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.