarepresentativebirthcohortof1037individualsborn
inDunedin,NewZealandin1972to1973andrecruitedatage18yearsfoundthatcannabisusewasassociated
withsignificantlypoorerperiodontalhealth(beta=0.10,95%CI0.050.16)[30].

OphthalmologicCannabiscausesconjunctivalvasodilation(redeyes)andreducesintraocularpressure[84].
Effectsofcannabisonvisionarepoorlyunderstood,butmayincludeincreasedphotosensitivityanddecreased
visualacuity

MEDICOLEGALCONTEXTUndertheUnitedNationsinternationalSingleConventiononNarcoticDrugs(as
amendedin1972),thecannabisplant,cannabisresinanditsextractsandtincturesareclassifiedunderSchedule
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I,meaninguseshouldbeallowedonlyformedicalandscientificpurposescannabisandcannabisresinarealso
inScheduleIV,meaninguseshouldbelimitedtomedicalandscientificresearch[85].Inpractice,thelegal
statusofcannabisanditsuseinhealthcarevarieswidelyinternationally[86].Possessionofsmallamountsis
legalinallorpartsofseveralcountries(Australia,Colombia,India,Spain,Uruguay)anddecriminalizedinmore
thantwodozen,chieflyinEuropeandLatinAmerica.Medicaluseislegalinaboutadozencountries,including
CanadaandpartsofAustralia.IntheUnitedStates,cannabisissubjecttocontradictorylegalregulationunder
stateandfederallaw.

Cannabisandallphytocannabinoids(ie,compoundsfoundintheCannabissativaplant)areclassifiedas
scheduleIcompoundsundertheUnitedStatesControlledSubstancesAct[87].ScheduleIcompounds,which
areconsideredtohavehighpotentialforabuseandnocurrentlyacceptedmedicaluseintheUnitedStates,
areillegaltopossessoruseunderfederallaw.

MedicaluseAsofSeptember2016,twentyfiveUSstates,theDistrictofColumbia,PuertoRico,andGuam
authorizemedicaluseofcannabis,althoughnotallprogramsareoperational[88].Anadditional17stateshave
limitedprogramsthatauthorizeuseofhighcannabidiol/lowdelta9tetrahydrocannabinol(THC)cannabis
formulationsfortreatmentofchildhoodepilepsy,especiallyrefractoryseizures.Cannabidiolisaphytocannabinoid
withoutpsychoactiveeffects,sohaslittleornoabuseliability.(See"Seizuresandepilepsyinchildren:Refractory
seizuresandprognosis",sectionon'Cannabinoids'.)

Inthesestates,licensedclinicianscanrecommendorcertifypatientswithcertainspecifiedconditions(whichvary
bystate)toobtainmedicalcannabisfromstatelicenseddispensaries(or,inafewstates,growtheirown)[89].
FederalcourtshaveruledthatsuchrecommendationstopatientsarefreespeechprotectedundertheFirst
Amendmentanddonotviolatefederallawsregulatingprescribingofcontrolledsubstances.Severalstates,
includingAlaska,Colorado,Oregon,andWashington,aswellastheDistrictofColumbiahavelegalized
recreationaluseofcannabis.

Thereareahandfulofapprovedmedicalusesinnumerouscountriesforcannabis,cannabisderivedproducts,or
syntheticcannabinoids.(See'Syntheticcannabinoids'below.)

AcannabisextractwithequalproportionsofTHCandcannabidiol(nabiximols,Sativex)isapprovedformedical
usein27countries(includingCanada),butnotintheUnitedStates,fortreatmentofpainandmusclespasticity
duetomultiplesclerosis.(See"Symptommanagementofmultiplesclerosisinadults",sectionon'Cannabinoids'.)

Cliniciansrecommendingcannabisformedicaltreatmentshouldconsider:

PriorexperiencewithcannabisPatientswithnopriorexperiencewithcannabisaremorelikelyto
experiencethepsychoactiveeffectsasdysphoricratherthanpleasurable.Patientswhoareregularcannabis
usersaremorelikelytobetoleranttosomeoftheadverseeffects,eg,cognitiveandpsychomotor
impairment.

CannabinoidcontentDosingofcannabisisdeterminedbythemeansofadministration,frequency,and
amountusedaswellasthecannabinoidcontentoftherecommendedstrain(especiallyintermsofTHCand
THC:cannabidiolratio).Somestatesrequirelabelingofmedicalcannabisstrainsordosingunitswiththeir
contentofmajorcannabinoidssuchasTHCandcannabidiol.StatesthathavelegalizedonlylowTHC:high
cannabidiolmedicalcannabistypicallyhaveamaximumpermittedTHCcontent.

Routeofadministration:

Smokedandinhaledcannabishavearapidonsetofeffect(typicallyminutes)andrelativelyshort
durationofaction(typicallytwotofourhours).Theseroutesarepreferredbysomepatientsbecause
theyallowfrequentandprecisetitrationofdosetoeffect(eg,analgesia).
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Oralcannabishasaslowonsetofeffect(typicallyhalftoonehour)andlongdurationofaction(typically
4to12hours).Thismayleadtoinadvertentoverdosingwhenpatientsdontexperienceeffectsassoon
astheyexpect,theymaytakeanotherdose,resultinginacumulativeoverdose.Thisisespeciallylikely
bypatientsfamiliarwiththerapidonsetofsmokedorinhaledcannabis.

DruginteractionsTHChaspotentialdrugdruginteractionswithothermedications[90].THCisasubstrate
fortheCYP2C9andCYP3A4drugmetabolizingenzymes,somayinteractpharmacokineticallywithother
substancesmetabolizedbytheseenzymes,suchastricyclicantidepressants(2C9),proteaseinhibitors
(3A4),orsildenafil(2C9,3A4)[91].Theclinicalsignificanceoftheseinteractionshasnotbeenestablished.

SedativeeffectAsacentralnervoussystem(althoughnotrespiratory)depressant,THCpotentiatesthe
sedativeeffectsofothercentralnervoussystemdepressantssuchasalcoholandbenzodiazepines.This
additiveinteractionisespeciallyrelevantwhendrivingoroperatingheavymachinery.Asanexample,a2015
blindedcontrolledstudyoftheeffectsofinhaled(vaporized)cannabisandoralalcoholonsimulateddriving
performancefoundthata5mcg/LbloodTHCconcentrationcombinedwitha0.05g/210Lbreathalcohol
concentrationproducedthesameimpairmentasa0.08g/210Lalcoholconcentration[92].

Thereislittleinformationfromcontrolledclinicaltrialsregardingcontraindicationstouseofmedicalcannabis.
Basedonknownadverseeffectsofrecreationalcannabisuse,itseemsprudenttoavoidrecommendingmedical
cannabistoindividualswithahistoryofschizophrenia,arecentacutemyocardialinfarctionorepisodeofcardiac
tachyarrhythmia,orwhomustdriveoroperateheavymachinery.

SyntheticcannabinoidsSyntheticcannabinoidshavebeenapprovedinsomecountriesforspecificclinical
indications.

Dronabinol(MarinolsyntheticTHC)andnabilone(aTHCanalogue,eg,Cesamet)areclassifiedunderschedule
IIIoftheControlledSubstancesActintheUnitedStates(andsimilarschedulesinothercountries)andapproved
bytheUSFoodandDrugAdministrationfororaladministrationinthetreatmentof:

AnorexiaassociatedwithweightlossinpatientswithAIDS.(See"Palliativecare:Assessmentand
managementofanorexiaandcachexia",sectionon'Dronabinol'.)

Nauseaandvomitingassociatedwithcancerchemotherapyinpatientswhohavefailedtorespond
adequatelytoconventionalantiemetictreatments.(See"Preventionandtreatmentofchemotherapyinduced
nauseaandvomitinginadults",sectionon'Pooremesiscontrol/rescuetherapy'.)

Dronabinolandnabilonearepsychoactive,whichisoftenexperiencedasanadverseeffectbycannabisnave
patients.Theyappeartohavelittleabuseordiversionliability[93],perhapsbecausetheoralrouteof
administrationdoesnotprovidetherapidonsetandintenseeuphoriadesiredbythetypicalrecreationaldrug
user.

Syntheticcannabinoidsarediscussedfurtherseparately.(See"Cannabisuseanddisorder:Pathogenesisand
pharmacology",sectionon'Syntheticcannabinoids'.)

SUMMARY

Cannabisisthemostcommonlyusedillegalpsychoactivesubstance,usedbyanestimated182million
individualsworldwide(3.8percentofthe15to64yearoldpopulationin2014andanestimated36million
communitylivingindividuals(13.5percentofthose12yearsandolder)intheUnitedStatesin2015.(See
'Cannabisuse'above.)

RatesofcannabisuseintheUnitedStatesarehigherinyoungadultmenwithlowincomesandnocollege
educationthanamongotherpopulationgroups.Approximatelyoneineightcurrentregularcannabisusers
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developsacannabisusedisorder.(See'Cannabisuse'aboveand'Cannabisusedisorder'above.)

Adolescentcannabisuseisstronglyassociatedwithlowereducationalattainmentandincreaseduseofother
drugs,buttheseassociationsarenotclearlycausal.(See'Psychosocialfunctioningandhealth'above.)

Individualswithcannabisuseorcannabisusedisorderoftenuseotherpsychoactivesubstances,especially
alcoholandtobacco.Substantialbidirectionalcomorbidityisseenbetweencannabisusedisorder,
schizophrenia,andseveralotherpsychiatricdisorders,includingdepression,bipolardisorder(mania),
anxietydisorders,andantisocialpersonalitydisorder.(See'Psychiatriccomorbidity'above.)

Cannabisacutelyimpairsattention,concentration,episodicmemory,associativelearning,andmotor
coordinationinadosedependentmanner.Longtermcannabisuseisassociatedwithimpairmentofverbal
memoryandcognitiveprocessingspeed,whichresolvesafteratleastamonthofabstinence.(See
'Neuropsychologicaleffects'above.)

Substantialevidencesuggeststhatchroniccannabisuse,especiallyduringadolescence,isassociatedwith
laterdevelopmentofschizophrenia.Themechanismsresponsiblefortheassociationbetweencannabisuse
andschizophreniaremainunclear.Someexpertsbelievethatearlycannabisuseisacausalfactorin
developingschizophrenia.(See'Psychoticdisorders'above.)

Chroniccannabisusehasnotbeenfoundtobeassociatedwithseriousorchronicmedicalconditionsor
deathfrommedicalconditions.Cannabisusemaybeassociatedwithdeathfrommotorvehicleaccidents.
(See'Adverseeffectsofcannabisuse'above.)

Cannabissmokingisassociatedwithacute,transientrespiratorysymptoms,butchronicuseisnotassociated
withimpairedlungfunction.(See'Pulmonary'above.)

Cannabissmokingacutelyincreasessympatheticactivityandmyocardialoxygendemand,andisassociated
withasmallincreasedriskofmyocardialinfarctionandstroke.(See'Cardiovascular'above.)

Cannabisuseisalsoassociatedwithperiodontaldisease,hyperemesissyndrome,andalowerspermcount.
Hyperemesissyndromeisarelativelyrareconditioninvolvingepisodicseverenauseaandvomitingand
abdominalpain.Frequentcannabissmokinghasbeenassociatedwithalowerspermcounttheclinical
significanceofthisfindingisunknown.(See'Dental'aboveand'Hyperemesissyndrome'aboveand
'Reproductive'above.)

ACKNOWLEDGMENTSTheeditorialstaffatUpToDatewouldliketoacknowledgeJohnBailey,MD,Robert
DuPont,MD,andScottTeitelbaum,MD,whocontributedtoanearlierversionofthistopicreview.

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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