National Institute on Drug Abuse (NIDA) Marijuana7 What is the scope of marijuana use in the United...
56
1 National Institute on Drug Abuse (NIDA) Marijuana Last Updated June 2018 https://www.drugabuse.gov
Transcript of National Institute on Drug Abuse (NIDA) Marijuana7 What is the scope of marijuana use in the United...
1
NationalInstituteonDrugAbuse(NIDA)
Marijuana
LastUpdatedJune2018
https://www.drugabuse.gov
2
TableofContents
Marijuana
LetterFromtheDirector
Whatismarijuana?
WhatisthescopeofmarijuanauseintheUnitedStates?
Whataremarijuanaeffects?
Howdoesmarijuanaproduceitseffects?
Doesmarijuanauseaffectdriving?
Ismarijuanaaddictive?
Whataremarijuana'slong-termeffectsonthebrain?
Ismarijuanaagatewaydrug?
Howdoesmarijuanauseaffectschool,work,andsociallife?
Istherealinkbetweenmarijuanauseandpsychiatricdisorders?
Whataremarijuana'seffectsonlunghealth?
Whataremarijuana’seffectsonotheraspectsofphysicalhealth?
Ismarijuanasafeandeffectiveasmedicine?
Whataretheeffectsofsecondhandexposuretomarijuanasmoke?
Canmarijuanauseduringandafterpregnancyharmthebaby?
AvailableTreatmentsforMarijuanaUseDisorders
WherecanIgetfurtherinformationaboutmarijuana?
References
3
LetterFromtheDirector
Changesinmarijuanapoliciesacrossstateslegalizingmarijuanaformedical
and/orrecreationalusesuggestthatmarijuanaisgaininggreateracceptancein
oursociety.Thus,itisparticularlyimportantforpeopletounderstandwhatis
knownaboutboththeadversehealtheffectsandthepotentialtherapeutic
benefitslinkedtomarijuana.
Becausemarijuanaimpairsshort-termmemoryandjudgmentanddistorts
perception,itcanimpairperformanceinschooloratworkandmakeit
dangeroustodrive.Italsoaffectsbrainsystemsthatarestillmaturingthrough
youngadulthood,soregularusebyteensmayhavenegativeandlong-lasting
effectsontheircognitivedevelopment,puttingthematacompetitive
disadvantageandpossiblyinterferingwiththeirwell-beinginotherways.Also,
contrarytopopularbelief,marijuanacanbeaddictive,anditsuseduring
adolescencemaymakeotherformsofproblemuseoraddictionmorelikely.
PhotobytheNIDA
4
Whethersmokingorotherwiseconsumingmarijuanahastherapeuticbenefits
thatoutweighitshealthrisksisstillanopenquestionthatsciencehasnot
resolved.Althoughmanystatesnowpermitdispensingmarijuanaformedicinal
purposesandthereismountinganecdotalevidencefortheefficacyof
marijuana-derivedcompounds,theU.S.FoodandDrugAdministrationhasnot
approved"medicalmarijuana."However,safemedicinesbasedoncannabinoid
chemicalsderivedfromthemarijuanaplanthavebeenavailablefordecades
andmorearebeingdeveloped.
ThisResearchReportisintendedasausefulsummaryofwhatthemostup-to-
datesciencehastosayaboutmarijuanaanditseffectsonthosewhouseitat
anyage.
NoraD.Volkow,M.D.
Director
NationalInstituteonDrugAbuse
SeeAlso:
MessagefromtheNIDADirector-Marijuana’sLastingEffectsontheBrain,
(March2013)
5
Whatismarijuana?
Marijuana—alsocalledweed,herb,pot,grass,bud,ganja,MaryJane,anda
vastnumberofotherslangterms—isagreenish-graymixtureofthe
driedflowersofCannabissativa.Somepeoplesmokemarijuanainhand-rolled
cigarettescalledjoints;inpipes,waterpipes(sometimescalledbongs),or
inblunts(marijuanarolledincigarwraps). Marijuanacanalsobeusedtobrew
teaand,particularlywhenitissoldorconsumedformedicinalpurposes,is
frequentlymixedintofoods(edibles)suchasbrownies,cookies,orcandies.
Vaporizersarealsoincreasinglyusedtoconsumemarijuana.Strongerformsof
marijuanaincludesinsemilla(fromspeciallytendedfemaleplants)and
concentratedresinscontaininghighdosesofmarijuana’sactiveingredients,
includinghoneylikehashoil,waxybudder,andhardamberlikeshatter.These
resinsareincreasinglypopularamongthosewhousethembothrecreationally
andmedically.
Themainpsychoactive(mind-altering)chemicalinmarijuana,responsiblefor
Imageby©iStock.com/nicoolay
1
6
mostoftheintoxicatingeffectsthatpeopleseek,isdelta-9-tetrahydrocannabinol
(THC).Thechemicalisfoundinresinproducedbytheleavesandbuds
primarilyofthefemalecannabisplant.Theplantalsocontainsmorethan500
otherchemicals,includingmorethan100compoundsthatarechemically
relatedtoTHC,calledcannabinoids.2
7
Whatisthescopeofmarijuanausein
theUnitedStates?
Marijuanaisthemostcommonlyusedillicitdrug(22.2millionpeoplehaveused
itinthepastmonth)accordingtothe2015NationalSurveyonDrugUseand
Health. Itsuseismoreprevalentamongmenthanwomen—agendergapthat
widenedintheyears2007to2014.
Marijuanauseiswidespreadamongadolescentsandyoungadults.According
totheMonitoringtheFuturesurvey—anannualsurveyofdruguseandattitudes
amongtheNation’smiddleandhighschoolstudents—mostmeasuresof
marijuanauseby8th,10th,and12thgraderspeakedinthemid-to-late1990s
andthenbeganaperiodofgradualdeclinethroughthemid-2000sbefore
levellingoff.Mostmeasuresshowedsomedeclineagaininthepast5years.
Teens’perceptionsoftherisksofmarijuanausehavesteadilydeclinedoverthe
pastdecade,possiblyrelatedtoincreasingpublicdebateaboutlegalizingor
looseningrestrictionsonmarijuanaformedicinalandrecreationaluse.In2016,
9.4percentof8thgradersreportedmarijuanauseinthepastyearand5.4
percentinthepastmonth(currentuse).Among10thgraders,23.9percenthad
usedmarijuanainthepastyearand14.0percentinthepastmonth.Ratesof
useamong12thgraderswerehigherstill:35.6percenthadusedmarijuana
duringtheyearpriortothesurveyand22.5percentusedinthepastmonth;6.0
percentsaidtheyusedmarijuanadailyornear-daily.
Medicalemergenciespossiblyrelatedtomarijuanausehavealsoincreased.
TheDrugAbuseWarningNetwork(DAWN),asystemformonitoringthehealth
impactofdrugs,estimatedthatin2011,therewerenearly456,000drug-related
emergencydepartmentvisitsintheUnitedStatesinwhichmarijuanausewas
mentionedinthemedicalrecord(a21percentincreaseover2009).Abouttwo-
thirdsofpatientsweremaleand13percentwerebetweentheagesof12and
17. Itisunknownwhetherthisincreaseisduetoincreaseduse,
increasedpotencyofmarijuana(amountofTHCitcontains),orotherfactors.It
shouldbenoted,however,thatmentionsofmarijuanainmedicalrecordsdonot
necessarilyindicatethattheseemergenciesweredirectlyrelatedtomarijuana
intoxication.
3
4
5
6
8
Whataremarijuanaeffects?
Whenmarijuanaissmoked,THCandotherchemicalsintheplantpassfromthe
lungsintothebloodstream,whichrapidlycarriesthemthroughoutthebodyto
thebrain.Thepersonbeginstoexperienceeffectsalmostimmediately(see
"Howdoesmarijuanaproduceitseffects?").Manypeopleexperiencea
pleasanteuphoriaandsenseofrelaxation.Othercommoneffects,whichmay
varydramaticallyamongdifferentpeople,includeheightenedsensory
perception(e.g.,brightercolors),laughter,alteredperceptionoftime,and
increasedappetite.
Ifmarijuanaisconsumedinfoodsorbeverages,theseeffectsaresomewhat
delayed—usuallyappearingafter30minutesto1hour—becausethedrugmust
firstpassthroughthedigestivesystem.Eatingordrinkingmarijuanadelivers
significantlylessTHCintothebloodstreamthansmokinganequivalentamount
oftheplant.Becauseofthedelayedeffects,peoplemayinadvertentlyconsume
moreTHCthantheyintendto.
Pleasantexperienceswithmarijuanaarebynomeansuniversal.Insteadof
relaxationandeuphoria,somepeopleexperienceanxiety,fear,distrust,or
panic.Theseeffectsaremorecommonwhenapersontakestoomuch,the
marijuanahasanunexpectedlyhighpotency,orthepersonisinexperienced.
Peoplewhohavetakenlargedosesofmarijuanamayexperienceanacute
psychosis,whichincludeshallucinations,delusions,andalossofthesenseof
personalidentity.Theseunpleasantbuttemporaryreactionsaredistinctfrom
longer-lastingpsychoticdisorders,suchasschizophrenia,thatmaybe
associatedwiththeuseofmarijuanainvulnerableindividuals.(See"Istherea
linkbetweenmarijuanauseandpsychiatricdisorders?")
AlthoughdetectableamountsofTHCmayremaininthebodyfordaysoreven
weeksafteruse,thenoticeableeffectsofsmokedmarijuanagenerallylastfrom
1to3hours,andthoseofmarijuanaconsumedinfoodordrinkmaylastfor
manyhours.
9
Howdoesmarijuanaproduceits
effects?
THC’schemicalstructureissimilartothebrainchemicalanandamide.Similarity
instructureallowsthebodytorecognizeTHCandtoalternormalbrain
communication.
Endogenouscannabinoidssuchasanandamide(seefigure)functionas
neurotransmittersbecausetheysendchemicalmessagesbetweennervecells
(neurons)throughoutthenervoussystem.Theyaffectbrainareasthatinfluence
pleasure,memory,thinking,concentration,movement,coordination,and
sensoryandtimeperception.Becauseofthissimilarity,THCisabletoattachto
moleculescalledcannabinoidreceptorsonneuronsinthesebrainareasand
activatethem,disruptingvariousmentalandphysicalfunctionsandcausingthe
effectsdescribedearlier.Theneuralcommunicationnetworkthatusesthese
cannabinoidneurotransmitters,knownastheendocannabinoidsystem,playsa
ImagebytheNIDA
THC’schemicalstructureissimilartothebrainchemicalanandamide.Similarityin
structureallowsdrugstoberecognizedbythebodyandtoalternormalbrain
communication.
10
criticalroleinthenervoussystem’snormalfunctioning,sointerferingwithitcan
haveprofoundeffects.
Forexample,THCisabletoalterthefunctioningofthehippocampus(see
"Marijuana,Memory,andtheHippocampus")andorbitofrontalcortex,brain
areasthatenableapersontoformnewmemoriesandshifthisorherattentional
focus.Asaresult,usingmarijuanacausesimpairedthinkingandinterfereswith
aperson’sabilitytolearnandperformcomplicatedtasks.THCalsodisrupts
functioningofthecerebellumandbasalganglia,brainareasthatregulate
balance,posture,coordination,andreactiontime.Thisisthereasonpeople
whohaveusedmarijuanamaynotbeabletodrivesafely(see"Doesmarijuana
useaffectdriving?")andmayhaveproblemsplayingsportsorengagingin
otherphysicalactivities.
Peoplewhohavetakenlargedosesofthedrugmayexperienceanacute
psychosis,whichincludeshallucinations,delusions,andalossofthe
senseofpersonalidentity.
THC,actingthroughcannabinoidreceptors,alsoactivatesthebrain’sreward
system,whichincludesregionsthatgoverntheresponsetohealthypleasurable
behaviorssuchassexandeating.Likemostotherdrugsthatpeoplemisuse,
THCstimulatesneuronsintherewardsystemtoreleasethesignalingchemical
dopamineatlevelshigherthantypicallyobservedinresponsetonaturalstimuli.
Thisfloodofdopaminecontributestothepleasurable"high"thatthoseusewho
recreationalmarijuanaseek.
11
Diagramshowingdifferentpartsofthebrainanddescribingmarijuana'seffectsonthe
brain
12
Doesmarijuanauseaffectdriving?
Marijuanasignificantlyimpairsjudgment,motorcoordination,andreactiontime,
andstudieshavefoundadirectrelationshipbetweenbloodTHCconcentration
andimpaireddrivingability.
Marijuanaistheillicitdrugmostfrequentlyfoundinthebloodofdriverswho
havebeeninvolvedinvehiclecrashes,includingfatalones. Twolarge
EuropeanstudiesfoundthatdriverswithTHCintheirbloodwereroughlytwice
aslikelytobeculpableforafatalcrashthandriverswhohadnotuseddrugsor
alcohol. However,theroleplayedbymarijuanaincrashesisoftenunclear
becauseitcanbedetectedinbodyfluidsfordaysorevenweeksafter
intoxicationandbecausepeoplefrequentlycombineitwithalcohol.Those
involvedinvehiclecrasheswithTHCintheirblood,particularlyhigherlevels,
arethreetoseventimesmorelikelytoberesponsiblefortheincidentthan
driverswhohadnotuseddrugsoralcohol.Theriskassociatedwithmarijuana
incombinationwithalcoholappearstobegreaterthanthatforeitherdrugby
itself.
Photoby©iStock.com/MadCircles
7–9
10
11,12
8
13
Severalmeta-analysesofmultiplestudiesfoundthattheriskofbeinginvolved
inacrashsignificantlyincreasedaftermarijuanause —inafewcases,therisk
doubledormorethandoubled. However,alargecase-controlstudy
conductedbytheNationalHighwayTrafficSafetyAdministrationfoundno
significantincreasedcrashriskattributabletocannabisaftercontrollingfor
drivers’age,gender,race,andpresenceofalcohol.
13
14–16
17
14
Ismarijuanaaddictive?
Marijuanausecanleadtothedevelopmentofproblemuse,knownasa
marijuanausedisorder,whichtakestheformofaddictioninseverecases.
Recentdatasuggestthat30percentofthosewhousemarijuanamayhave
somedegreeofmarijuanausedisorder. Peoplewhobeginusingmarijuana
beforetheageof18arefourtoseventimesmorelikelytodevelopamarijuana
usedisorderthanadults.
Marijuanausedisordersareoftenassociatedwithdependence—inwhicha
personfeelswithdrawalsymptomswhennottakingthedrug.Peoplewhouse
marijuanafrequentlyoftenreportirritability,moodandsleepdifficulties,
decreasedappetite,cravings,restlessness,and/orvariousformsofphysical
discomfortthatpeakwithinthefirstweekafterquittingandlastupto2
weeks. Marijuanadependenceoccurswhenthebrainadaptstolarge
amountsofthedrugbyreducingproductionofandsensitivitytoitsown
endocannabinoidneurotransmitters.
Marijuanausedisorderbecomesaddictionwhenthepersoncannotstopusing
thedrugeventhoughitinterfereswithmanyaspectsofhisorherlife.Estimates
ofthenumberofpeopleaddictedtomarijuanaarecontroversial,inpart
becauseepidemiologicalstudiesofsubstanceuseoftenusedependenceasa
proxyforaddictioneventhoughitispossibletobedependentwithoutbeing
addicted.Thosestudiessuggestthat9percentofpeoplewhousemarijuana
willbecomedependentonit, risingtoabout17percentinthosewhostart
usingintheirteens.
In2015,about4.0millionpeopleintheUnitedStatesmetthediagnosticcriteria
foramarijuanausedisorder; 138,000voluntarilysoughttreatmentfortheir
marijuanause.
18
19
20,21
22,23
24,25
26,27
3
28
15
RisingPotency
Marijuanapotency,asdetectedinconfiscatedsamples,hassteadily
increasedoverthepastfewdecades. Intheearly1990s,theaverageTHC
contentinconfiscatedmarijuanasampleswasroughly3.8percent.In
2014,itwas12.2percent.Theaveragemarijuanaextractcontainsmore
than50percentTHC,withsomesamplesexceeding80percent.These
trendsraiseconcernsthattheconsequencesofmarijuanausecouldbe
worsethaninthepast,particularlyamongthosewhoarenewtomarijuana
useorinyoungpeople,whosebrainsarestilldeveloping(see"Whatare
marijuana’slong-termeffectsonthebrain?").
Researchersdonotyetknowthefullextentoftheconsequenceswhenthe
bodyandbrain(especiallythedevelopingbrain)areexposedtohigh
concentrationsofTHCorwhethertherecentincreasesinemergency
departmentvisitsbypeopletestingpositiveformarijuanaarerelatedto
risingpotency.Theextenttowhichpeopleadjustforincreasedpotencyby
usinglessorbysmokingitdifferentlyisalsounknown.Recentstudies
suggestthatexperiencedpeoplemayadjusttheamounttheysmokeand
howmuchtheyinhalebasedonthebelievedstrengthofthemarijuana
theyareusing,buttheyarenotabletofullycompensateforvariationsin
potency.
2
30,31
16
Whataremarijuana'slong-term
effectsonthebrain?
Substantialevidencefromanimalresearchandagrowingnumberofstudiesin
humansindicatethatmarijuanaexposureduringdevelopmentcancauselong-
termorpossiblypermanentadversechangesinthebrain.RatsexposedtoTHC
beforebirth,soonafterbirth,orduringadolescenceshownotableproblemswith
specificlearningandmemorytaskslaterinlife. Cognitiveimpairmentsin
adultratsexposedtoTHCduringadolescenceareassociatedwithstructural
andfunctionalchangesinthehippocampus. Studiesinratsalsoshowthat
adolescentexposuretoTHCisassociatedwithanalteredrewardsystem,
increasingthelikelihoodthatananimalwillself-administerotherdrugs(e.g.,
heroin)whengivenanopportunity(see"Ismarijuanaagatewaydrug?").
Imagingstudiesofmarijuana’simpactonbrainstructureinhumanshaveshown
conflictingresults.Somestudiessuggestregularmarijuanauseinadolescence
isassociatedwithalteredconnectivityandreducedvolumeofspecificbrain
regionsinvolvedinabroadrangeofexecutivefunctionssuchasmemory,
learning,andimpulsecontrolcomparedtopeoplewhodonotuse. Other
studieshavenotfoundsignificantstructuraldifferencesbetweenthebrainsof
peoplewhodoanddonotusethedrug.
Severalstudies,includingtwolargelongitudinalstudies,suggestthatmarijuana
usecancausefunctionalimpairmentincognitiveabilitiesbutthatthedegree
and/ordurationoftheimpairmentdependsontheagewhenapersonbegan
usingandhowmuchandhowlongheorsheused.
Amongnearly4,000youngadultsintheCoronaryArteryRiskDevelopmentin
YoungAdultsstudytrackedovera25-yearperioduntilmid-adulthood,
cumulativelifetimeexposuretomarijuanawasassociatedwithlowerscoreson
atestofverbalmemorybutdidnotaffectothercognitiveabilitiessuchas
processingspeedorexecutivefunction.Theeffectwassizeableandsignificant
evenaftereliminatingthoseinvolvedwithcurrentuseandafteradjustingfor
confoundingfactorssuchasdemographicfactors,otherdrugandalcoholuse,
andotherpsychiatricconditionssuchasdepression.
32–34
35–37
38,39
40
41
42
17
AlargelongitudinalstudyinNewZealandfoundthatpersistentmarijuanause
disorderwithfrequentusestartinginadolescencewasassociatedwithalossof
anaverageof6orupto8IQpointsmeasuredinmid-adulthood. Significantly,
inthatstudy,thosewhousedmarijuanaheavilyasteenagersandquitusingas
adultsdidnotrecoverthelostIQpoints.Peoplewhoonlybeganusing
marijuanaheavilyinadulthooddidnotloseIQpoints.Theseresultssuggest
thatmarijuanahasitsstrongestlong-termimpactonyoungpeoplewhose
brainsarestillbusybuildingnewconnectionsandmaturinginotherways.The
endocannabinoidsystemisknowntoplayanimportantroleintheproper
formationofsynapses(theconnectionsbetweenneurons)duringearlybrain
development,andasimilarrolehasbeenproposedfortherefinementofneural
connectionsduringadolescence.Ifthelong-termeffectsofmarijuanauseon
cognitivefunctioningorIQareupheldbyfutureresearch,thismaybeone
avenuebywhichmarijuanauseduringadolescenceproducesitslong-term
effects.
However,recentresultsfromtwoprospectivelongitudinaltwinstudiesdidnot
supportacausalrelationshipbetweenmarijuanauseandIQloss.Thosewho
usedmarijuanadidshowasignificantdeclineinverbalability(equivalentto4
IQpoints)andingeneralknowledgebetweenthepreteenyears(ages9to12,
beforeuse)andlateadolescence/earlyadulthood(ages17to20).However,at
thestartofthestudy,thosewhowoulduseinthefuturealreadyhadlower
scoresonthesemeasuresthanthosewhowouldnotuseinthefuture,andno
predictabledifferencewasfoundbetweentwinswhenoneusedmarijuanaand
onedidnot.ThissuggeststhatobservedIQdeclines,atleastacross
adolescence,maybecausedbysharedfamilialfactors(e.g.,genetics,family
environment),notbymarijuanauseitself. Itshouldbenoted,though,that
thesestudieswereshorterindurationthantheNewZealandstudyanddidnot
exploretheimpactofthedoseofmarijuana(i.e.,heavyuse)orthedevelopment
ofacannabisusedisorder;thismayhavemaskedadose-ordiagnosis-
dependenteffect.
Theabilitytodrawdefinitiveconclusionsaboutmarijuana’slong-termimpacton
thehumanbrainfrompaststudiesisoftenlimitedbythefactthatstudy
participantsusemultiplesubstances,andthereisoftenlimiteddataaboutthe
participants’healthormentalfunctioningpriortothestudy.Overthenext
decade,theNationalInstitutesofHealthisfundingtheAdolescentBrain
43
44
45
18
CognitiveDevelopment(ABCD)study—amajorlongitudinalstudythatwilltrack
alargesampleofyoungAmericansfromlatechildhood(beforefirstuseof
drugs)toearlyadulthood.Thestudywilluseneuroimagingandotheradvanced
toolstoclarifypreciselyhowandtowhatextentmarijuanaandother
substances,aloneandincombination,affectadolescentbraindevelopment.
Marijuana,Memory,andtheHippocampus
Distributionofcannabinoidreceptorsintheratbrain.Brainimagerevealshigh
levels(showninorangeandyellow)ofcannabinoidreceptorsinmanyareas,
includingthecortex,hippocampus,cerebellum,andnucleusaccumbens
(ventralstriatum).
MemoryimpairmentfrommarijuanauseoccursbecauseTHCaltershowthe
hippocampus,abrainarearesponsibleformemoryformation,processes
information.Mostoftheevidencesupportingthisassertioncomesfromanimal
studies.Forexample,ratsexposedtoTHCinutero,soonafterbirth,orduring
adolescence,shownotableproblemswithspecificlearning/memorytaskslater
inlife.Moreover,cognitiveimpairmentinadultratsisassociatedwithstructural
andfunctionalchangesinthehippocampusfromTHCexposureduring
adolescence.
ImagebytheNIDA
19
Aspeopleage,theyloseneuronsinthehippocampus,whichdecreasestheir
abilitytolearnnewinformation.ChronicTHCexposuremayhastenage-related
lossofhippocampalneurons.Inonestudy,ratsexposedtoTHCeverydayfor8
months(approximately30percentoftheirlifespan)showedalevelofnervecell
lossat11to12monthsofagethatequaledthatofunexposedanimalstwice
theirage.
20
Ismarijuanaagatewaydrug?
Someresearchsuggeststhatmarijuanauseislikelytoprecedeuseofotherlicit
andillicitsubstances andthedevelopmentofaddictiontoothersubstances.
Forinstance,astudyusinglongitudinaldatafromtheNationalEpidemiological
StudyofAlcoholUseandRelatedDisordersfoundthatadultswhoreported
marijuanauseduringthefirstwaveofthesurveyweremorelikelythanadults
whodidnotusemarijuanatodevelopanalcoholusedisorderwithin3years;
peoplewhousedmarijuanaandalreadyhadanalcoholusedisorderatthe
outsetwereatgreaterriskoftheiralcoholusedisorderworsening. Marijuana
useisalsolinkedtoothersubstanceusedisordersincludingnicotineaddiction.
Earlyexposuretocannabinoidsinadolescentrodentsdecreasesthereactivity
ofbraindopaminerewardcenterslaterinadulthood. Totheextentthatthese
findingsgeneralizetohumans,thiscouldhelpexplaintheincreased
vulnerabilityforaddictiontoothersubstancesofmisuselaterinlifethatmost
epidemiologicalstudieshavereportedforpeoplewhobeginmarijuanause
earlyinlife. ItisalsoconsistentwithanimalexperimentsshowingTHC’s
abilityto"prime"thebrainforenhancedresponsestootherdrugs. For
example,ratspreviouslyadministeredTHCshowheightenedbehavioral
responsenotonlywhenfurtherexposedtoTHCbutalsowhenexposedtoother
drugssuchasmorphine—aphenomenoncalledcross-sensitization.
Thesefindingsareconsistentwiththeideaofmarijuanaasa"gatewaydrug."
However,themajorityofpeoplewhousemarijuanadonotgoontouseother,
"harder"substances.Also,cross-sensitizationisnotuniquetomarijuana.
Alcoholandnicotinealsoprimethebrainforaheightenedresponsetoother
drugs andare,likemarijuana,alsotypicallyusedbeforeapersonprogresses
toother,moreharmfulsubstances.
Itisimportanttonotethatotherfactorsbesidesbiologicalmechanisms,suchas
aperson’ssocialenvironment,arealsocriticalinaperson’sriskfordruguse.
Analternativetothegateway-drughypothesisisthatpeoplewhoaremore
vulnerabletodrug-takingaresimplymorelikelytostartwithreadilyavailable
substancessuchasmarijuana,tobacco,oralcohol,andtheirsubsequentsocial
46
47
48
49
50
51
52
21
interactionswithotherswhousedrugsincreasestheirchancesoftryingother
drugs.Furtherresearchisneededtoexplorethisquestion.
22
Howdoesmarijuanauseaffect
school,work,andsociallife?
Researchhasshownthatmarijuana’snegativeeffectsonattention,memory,
andlearningcanlastfordaysorweeksaftertheacuteeffectsofthedrugwear
off,dependingontheperson’shistorywiththedrug. Consequently,someone
whosmokesmarijuanadailymaybefunctioningatareducedintellectuallevel
mostorallofthetime.Considerableevidencesuggeststhatstudentswho
smokemarijuanahavepoorereducationaloutcomesthantheirnonsmoking
peers.Forexample,areviewof48relevantstudiesfoundmarijuanausetobe
associatedwithreducededucationalattainment(i.e.,reducedchancesof
graduating). ArecentanalysisusingdatafromthreelargestudiesinAustralia
andNewZealandfoundthatadolescentswhousedmarijuanaregularlywere
significantlylesslikelythantheirnon-usingpeerstofinishhighschoolorobtain
adegree.Theyalsohadamuchhigherchanceofdevelopingdependence,
usingotherdrugs,andattemptingsuicide. Severalstudieshavealsolinked
heavymarijuanausetolowerincome,greaterwelfaredependence,
unemployment,criminalbehavior,andlowerlifesatisfaction.
Imageby©iStock.com/AntonioGuillem
53
54
55
56,57
23
Towhatdegreemarijuanauseisdirectlycausalintheseassociationsremains
anopenquestionrequiringfurtherresearch.Itispossiblethatotherfactors
independentlypredisposepeopletobothmarijuanauseandvariousnegative
lifeoutcomessuchasschooldropout. Thatsaid,peoplereportaperceived
influenceoftheirmarijuanauseonpooroutcomesonavarietyoflife
satisfactionandachievementmeasures.Onestudy,forexample,compared
peopleinvolvedwithcurrentandformerlong-term,heavyuseofmarijuanawith
acontrolgroupwhoreportedsmokingmarijuanaatleastonceintheirlivesbut
notmorethan50times. Allparticipantshadsimilareducationandincome
backgrounds,butsignificantdifferenceswerefoundintheireducational
attainment:Fewerofthosewhoengagedinheavycannabisusecompleted
college,andmorehadyearlyhouseholdincomesoflessthan$30,000.When
askedhowmarijuanaaffectedtheircognitiveabilities,careerachievements,
sociallives,andphysicalandmentalhealth,themajorityofthosewhoused
heavilyreportedthatmarijuanahadnegativeeffectsinalltheseareasoftheir
lives.
Studieshavealsosuggestedspecificlinksbetweenmarijuanauseandadverse
consequencesintheworkplace,suchasincreasedriskforinjuryor
accidents. Onestudyamongpostalworkersfoundthatemployeeswhotested
positiveformarijuanaonapre-employmenturinedrugtesthad55percent
moreindustrialaccidents,85percentmoreinjuries,and75percentgreater
absenteeismcomparedwiththosewhotestednegativeformarijuanause.
58
59
60
61
24
Istherealinkbetweenmarijuanause
andpsychiatricdisorders?
Severalstudieshavelinkedmarijuanausetoincreasedriskforpsychiatric
disorders,includingpsychosis(schizophrenia),depression,anxiety,and
substanceusedisorders,butwhetherandtowhatextentitactuallycauses
theseconditionsisnotalwayseasytodetermine. Theamountofdrugused,
theageatfirstuse,andgeneticvulnerabilityhaveallbeenshowntoinfluence
thisrelationship.Thestrongestevidencetodateconcernslinksbetween
marijuanauseandsubstanceusedisordersandbetweenmarijuanauseand
psychiatricdisordersinthosewithapreexistinggeneticorothervulnerability.
ResearchusinglongitudinaldatafromtheNationalEpidemiologicalSurveyon
AlcoholandRelatedConditionsexaminedassociationsbetweenmarijuana
use,moodandanxietydisorders,andsubstanceusedisorders.Afteradjusting
forvariousconfoundingfactors,noassociationbetweenmarijuanauseand
moodandanxietydisorderswasfound.Theonlysignificantassociationswere
increasedriskofalcoholusedisorders,nicotinedependence,marijuanause
disorder,andotherdrugusedisorders.
Recentresearch(see"AKT1GeneVariationsandPsychosis")hasfoundthat
peoplewhousemarijuanaandcarryaspecificvariantoftheAKT1gene,which
codesforanenzymethataffectsdopaminesignalinginthestriatum,areat
increasedriskofdevelopingpsychosis.Thestriatumisanareaofthebrainthat
becomesactivatedandfloodedwithdopaminewhencertainstimuliarepresent.
Onestudyfoundthattheriskofpsychosisamongthosewiththisvariantwas
seventimeshigherforthosewhousedmarijuanadailycomparedwiththose
whouseditinfrequentlyorusednoneatall.
32
62
63
64
25
Anotherstudyfoundanincreasedriskofpsychosisamongadultswhohadused
marijuanainadolescenceandalsocarriedaspecificvariantofthegenefor
catechol-O-methyltransferase(COMT),anenzymethatdegrades
neurotransmitterssuchasdopamineandnorepinephrine (see"Genetic
VariationsinCOMTInfluencestheHarmfulEffectsofAbusedDrugs").
Marijuanausehasalsobeenshowntoworsenthecourseofillnessinpatients
whoalreadyhaveschizophrenia.Asmentionedpreviously,marijuanacan
produceanacutepsychoticreactioninnon-schizophrenicpeoplewhouse
marijuana,especiallyathighdoses,althoughthisfadesasthedrugwearsoff.
Whetheradolescentmarijuanausecancontributetodevelopingpsychosislaterin
adulthoodappearstodependonwhetherapersonalreadyhasageneticallybased
vulnerabilitytothedisorder.TheAKT1genegovernsanenzymethataffectsbrain
signalinginvolvingtheneurotransmitterdopamine.Altereddopaminesignalingis
knowntobeinvolvedinschizophrenia.AKT1cantakeoneofthreeformsinaspecific
regionofthegeneimplicatedinsusceptibilitytoschizophrenia:T/T,C/T,andC/C.
Thosewhousemarijuanadaily(greenbars)withtheC/Cvarianthaveaseventimes
higherriskofdevelopingpsychosisthanthosewhouseitinfrequentlyorusenoneat
all.TheriskforpsychosisamongthosewiththeT/Tvariantwasunaffectedby
whethertheyusedmarijuana.
Source:DiFortietal.BiolPsychiatry.2012.
65
26
Inconsistentandmodestassociationshavebeenreportedbetweenmarijuana
useandsuicidalthoughtsandattemptedsuicideamongteens. Marijuana
hasalsobeenassociatedwithanamotivationalsyndrome,definedasa
diminishedorabsentdrivetoengageintypicallyrewardingactivities.Because
oftheroleoftheendocannabinoidsysteminregulatingmoodandreward,ithas
beenhypothesizedthatbrainchangesresultingfromearlyuseofmarijuana
mayunderlietheseassociations,butmoreresearchisneededtoverifythat
suchlinksexistandbetterunderstandthem.
Theinfluenceofadolescentmarijuanauseonadultpsychosisisaffectedbygenetic
variables.Thisfigureshowsthatvariationsinagenecanaffectthelikelihoodof
developingpsychosisinadulthoodfollowingexposuretocannabisinadolescence.
TheCOMTgenegovernsanenzymethatbreaksdowndopamine,abrainchemical
involvedinschizophrenia.Itcomesintwoforms:"Met"and"Val."Individualswithone
ortwocopiesoftheValvarianthaveahigherriskofdevelopingschizophrenic-type
disordersiftheyusedcannabisduringadolescence(darkbars).Thosewithonlythe
Metvariantwereunaffectedbycannabisuse.
Source:Caspietal.BiolPsychiatry.2005.
66,67
27
AdverseConsequencesofMarijuanaUse
Acute(presentduringintoxication)
Impairedshort-termmemory
Impairedattention,judgment,andothercognitivefunctions
Impairedcoordinationandbalance
Increasedheartrate
Anxiety,paranoia
Psychosis(uncommon)
Persistent(lastinglongerthanintoxication,butmaynotbe
permanent)
Impairedlearningandcoordination
Photoby©getttyimages.com/Fuse
28
Sleepproblems
Long-term(cumulativeeffectsofrepeateduse)
Potentialformarijuanaaddiction
ImpairmentsinlearningandmemorywithpotentiallossofIQ*
Increasedriskofchroniccough,bronchitis
Increasedriskofotherdrugandalcoholusedisorders
Increasedriskofschizophreniainpeoplewithgeneticvulnerability**
*LossofIQamongindividualswithpersistentmarijuanausedisorderwho
beganusingheavilyduringadolescence
**Theseareoftenreportedco-occurringsymptoms/disorderswithchronic
marijuanause.However,researchhasnotyetdeterminedwhether
marijuanaiscausalorjustassociatedwiththesementalproblems.
29
Whataremarijuana'seffectsonlung
health?
Liketobaccosmoke,marijuanasmokeisanirritanttothethroatandlungsand
cancauseaheavycoughduringuse.Italsocontainslevelsofvolatile
chemicalsandtarthataresimilartotobaccosmoke,raisingconcernsaboutrisk
forcancerandlungdisease.
Marijuanasmokingisassociatedwithlargeairwayinflammation,increased
airwayresistance,andlunghyperinflation,andthosewhosmokemarijuana
regularlyreportmoresymptomsofchronicbronchitisthanthosewhodonot
smoke. Onestudyfoundthatpeoplewhofrequentlysmokemarijuanahad
moreoutpatientmedicalvisitsforrespiratoryproblemsthanthosewhodonot
smoke. Somecasestudieshavesuggestedthat,becauseofTHC’simmune-
suppressingeffects,smokingmarijuanamightincreasesusceptibilitytolung
infections,suchaspneumonia,inpeoplewithimmunedeficiencies;however,a
largeAIDScohortstudydidnotconfirmsuchanassociation. Smoking
marijuanamayalsoreducetherespiratorysystem’simmuneresponse,
increasingthelikelihoodofthepersonacquiringrespiratoryinfections,
includingpneumonia. Animalandhumanstudieshavenotfoundthat
marijuanaincreasesriskforemphysema.
Whethersmokingmarijuanacauseslungcancer,ascigarettesmokingdoes,
remainsanopenquestion. Marijuanasmokecontainscarcinogenic
combustionproducts,includingabout50percentmorebenzopreneand75
percentmorebenzanthracene(andmorephenols,vinylchlorides,
nitrosamines,reactiveoxygenspecies)thancigarettesmoke. Becauseofhow
itistypicallysmoked(deeperinhale,heldforlonger),marijuanasmokingleads
tofourtimesthedepositionoftarcomparedtocigarettesmoking. However,
whileafewsmall,uncontrolledstudieshavesuggestedthatheavy,regular
marijuanasmokingcouldincreaseriskforrespiratorycancers,well-designed
populationstudieshavefailedtofindanincreasedriskoflungcancer
associatedwithmarijuanause.
Onecomplexityincomparingthelung-healthrisksofmarijuanaandtobacco
68
68,69
70
68
69
68
68,71
68
72
68
30
concernstheverydifferentwaysthetwosubstancesareused.Whilepeople
whosmokemarijuanaofteninhalemoredeeplyandholdthesmokeintheir
lungsforalongerdurationthanistypicalwithcigarettes,marijuana’seffectslast
longer,sopeoplewhousemarijuanamaysmokelessfrequentlythanthose
whosmokecigarettes.
Additionally,thefactthatmanypeopleusebothmarijuanaandtobaccomakes
determiningmarijuana’sprecisecontributiontolungcancerrisk,ifany,difficult
toestablish.CellcultureandanimalstudieshavealsosuggestedTHCand
CBDmayhaveantitumoreffects,andthishasbeenproposedasonereason
whystrongerexpectedassociationsarenotseenbetweenmarijuanauseand
lungcancer,butmoreresearchisneededonthisquestion.68
31
Whataremarijuana’seffectsonother
aspectsofphysicalhealth?
Withinafewminutesafterinhalingmarijuanasmoke,aperson’sheartrate
speedsup,thebreathingpassagesrelaxandbecomeenlarged,andblood
vesselsintheeyesexpand,makingtheeyeslookbloodshot.Theheartrate—
normally70to80beatsperminute—mayincreaseby20to50beatsperminute
ormayevendoubleinsomecases.Takingotherdrugswithmarijuanacan
amplifythiseffect.
Limitedevidencesuggeststhataperson’sriskofheartattackduringthefirst
houraftersmokingmarijuanaisnearlyfivetimeshisorherusualrisk. This
observationcouldbepartlyexplainedbymarijuanaraisingbloodpressure(in
somecases)andheartrateandreducingtheblood’scapacitytocarry
oxygen. Marijuanamayalsocauseorthostatichypotension(headrushor
dizzinessonstandingup),possiblyraisingdangerfromfaintingandfalls.
Tolerancetosomecardiovasculareffectsoftendevelopswithrepeated
exposure. Thesehealtheffectsneedtobeexaminedmoreclosely,particularly
giventheincreasinguseof"medicalmarijuana"bypeoplewithhealthissues
andolderadultswhomayhaveincreasedbaselinevulnerabilityduetoage-
relatedcardiovascularriskfactors(see"Ismarijuanasafeandeffectiveas
medicine?").
Afewstudieshaveshownaclearlinkbetweenmarijuanauseinadolescence
andincreasedriskforanaggressiveformoftesticularcancer
(nonseminomatoustesticulargermcelltumor)thatpredominantlystrikesyoung
adultmales. Theearlyonsetoftesticularcancerscomparedtolungand
mostothercancersindicatesthat,whateverthenatureofmarijuana’s
contribution,itmayaccumulateoverjustafewyearsofuse.
Studieshaveshownthatinrarecases,chronicuseofmarijuanacanleadto
CannabinoidHyperemesisSyndrome—aconditionmarkedbyrecurrentbouts
ofseverenausea,vomiting,anddehydration.Thissyndromehasbeenfoundto
occurinpersonsunder50yearsofageandwithalonghistoryofmarijuana
use.CannabinoidHyperemesisSyndromecanleadsuffererstomakefrequent
73
74
75
76,77
32
tripstotheemergencyroom,butmayberesolvedwhenapersonstopsusing
marijuana.78
33
Ismarijuanasafeandeffectiveas
medicine?
Thepotentialmedicinalpropertiesofmarijuanaanditscomponentshavebeen
thesubjectofresearchandheateddebatefordecades.THCitselfhasproven
medicalbenefitsinparticularformulations.TheU.S.FoodandDrug
Administration(FDA)hasapprovedTHC-basedmedications,dronabinol
(Marinol )andnabilone(Cesamet ),prescribedinpillformforthetreatmentof
nauseainpatientsundergoingcancerchemotherapyandtostimulateappetite
inpatientswithwastingsyndromeduetoAIDS.TheFDAalsoapprovedaCBD-
basedliquidmedicationcalledEpidiolex forthetreatmentoftwoformsof
severechildhoodepilepsy,DravetsyndromeandLennox-Gastautsyndrome.
It’sbeingdeliveredtopatientsinareliabledosageformandthrougha
reproduciblerouteofdeliverytoensurethatpatientsderivetheanticipated
benefits.CBDdoesnothavetherewardingpropertiesofTHC.
Inaddition,severalothermarijuana-basedmedicationshavebeenapprovedor
areundergoingclinicaltrials.Nabiximols(Sativex ),amouthspraythatis
currentlyavailableintheUnitedKingdom,Canada,andseveralEuropean
countriesfortreatingthespasticityandneuropathicpainthatmayaccompany
multiplesclerosis,combinesTHCwithanotherchemicalfoundinmarijuana
calledcannabidiol(CBD).
Researchersgenerallyconsidermedicationslikethese,whichusepurified
chemicalsderivedfromorbasedonthoseinthemarijuanaplant,tobemore
promisingtherapeuticallythanuseofthewholemarijuanaplantoritscrude
extracts.Developmentofdrugsfrombotanicalssuchasthemarijuanaplant
posesnumerouschallenges.Botanicalsmaycontainhundredsofunknown,
activechemicals,anditcanbedifficulttodevelopaproductwithaccurateand
consistentdosesofthesechemicals.Useofmarijuanaasmedicinealsoposes
otherproblemssuchastheadversehealtheffectsofsmokingandTHC-induced
cognitiveimpairment.Nevertheless,agrowingnumberofstateshavelegalized
dispensingofmarijuanaoritsextractstopeoplewitharangeofmedical
conditions.
® ®
®
®
34
Anadditionalconcernwith"medicalmarijuana"isthatlittleisknownaboutthe
long-termimpactofitsusebypeoplewithhealth-and/orage-related
vulnerabilities—suchasolderadultsorpeoplewithcancer,AIDS,
cardiovasculardisease,multiplesclerosis,orotherneurodegenerative
diseases.Furtherresearchwillbeneededtodeterminewhetherpeoplewhose
healthhasbeencompromisedbydiseaseoritstreatment(e.g.,chemotherapy)
areatgreaterriskforadversehealthoutcomesfrommarijuanause.
MedicalMarijuanaLegalizationandPrescriptionOpioid
UseOutcomes
TworecentstudiesinJAMAInternalMedicinereportanassociation
betweennotonlymedicalmarijuanalaws(MML)butalsoprotectedaccess
todispensariesandtheirassociationwithopioidprescriptionpatterns
basedonMedicaidorMedicarePartDprescriptiondata.Thefirststudy
foundthatMedicarePartDprescriptionsfilledforallopioidsdecreasedin
stateswithMMLby2.11milliondailydosesperyearperstate.Instates
withmedicalcannabisdispensaries,prescriptionsdecreasedby3.742
milliondailydosesperyearperstate. Similarly,thesecondstudy
examinedMedicaidprescriptiondataandfoundthatMMLsandadult-use
marijuanalawswereassociatedwithloweropioidprescribingrates(5.88%
and6.38%lower,respectively).
Additionally,NIDAfundedtwostudiesthatexploredtherelationship
betweenmarijuanalegalizationandadverseoutcomesassociatedwith
prescriptionopioids.Thefirststudyfoundanassociationbetweenmedical
marijuanalegalizationandareductioninoverdosedeathsfromopioid
painrelievers;aneffectthatstrengthenedineachyearfollowingthe
implementationoflegislation. ThesecondNIDA-fundedstudywasa
moredetailedanalysisbytheRANDCorporationthatshowedlegally
protectedaccesstomedicalmarijuanadispensariesisassociatedwith
lowerlevelsofopioidprescribing,lowerself-reportofnonmedical
prescriptionopioiduse,lowertreatmentadmissionsforprescriptionopioid
usedisorders,andreductioninprescriptionopioidoverdosedeaths.
Notably,thereductionindeathswaspresentonlyinstateswith
dispensaries(notjustmedicalmarijuanalaws)andwasgreaterinstates
withactivedispensaries.Itshouldbenotedthatthepopulation-based
79
80
81
82
35
natureofthesestudies,andthetwoabove,donotestablishacausal
relationshiporgiveevidenceforchangesinindividualpainpatient
behaviorandcautionshouldbeusedwheninterpretingtheirresults.
Todate,researchintotheeffectsofcannabisonopioiduseinpainpatients
ismixed.Somedatasuggestthatmedicalcannabistreatmentmayreduce
thedoseofopioidsrequiredforpainrelief, whileanotherNIH-funded
studyfoundthatcannabisuseappearstoincreasetheriskofdeveloping
nonmedicalprescriptionopioiduseandopioidusedisorder. Thoughno
singlestudyisdefinitive,theycumulativelysuggestthatmedicalmarijuana
productsmayplayaroleinreducingtheuseofopioidsneededtocontrol
painbutthattheseproductsdon’tcomewithoutrisk.Moreresearchis
neededtoinvestigatethepotentialtherapeuticroleofmarijuanaincluding
itsroleasatreatmentoptionforopioidusedisorderanditsabilitytoreduce
specifictypesofpain.
83,84
85
36
Whataretheeffectsofsecondhand
exposuretomarijuanasmoke?
Peopleoftenaskaboutthepossiblepsychoactiveeffectofexposureto
secondhandmarijuanasmokeandwhetherapersonwhohasinhaled
secondhandmarijuanasmokecouldfailadrugtest.Researchersmeasuredthe
amountofTHCinthebloodofpeoplewhodonotsmokemarijuanaandhad
spent3hoursinawell-ventilatedspacewithpeoplecasuallysmoking
marijuana;THCwaspresentinthebloodofthenonsmokingparticipants,but
theamountwaswellbelowthelevelneededtofailadrugtest.Anotherstudy
thatvariedthelevelsofventilationandthepotencyofthemarijuanafoundthat
somenonsmokingparticipantsexposedforanhourtohigh-THCmarijuana
(11.3percentTHCconcentration)inanunventilatedroomshowedpositive
urineassaysinthehoursdirectlyfollowingexposure ;afollow-upstudy
showedthatnonsmokingpeopleinaconfinedspacewithpeoplesmokinghigh-
THCmarijuanareportedmildsubjectiveeffectsofthedrug—a"contacthigh"—
anddisplayedmildimpairmentsonperformanceinmotortasks.
Theknownhealthrisksofsecondhandexposuretocigarettesmoke—tothe
heartorlungs,forinstance—raisequestionsaboutwhethersecondhand
exposuretomarijuanasmokeposessimilarhealthrisks.Atthispoint,verylittle
researchonthisquestionhasbeenconducted.A2016studyinratsfoundthat
secondhandexposuretomarijuanasmokeaffectedameasureofbloodvessel
functionasmuchassecondhandtobaccosmoke,andtheeffectslasted
longer. Oneminuteofexposuretosecondhandmarijuanasmokeimpaired
flow-mediateddilation(theextenttowhicharteriesenlargeinresponseto
increasedbloodflow)ofthefemoralarterythatlastedforatleast90minutes;
impairmentfrom1minuteofsecondhandtobaccoexposurewasrecovered
within30minutes.TheeffectsofmarijuanasmokewereindependentofTHC
concentration;i.e.,whenTHCwasremoved,theimpairmentwasstillpresent.
Thisresearchhasnotyetbeenconductedwithhumansubjects,butthetoxins
andtarlevelsknowntobepresentinmarijuanasmoke(see“Whatare
marijuana’seffectsonlunghealth?”)raiseconcernsaboutexposureamong
vulnerablepopulations,suchaschildrenandpeoplewithasthma.
86
87
88
37
Canmarijuanauseduringandafter
pregnancyharmthebaby?
Moreresearchisneededonhowmarijuanauseduringpregnancycouldimpact
thehealthanddevelopmentofinfants,givenchangingpoliciesaboutaccessto
marijuana,aswellassignificantincreasesoverthelastdecadeinthenumber
ofpregnantwomenseekingsubstanceusedisordertreatmentformarijuana
use. Onestudyfoundthatabout20%ofpregnantwomen24-years-oldand
youngerscreenedpositiveformarijuana.However,thisstudyalsofoundthat
womenwereabouttwiceaslikelytoscreenpositiveformarijuanauseviaa
drugtestthantheystateinself-reportedmeasures.Thissuggeststhatself-
reportedratesofmarijuanauseinpregnantfemalesmaynotbeanaccurate
measureofmarijuanause. Additionally,inonestudyofdispensaries,
nonmedicalpersonnelatmarijuanadispensarieswererecommending
marijuanatopregnantwomenfornausea,butmedicalexpertswarnagainstit.
Photoby©Thinkstock.com/CreatasImages
89
90
38
Thereisnohumanresearchconnectingmarijuanausetothechanceof
miscarriage, althoughanimalstudiesindicatethattheriskformiscarriage
increasesifmarijuanaisusedearlyinpregnancy. Someassociationshave
beenfoundbetweenmarijuanauseduringpregnancyandfuture
developmentalandhyperactivitydisordersinchildren. Evidenceismixed
astowhethermarijuanausebypregnantwomenisassociatedwithlowbirth
weight orprematurebirth, althoughlong-termusemayelevatethese
risks. Researchhasshownthatpregnantwomenwhousemarijuanahavea
2.3timesgreaterriskofstillbirth. Giventhepotentialofmarijuanato
negativelyimpactthedevelopingbrain,theAmericanCollegeofObstetricians
andGynecologistsrecommendsthatobstetrician-gynecologistscounselwomen
againstusingmarijuanawhiletryingtogetpregnant,duringpregnancy,and
whiletheyarebreastfeeding.
Somewomenreportusingmarijuanatotreatseverenauseaassociatedwith
theirpregnancy; however,thereisnoresearchconfirmingthatthisisa
safepractice,anditisgenerallynotrecommended.Womenconsideringusing
91,92
93
94–97
98–102 101
100
103
104
RecentTrendsinTreatmentAdmissionsforMarijuanaUseDuringPregnancy
Source:Martinetal.,2015
105,106
39
medicalmarijuanawhilepregnantshouldnotdosowithoutcheckingwiththeir
healthcareproviders.Animalstudieshaveshownthatmoderateconcentrations
ofTHC,whenadministeredtomotherswhilepregnantornursing,couldhave
long-lastingeffectsonthechild,includingincreasingstressresponsivityand
abnormalpatternsofsocialinteractions. Animalstudiesalsoshowlearning
deficitsinprenatallyexposedindividuals.
Humanresearchhasshownthatsomebabiesborntowomenwhoused
marijuanaduringtheirpregnanciesdisplayalteredresponsestovisualstimuli,
increasedtrembling,andahigh-pitchedcry, whichcouldindicateproblems
withneurologicaldevelopment. Inschool,marijuana-exposedchildrenare
morelikelytoshowgapsinproblem-solvingskills,memory, andtheabilityto
remainattentive. Moreresearchisneeded,however,todisentangle
marijuana-specificeffectsfromthoseofotherenvironmentalfactorsthatcould
beassociatedwithamother'smarijuanause,suchasanimpoverishedhome
environmentorthemother'suseofotherdrugs. Prenatalmarijuanaexposure
isalsoassociatedwithanincreasedlikelihoodofapersonusingmarijuanaas
ayoungadult,evenwhenotherfactorsthatinfluencedruguseare
considered. Moreinformationonmarijuanauseduringpregnancycanbe
foundintheNIDA'sSubstanceUseinWomenResearchReport.
Verylittleisknownaboutmarijuanauseandbreastfeeding.Onestudysuggests
thatmoderateamountsofTHCfindtheirwayintobreastmilkwhenanursing
motherusesmarijuana. SomeevidenceshowsthatexposuretoTHCthrough
breastmilkinthefirstmonthoflifecouldresultindecreasedmotordevelopment
at1yearofage. TherehavebeennostudiestodetermineifexposuretoTHC
duringnursingislinkedtoeffectslaterinthechild'slife.Withregularuse,THC
canaccumulateinhumanbreastmilktohighconcentrations. Becausea
baby'sbrainisstillforming,THCconsumedinbreastmilkcouldaffectbrain
development.Givenalltheseuncertainties,nursingmothersarediscouraged
fromusingmarijuana. Newmothersusingmedicalmarijuanashouldbe
vigilantaboutcoordinatingcarebetweenthedoctorrecommendingtheir
marijuanauseandthepediatriciancaringfortheirbaby.
107
33,108
109
110
111
112
102
113
114
115
98
104,116
40
AvailableTreatmentsforMarijuana
UseDisorders
Marijuanausedisordersappeartobeverysimilartoothersubstanceuse
disorders,althoughthelong-termclinicaloutcomesmaybelesssevere.On
average,adultsseekingtreatmentformarijuanausedisordershaveused
marijuananearlyeverydayformorethan10yearsandhaveattemptedtoquit
morethansixtimes. Peoplewithmarijuanausedisorders,especially
adolescents,oftenalsosufferfromotherpsychiatricdisorders
(comorbidity). Theymayalsouseorbeaddictedtoothersubstances,suchas
cocaineoralcohol.Availablestudiesindicatethateffectivelytreatingthemental
healthdisorderwithstandardtreatmentsinvolvingmedicationsandbehavioral
therapiesmayhelpreducemarijuanause,particularlyamongthoseinvolved
withheavyuseandthosewithmorechronicmentaldisorders.Thefollowing
behavioraltreatmentshaveshownpromise:
Cognitive-behavioraltherapy:Aformofpsychotherapythatteachespeople
strategiestoidentifyandcorrectproblematicbehaviorsinordertoenhance
self-control,stopdruguse,andaddressarangeofotherproblemsthatoften
co-occurwiththem.
Contingencymanagement:Atherapeuticmanagementapproachbasedon
frequentmonitoringofthetargetbehaviorandtheprovision(orremoval)of
tangible,positiverewardswhenthetargetbehavioroccurs(ordoesnot).
Motivationalenhancementtherapy:Asystematicformofintervention
designedtoproducerapid,internallymotivatedchange;thetherapydoes
notattempttotreattheperson,butrathermobilizehisorherowninternal
resourcesforchangeandengagementintreatment.
Currently,theFDAhasnotapprovedanymedicationsforthetreatmentof
marijuanausedisorder,butresearchisactiveinthisarea.Becausesleep
problemsfeatureprominentlyinmarijuanawithdrawal,somestudiesare
examiningtheeffectivenessofmedicationsthataidinsleep.Medicationsthat
haveshownpromiseinearlystudiesorsmallclinicaltrialsincludethesleepaid
zolpidem(Ambien ),ananti-anxiety/anti-stressmedicationcalledbuspirone
117
118
®
®
41
(BuSpar ),andananti-epilepticdrugcalledgabapentin
(Horizant ,Neurontin )thatmayimprovesleepand,possibly,executive
function.OtheragentsbeingstudiedincludethenutritionalsupplementN-
acetylcysteineandchemicalscalledFAAHinhibitors,whichmayreduce
withdrawalbyinhibitingthebreakdownofthebody’sowncannabinoids.Future
directionsincludethestudyofsubstancescalledallostericmodulatorsthat
interactwithcannabinoidreceptorstoinhibitTHC’srewardingeffects.
®
® ®
42
WherecanIgetfurtherinformation
aboutmarijuana?
Tolearnmoreaboutmarijuanaandotherdrugs,visittheNIDAwebsiteat
drugabuse.govorcontacttheDrugPubsResearchDisseminationCenterat
877-NIDA-NIH(877-643-2644;TTY/TDD:240-645-0228).
TheNIDAwebsiteincludes:
informationaboutdrugsandrelatedhealthconsequences
NIDApublications,news,andevents
resourcesforhealthcareprofessionals
fundinginformation(includingprogramannouncementsanddeadlines)
internationalactivities
linkstorelatedwebsites(accesstowebsitesofmanyotherorganizationsin
thefield)
informationinSpanish(enespañol)
NIDAwebsitesandwebpages
drugabuse.gov
teens.drugabuse.gov
easyread.drugabuse.gov
drugabuse.gov/drugs-abuse/marijuana
drugabuse.gov/related-topics/hivaids
researchstudies.drugabuse.gov
irp.drugabuse.gov
43
Forphysicianinformation
NIDAMED:drugabuse.gov/nidamed
Otherwebsites
Informationaboutmarijuanaisalsoavailablethroughthefollowingwebsites:
SubstanceAbuseandMentalHealthServicesAdministration:samhsa.gov
DrugEnforcementAdministration:dea.gov
MonitoringtheFuture:monitoringthefuture.org/
PartnershipforDrug-FreeKids:drugfree.org/drug-guide
Thispublicationisavailableforyouruseandmaybereproducedinits
entiretywithoutpermissionfromtheNIDA.Citationofthesourceis
appreciated,usingthefollowinglanguage:Source:NationalInstituteon
DrugAbuse;NationalInstitutesofHealth;U.S.DepartmentofHealthand
HumanServices.
44
References
1. TimberlakeDS.Acomparisonofdruguseanddependencebetweenblunt
smokersandothercannabisusers.SubstUseMisuse.2009;44(3):401-415.
doi:10.1080/10826080802347651.
2. MehmedicZ,ChandraS,SladeD,etal.PotencytrendsofΔ9-THCand
othercannabinoidsinconfiscatedcannabispreparationsfrom1993to
2008.JForensicSci.2010;55(5):1209-1217.doi:10.1111/j.1556-
4029.2010.01441.x.
3. Resultsfromthe2015NationalSurveyonDrugUseandHealth:Detailed
Tables,SAMHSA,CBHSQ.
http://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-
2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.htm.Accessed
October11,2016.
4. CarlinerH,MauroPM,BrownQL,etal.Thewideninggendergapin
marijuanauseprevalenceintheU.S.duringaperiodofeconomicchange,
2002-2014.DrugAlcoholDepend.2016;170:51-58.
doi:10.1016/j.drugalcdep.2016.10.042.
5. JohnstonL,O’MalleyP,MiechR,BachmanJ,SchulenbergJ.Monitoringthe
FutureNationalSurveyResultsonDrugUse:1975-2016:Overview:Key
FindingsonAdolescentDrugUse.AnnArbor,MI:InstituteforSocial
Research,TheUniversityofMichigan;2016.
6. CenterforBehavioralHealthStatisticsandQuality(CBHSQ).DrugAbuse
WarningNetwork:2011:SelectedTablesofNationalEstimatesofDrug-
RelatedEmergencyDepartmentVisits.Rockville,MD:SubstanceAbuse
andMentalHealthServicesAdministration;2013.
7. LennéMG,DietzePM,TriggsTJ,WalmsleyS,MurphyB,RedmanJR.The
effectsofcannabisandalcoholonsimulatedarterialdriving:Influencesof
drivingexperienceandtaskdemand.AccidAnalPrev.2010;42(3):859-866.
doi:10.1016/j.aap.2009.04.021.
8. HartmanRL,HuestisMA.Cannabiseffectsondrivingskills.ClinChem.
2013;59(3):478-492.doi:10.1373/clinchem.2012.194381.
45
9. HartmanRL,BrownTL,MilavetzG,etal.Cannabiseffectsondrivinglateral
controlwithandwithoutalcohol.DrugAlcoholDepend.2015;154:25-37.
doi:10.1016/j.drugalcdep.2015.06.015.
10. BradyJE,LiG.TrendsinAlcoholandOtherDrugsDetectedinFatally
InjuredDriversintheUnitedStates,1999–2010.AmJEpidemiol.January
2014:kwt327.doi:10.1093/aje/kwt327.
11. BiechelerM-B,PeytavinJ-F,SamGroup,FacyF,MartineauH.SAMsurvey
on“drugsandfatalaccidents”:searchofsubstancesconsumedand
comparisonbetweendriversinvolvedundertheinfluenceofalcoholor
cannabis.TrafficInjPrev.2008;9(1):11-21.
doi:10.1080/15389580701737561.
12. DRUIDFinalReport:WorkPerformed,MainResultsand
Recommendations.EUDRUIDProgramme;2012.
http://www.roadsafetyobservatory.com/Evidence/Details/10940.
13. ElvikR.Riskofroadaccidentassociatedwiththeuseofdrugs:asystematic
reviewandmeta-analysisofevidencefromepidemiologicalstudies.Accid
AnalPrev.2013;60:254-267.doi:10.1016/j.aap.2012.06.017.
14. RamaekersJG,BerghausG,vanLaarM,DrummerOH.Doserelatedriskof
motorvehiclecrashesaftercannabisuse.DrugAlcoholDepend.
2004;73(2):109-119.
15. LiM-C,BradyJE,DiMaggioCJ,LusardiAR,TzongKY,LiG.MarijuanaUse
andMotorVehicleCrashes.EpidemiolRev.2012;34(1):65-72.
doi:10.1093/epirev/mxr017.
16. AsbridgeM,HaydenJA,CartwrightJL.Acutecannabisconsumptionand
motorvehiclecollisionrisk:systematicreviewofobservationalstudiesand
meta-analysis.BMJ.2012;344:e536.doi:10.1136/bmj.e536.
17. ComptonRP,BerningA.DrugandAlcoholCrashRisk.Washington,DC:
NationalHighwayTrafficSafetyAdministration;2015.DOTHA812117.
18. HasinDS,SahaTD,KerridgeBT,etal.PrevalenceofMarijuanaUse
DisordersintheUnitedStatesBetween2001-2002and2012-2013.JAMA
Psychiatry.2015;72(12):1235-1242.
doi:10.1001/jamapsychiatry.2015.1858.
46
19. WintersKC,LeeC-YS.Likelihoodofdevelopinganalcoholandcannabis
usedisorderduringyouth:Associationwithrecentuseandage.Drug
AlcoholDepend.2008;92(1-3):239-247.
doi:10.1016/j.drugalcdep.2007.08.005.
20. BudneyAJ,HughesJR.Thecannabiswithdrawalsyndrome.CurrOpin
Psychiatry.2006;19(3):233-238.doi:10.1097/01.yco.0000218592.00689.e5.
21. GorelickDA,LevinKH,CopersinoML,etal.DiagnosticCriteriafor
CannabisWithdrawalSyndrome.DrugAlcoholDepend.2012;123(1-3):141-
147.doi:10.1016/j.drugalcdep.2011.11.007.
22. RotterA,BayerleinK,HansbauerM,etal.CB1andCB2receptor
expressionandpromotermethylationinpatientswithcannabis
dependence.EurAddictRes.2013;19(1):13-20.doi:10.1159/000338642.
23. MorganCJA,PageE,SchaeferC,etal.Cerebrospinalfluidanandamide
levels,cannabisuseandpsychotic-likesymptoms.BrJPsychiatryJMent
Sci.2013;202(5):381-382.doi:10.1192/bjp.bp.112.121178.
24. AnthonyJC,WarnerLA,KesslerRC.Comparativeepidemiologyof
dependenceontobacco,alcohol,controlledsubstances,andinhalants:
BasicfindingsfromtheNationalComorbiditySurvey.ExpClin
Psychopharmacol.1994;2(3):244-268.doi:10.1037/1064-1297.2.3.244.
25. Lopez-QuinteroC,PérezdelosCobosJ,HasinDS,etal.Probabilityand
predictorsoftransitionfromfirstusetodependenceonnicotine,alcohol,
cannabis,andcocaine:resultsoftheNationalEpidemiologicSurveyon
AlcoholandRelatedConditions(NESARC).DrugAlcoholDepend.
2011;115(1-2):120-130.doi:10.1016/j.drugalcdep.2010.11.004.
26. AnthonyJC.Theepidemiologyofcannabisdependence.In:RoffmanRA,
StephensRS,eds.CannabisDependence:ItsNature,Consequencesand
Treatment.Cambridge,UK:CambridgeUniversityPress;2006:58-105.
27. HallWD,PaculaRL.CannabisUseandDependence:PublicHealthand
PublicPolicy.Cambridge,UK:CambridgeUniversityPress;2003.
28. CenterforBehavioralHealthStatisticsandQuality(CBHSQ).Treatment
EpisodeDataSet(TEDS):2003-2013.NationalAdmissionstoSubstance
AbuseTreatmentServices.Rockville,MD:SubstanceAbuseandMental
HealthServicesAdministration;2015.BHSISSeriesS-75,HHSPublication
47
No.(SMA)15-4934.
29. OfficeofNationalDrugControlPolicy.NationalDrugControlStrategy:Data
Supplement2015.
https://www.whitehouse.gov/sites/default/files/ondcp/policy-and-
research/2015_data_supplement_final.pdf.Published2015.Accessed
January5,2017.
30. FreemanTP,MorganCJA,HindochaC,SchaferG,DasRK,CurranHV.Just
say“know”:howdocannabinoidconcentrationsinfluenceusers’estimates
ofcannabispotencyandtheamounttheyrollinjoints?AddictAbingdon
Engl.2014;109(10):1686-1694.doi:10.1111/add.12634.
31. vanderPolP,LiebregtsN,BruntT,etal.Cross-sectionalandprospective
relationofcannabispotency,dosingandsmokingbehaviourwithcannabis
dependence:anecologicalstudy.AddictAbingdonEngl.2014;109(7):1101-
1109.doi:10.1111/add.12508.
32. CampolongoP,TrezzaV,CassanoT,etal.Perinatalexposuretodelta-9-
tetrahydrocannabinolcausesenduringcognitivedeficitsassociatedwith
alterationofcorticalgeneexpressionandneurotransmissioninrats.Addict
Biol.2007;12(3-4):485-495.doi:10.1111/j.1369-1600.2007.00074.x.
33. AntonelliT,TomasiniMC,TattoliM,etal.PrenatalexposuretotheCB1
receptoragonistWIN55,212-2causeslearningdisruptionassociatedwith
impairedcorticalNMDAreceptorfunctionandemotionalreactivitychanges
inratoffspring.CerebCortexNYN1991.2005;15(12):2013-2020.
doi:10.1093/cercor/bhi076.
34. VerricoCD,GuH,PetersonML,SampsonAR,LewisDA.RepeatedΔ9-
tetrahydrocannabinolexposureinadolescentmonkeys:persistenteffects
selectiveforspatialworkingmemory.AmJPsychiatry.2014;171(4):416-
425.doi:10.1176/appi.ajp.2013.13030335.
35. RubinoT,RealiniN,BraidaD,etal.Changesinhippocampalmorphology
andneuroplasticityinducedbyadolescentTHCtreatmentareassociated
withcognitiveimpairmentinadulthood.Hippocampus.2009;19(8):763-772.
doi:10.1002/hipo.20554.
36. GleasonKA,BirnbaumSG,ShuklaA,GhoseS.Susceptibilityofthe
adolescentbraintocannabinoids:long-termhippocampaleffectsand
relevancetoschizophrenia.TranslPsychiatry.2012;2:e199.
48
doi:10.1038/tp.2012.122.
37. QuinnHR,MatsumotoI,CallaghanPD,etal.Adolescentratsfindrepeated
Delta(9)-THClessaversivethanadultratsbutdisplaygreaterresidual
cognitivedeficitsandchangesinhippocampalproteinexpressionfollowing
exposure.NeuropsychopharmacolOffPublAmColl
Neuropsychopharmacol.2008;33(5):1113-1126.
doi:10.1038/sj.npp.1301475.
38. BatallaA,BhattacharyyaS,YücelM,etal.Structuralandfunctionalimaging
studiesinchroniccannabisusers:asystematicreviewofadolescentand
adultfindings.PloSOne.2013;8(2):e55821.
doi:10.1371/journal.pone.0055821.
39. FilbeyFM,AslanS,CalhounVD,etal.Long-termeffectsofmarijuanause
onthebrain.ProcNatlAcadSciUSA.2014;111(47):16913-16918.
doi:10.1073/pnas.1415297111.
40. PagliaccioD,BarchDM,BogdanR,etal.Sharedpredispositioninthe
associationbetweencannabisuseandsubcorticalbrainstructure.JAMA
Psychiatry.2015;72(10):994-1001.doi:10.1001/jamapsychiatry.2015.1054.
41. VolkowND,SwansonJM,EvinsAE,etal.Effectsofcannabisuseonhuman
behavior,includingcognition,motivation,andpsychosis:areview.JAMA
Psychiatry.2016;73(3):292-297.doi:10.1001/jamapsychiatry.2015.3278.
42. AuerR,VittinghoffE,YaffeK,etal.Associationbetweenlifetimemarijuana
useandcognitivefunctioninmiddleage:theCoronaryArteryRisk
DevelopmentinYoungAdults(CARDIA)Study.JAMAInternMed.February
2016.doi:10.1001/jamainternmed.2015.7841.
43. MeierMH,CaspiA,AmblerA,etal.Persistentcannabisusersshow
neuropsychologicaldeclinefromchildhoodtomidlife.ProcNatlAcadSciU
SA.2012;109(40):E2657-E2664.doi:10.1073/pnas.1206820109.
44. RubinoT,ZamberlettiE,ParolaroD.Adolescentexposuretocannabisasa
riskfactorforpsychiatricdisorders.JPsychopharmacolOxfEngl.
2012;26(1):177-188.doi:10.1177/0269881111405362.
45. JacksonNJ,IsenJD,KhoddamR,etal.Impactofadolescentmarijuanause
onintelligence:Resultsfromtwolongitudinaltwinstudies.ProcNatlAcad
SciUSA.2016;113(5):E500-E508.doi:10.1073/pnas.1516648113.
49
46. Secades-VillaR,Garcia-RodríguezO,JinCJ,WangS,BlancoC.Probability
andpredictorsofthecannabisgatewayeffect:anationalstudy.IntJDrug
Policy.2015;26(2):135-142.doi:10.1016/j.drugpo.2014.07.011.
47. WeinbergerAH,PlattJ,GoodwinRD.Iscannabisuseassociatedwithan
increasedriskofonsetandpersistenceofalcoholusedisorders?Athree-
yearprospectivestudyamongadultsintheUnitedStates.DrugAlcohol
Depend.February2016.doi:10.1016/j.drugalcdep.2016.01.014.
48. PistisM,PerraS,PillollaG,MelisM,MuntoniAL,GessaGL.Adolescent
exposuretocannabinoidsinduceslong-lastingchangesintheresponseto
drugsofabuseofratmidbraindopamineneurons.BiolPsychiatry.
2004;56(2):86-94.doi:10.1016/j.biopsych.2004.05.006.
49. AgrawalA,NealeMC,PrescottCA,KendlerKS.Atwinstudyofearly
cannabisuseandsubsequentuseandabuse/dependenceofotherillicit
drugs.PsycholMed.2004;34(7):1227-1237.
50. PanlilioLV,ZanettiniC,BarnesC,SolinasM,GoldbergSR.Priorexposure
toTHCincreasestheaddictiveeffectsofnicotineinrats.
NeuropsychopharmacolOffPublAmCollNeuropsychopharmacol.
2013;38(7):1198-1208.doi:10.1038/npp.2013.16.
51. CadoniC,PisanuA,SolinasM,AcquasE,DiChiaraG.Behavioural
sensitizationafterrepeatedexposuretoDelta9-tetrahydrocannabinoland
cross-sensitizationwithmorphine.Psychopharmacology(Berl).
2001;158(3):259-266.doi:10.1007/s002130100875.
52. LevineA,HuangY,DrisaldiB,etal.Molecularmechanismforagateway
drug:epigeneticchangesinitiatedbynicotineprimegeneexpressionby
cocaine.SciTranslMed.2011;3(107):107ra109.
doi:10.1126/scitranslmed.3003062.
53. SchweinsburgAD,BrownSA,TapertSF.Theinfluenceofmarijuanauseon
neurocognitivefunctioninginadolescents.CurrDrugAbuseRev.
2008;1(1):99-111.
54. MacleodJ,OakesR,CopelloA,etal.Psychologicalandsocialsequelaeof
cannabisandotherillicitdrugusebyyoungpeople:asystematicreviewof
longitudinal,generalpopulationstudies.LancetLondEngl.
2004;363(9421):1579-1588.doi:10.1016/S0140-6736(04)16200-4.
50
55. SilinsE,HorwoodLJ,PattonGC,etal.Youngadultsequelaeofadolescent
cannabisuse:anintegrativeanalysis.LancetPsychiatry.2014;1(4):286-
293.doi:10.1016/S2215-0366(14)70307-4.
56. FergussonDM,BodenJM.Cannabisuseandlaterlifeoutcomes.Addict
AbingdonEngl.2008;103(6):969-976;discussion977-978.
doi:10.1111/j.1360-0443.2008.02221.x.
57. BrookJS,LeeJY,FinchSJ,SeltzerN,BrookDW.Adultworkcommitment,
financialstability,andsocialenvironmentasrelatedtotrajectoriesof
marijuanausebeginninginadolescence.SubstAbuse.2013;34(3):298-
305.doi:10.1080/08897077.2013.775092.
58. McCaffreyDF,PaculaRL,HanB,EllicksonP.MarijuanaUseandHigh
SchoolDropout:TheInfluenceofUnobservables.HealthEcon.
2010;19(11):1281-1299.doi:10.1002/hec.1561.
59. GruberAJ,PopeHG,HudsonJI,Yurgelun-ToddD.Attributesoflong-term
heavycannabisusers:acase-controlstudy.PsycholMed.2003;33(8):1415-
1422.
60. MacdonaldS,HallW,RomanP,StockwellT,CoghlanM,NesvaagS.
Testingforcannabisinthework-place:areviewoftheevidence.Addict
AbingdonEngl.2010;105(3):408-416.doi:10.1111/j.1360-
0443.2009.02808.x.
61. ZwerlingC,RyanJ,OravEJ.Theefficacyofpreemploymentdrugscreening
formarijuanaandcocaineinpredictingemploymentoutcome.JAMA.
1990;264(20):2639-2643.
62. RadhakrishnanR,WilkinsonST,D’SouzaDC.GonetoPot-AReviewofthe
AssociationbetweenCannabisandPsychosis.FrontPsychiatry.2014;5:54.
doi:10.3389/fpsyt.2014.00054.
63. BlancoC,HasinDS,WallMM,etal.CannabisUseandRiskofPsychiatric
Disorders:ProspectiveEvidenceFromaUSNationalLongitudinalStudy.
JAMAPsychiatry.February2016.doi:10.1001/jamapsychiatry.2015.3229.
64. DiFortiM,IyegbeC,SallisH,etal.ConfirmationthattheAKT1(rs2494732)
genotypeinfluencestheriskofpsychosisincannabisusers.BiolPsychiatry.
2012;72(10):811-816.doi:10.1016/j.biopsych.2012.06.020.
51
65. CaspiA,MoffittTE,CannonM,etal.Moderationoftheeffectofadolescent-
onsetcannabisuseonadultpsychosisbyafunctionalpolymorphisminthe
catechol-O-methyltransferasegene:longitudinalevidenceofageneX
environmentinteraction.BiolPsychiatry.2005;57(10):1117-1127.
doi:10.1016/j.biopsych.2005.01.026.
66. DelforterieMJ,LynskeyMT,HuizinkAC,etal.Therelationshipbetween
cannabisinvolvementandsuicidalthoughtsandbehaviors.DrugAlcohol
Depend.2015;150:98-104.doi:10.1016/j.drugalcdep.2015.02.019.
67. BorgesG,BaggeCL,OrozcoR.Aliteraturereviewandmeta-analysesof
cannabisuseandsuicidality.JAffectDisord.2016;195:63-74.
doi:10.1016/j.jad.2016.02.007.
68. TashkinDP.Effectsofmarijuanasmokingonthelung.AnnAmThoracSoc.
2013;10(3):239-247.doi:10.1513/AnnalsATS.201212-127FR.
69. OwenKP,SutterME,AlbertsonTE.Marijuana:respiratorytracteffects.Clin
RevAllergyImmunol.2014;46(1):65-81.doi:10.1007/s12016-013-8374-y.
70. PolenMR,SidneyS,TekawaIS,SadlerM,FriedmanGD.Healthcareuse
byfrequentmarijuanasmokerswhodonotsmoketobacco.WestJMed.
1993;158(6):596-601.
71. HashibeM,MorgensternH,CuiY,etal.Marijuanauseandtheriskoflung
andupperaerodigestivetractcancers:resultsofapopulation-basedcase-
controlstudy.CancerEpidemiolBiomarkPrevPublAmAssocCancerRes
CosponsoredAmSocPrevOncol.2006;15(10):1829-1834.
doi:10.1158/1055-9965.EPI-06-0330.
72. HancoxRJ,PoultonR,ElyM,etal.Effectsofcannabisonlungfunction:a
population-basedcohortstudy.EurRespirJ.2010;35(1):42-47.
doi:10.1183/09031936.00065009.
73. MittlemanMA,LewisRA,MaclureM,SherwoodJB,MullerJE.Triggering
MyocardialInfarctionbyMarijuana.Circulation.2001;103(23):2805-2809.
doi:10.1161/01.CIR.103.23.2805.
74. ThomasG,KlonerRA,RezkallaS.Adversecardiovascular,
cerebrovascular,andperipheralvasculareffectsofmarijuanainhalation:
whatcardiologistsneedtoknow.AmJCardiol.2014;113(1):187-190.
doi:10.1016/j.amjcard.2013.09.042.
52
75. JonesRT.Cardiovascularsystemeffectsofmarijuana.JClinPharmacol.
2002;42(11Suppl):58S-63S.
76. LacsonJCA,CarrollJD,TuazonE,CastelaoEJ,BernsteinL,CortessisVK.
Population-basedcase-controlstudyofrecreationaldruguseandtestis
cancerriskconfirmsanassociationbetweenmarijuanauseand
nonseminomarisk.Cancer.2012;118(21):5374-5383.
doi:10.1002/cncr.27554.
77. DalingJR,DoodyDR,SunX,etal.Associationofmarijuanauseandthe
incidenceoftesticulargermcelltumors.Cancer.2009;115(6):1215-1223.
doi:10.1002/cncr.24159.
78. GalliJA,SawayaRA,FriedenbergFK.CannabinoidHyperemesis
Syndrome.CurrDrugAbuseRev.2011;4(4):241-249.
79. AssociationBetweenUSStateMedicalCannabisLawsandOpioid
PrescribingintheMedicarePartDPopulation|AdolescentMedicine|JAMA
InternalMedicine|JAMA
Network.https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2676999.
AccessedMay1,2018.
80. AssociationofMedicalandAdult-UseMarijuanaLawsWithOpioid
PrescribingforMedicaidEnrollees|AdolescentMedicine|JAMAInternal
Medicine|JAMA
Network.https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2677000.
AccessedMay1,2018.
81. BachhuberMA,SalonerB,CunninghamCO,BarryCL.Medicalcannabis
lawsandopioidanalgesicoverdosemortalityintheUnitedStates,1999-
2010.JAMAInternMed.2014;174(10):1668-1673.
doi:10.1001/jamainternmed.2014.4005
82. PowellD,PaculaRL,JacobsonM.DoMedicalMarijuanaLawsReduce
AddictionandDeathsRelatedtoPainKillers?RANDCorporation;
2015.https://www.rand.org/pubs/external_publications/EP67480.html.
AccessedApril6,2017.
83. AbramsDI,CoueyP,ShadeSB,KellyME,BenowitzNL.Cannabinoid-
opioidinteractioninchronicpain.ClinPharmacolTher.2011;90(6):844-
851.doi:10.1038/clpt.2011.188
53
84. LynchME,ClarkAJ.Cannabisreducesopioiddoseinthetreatmentof
chronicnon-cancerpain.JPainSymptomManage.2003;25(6):496-498.
85. OlfsonM,WallMM,LiuS-M,BlancoC.CannabisUseandRiskof
PrescriptionOpioidUseDisorderintheUnitedStates.AmJPsychiatry.
2017;175(1):47-53.doi:10.1176/appi.ajp.2017.17040413
86. RöhrichJ,SchimmelI,ZörntleinS,etal.Concentrationsofdelta9-
tetrahydrocannabinoland11-nor-9-carboxytetrahydrocannabinolinblood
andurineafterpassiveexposuretoCannabissmokeinacoffeeshop.J
AnalToxicol.2010;34(4):196-203.
87. ConeEJ,BigelowGE,HerrmannES,etal.Non-smokerexposureto
secondhandcannabissmoke.I.Urinescreeningandconfirmationresults.J
AnalToxicol.2015;39(1):1-12.doi:10.1093/jat/bku116.
88. WangX,DerakhshandehR,LiuJ,etal.OneMinuteofMarijuana
SecondhandSmokeExposureSubstantiallyImpairsVascularEndothelial
Function.JAmHeartAssoc.2016;5(8).doi:10.1161/JAHA.116.003858.
89. MartinCE,LonginakerN,MarkK,ChisolmMS,TerplanM.Recenttrendsin
treatmentadmissionsformarijuanauseduringpregnancy.JAddictMed.
2015;9(2):99-104.doi:10.1097/ADM.0000000000000095.
90. Young-WolffKC,TuckerL-Y,AlexeeffS,etal.TrendsinSelf-reportedand
BiochemicallyTestedMarijuanaUseAmongPregnantFemalesin
CaliforniaFrom2009-2016.JAMA.2017;318(24):2490.
doi:10.1001/jama.2017.17225
91. KlineJ,HutzlerM,LevinB,SteinZ,SusserM,WarburtonD.Marijuanaand
spontaneousabortionofknownkaryotype.PaediatrPerinatEpidemiol.
1991;5(3):320-332.
92. WilcoxAJ,WeinbergCR,BairdDD.Riskfactorsforearlypregnancyloss.
EpidemiolCambMass.1990;1(5):382-385.
93. AschRH,SmithCG.Effectsofdelta9-THC,theprincipalpsychoactive
componentofmarijuana,duringpregnancyintherhesusmonkey.JReprod
Med.1986;31(12):1071-1081.
94. CampolongoP,TrezzaV,RatanoP,PalmeryM,CuomoV.Developmental
consequencesofperinatalcannabisexposure:behavioraland
54
neuroendocrineeffectsinadultrodents.Psychopharmacology(Berl).
2011;214(1):5-15.doi:10.1007/s00213-010-1892-x.
95. FriedPA,WatkinsonB,GrayR.Afollow-upstudyofattentionalbehaviorin
6-year-oldchildrenexposedprenatallytomarihuana,cigarettes,and
alcohol.NeurotoxicolTeratol.1992;14(5):299-311.
96. GoldschmidtL,DayNL,RichardsonGA.Effectsofprenatalmarijuana
exposureonchildbehaviorproblemsatage10.NeurotoxicolTeratol.
2000;22(3):325-336.
97. FriedPA,SmithAM.Aliteraturereviewoftheconsequencesofprenatal
marihuanaexposure.Anemergingthemeofadeficiencyinaspectsof
executivefunction.NeurotoxicolTeratol.2001;23(1):1-11.
98. JanisseJJ,BaileyBA,AgerJ,SokolRJ.Alcohol,tobacco,cocaine,and
marijuanause:relativecontributionstopretermdeliveryandfetalgrowth
restriction.SubstAbuse.2014;35(1):60-67.
doi:10.1080/08897077.2013.804483.
99. HayatbakhshMR,FlenadyVJ,GibbonsKS,etal.Birthoutcomesassociated
withcannabisusebeforeandduringpregnancy.PediatrRes.
2012;71(2):215-219.doi:10.1038/pr.2011.25.
100. ShionoPH,KlebanoffMA,NugentRP,etal.Theimpactofcocaineand
marijuanauseonlowbirthweightandpretermbirth:amulticenterstudy.Am
JObstetGynecol.1995;172(1Pt1):19-27.
101. MarkK,DesaiA,TerplanM.Marijuanauseandpregnancy:prevalence,
associatedcharacteristics,andbirthoutcomes.ArchWomensMentHealth.
2016;19(1):105-111.doi:10.1007/s00737-015-0529-9.
102. SchempfAH,StrobinoDM.IllicitDrugUseandAdverseBirthOutcomes:IsIt
DrugsorContext?JUrbanHealthBullNYAcadMed.2008;85(6):858-873.
doi:10.1007/s11524-008-9315-6.
103. Tobacco,druguseinpregnancycandoubleriskofstillbirth.
https://www.nichd.nih.gov/news/releases/Pages/121113-stillbirth-drug-
use.aspx.AccessedDecember16,2016.
104. MarijuanaUseDuringPregnancyandLactation-ACOG.ACOG.
http://www.acog.org/Resources-And-Publications/Committee-
55
Opinions/Committee-on-Obstetric-Practice/Marijuana-Use-During-
Pregnancy-and-Lactation.PublishedJuly2015.AccessedOctober12,
2016.
105. RobersonEK,PatrickWK,HurwitzEL.Marijuanauseandmaternal
experiencesofseverenauseaduringpregnancyinHawai’i.HawaiiJMed
PublicHealthJAsiaPacMedPublicHealth.2014;73(9):283-287.
106. WestfallRE,JanssenPA,LucasP,CaplerR.Surveyofmedicinalcannabis
useamongchildbearingwomen:patternsofitsuseinpregnancyand
retroactiveself-assessmentofitsefficacyagainst“morningsickness.”
ComplementTherClinPract.2006;12(1):27-33.
doi:10.1016/j.ctcp.2005.09.006.
107. TrezzaV,CampolongoP,CassanoT,etal.Effectsofperinatalexposureto
delta-9-tetrahydrocannabinolontheemotionalreactivityoftheoffspring:a
longitudinalbehavioralstudyinWistarrats.Psychopharmacology(Berl).
2008;198(4):529-537.doi:10.1007/s00213-008-1162-3.
108. MereuG,FàM,FerraroL,etal.Prenatalexposuretoacannabinoidagonist
producesmemorydeficitslinkedtodysfunctioninhippocampallong-term
potentiationandglutamaterelease.ProcNatlAcadSciUSA.
2003;100(8):4915-4920.doi:10.1073/pnas.0537849100.
109. FriedPA,MakinJE.Neonatalbehaviouralcorrelatesofprenatalexposureto
marihuana,cigarettesandalcoholinalowriskpopulation.Neurotoxicol
Teratol.1987;9(1):1-7.
110. deMoraesBarrosMC,GuinsburgR,MitsuhiroS,ChalemE,LaranjeiraRR.
Neurobehavioralprofileofhealthyfull-termnewborninfantsofadolescent
mothers.EarlyHumDev.2008;84(5):281-287.
doi:10.1016/j.earlhumdev.2007.07.001.
111. RichardsonGA,RyanC,WillfordJ,DayNL,GoldschmidtL.Prenatalalcohol
andmarijuanaexposure:effectsonneuropsychologicaloutcomesat10
years.NeurotoxicolTeratol.2002;24(3):309-320.
112. GoldschmidtL,DayNL,RichardsonGA.Effectsofprenatalmarijuana
exposureonchildbehaviorproblemsatage10.NeurotoxicolTeratol.
2000;22(3):325-336.
113. SononKE,RichardsonGA,CorneliusJR,KimKH,DayNL.Prenatal
56
marijuanaexposurepredictsmarijuanauseinyoungadulthood.
NeurotoxicolTeratol.2015;47:10-15.doi:10.1016/j.ntt.2014.11.003.
114. Perez-ReyesM,WallME.Presenceofdelta9-tetrahydrocannabinolin
humanmilk.NEnglJMed.1982;307(13):819-820.
doi:10.1056/NEJM198209233071311.
115. AstleySJ,LittleRE.Maternalmarijuanauseduringlactationandinfant
developmentatoneyear.NeurotoxicolTeratol.1990;12(2):161-168.
116. DjulusJ,MorettiM,KorenG.Marijuanauseandbreastfeeding.CanFam
PhysicianMédecinFamCan.2005;51:349-350.
117. BudneyAJ,RoffmanR,StephensRS,WalkerD.MarijuanaDependence
andItsTreatment.AddictSciClinPract.2007;4(1):4-16.
118. DiamondG,Panichelli-MindelSM,SheraD,DennisM,TimsF,UngemackJ.
PsychiatricSyndromesinAdolescentswithMarijuanaAbuseand
DependencyinOutpatientTreatment.JChildAdolescSubstAbuse.
2006;15(4):37-54.doi:10.1300/J029v15n04_02.
