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NationalInstituteonDrugAbuse(NIDA)
Cocaine
LastUpdatedMay2016
https://www.drugabuse.gov
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TableofContents
Cocaine
Whatiscocaine?
WhatisthescopeofcocaineuseintheUnitedStates?
Howiscocaineused?
Howdoescocaineproduceitseffects?
Whataresomewaysthatcocainechangesthebrain?
Whataretheshort-termeffectsofcocaineuse?
Whatarethelong-termeffectsofcocaineuse?
WhyarecocaineusersatriskforcontractingHIV/AIDSandhepatitis?
Whataretheeffectsofmaternalcocaineuse?
Howiscocaineaddictiontreated?
Howiscutting-edgesciencehelpingusbetterunderstandaddiction?
References
WherecanIgetfurtherinformationaboutcocaine?
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Whatiscocaine?
Cocaineisapowerfullyaddictivestimulantdrug.Forthousandsof
years,peopleinSouthAmericahavechewedandingestedcocaleaves
(Erythroxyloncoca),thesourceofcocaine,fortheirstimulant
effects. Thepurifiedchemical,cocainehydrochloride,wasisolated
fromtheplantmorethan100yearsago.Intheearly1900s,purified
cocainewasthemainactiveingredientinmanytonicsandelixirs
developedtotreatawidevarietyofillnessesandwasevenan
ingredientintheearlyformulationsofCoca-Cola .Beforethe
developmentofsyntheticlocalanesthetic,surgeonsusedcocaineto
blockpain. However,researchhassinceshownthatcocaineisa
powerfullyaddictivesubstancethatcanalterbrainstructureand
functionifusedrepeatedly.
Today,cocaineisaScheduleIIdrug,whichmeansthatithashigh
potentialforabusebutcanbeadministeredbyadoctorforlegitimate
medicaluses,suchaslocalanesthesiaforsomeeye,ear,andthroat
surgeries.Asastreetdrug,cocaineappearsasafine,white,crystalline
powderandisalsoknownasCoke,C,Snow,Powder,orBlow.Street
dealersoftendilute(or“cut”)itwithnon-psychoactivesubstancessuch
ascornstarch,talcumpowder,flour,orbakingsodatoincreasetheir
profits.Theymayalsoadulteratecocainewithotherdrugslikeprocaine
Photoby©iStock.com/RafalCichawa
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(achemicallyrelatedlocalanesthetic)oramphetamine(another
psychoactivestimulant). Someuserscombinecocainewithheroin—
calledaSpeedball.
Peopleabusetwochemicalformsofcocaine:thewater-soluble
hydrochloridesaltandthewater-insolublecocainebase(orfreebase).
Usersinjectorsnortthehydrochloridesalt,whichisapowder.The
baseformofcocaineiscreatedbyprocessingthedrugwithammonia
orsodiumbicarbonate(bakingsoda)andwater,thenheatingitto
removethehydrochloridetoproduceasmokablesubstance.Theterm
crack,whichisthestreetnamegiventofreebasecocaine,referstothe
cracklingsoundheardwhenthemixtureissmoked.
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Whatisthescopeofcocaine
useintheUnitedStates?
AccordingtotheNationalSurveyonDrugUseandHealth(NSDUH),
cocaineusehasremainedrelativelystablesince2009.In2014,there
wereanestimated1.5millioncurrent(past-month)cocaineusersaged
12orolder(0.6percentofthepopulation).Adultsaged18to25years
haveahigherrateofcurrentcocaineusethananyotheragegroup,
with1.4percentofyoungadultsreportingpast-monthcocaineuse.
The2015MonitoringtheFuturesurvey,whichannuallysurveysteen
attitudesanddruguse,reportsasignificantdeclinein30-day
prevalenceofpowdercocaineuseamong8th,10th,and12thgraders
frompeakuseinthelate1990s.In2014,1.1percentof12thgraders
andonly0.8percentof10thandhalfapercentof8thgradersreported
usingcocaineinthepastmonth.
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Source:UniversityofMichigan,MonitoringtheFuturenationalresultsondruguse:
1975-2015:overview,keyfindingsonadolescentdruguse,2016.
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Repeatedcocaineusecanproduceaddictionandotheradversehealth
consequences.In2014,accordingtotheNSDUH,about913,000
AmericansmettheDiagnosticandStatisticalManualofMental
Disorderscriteriafordependenceorabuseofcocaine(inanyform)
duringthepast12months.Further,datafromthe2011DrugAbuse
WarningNetwork(DAWN)reportshowedthatcocainewasinvolvedin
505,224ofthenearly1.3millionvisitstoemergencydepartmentsfor
drugmisuseorabuse.Thistranslatestooveroneinthreedrugmisuse
orabuse-relatedemergencydepartmentvisits(40percent)that
involvedcocaine.
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Howiscocaineused?
Usersprimarilyadministercocaineorally,intranasally,intravenously,
orbyinhalation.Whenpeoplesnortthedrug(intranasaluse),they
inhalecocainepowderthroughthenostrils,whereitisabsorbedinto
thebloodstreamthroughthenasaltissues.Usersalsomayrubthe
drugontotheirgums(oraluse).Dissolvingcocaineinwaterand
injectingit(intravenoususe)releasesthedrugdirectlyintothe
bloodstreamandheightenstheintensityofitseffects.Whenpeople
smokecocaine(inhalation),theyinhaleitsvapororsmokeintothe
lungs,whereabsorptionintothebloodstreamisalmostasrapidasby
injection.Thisfasteuphoriceffectisoneofthereasonsthatcrack
becameenormouslypopularinthemid-1980s.
PhotobyDEA/
Cocaine
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Cocaineuserangesfromoccasionaltorepeatedorcompulsiveuse,
withavarietyofpatternsbetweentheseextremes.Anyrouteof
administrationcanpotentiallyleadtoabsorptionoftoxicamountsof
cocaine,causingheartattacks,strokes,orseizures—allofwhichcan
resultinsuddendeath.
PhotobyDEA/
Crackcocaine
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Howdoescocaineproduceits
effects?
Thebrain’smesolimbicdopaminesystem,itsrewardpathway,is
stimulatedbyalltypesofreinforcingstimuli,suchasfood,sex,and
manydrugsofabuse,includingcocaine. Thispathwayoriginatesina
regionofthemidbraincalledtheventraltegmentalareaandextends
tothenucleusaccumbens,oneofthebrain’skeyrewardareas.
Besidesreward,thiscircuitalsoregulatesemotionsandmotivation.
Inthenormalcommunicationprocess,dopamineisreleasedbya
neuronintothesynapse(thesmallgapbetweentwoneurons),whereit
bindstospecializedproteinscalleddopaminereceptorsonthe
neighboringneuron.Bythisprocess,dopamineactsasachemical
messenger,carryingasignalfromneurontoneuron.Another
specializedproteincalledatransporterremovesdopaminefromthe
synapsetoberecycledforfurtheruse.
Drugsofabusecaninterferewiththisnormalcommunicationprocess.
Forexample,cocaineactsbybindingtothedopaminetransporter,
blockingtheremovalofdopaminefromthesynapse.Dopaminethen
accumulatesinthesynapsetoproduceanamplifiedsignaltothe
receivingneurons.Thisiswhatcausestheeuphoriacommonly
experiencedimmediatelyaftertakingthedrug(seethevideo"Brain
Reward:UnderstandingHowtheBrainRespondstoNaturalRewards
andDrugsofAbuse").
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ImagebyNIDA
Cocaineinthebrain:Inthenormalneuralcommunicationprocess,
dopamineisreleasedbyaneuronintothesynapse,whereitcanbindto
dopaminereceptorsonneighboringneurons.Normally,dopamineisthen
recycledbackintothetransmittingneuronbyaspecializedproteincalled
thedopaminetransporter.Ifcocaineispresent,itattachestothe
dopaminetransporterandblocksthenormalrecyclingprocess,resultingin
abuildupofdopamineinthesynapse,whichcontributestothe
pleasurableeffectsofcocaine.
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Whataresomewaysthat
cocainechangesthebrain?
Useofcocaine,likeotherdrugsofabuse,induceslong-termchangesin
thebrain.Animalstudiesshowthatcocaineexposurecancause
significantneuroadaptationsinneuronsthatreleasetheexcitatory
neurotransmitterglutamate. Animalschronicallyexposedtococaine
demonstrateprofoundchangesinglutamateneurotransmission—
includinghowmuchisreleasedandthelevelofreceptorproteins—in
therewardpathway,particularlythenucleusaccumbens.The
glutamatesystemmaybeanopportunetargetforanti-addiction
medicationdevelopment,withthegoalofreversingthecocaine-
inducedneuroadaptationsthatcontributetothedrivetousethedrug.
Althoughaddictionresearchershavefocusedonadaptationsinthe
brain’srewardsystem,drugsalsoaffectthebrainpathwaysthat
respondtostress.Stresscancontributetococainerelapse,and
cocaineusedisordersfrequentlyco-occurwithstress-related
disorders. Thestresscircuitsofthebrainaredistinctfromthereward
pathway,butresearchindicatesthatthereareimportantwaysthat
theyoverlap.Theventraltegmentalareaseemstoactasacritical
integrationsiteinthebrainthatrelaysinformationaboutbothstress
anddrugcuestootherareasofthebrain,includingonesthatdrive
cocaineseeking. Animalsthathavereceivedcocainerepeatedlyare
morelikelytoseekthedruginresponsetostress,andthemoreofthe
drugtheyhavetaken,themorestressaffectsthisbehavior. Research
suggeststhatcocaineelevatesstresshormones,inducing
neuroadaptationsthatfurtherincreasesensitivitytothedrugandcues
associatedwithit.
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Chroniccocaineexposureaffectsmanyotherareasofthebraintoo.For
example,animalresearchindicatesthatcocainediminishesfunctioning
intheorbitofrontalcortex(OFC),whichappearstounderliethepoor
decision-making,inabilitytoadapttonegativeconsequencesofdrug
use,andlackofself-insightshownbypeopleaddictedtococaine. A
studyusingoptogenetictechnology,whichuseslighttoactivate
specific,genetically-modifiedneurons,foundthatstimulatingtheOFC
restoresadaptivelearninginanimals.Thisintriguingresultsuggests
thatstrengtheningOFCactivitymaybeagoodtherapeuticapproachto
improveinsightandawarenessoftheconsequencesofdruguse
amongpeopleaddictedtococaine.
Brainimagesshowingdecreasedglucosemetabolism,whichindicates
reducedactivity,intheorbitofrontalcortex(OFC)inacontrolsubject(left)
andacocaine-addictedsubject(right).
VolkowND,WantG-J,FowlerJS,TomasiD,TelandF.Addiction:beyond
dopaminerewardcircuitry.ProcNatlAcadSciUSA.2011;108(37):15037-
15042.
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Whataretheshort-term
effectsofcocaineuse?
Cocaine’seffectsappearalmostimmediatelyafterasingledoseand
disappearwithinafewminutestoanhour.Smallamountsofcocaine
usuallymaketheuserfeeleuphoric,energetic,talkative,mentally
alert,andhypersensitivetosight,sound,andtouch.Thedrugcanalso
temporarilydecreasetheneedforfoodandsleep. Someusersfind
thatcocainehelpsthemperformsimplephysicalandintellectualtasks
morequickly,althoughothersexperiencetheoppositeeffect.
Thedurationofcocaine’seuphoriceffectsdependupontherouteof
administration.Thefasterthedrugisabsorbed,themoreintensethe
resultinghigh,butalsotheshorteritsduration.Snortingcocaine
producesarelativelyslowonsetofthehigh,butitmaylastfrom15to
30minutes.Incontrast,thehighfromsmokingismoreimmediatebut
maylastonly5to10minutes.
Short-termphysiologicaleffectsofcocaineuseincludeconstricted
bloodvessels;dilatedpupils;andincreasedbodytemperature,heart
rate,andbloodpressure. Largeamountsofcocainemayintensifythe
user’shighbutcanalsoleadtobizarre,erratic,andviolentbehavior.
Somecocaineusersreportfeelingsofrestlessness,irritability,anxiety,
panic,andparanoia. Usersmayalsoexperiencetremors,vertigo,and
muscletwitches.
Severemedicalcomplicationscanoccurwithcocaineuse.Someofthe
mostfrequentarecardiovasculareffects,includingdisturbancesin
heartrhythmandheartattacks;neurologicaleffects,including
headaches,seizures,strokes,andcoma;andgastrointestinal
complications,includingabdominalpainandnausea. Inrare
instances,suddendeathcanoccuronthefirstuseofcocaineor
unexpectedlythereafter.Cocaine-relateddeathsareoftenaresultof
cardiacarrestorseizures (see"NationalOverdoseDeaths:Numberof
DeathsfromCocaine").Manycocaineusersalsousealcohol,andthis
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combinationcanbeparticularlydangerous.Thetwosubstancesreact
toproducecocaethylene,whichmaypotentiatethetoxiceffectsof
cocaineandalcoholontheheart. Thecombinationofcocaineand
heroinisalsoverydangerous.Userscombinethesedrugsbecausethe
stimulatingeffectsofcocaineareoffsetbythesedatingeffectsof
heroin;however,thiscanleadtotakingahighdoseofheroinwithout
initiallyrealizingit.Becausecocaine'seffectswearoffsooner,thiscan
leadtoaheroinoverdose,inwhichtheuser'srespirationdangerously
slowsdownorstops,possiblyfatally.
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15
Whatarethelong-termeffects
ofcocaineuse?
Withrepeatedexposuretococaine,thebrainstartstoadaptsothat
therewardpathwaybecomeslesssensitivetonaturalreinforcers
(see"WhatAreSomeWaysthatCocaineChangestheBrain?").Atthe
sametime,circuitsinvolvedinstressbecomeincreasinglysensitive,
leadingtoincreaseddispleasureandnegativemoodswhennottaking
thedrug,whicharesignsofwithdrawal.Thesecombinedeffectsmake
theusermorelikelytofocusonseekingthedruginsteadof
relationships,food,orothernaturalrewards.
Withregularuse,tolerancemaydevelopsothathigherdoses,more
frequentuseofcocaine,orbothareneededtoproducethesamelevel
ofpleasureandrelieffromwithdrawalexperiencedinitially. Atthe
sametime,userscanalsodevelopsensitization,inwhichlesscocaine
isneededtoproduceanxiety,convulsions,orothertoxiceffects.
Tolerancetococainerewardandsensitizationtococainetoxicitycan
increasetheriskofoverdoseinaregularuser.
Userstakecocaineinbinges,inwhichcocaineisusedrepeatedlyand
atincreasinglyhigherdoses.Thiscanleadtoincreasedirritability,
restlessness,panicattacks,paranoia,andevenafull-blownpsychosis,
inwhichtheindividuallosestouchwithrealityandexperiences
auditoryhallucinations. Withincreasingdosesorhigherfrequencyof
use,theriskofadversepsychologicalorphysiologicaleffects
increases. Animalresearchsuggeststhatbingingoncocaineduring
adolescenceenhancessensitivitytotherewardingeffectsofcocaine
andMDMA(EcstasyorMolly). Thus,bingeuseofcocaineduring
adolescencemayfurtherincreasevulnerabilitytocontinueduseofthe
drugamongsomepeople.
Specificroutesofcocaineadministrationcanproducetheirown
adverseeffects.Regularlysnortingcocainecanleadtolossofsenseof
smell,nosebleeds,problemswithswallowing,hoarseness,andan
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2,7
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16
overallirritationofthenasalseptumleadingtoachronicallyinflamed,
runnynose. Smokingcrackcocainedamagesthelungsandcan
worsenasthma. Peoplewhoinjectcocainehavepuncturemarks
calledtracks,mostcommonlyintheirforearms, andtheyareatriskof
contractinginfectiousdiseaseslikeHIVandhepatitisC(see"WhyAre
CocaineUsersatRiskforContractingHIVandHepatitis?").Theyalso
mayexperienceallergicreactions,eithertothedrugitselforto
additivesinstreetcocaine,whichinseverecasescanresultindeath.
Cocainedamagesmanyotherorgansinthebody.Itreducesbloodflow
inthegastrointestinaltract,whichcanleadtotearsandulcerations.
Manychroniccocaineuserslosetheirappetiteandexperience
significantweightlossandmalnourishment.Cocainehassignificant
andwell-recognizedtoxiceffectsontheheartandcardiovascular
system. Chestpainthatfeelslikeaheartattackiscommonand
sendsmanycocaineuserstotheemergencyroom. Cocaineuseis
linkedwithincreasedriskofstroke, aswellasinflammationofthe
heartmuscle,deteriorationoftheabilityofthehearttocontract,and
aorticruptures.
Inadditiontotheincreasedriskforstrokeandseizures,other
neurologicalproblemscanoccurwithlong-termcocaineuse. There
havebeenreportsofintracerebralhemorrhage,orbleedingwithinthe
brain,andballoon-likebulgesinthewallsofcerebralbloodvessels.
Movementdisorders,includingParkinson’sdisease,mayalsooccur
aftermanyyearsofcocaineuse. Generally,studiessuggestthata
widerangeofcognitivefunctionsareimpairedwithlong-termcocaine
use—suchassustainingattention,impulseinhibition,memory,making
decisionsinvolvingrewardsorpunishments,andperformingmotor
tasks.
Formercocaineusersareathighriskforrelapse,evenfollowinglong
periodsofabstinence.Researchindicatesthatduringperiodsof
abstinence,thememoryofthecocaineexperienceorexposuretocues
associatedwithdrugusecantriggerstrongcravings,whichcanleadto
relapse.
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7,18
7
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Whyarecocaineusersatrisk
forcontractingHIV/AIDSand
hepatitis?
Drugintoxicationandaddictioncancompromisejudgmentand
decision-makingandpotentiallyleadtoriskysexualbehavior,including
tradingsexfordrugs,andneedlesharing.Thisincreasesacocaine
user’sriskforcontractinginfectiousdiseasessuchasHIVandhepatitis
C(HCV). TherearenovaccinestopreventHIVorHCVinfections.
StudiesthatexaminepatternsofHIVinfectionandprogressionhave
demonstratedthatcocaineuseacceleratesHIVinfection. Research
indicatesthatcocaineimpairsimmunecellfunction, promotes
replicationoftheHIVvirus,andpotentiatesthedamagingeffectsof
HIVondifferenttypesofcellsinthebrainandspinalcord,resultingin
furtherdamage. Studiesalsosuggestthatcocaineuseaccelerates
thedevelopmentofNeuroAIDS,neurologicalconditionsassociatedwith
HIVinfection.SymptomsofNeuroAIDSincludememoryloss,
movementproblems,andvisionimpairment.
CocaineuserswithHIVoftenhaveadvancedprogressionofthe
disease,withincreasedviralloadandaccelerateddecreasesinCD4+
cellcounts.InfectionwithHIVincreasesriskforco-infectionwithHCV,
avirusthataffectstheliver. Co-infectioncanleadtoseriousillnesses
—includingproblemswiththeimmunesystemandneurologic
conditions.Livercomplicationsareverycommon,withmanyco-
infectedindividualsdyingofchronicliverdiseaseandcancer.
AlthoughthelinkbetweeninjectiondruguseandHIV/HCViswell
established,morestudiesareneededtounderstandthemolecular
mechanismsunderlyingthisincreasedriskofco-infectioninnon-
injectingsubstanceusers.
Theinteractionofsubstanceuse,HIV,andhepatitismayaccelerate
diseaseprogression.Forexample,HIVspeedsthecourseofHCV
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infectionbyacceleratingtheprogressionofhepatitis-associatedliver
disease. ResearchhaslinkedHIV/HCVco-infectionwithincreased
mortalitywhencomparedtoeitherinfectionalone. Substanceuse
andco-infectionlikelynegativelyinfluenceHIVdiseaseprogressionand
theabilityofthebodytomarshalanimmuneresponse.
PatientswithHIV/HCVco-infectioncanbenefitfromsubstanceabuse
treatmentandantiretroviraltherapies,whenclosely
monitored. Antiretroviraltreatmentisnoteffectiveforeveryoneand
canhavesignificantsideeffects,necessitatingclosemedical
supervision.TestingforHIVandHCVisrecommendedforanyindividual
whohaseverinjecteddrugs,sincethediseaseishighlytransmissible
viainjection.
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Whataretheeffectsof
maternalcocaineuse?
Mostwomenwhoareaddictedtococaineareofchildbearingage.
Estimatessuggestthatabout5percentofpregnantwomenuseoneor
moreaddictivesubstances, andtherearearound750,000cocaine-
exposedpregnancieseveryyear. Althoughwomenmaybereluctant
toreportsubstanceusepatternsbecauseofsocialstigmaandfearof
losingcustodyoftheirchildren,theyshouldbeawarethatdruguse
whilepregnantisassociatedwithspecificrisksthatmaybereduced
withappropriatecare.
Cocaineuseduringpregnancyisassociatedwithmaternalmigraines
andseizures,prematuremembranerupture,andseparationofthe
placentalliningfromtheuteruspriortodelivery. Pregnancyis
accompaniedbynormalcardiovascularchanges,andcocaineuse
exacerbatesthese—sometimesleadingtoseriousproblemswithhigh
bloodpressure(hypertensivecrises),spontaneousmiscarriage,
pretermlabor,anddifficultdelivery. Cocaine-usingpregnantwomen
mustreceiveappropriatemedicalandpsychologicalcare—including
addictiontreatment—toreducetheserisks.
Sex-specificaddictiontreatmentandcomprehensiveservices—
includingprenatalcare,mentalhealthcounseling,
vocational/employmentassistance,andparentingskillstraining—can
promotedrugabstinenceandotherpositivehealthbehaviors.
Motivationalincentives/contingencymanagement(see"Behavioral
Interventions")asanadjuncttootheraddictiontreatmentisa
particularlypromisingstrategytoengagewomeninprenatalcareand
counselingforsubstanceuse.
Itisdifficulttoestimatethefullextentoftheconsequencesof
maternaldruguseandtodeterminethespecifichazardofaparticular
drugtotheunbornchild.Thisisbecausemultiplefactors—suchasthe
amountandnumberofalldrugsused,includingnicotineoralcohol;
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extentofprenatalcare;exposuretoviolenceintheenvironment;
socioeconomicconditions;maternalnutrition;otherhealthconditions;
andexposuretosexuallytransmitteddiseases—canallinteractto
influencematernalandchildoutcomes. Similarly,parenting
styles,qualityofcareduringearlychildhood,exposuretoviolence,and
continuedparentaldrugusearestrongenvironmentalfactors
influencingoutcomes.
Babiesborntomotherswhousecocaineduringpregnancyareoften
prematurelydelivered,havelowbirthweightsandsmallerhead
circumferences,andareshorterinlengththanbabiesborntomothers
whodonotusecocaine. Direpredictionsofreducedintelligence
andsocialskillsinbabiesborntomotherswhousedcrackcocaine
whilepregnantduringthe1980s—so-called"crackbabies"—were
grosslyexaggerated.However,thefactthatmostofthesechildrendo
notshowseriousovertdeficitsshouldnotbeoverinterpretedto
indicatethatthereisnocauseforconcern.
Usingsophisticatedtechnologies,scientistsarenowfindingthat
exposuretococaineduringfetaldevelopmentmayleadtosubtle,yet
significant,laterdeficitsinsomechildren. Theseincludebehavior
problems(e.g.,difficultieswithself-regulation)anddeficitsinsome
aspectsofcognitiveperformance,informationprocessing,and
sustainedattentiontotasks—abilitiesthatareimportantforthe
realizationofachild’sfullpotential. Somedeficitspersistintothe
lateryears,withprenatallyexposedadolescentsshowingincreased
riskforsubtleproblemswithlanguageandmemory. Brainscansin
teenssuggeststhatat-restfunctioningofsomebrainregions—
includingareasinvolvedinattention,planning,andlanguage—may
differfromthatofnon-exposedpeers. Moreresearchisneededon
thelong-termeffectsofprenatalcocaineexposure.
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Howiscocaineaddiction
treated?
In2013,cocaineaccountedforalmost6percentofalladmissionsto
drugabusetreatmentprograms.Themajorityofindividuals(68
percentin2013)whoseektreatmentforcocaineusesmokecrackand
arelikelytobepolydrugusers,meaningtheyusemorethanone
substance. Thosewhoprovidetreatmentforcocaineuseshould
recognizethatdrugaddictionisacomplexdiseaseinvolvingchanges
inthebrainaswellasawiderangeofsocial,familial,andother
environmentalfactors;therefore,treatmentofcocaineaddictionmust
addressthisbroadcontextaswellasanyotherco-occurringmental
disordersthatrequireadditionalbehavioralorpharmacological
interventions.
PharmacologicalApproaches
Presently,therearenomedicationsapprovedbytheU.S.Foodand
DrugAdministrationtotreatcocaineaddiction,thoughresearchersare
exploringavarietyofneurobiologicaltargets.Pastresearchhas
primarilyfocusedondopamine,butscientistshavealsofoundthat
cocaineuseinduceschangesinthebrainrelatedtoother
neurotransmitters—includingserotonin,gamma-aminobutyricacid
(GABA),norepinephrine,andglutamate. Researchersarecurrently
testingmedicationsthatactatthedopamineD receptor,asubtypeof
dopaminereceptorthatisabundantintheemotionandrewardcenters
ofthebrain. Otherresearchistestingcompounds(e.g.,N-
acetylcysteine)thatrestorethebalancebetweenexcitatory
(glutamate)andinhibitory(GABA)neurotransmission,whichis
disruptedbylong-termcocaineuse. Researchinanimalsisalso
lookingatmedications(e.g.,lorcaserin)thatactatserotonin
receptors.
Severalmedicationsmarketedforotherdiseasesshowpromisein
reducingcocaineusewithincontrolledclinicaltrials.Amongthese,
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disulfiram,whichisusedtotreatalcoholism,hasshownthemost
promise.Scientistsdonotyetknowexactlyhowdisulfiramreduces
cocaineuse,thoughitseffectsmayberelatedtoitsabilitytoinhibitan
enzymethatconvertsdopaminetonorepinephrine.However,
disulfiramdoesnotworkforeveryone.Pharmacogeneticstudiesare
revealingvariantsinthegenethatencodestheDBHenzymeand
seemstoinfluencedisulfiram’seffectivenessinreducingcocaine
use. Knowingapatient’sDBHgenotypecouldhelppredictwhether
disulfiramwouldbeaneffectivepharmacotherapyforcocaine
dependenceinthatperson.
Finally,researchershavedevelopedandconductedearlytestsona
cocainevaccinethatcouldhelpreducetheriskofrelapse.Thevaccine
stimulatestheimmunesystemtocreatecocaine-specificantibodies
thatbindtococaine,preventingitfromgettingintothebrain. In
additiontoshowingthevaccine’ssafety,aclinicaltrialfoundthat
patientswhoattainedhighantibodylevelssignificantlyreduced
cocaineuse. However,only38percentofthevaccinatedsubjects
attainedsufficientantibodylevelsandforonly2months.
Researchersareworkingtoimprovethecocainevaccinebyenhancing
thestrengthofbindingtococaineanditsabilitytoelicit
antibodies. Newvaccinetechnologies,includinggenetransferto
boostthespecificityandlevelofantibodiesproducedorenhancethe
metabolismofcocaine,mayalsoimprovetheeffectivenessofthis
treatment. Apharmacogeneticsstudywithasmallnumberof
patientssuggeststhatindividualswithaparticulargenotyperespond
welltothecocainevaccine—anintriguingfindingthatrequiresmore
research. 
Inadditiontotreatmentsforaddiction,researchersaredeveloping
medicalinterventionstoaddresstheacuteemergenciesthatresult
fromcocaineoverdose.Oneapproachbeingexploredistheuseof
geneticallyengineeredhumanenzymesinvolvedinthebreakdownof
cocaine,whichwouldcounterthebehavioralandtoxiceffectsofa
cocaineoverdose. Currently,researchersaretestingandrefining
theseenzymesinanimalresearch,withtheultimategoalofmovingto
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clinicaltrials.
BehavioralInterventions
Manybehavioraltreatmentsforcocaineaddictionhaveproventobe
effectiveinbothresidentialandoutpatientsettings.Indeed,behavioral
therapiesareoftentheonlyavailableandeffectivetreatmentsfor
manydrugproblems,includingstimulantaddictions.However,the
integrationofbehavioralandpharmacologicaltreatmentsmay
ultimatelyprovetobethemosteffectiveapproach.
Oneformofbehavioraltherapythatisshowingpositiveresultsin
peoplewithcocaineusedisordersiscontingencymanagement(CM),
alsocalledmotivationalincentives.Programsuseavoucherorprize-
basedsystemthatrewardspatientswhoabstainfromcocaineand
otherdrugs.Onthebasisofdrug-freeurinetests,thepatientsearn
points,orchips,whichcanbeexchangedforitemsthatencourage
healthyliving,suchasagymmembership,movietickets,ordinnerata
localrestaurant.CMmaybeparticularlyusefulforhelpingpatients
achieveinitialabstinencefromcocaineandstayintreatment.
Thisapproachhasrecentlybeenshowntobepracticalandeffectivein
communitytreatmentprograms.
ResearchindicatesthatCMbenefitsdiversepopulationsofcocaine
users.Forexample,studiesshowthatcocaine-dependentpregnant
womenandwomenwithyoungchildrenwhoparticipatedinaCM
programasanadjuncttoothersubstanceusedisordertreatmentwere
abletostayabstinentlongerthanthosewhoreceivedanequivalent
amountofvoucherswithnobehavioralrequirements. Patients
participatinginCMtreatmentforcocaineusewhoalsoexperienced
psychiatricsymptoms—suchasdepression,emotionaldistress,and
hostility—showedasignificantreductionintheseproblems,probably
relatedtoreductionsincocaineuse.
Cognitive-behavioraltherapy(CBT)isaneffectiveapproachfor
preventingrelapse.Thisapproachhelpspatientsdevelopcriticalskills
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thatsupportlong-termabstinence—includingtheabilitytorecognize
thesituationsinwhichtheyaremostlikelytousecocaine,avoidthese
situations,andcopemoreeffectivelywitharangeofproblems
associatedwithdruguse.Thistherapycanalsobeusedinconjunction
withothertreatments,therebymaximizingthebenefitsofboth.
Recently,researchersdevelopedacomputerizedformofCBT
(CBT4CBT)thatpatientsuseinaprivateroomofaclinic. This
interactivemultimediaprogramcloselyfollowsthekeylessonsand
skill-developmentactivitiesofin-personCBTinaseriesofmodules.
Moviespresentexamplesandinformationthatsupportthe
developmentofcopingskills;quizzes,games,andhomework
assignmentsreinforcethelessonsandprovideopportunitiestopractice
skills. StudieshaveshownthataddingCBT4CBTtoweekly
counselingboostedabstinence andincreasedtreatmentsuccess
ratesupto6monthsaftertreatment.
Therapeuticcommunities(TCs)—drug-freeresidencesinwhichpeople
inrecoveryfromsubstanceusedisordershelpeachotherto
understandandchangetheirbehaviors—canbeaneffectivetreatment
forpeoplewhousedrugs,includingcocaine. TCsmayrequirea6-to
12-monthstayandcanincludeonsitevocationalrehabilitationand
othersupportiveservicesthatfocusonsuccessfulre-integrationofthe
individualintosociety.TCscanalsoprovidesupportinotherimportant
areas—improvinglegal,employment,andmentalhealthoutcomes.
Regardlessofthespecifictypeofsubstanceusedisordertreatment,it
isimportantthatpatientsreceiveservicesthatmatchalloftheir
treatmentneeds.Forexample,anunemployedpatientwouldbenefit
fromvocationalrehabilitationorcareercounselingalongwithaddiction
treatment.Patientswithmaritalproblemsmayneedcouples
counseling.Onceinpatienttreatmentends,ongoingsupport—also
calledaftercare—canhelppeopleavoidrelapse.Researchindicates
thatpeoplewhoarecommittedtoabstinence,engageinself-help
behaviors,andbelievethattheyhavetheabilitytorefrainfromusing
cocaine(self-efficacy)aremorelikelytoabstain. Aftercareservesto
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reinforcethesetraitsandaddressproblemsthatmayincrease
vulnerabilitytorelapse,includingdepressionanddecliningself-
efficacy.
Scientistshavefoundpromisingresultsfromtelephone-based
counselingasalow-costmethodtodeliveraftercare.Forexample,
peoplewhomisusedstimulantswhoparticipatedinsevensessionsof
telephonecounselingshoweddecreasingdruguseduringthefirst3
months,whereasthosewhodidnotreceivecallsincreasedtheiruse.
Voucherincentivescanboostpatients'willingnesstoparticipatein
telephoneaftercare,doublingthenumberofsessionsreceived
accordingtoonestudy.
Community-basedrecoverygroups—suchasCocaineAnonymous—that
usea12-stepprogramcanalsobehelpfulinmaintainingabstinence.
Participantsmaybenefitfromthesupportivefellowshipandfrom
sharingwiththoseexperiencingcommonproblemsandissues.
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Howiscutting-edgescience
helpingusbetterunderstand
addiction?
Twocutting-edgeareasofscience,geneticsandbrainimaging,are
significantlyadvancingourunderstandingofcocaineaddiction.
Researchersestimatethatgeneticscontributes42to79percentofthe
riskforcocaineuseanddependence. Ofcourse,withacomplex
diseasesuchasaddiction,manydifferentgenesareinvolved,andtheir
expressioncanbeinfluencedbytheenvironment.Thereappearstobe
significantoverlapinthegenesthatputpeopleatriskforalladdictive
substances,perhapsindicatingacommonbiologicalpathwayfor
addictionregardlessofthedrug.
Ingenome-wideassociationstudies(GWAS),researchersexamine
whethercertaingenevariantsaremorefrequentlyfoundinpeoplewith
asubstanceusedisorder,whicheventuallymighthelpidentifythoseat
increasedriskfordrugaddiction. Identifyinggeneslinkedto
addictionisonlythefirststep.Candidate-generesearchexaminesthe
linksbetweensubstanceuseandspecificgenesthatencodeproteins
thatappeartoberelatedtoaddiction.Forexample,researchershave
foundconnectionsbetweenvariousaspectsofcocaineaddictionand
thegenesthatencodeforparticulardopaminereceptorsandthe
enzymesthatbreakdownthisneurotransmitter.
Becauseenvironmentalfactorstypicallyshapetheimpactofgeneson
diseaserisk,researchersmustalsoidentifyhowparticulargene-by-
environmentinteractionsinfluencethecourseofaddiction. Research
inthefieldofepigeneticsisuncoveringhowtheenvironmentinduces
long-termchangesingeneexpression—influencingthepatternofgene
expression—withoutalteringtheDNAsequence.
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Inanimalresearch,scientistsaredetermininghowlong-termcocaine
exposurechangesgeneexpressioninthebrain,particularlyinthe
rewardpathway.Studieshavelinkedspecificcocaine-induced
epigeneticchangestoneuroadaptations andbehavioralhallmarksof
addiction,suchassensitivitytococaine’srewardingeffects. The
epigeneticchangesinducedbycocainecanbepassedtothenext
generation,evenifthedrugexposuredoesnotoccurprenatally.
Althoughmuchmoregeneticandepigeneticresearchisneeded,
understandingaddictionatthemolecularleveloffersgreatpromisefor
improvingdiagnosis,forexamplebydiscoveringbiomarkersfor
diseaseseverityortreatmentresponse.
Althoughmoreresearchisneeded,brain-imagingmightbeusedto
detectbiomarkersfordrugaddictionvulnerability,asthese
technologieshaveyieldedinsightsintotheprocessesunderlying
cravingandhowmedicationsmayquellthebrain’sresponsetococaine
cues. Arelativelynewneuroimagingtechnologycalleddefault-mode
orresting-statefunctionalmagneticresonanceimaging(rs-fMRI)
revealsbrainactivitywhenpeoplearealertbutnotperforminga
particulartask;researchersusethistechniquetocomparefunctional
brainnetworksofpeoplewhohaveusedcocaineforalongtimeand
thosewhohavenot.Thesestudiessuggestthatthereisreduced
connectivitybetweenvariousbraincircuits andbetweenthetwo
hemispheres amongpeoplewithcocainedependence.Researchers
havealsocorrelatedreducedconnectivitybetweenparticularbrain
circuitswithimportantaddiction-relatedbehaviors,includingriskfor
relapse andimpulsivity.
Neuroimagingtechnologiesarealsodocumentinghowthebrainsof
cocaineusersmayrecoverafterperiodsofabstinence.Forexample,
thesetechniquesindicatethatyearsofcocaineuseareassociatedwith
reducedgreymatterinparticularbrainregions.However,peoplewho
maintainedcocaineabstinenceforapproximately9monthsshowed
greymatterlevelssimilartoorgreaterthanthoseofpeoplewhohad
neverusedthedrug. Furtheranalysisindicatedthattheincreased
greymatteroccurredinregionsotherthantheonesalteredbycocaine
use,suggestingthattheneurobiologicalchangesinvolvedinrecovery
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aremorecomplexthansimplyreversingthechangesrelatedto
addiction. Theresearchersalsofoundthatincreasedgreymatter
volumeinbrainregionsinvolvedwithbehavioralcontrolwere
associatedwithlongerdurationofabstinence.
fMRItechnologieshavealsorevealedthatabstinencefromcocainehas
important,restorativeeffectsonthebrain.Althoughcurrentcocaine
usersdemonstratedreducedbrainactivityinabraincircuitthat
mediatesresponseinhibitionduringamotorcontroltask,individuals
whohadattainedabstinenceforanaverageof8monthsshowed
similarpatternsofactivationandlevelsofperformancetothosewho
hadneverusedthedrug. Theresultssuggestthatabstinencehelps
restorethefunctioningofthisbraincircuit.
Researchersareengagedinseverallarge-scale,collaborativeprojects
tomapthehumanconnectome,whichisthebrain’snetworkof
interconnectedcircuits.Forexample,theNationalInstitutesofHealth
supportstheHumanConnectomeProjecttogeneratemapsofthe
developing,adult,andagingbrain.Byhavingamapofthetypical
brain,scientistswillfurtherunderstandhowneuralfunctioningdiffers
inbehavioraldisorders—knowledgethatwilldriveimproved
diagnosticsandtreatments.
74
74
75
29
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38
WherecanIgetfurther
informationaboutcocaine?
Tolearnmoreaboutcocaineandotherdrugsofabuse,visittheNIDA
websiteatwww.drugabuse.govorcontactDrugPubsat877-NIDA-NIH
(877-643-2644;TTY/TDD:240-645-0228).
NIDA'swebsiteincludes:
Informationondrugsofabuseandrelatedhealthconsequences
NIDApublications,news,andevents
Resourcesforhealthcareprofessionals,educators,andpatients
andfamilies
InformationonNIDAresearchstudiesandclinicaltrials
Fundinginformation(includingprogramannouncementsand
deadlines)
Internationalactivities
Linkstorelatedwebsites(accesstowebsitesofmanyother
organizationsinthefield)
InformationinSpanish(enespañol)
NIDAwebsitesandwebpages
www.drugabuse.gov
www.teens.drugabuse.gov
www.easyread.drugabuse.gov
www.drugabuse.gov/drugs-abuse/cocaine
www.researchstudies.drugabuse.gov
39
www.irp.drugabuse.gov
Forphysicianinformation
NIDAMED:www.drugabuse.gov/nidamed
Otherwebsites
Informationoncocaineabuseisalsoavailablethroughthefollowing
Website:
SubstanceAbuseandMentalHealthServices
Administration:www.samhsa.gov
DrugEnforcementAdministration:www.dea.gov
MonitoringtheFuture:www.monitoringthefuture.org/
ThePartnershipatDrugFree.org:www.drugfree.org/drug-guide
Thispublicationisavailableforyouruseandmaybereproducedin
itsentiretywithoutpermissionfromNIDA.Citationofthesource
isappreciated,usingthefollowinglanguage:Source:National
InstituteonDrugAbuse;NationalInstitutesofHealth;U.S.
DepartmentofHealthandHumanServices.