Cocaine Facts

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Whatiscocaine?

Cocaineisapowerfullyaddictivestimulantdrug.Forthousandsofyears,

peopleinSouthAmericahavechewedandingestedcocaleaves(Erythroxylon

coca),thesourceofcocaine,fortheirstimulanteffects. Thepurifiedchemical,

cocainehydrochloride,wasisolatedfromtheplantmorethan100yearsago.In

theearly1900s,purifiedcocainewasthemainactiveingredientinmanytonics

andelixirsdevelopedtotreatawidevarietyofillnessesandwasevenan

ingredientintheearlyformulationsofCoca-Cola .Beforethedevelopmentof

syntheticlocalanesthetic,surgeonsusedcocainetoblockpain. However,

researchhassinceshownthatcocaineisapowerfullyaddictivesubstancethat

canalterbrainstructureandfunctionifusedrepeatedly.

Today,cocaineisaScheduleIIdrug,whichmeansthatithashighpotentialfor

abusebutcanbeadministeredbyadoctorforlegitimatemedicaluses,suchas

localanesthesiaforsomeeye,ear,andthroatsurgeries.Asastreetdrug,

cocaineappearsasafine,white,crystallinepowderandisalsoknownasCoke,

C,Snow,Powder,orBlow.Streetdealersoftendilute(or“cut”)itwithnon-

psychoactivesubstancessuchascornstarch,talcumpowder,flour,orbaking

sodatoincreasetheirprofits.Theymayalsoadulteratecocainewithotherdrugs

likeprocaine(achemicallyrelatedlocalanesthetic)oramphetamine(another

psychoactivestimulant). Someuserscombinecocainewithheroin—calleda

Speedball.

Photoby©iStock.com/RafalCichawa

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Peopleabusetwochemicalformsofcocaine:thewater-solublehydrochloride

saltandthewater-insolublecocainebase(orfreebase).Usersinjectorsnort

thehydrochloridesalt,whichisapowder.Thebaseformofcocaineiscreated

byprocessingthedrugwithammoniaorsodiumbicarbonate(bakingsoda)and

water,thenheatingittoremovethehydrochloridetoproduceasmokable

substance.Thetermcrack,whichisthestreetnamegiventofreebasecocaine,

referstothecracklingsoundheardwhenthemixtureissmoked.2

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Whatisthescopeofcocaineusein

theUnitedStates?

AccordingtotheNationalSurveyonDrugUseandHealth(NSDUH),cocaine

usehasremainedrelativelystablesince2009.In2014,therewerean

estimated1.5millioncurrent(past-month)cocaineusersaged12orolder(0.6

percentofthepopulation).Adultsaged18to25yearshaveahigherrateof

currentcocaineusethananyotheragegroup,with1.4percentofyoungadults

reportingpast-monthcocaineuse.

The2015MonitoringtheFuturesurvey,whichannuallysurveysteenattitudes

anddruguse,reportsasignificantdeclinein30-dayprevalenceofpowder

cocaineuseamong8th,10th,and12thgradersfrompeakuseinthelate1990s.

In2014,1.1percentof12thgradersandonly0.8percentof10thandhalfa

percentof8thgradersreportedusingcocaineinthepastmonth.

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Source:UniversityofMichigan,MonitoringtheFuturenationalresultsondruguse:1975-

2015:overview,keyfindingsonadolescentdruguse,2016.

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Repeatedcocaineusecanproduceaddictionandotheradversehealth

consequences.In2014,accordingtotheNSDUH,about913,000Americans

mettheDiagnosticandStatisticalManualofMentalDisorderscriteriafor

dependenceorabuseofcocaine(inanyform)duringthepast12months.

Further,datafromthe2011DrugAbuseWarningNetwork(DAWN)report

showedthatcocainewasinvolvedin505,224ofthenearly1.3millionvisitsto

emergencydepartmentsfordrugmisuseorabuse.Thistranslatestooveronein

threedrugmisuseorabuse-relatedemergencydepartmentvisits(40percent)

thatinvolvedcocaine.6

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Howiscocaineused?

Usersprimarilyadministercocaineorally,intranasally,intravenously,orby

inhalation.Whenpeoplesnortthedrug(intranasaluse),theyinhalecocaine

powderthroughthenostrils,whereitisabsorbedintothebloodstreamthrough

thenasaltissues.Usersalsomayrubthedrugontotheirgums(oraluse).

Dissolvingcocaineinwaterandinjectingit(intravenoususe)releasesthedrug

directlyintothebloodstreamandheightenstheintensityofitseffects.When

peoplesmokecocaine(inhalation),theyinhaleitsvapororsmokeintothe

lungs,whereabsorptionintothebloodstreamisalmostasrapidasbyinjection.

Thisfasteuphoriceffectisoneofthereasonsthatcrackbecameenormously

popularinthemid-1980s.

PhotobyDEA/

Cocaine

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Cocaineuserangesfromoccasionaltorepeatedorcompulsiveuse,witha

varietyofpatternsbetweentheseextremes.Anyrouteofadministrationcan

potentiallyleadtoabsorptionoftoxicamountsofcocaine,causingheartattacks,

strokes,orseizures—allofwhichcanresultinsuddendeath.

PhotobyDEA/

Crackcocaine

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Howdoescocaineproduceits

effects?

Thebrain’smesolimbicdopaminesystem,itsrewardpathway,isstimulatedby

alltypesofreinforcingstimuli,suchasfood,sex,andmanydrugsofabuse,

includingcocaine. Thispathwayoriginatesinaregionofthemidbraincalled

theventraltegmentalareaandextendstothenucleusaccumbens,oneofthe

brain’skeyrewardareas. Besidesreward,thiscircuitalsoregulatesemotions

andmotivation.

Inthenormalcommunicationprocess,dopamineisreleasedbyaneuroninto

thesynapse(thesmallgapbetweentwoneurons),whereitbindstospecialized

proteinscalleddopaminereceptorsontheneighboringneuron.Bythisprocess,

dopamineactsasachemicalmessenger,carryingasignalfromneuronto

neuron.Anotherspecializedproteincalledatransporterremovesdopamine

fromthesynapsetoberecycledforfurtheruse.

Drugsofabusecaninterferewiththisnormalcommunicationprocess.For

example,cocaineactsbybindingtothedopaminetransporter,blockingthe

removalofdopaminefromthesynapse.Dopaminethenaccumulatesinthe

synapsetoproduceanamplifiedsignaltothereceivingneurons.Thisiswhat

causestheeuphoriacommonlyexperiencedimmediatelyaftertakingthedrug

(seethevideo"BrainReward:UnderstandingHowtheBrainRespondsto

NaturalRewardsandDrugsofAbuse").

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ImagebyNIDA

Cocaineinthebrain:Inthenormalneuralcommunicationprocess,dopamineis

releasedbyaneuronintothesynapse,whereitcanbindtodopaminereceptorson

neighboringneurons.Normally,dopamineisthenrecycledbackintothetransmitting

neuronbyaspecializedproteincalledthedopaminetransporter.Ifcocaineispresent,

itattachestothedopaminetransporterandblocksthenormalrecyclingprocess,

resultinginabuildupofdopamineinthesynapse,whichcontributestothepleasurable

effectsofcocaine.

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Whataresomewaysthatcocaine

changesthebrain?

Useofcocaine,likeotherdrugsofabuse,induceslong-termchangesinthe

brain.Animalstudiesshowthatcocaineexposurecancausesignificant

neuroadaptationsinneuronsthatreleasetheexcitatoryneurotransmitter

glutamate. Animalschronicallyexposedtococainedemonstrateprofound

changesinglutamateneurotransmission—includinghowmuchisreleasedand

thelevelofreceptorproteins—intherewardpathway,particularlythenucleus

accumbens.Theglutamatesystemmaybeanopportunetargetforanti-

addictionmedicationdevelopment,withthegoalofreversingthecocaine-

inducedneuroadaptationsthatcontributetothedrivetousethedrug.

Althoughaddictionresearchershavefocusedonadaptationsinthebrain’s

rewardsystem,drugsalsoaffectthebrainpathwaysthatrespondtostress.

Stresscancontributetococainerelapse,andcocaineusedisordersfrequently

co-occurwithstress-relateddisorders. Thestresscircuitsofthebrainare

distinctfromtherewardpathway,butresearchindicatesthatthereareimportant

waysthattheyoverlap.Theventraltegmentalareaseemstoactasacritical

integrationsiteinthebrainthatrelaysinformationaboutbothstressanddrug

cuestootherareasofthebrain,includingonesthatdrivecocaineseeking.

Animalsthathavereceivedcocainerepeatedlyaremorelikelytoseekthedrug

inresponsetostress,andthemoreofthedrugtheyhavetaken,themorestress

affectsthisbehavior. Researchsuggeststhatcocaineelevatesstress

hormones,inducingneuroadaptationsthatfurtherincreasesensitivitytothe

drugandcuesassociatedwithit.

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Chroniccocaineexposureaffectsmanyotherareasofthebraintoo.For

example,animalresearchindicatesthatcocainediminishesfunctioninginthe

orbitofrontalcortex(OFC),whichappearstounderliethepoordecision-making,

inabilitytoadapttonegativeconsequencesofdruguse,andlackofself-insight

shownbypeopleaddictedtococaine. Astudyusingoptogenetictechnology,

whichuseslighttoactivatespecific,genetically-modifiedneurons,foundthat

stimulatingtheOFCrestoresadaptivelearninginanimals.Thisintriguingresult

suggeststhatstrengtheningOFCactivitymaybeagoodtherapeuticapproach

toimproveinsightandawarenessoftheconsequencesofdruguseamong

peopleaddictedtococaine.

Brainimagesshowingdecreasedglucosemetabolism,whichindicatesreduced

activity,intheorbitofrontalcortex(OFC)inacontrolsubject(left)andacocaine-

addictedsubject(right).

VolkowND,WantG-J,FowlerJS,TomasiD,TelandF.Addiction:beyonddopamine

rewardcircuitry.ProcNatlAcadSciUSA.2011;108(37):15037-15042.

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Whataretheshort-termeffectsof

cocaineuse?

Cocaine’seffectsappearalmostimmediatelyafterasingledoseanddisappear

withinafewminutestoanhour.Smallamountsofcocaineusuallymakethe

userfeeleuphoric,energetic,talkative,mentallyalert,andhypersensitiveto

sight,sound,andtouch.Thedrugcanalsotemporarilydecreasetheneedfor

foodandsleep. Someusersfindthatcocainehelpsthemperformsimple

physicalandintellectualtasksmorequickly,althoughothersexperiencethe

oppositeeffect.

Thedurationofcocaine’seuphoriceffectsdependupontherouteof

administration.Thefasterthedrugisabsorbed,themoreintensetheresulting

high,butalsotheshorteritsduration.Snortingcocaineproducesarelatively

slowonsetofthehigh,butitmaylastfrom15to30minutes.Incontrast,thehigh

fromsmokingismoreimmediatebutmaylastonly5to10minutes.

Short-termphysiologicaleffectsofcocaineuseincludeconstrictedblood

vessels;dilatedpupils;andincreasedbodytemperature,heartrate,andblood

pressure. Largeamountsofcocainemayintensifytheuser’shighbutcanalso

leadtobizarre,erratic,andviolentbehavior.Somecocaineusersreport

feelingsofrestlessness,irritability,anxiety,panic,andparanoia. Usersmay

alsoexperiencetremors,vertigo,andmuscletwitches.

Severemedicalcomplicationscanoccurwithcocaineuse.Someofthemost

frequentarecardiovasculareffects,includingdisturbancesinheartrhythmand

heartattacks;neurologicaleffects,includingheadaches,seizures,strokes,and

coma;andgastrointestinalcomplications,includingabdominalpainand

nausea. Inrareinstances,suddendeathcanoccuronthefirstuseofcocaine

orunexpectedlythereafter.Cocaine-relateddeathsareoftenaresultofcardiac

arrestorseizures (see"NationalOverdoseDeaths:NumberofDeathsfrom

Cocaine").Manycocaineusersalsousealcohol,andthiscombinationcanbe

particularlydangerous.Thetwosubstancesreacttoproducecocaethylene,

whichmaypotentiatethetoxiceffectsofcocaineandalcoholontheheart. The

combinationofcocaineandheroinisalsoverydangerous.Userscombine

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thesedrugsbecausethestimulatingeffectsofcocaineareoffsetbythesedating

effectsofheroin;however,thiscanleadtotakingahighdoseofheroinwithout

initiallyrealizingit.Becausecocaine'seffectswearoffsooner,thiscanleadtoa

heroinoverdose,inwhichtheuser'srespirationdangerouslyslowsdownor

stops,possiblyfatally.

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Whatarethelong-termeffectsof

cocaineuse?

Withrepeatedexposuretococaine,thebrainstartstoadaptsothatthereward

pathwaybecomeslesssensitivetonaturalreinforcers (see"WhatAreSome

WaysthatCocaineChangestheBrain?").Atthesametime,circuitsinvolvedin

stressbecomeincreasinglysensitive,leadingtoincreaseddispleasureand

negativemoodswhennottakingthedrug,whicharesignsofwithdrawal.These

combinedeffectsmaketheusermorelikelytofocusonseekingthedrug

insteadofrelationships,food,orothernaturalrewards.

Withregularuse,tolerancemaydevelopsothathigherdoses,morefrequent

useofcocaine,orbothareneededtoproducethesamelevelofpleasureand

relieffromwithdrawalexperiencedinitially. Atthesametime,userscanalso

developsensitization,inwhichlesscocaineisneededtoproduceanxiety,

convulsions,orothertoxiceffects. Tolerancetococainerewardand

sensitizationtococainetoxicitycanincreasetheriskofoverdoseina

regularuser.

Userstakecocaineinbinges,inwhichcocaineisusedrepeatedlyandat

increasinglyhigherdoses.Thiscanleadtoincreasedirritability,restlessness,

panicattacks,paranoia,andevenafull-blownpsychosis,inwhichthe

individuallosestouchwithrealityandexperiencesauditoryhallucinations.

Withincreasingdosesorhigherfrequencyofuse,theriskofadverse

psychologicalorphysiologicaleffectsincreases. Animalresearchsuggests

thatbingingoncocaineduringadolescenceenhancessensitivitytothe

rewardingeffectsofcocaineandMDMA(EcstasyorMolly). Thus,bingeuseof

cocaineduringadolescencemayfurtherincreasevulnerabilitytocontinueduse

ofthedrugamongsomepeople.

Specificroutesofcocaineadministrationcanproducetheirownadverseeffects.

Regularlysnortingcocainecanleadtolossofsenseofsmell,nosebleeds,

problemswithswallowing,hoarseness,andanoverallirritationofthenasal

septumleadingtoachronicallyinflamed,runnynose. Smokingcrackcocaine

damagesthelungsandcanworsenasthma. Peoplewhoinjectcocainehave

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puncturemarkscalledtracks,mostcommonlyintheirforearms, andtheyareat

riskofcontractinginfectiousdiseaseslikeHIVandhepatitisC(see"WhyAre

CocaineUsersatRiskforContractingHIVandHepatitis?").Theyalsomay

experienceallergicreactions,eithertothedrugitselfortoadditivesinstreet

cocaine,whichinseverecasescanresultindeath.

Cocainedamagesmanyotherorgansinthebody.Itreducesbloodflowinthe

gastrointestinaltract,whichcanleadtotearsandulcerations. Manychronic

cocaineuserslosetheirappetiteandexperiencesignificantweightloss

andmalnourishment.Cocainehassignificantandwell-recognizedtoxiceffects

ontheheartandcardiovascularsystem. Chestpainthatfeelslikeaheart

attackiscommonandsendsmanycocaineuserstotheemergencyroom.

Cocaineuseislinkedwithincreasedriskofstroke, aswellasinflammationof

theheartmuscle,deteriorationoftheabilityofthehearttocontract,andaortic

ruptures.

Inadditiontotheincreasedriskforstrokeandseizures,otherneurological

problemscanoccurwithlong-termcocaineuse. Therehavebeenreportsof

intracerebralhemorrhage,orbleedingwithinthebrain,andballoon-likebulges

inthewallsofcerebralbloodvessels. Movementdisorders,including

Parkinson’sdisease,mayalsooccuraftermanyyearsofcocaineuse.

Generally,studiessuggestthatawiderangeofcognitivefunctionsareimpaired

withlong-termcocaineuse—suchassustainingattention,impulseinhibition,

memory,makingdecisionsinvolvingrewardsorpunishments,andperforming

motortasks.

Formercocaineusersareathighriskforrelapse,evenfollowinglongperiodsof

abstinence.Researchindicatesthatduringperiodsofabstinence,thememory

ofthecocaineexperienceorexposuretocuesassociatedwithdrugusecan

triggerstrongcravings,whichcanleadtorelapse.

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Whyarecocaineusersatriskfor

contractingHIV/AIDSandhepatitis?

Drugintoxicationandaddictioncancompromisejudgmentanddecision-

makingandpotentiallyleadtoriskysexualbehavior,includingtradingsexfor

drugs,andneedlesharing.Thisincreasesacocaineuser’sriskforcontracting

infectiousdiseasessuchasHIVandhepatitisC(HCV). Therearenovaccines

topreventHIVorHCVinfections.

StudiesthatexaminepatternsofHIVinfectionandprogressionhave

demonstratedthatcocaineuseacceleratesHIVinfection. Researchindicates

thatcocaineimpairsimmunecellfunction, promotesreplicationoftheHIV

virus,andpotentiatesthedamagingeffectsofHIVondifferenttypesofcellsin

thebrainandspinalcord,resultinginfurtherdamage. Studiesalsosuggest

thatcocaineuseacceleratesthedevelopmentofNeuroAIDS,neurological

conditionsassociatedwithHIVinfection.SymptomsofNeuroAIDSinclude

memoryloss,movementproblems,andvisionimpairment.

CocaineuserswithHIVoftenhaveadvancedprogressionofthedisease,with

increasedviralloadandaccelerateddecreasesinCD4+cellcounts.Infection

withHIVincreasesriskforco-infectionwithHCV,avirusthataffectstheliver.

Co-infectioncanleadtoseriousillnesses—includingproblemswiththeimmune

systemandneurologicconditions.Livercomplicationsareverycommon,with

manyco-infectedindividualsdyingofchronicliverdiseaseandcancer.

AlthoughthelinkbetweeninjectiondruguseandHIV/HCViswellestablished,

morestudiesareneededtounderstandthemolecularmechanismsunderlying

thisincreasedriskofco-infectioninnon-injectingsubstanceusers.

Theinteractionofsubstanceuse,HIV,andhepatitismayacceleratedisease

progression.Forexample,HIVspeedsthecourseofHCVinfectionby

acceleratingtheprogressionofhepatitis-associatedliverdisease. Research

haslinkedHIV/HCVco-infectionwithincreasedmortalitywhencompared

toeitherinfectionalone. Substanceuseandco-infectionlikelynegatively

influenceHIVdiseaseprogressionandtheabilityofthebodytomarshalan

immuneresponse.

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PatientswithHIV/HCVco-infectioncanbenefitfromsubstanceabusetreatment

andantiretroviraltherapies,whencloselymonitored. Antiretroviraltreatment

isnoteffectiveforeveryoneandcanhavesignificantsideeffects,necessitating

closemedicalsupervision.TestingforHIVandHCVisrecommendedforany

individualwhohaseverinjecteddrugs,sincethediseaseishighly

transmissibleviainjection.

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Whataretheeffectsofmaternal

cocaineuse?

Mostwomenwhoareaddictedtococaineareofchildbearingage.Estimates

suggestthatabout5percentofpregnantwomenuseoneormoreaddictive

substances, andtherearearound750,000cocaine-exposedpregnancies

everyyear. Althoughwomenmaybereluctanttoreportsubstanceuse

patternsbecauseofsocialstigmaandfearoflosingcustodyoftheirchildren,

theyshouldbeawarethatdrugusewhilepregnantisassociatedwithspecific

risksthatmaybereducedwithappropriatecare.

Cocaineuseduringpregnancyisassociatedwithmaternalmigrainesand

seizures,prematuremembranerupture,andseparationoftheplacentallining

fromtheuteruspriortodelivery. Pregnancyisaccompaniedbynormal

cardiovascularchanges,andcocaineuseexacerbatesthese—sometimes

leadingtoseriousproblemswithhighbloodpressure(hypertensivecrises),

spontaneousmiscarriage,pretermlabor,anddifficultdelivery. Cocaine-using

pregnantwomenmustreceiveappropriatemedicalandpsychologicalcare—

includingaddictiontreatment—toreducetheserisks.

Sex-specificaddictiontreatmentandcomprehensiveservices—including

prenatalcare,mentalhealthcounseling,vocational/employmentassistance,

andparentingskillstraining—canpromotedrugabstinenceandotherpositive

healthbehaviors. Motivationalincentives/contingencymanagement(see

"BehavioralInterventions")asanadjuncttootheraddictiontreatmentisa

particularlypromisingstrategytoengagewomeninprenatalcareand

counselingforsubstanceuse.

Itisdifficulttoestimatethefullextentoftheconsequencesofmaternaldruguse

andtodeterminethespecifichazardofaparticulardrugtotheunbornchild.

Thisisbecausemultiplefactors—suchastheamountandnumberofalldrugs

used,includingnicotineoralcohol;extentofprenatalcare;exposuretoviolence

intheenvironment;socioeconomicconditions;maternalnutrition;otherhealth

conditions;andexposuretosexuallytransmitteddiseases—canallinteractto

influencematernalandchildoutcomes. Similarly,parentingstyles,

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qualityofcareduringearlychildhood,exposuretoviolence,andcontinued

parentaldrugusearestrongenvironmentalfactorsinfluencingoutcomes.

Babiesborntomotherswhousecocaineduringpregnancyareoften

prematurelydelivered,havelowbirthweightsandsmallerhead

circumferences,andareshorterinlengththanbabiesborntomotherswhodo

notusecocaine. Direpredictionsofreducedintelligenceandsocialskills

inbabiesborntomotherswhousedcrackcocainewhilepregnantduringthe

1980s—so-called"crackbabies"—weregrosslyexaggerated.However,thefact

thatmostofthesechildrendonotshowseriousovertdeficitsshouldnotbe

overinterpretedtoindicatethatthereisnocauseforconcern.

Usingsophisticatedtechnologies,scientistsarenowfindingthatexposureto

cocaineduringfetaldevelopmentmayleadtosubtle,yetsignificant,later

deficitsinsomechildren. Theseincludebehaviorproblems(e.g.,difficulties

withself-regulation)anddeficitsinsomeaspectsofcognitiveperformance,

informationprocessing,andsustainedattentiontotasks—abilitiesthatare

importantfortherealizationofachild’sfullpotential. Somedeficitspersist

intothelateryears,withprenatallyexposedadolescentsshowingincreasedrisk

forsubtleproblemswithlanguageandmemory. Brainscansinteens

suggeststhatat-restfunctioningofsomebrainregions—includingareas

involvedinattention,planning,andlanguage—maydifferfromthatofnon-

exposedpeers. Moreresearchisneededonthelong-termeffectsofprenatal

cocaineexposure.

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Howiscocaineaddictiontreated?

In2013,cocaineaccountedforalmost6percentofalladmissionstodrugabuse

treatmentprograms.Themajorityofindividuals(68percentin2013)whoseek

treatmentforcocaineusesmokecrackandarelikelytobepolydrugusers,

meaningtheyusemorethanonesubstance. Thosewhoprovidetreatmentfor

cocaineuseshouldrecognizethatdrugaddictionisacomplexdisease

involvingchangesinthebrainaswellasawiderangeofsocial,familial,and

otherenvironmentalfactors;therefore,treatmentofcocaineaddictionmust

addressthisbroadcontextaswellasanyotherco-occurringmentaldisorders

thatrequireadditionalbehavioralorpharmacologicalinterventions.

PharmacologicalApproaches

Presently,therearenomedicationsapprovedbytheU.S.FoodandDrug

Administrationtotreatcocaineaddiction,thoughresearchersareexploringa

varietyofneurobiologicaltargets.Pastresearchhasprimarilyfocusedon

dopamine,butscientistshavealsofoundthatcocaineuseinduceschangesin

thebrainrelatedtootherneurotransmitters—includingserotonin,gamma-

aminobutyricacid(GABA),norepinephrine,andglutamate. Researchersare

currentlytestingmedicationsthatactatthedopamineD receptor,asubtypeof

dopaminereceptorthatisabundantintheemotionandrewardcentersofthe

brain. Otherresearchistestingcompounds(e.g.,N-acetylcysteine)that

restorethebalancebetweenexcitatory(glutamate)andinhibitory(GABA)

neurotransmission,whichisdisruptedbylong-termcocaineuse. Researchin

animalsisalsolookingatmedications(e.g.,lorcaserin)thatactatserotonin

receptors.

Severalmedicationsmarketedforotherdiseasesshowpromiseinreducing

cocaineusewithincontrolledclinicaltrials.Amongthese,disulfiram,whichis

usedtotreatalcoholism,hasshownthemostpromise.Scientistsdonotyet

knowexactlyhowdisulfiramreducescocaineuse,thoughitseffectsmaybe

relatedtoitsabilitytoinhibitanenzymethatconvertsdopamineto

norepinephrine.However,disulfiramdoesnotworkforeveryone.

Pharmacogeneticstudiesarerevealingvariantsinthegenethatencodes

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theDBHenzymeandseemstoinfluencedisulfiram’seffectivenessinreducing

cocaineuse. Knowingapatient’sDBHgenotypecouldhelppredict

whetherdisulfiramwouldbeaneffectivepharmacotherapyforcocaine

dependenceinthatperson.

Finally,researchershavedevelopedandconductedearlytestsonacocaine

vaccinethatcouldhelpreducetheriskofrelapse.Thevaccinestimulatesthe

immunesystemtocreatecocaine-specificantibodiesthatbindtococaine,

preventingitfromgettingintothebrain. Inadditiontoshowingthevaccine’s

safety,aclinicaltrialfoundthatpatientswhoattainedhighantibodylevels

significantlyreducedcocaineuse. However,only38percentofthevaccinated

subjectsattainedsufficientantibodylevelsandforonly2months.

Researchersareworkingtoimprovethecocainevaccinebyenhancingthe

strengthofbindingtococaineanditsabilitytoelicitantibodies. New

vaccinetechnologies,includinggenetransfertoboostthespecificityandlevel

ofantibodiesproducedorenhancethemetabolismofcocaine,mayalso

improvetheeffectivenessofthistreatment. Apharmacogeneticsstudywitha

smallnumberofpatientssuggeststhatindividualswithaparticulargenotype

respondwelltothecocainevaccine—anintriguingfindingthatrequiresmore

research.

Inadditiontotreatmentsforaddiction,researchersaredevelopingmedical

interventionstoaddresstheacuteemergenciesthatresultfromcocaine

overdose.Oneapproachbeingexploredistheuseofgeneticallyengineered

humanenzymesinvolvedinthebreakdownofcocaine,whichwould

counterthebehavioralandtoxiceffectsofacocaineoverdose. Currently,

researchersaretestingandrefiningtheseenzymesinanimalresearch,withthe

ultimategoalofmovingtoclinicaltrials.

BehavioralInterventions

Manybehavioraltreatmentsforcocaineaddictionhaveproventobeeffectivein

bothresidentialandoutpatientsettings.Indeed,behavioraltherapiesareoften

theonlyavailableandeffectivetreatmentsformanydrugproblems,including

stimulantaddictions.However,theintegrationofbehavioraland

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pharmacologicaltreatmentsmayultimatelyprovetobethemosteffective

approach.

Oneformofbehavioraltherapythatisshowingpositiveresultsinpeoplewith

cocaineusedisordersiscontingencymanagement(CM),alsocalled

motivationalincentives.Programsuseavoucherorprize-basedsystemthat

rewardspatientswhoabstainfromcocaineandotherdrugs.Onthebasisof

drug-freeurinetests,thepatientsearnpoints,orchips,whichcanbe

exchangedforitemsthatencouragehealthyliving,suchasagymmembership,

movietickets,ordinneratalocalrestaurant.CMmaybeparticularlyusefulfor

helpingpatientsachieveinitialabstinencefromcocaineandstayin

treatment. Thisapproachhasrecentlybeenshowntobepracticaland

effectiveincommunitytreatmentprograms.

ResearchindicatesthatCMbenefitsdiversepopulationsofcocaineusers.For

example,studiesshowthatcocaine-dependentpregnantwomenandwomen

withyoungchildrenwhoparticipatedinaCMprogramasanadjuncttoother

substanceusedisordertreatmentwereabletostayabstinentlongerthanthose

whoreceivedanequivalentamountofvoucherswithnobehavioral

requirements. PatientsparticipatinginCMtreatmentforcocaineusewhoalso

experiencedpsychiatricsymptoms—suchasdepression,emotionaldistress,

andhostility—showedasignificantreductionintheseproblems,probably

relatedtoreductionsincocaineuse.

Cognitive-behavioraltherapy(CBT)isaneffectiveapproachforpreventing

relapse.Thisapproachhelpspatientsdevelopcriticalskillsthatsupportlong-

termabstinence—includingtheabilitytorecognizethesituationsinwhichthey

aremostlikelytousecocaine,avoidthesesituations,andcopemoreeffectively

witharangeofproblemsassociatedwithdruguse.Thistherapycanalsobe

usedinconjunctionwithothertreatments,therebymaximizingthebenefitsof

both.

Recently,researchersdevelopedacomputerizedformofCBT(CBT4CBT)that

patientsuseinaprivateroomofaclinic. Thisinteractivemultimedia

programcloselyfollowsthekeylessonsandskill-developmentactivitiesofin-

personCBTinaseriesofmodules.Moviespresentexamplesandinformation

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thatsupportthedevelopmentofcopingskills;quizzes,games,andhomework

assignmentsreinforcethelessonsandprovideopportunitiestopractice

skills. StudieshaveshownthataddingCBT4CBTtoweeklycounseling

boostedabstinence andincreasedtreatmentsuccessratesupto6months

aftertreatment.

Therapeuticcommunities(TCs)—drug-freeresidencesinwhichpeoplein

recoveryfromsubstanceusedisordershelpeachothertounderstandand

changetheirbehaviors—canbeaneffectivetreatmentforpeoplewhouse

drugs,includingcocaine. TCsmayrequirea6-to12-monthstayandcan

includeonsitevocationalrehabilitationandothersupportiveservicesthatfocus

onsuccessfulre-integrationoftheindividualintosociety.TCscanalsoprovide

supportinotherimportantareas—improvinglegal,employment,andmental

healthoutcomes.

Regardlessofthespecifictypeofsubstanceusedisordertreatment,itis

importantthatpatientsreceiveservicesthatmatchalloftheirtreatmentneeds.

Forexample,anunemployedpatientwouldbenefitfromvocational

rehabilitationorcareercounselingalongwithaddictiontreatment.Patientswith

maritalproblemsmayneedcouplescounseling.Onceinpatienttreatmentends,

ongoingsupport—alsocalledaftercare—canhelppeopleavoidrelapse.

Researchindicatesthatpeoplewhoarecommittedtoabstinence,engagein

self-helpbehaviors,andbelievethattheyhavetheabilitytorefrainfromusing

cocaine(self-efficacy)aremorelikelytoabstain. Aftercareservestoreinforce

thesetraitsandaddressproblemsthatmayincreasevulnerabilitytorelapse,

includingdepressionanddecliningself-efficacy.

Scientistshavefoundpromisingresultsfromtelephone-basedcounselingasa

low-costmethodtodeliveraftercare.Forexample,peoplewhomisused

stimulantswhoparticipatedinsevensessionsoftelephonecounselingshowed

decreasingdruguseduringthefirst3months,whereasthosewhodidnot

receivecallsincreasedtheiruse. Voucherincentivescanboost

patients'willingnesstoparticipateintelephoneaftercare,doublingthenumber

ofsessionsreceivedaccordingtoonestudy.

Community-basedrecoverygroups—suchasCocaineAnonymous—thatusea

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12-stepprogramcanalsobehelpfulinmaintainingabstinence.Participants

maybenefitfromthesupportivefellowshipandfromsharingwiththose

experiencingcommonproblemsandissues.62

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Howiscutting-edgesciencehelping

usbetterunderstandaddiction?

Twocutting-edgeareasofscience,geneticsandbrainimaging,aresignificantly

advancingourunderstandingofcocaineaddiction.

Researchersestimatethatgeneticscontributes42to79percentoftheriskfor

cocaineuseanddependence. Ofcourse,withacomplexdiseasesuchas

addiction,manydifferentgenesareinvolved,andtheirexpressioncanbe

influencedbytheenvironment.Thereappearstobesignificantoverlapinthe

genesthatputpeopleatriskforalladdictivesubstances,perhapsindicatinga

commonbiologicalpathwayforaddictionregardlessofthedrug.

Ingenome-wideassociationstudies(GWAS),researchersexaminewhether

certaingenevariantsaremorefrequentlyfoundinpeoplewithasubstanceuse

disorder,whicheventuallymighthelpidentifythoseatincreasedriskfordrug

addiction. Identifyinggeneslinkedtoaddictionisonlythefirststep.

Candidate-generesearchexaminesthelinksbetweensubstanceuseand

specificgenesthatencodeproteinsthatappeartoberelatedtoaddiction.For

example,researchershavefoundconnectionsbetweenvariousaspectsof

cocaineaddictionandthegenesthatencodeforparticulardopaminereceptors

andtheenzymesthatbreakdownthisneurotransmitter.

Becauseenvironmentalfactorstypicallyshapetheimpactofgenesondisease

risk,researchersmustalsoidentifyhowparticulargene-by-environment

interactionsinfluencethecourseofaddiction. Researchinthefieldof

epigeneticsisuncoveringhowtheenvironmentinduceslong-termchangesin

geneexpression—influencingthepatternofgeneexpression—withoutaltering

theDNAsequence.

Inanimalresearch,scientistsaredetermininghowlong-termcocaineexposure

changesgeneexpressioninthebrain,particularlyintherewardpathway.

Studieshavelinkedspecificcocaine-inducedepigeneticchangesto

neuroadaptations andbehavioralhallmarksofaddiction,suchassensitivityto

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cocaine’srewardingeffects. Theepigeneticchangesinducedbycocaine

canbepassedtothenextgeneration,evenifthedrugexposuredoesnotoccur

prenatally. Althoughmuchmoregeneticandepigeneticresearchisneeded,

understandingaddictionatthemolecularleveloffersgreatpromisefor

improvingdiagnosis,forexamplebydiscoveringbiomarkersfordisease

severityortreatmentresponse.

Althoughmoreresearchisneeded,brain-imagingmightbeusedtodetect

biomarkersfordrugaddictionvulnerability,asthesetechnologieshaveyielded

insightsintotheprocessesunderlyingcravingandhowmedicationsmayquell

thebrain’sresponsetococainecues. Arelativelynewneuroimaging

technologycalleddefault-modeorresting-statefunctionalmagneticresonance

imaging(rs-fMRI)revealsbrainactivitywhenpeoplearealertbutnotperforming

aparticulartask;researchersusethistechniquetocomparefunctionalbrain

networksofpeoplewhohaveusedcocaineforalongtimeandthosewhohave

not.Thesestudiessuggestthatthereisreducedconnectivitybetweenvarious

braincircuits andbetweenthetwohemispheres amongpeoplewith

cocainedependence.Researchershavealsocorrelatedreducedconnectivity

betweenparticularbraincircuitswithimportantaddiction-relatedbehaviors,

includingriskforrelapse andimpulsivity.

Neuroimagingtechnologiesarealsodocumentinghowthebrainsofcocaine

usersmayrecoverafterperiodsofabstinence.Forexample,thesetechniques

indicatethatyearsofcocaineuseareassociatedwithreducedgreymatterin

particularbrainregions.However,peoplewhomaintainedcocaineabstinence

forapproximately9monthsshowedgreymatterlevelssimilartoorgreaterthan

thoseofpeoplewhohadneverusedthedrug. Furtheranalysisindicatedthat

theincreasedgreymatteroccurredinregionsotherthantheonesalteredby

cocaineuse,suggestingthattheneurobiologicalchangesinvolvedinrecovery

aremorecomplexthansimplyreversingthechangesrelatedtoaddiction. The

researchersalsofoundthatincreasedgreymattervolumeinbrainregions

involvedwithbehavioralcontrolwereassociatedwithlongerdurationof

abstinence.

fMRItechnologieshavealsorevealedthatabstinencefromcocainehas

important,restorativeeffectsonthebrain.Althoughcurrentcocaineusers

demonstratedreducedbrainactivityinabraincircuitthatmediatesresponse

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inhibitionduringamotorcontroltask,individualswhohadattainedabstinence

foranaverageof8monthsshowedsimilarpatternsofactivationandlevelsof

performancetothosewhohadneverusedthedrug. Theresultssuggestthat

abstinencehelpsrestorethefunctioningofthisbraincircuit.

Researchersareengagedinseverallarge-scale,collaborativeprojectstomap

thehumanconnectome,whichisthebrain’snetworkofinterconnectedcircuits.

Forexample,theNationalInstitutesofHealthsupportstheHumanConnectome

Projecttogeneratemapsofthedeveloping,adult,andagingbrain.Byhavinga

mapofthetypicalbrain,scientistswillfurtherunderstandhowneural

functioningdiffersinbehavioraldisorders—knowledgethatwilldriveimproved

diagnosticsandtreatments.

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WherecanIgetfurtherinformation

aboutcocaine?

Tolearnmoreaboutcocaineandotherdrugsofabuse,visittheNIDAwebsiteat

www.drugabuse.govorcontactDrugPubsat877-NIDA-NIH(877-643-2644;

TTY/TDD:240-645-0228).

NIDA'swebsiteincludes:

Informationondrugsofabuseandrelatedhealthconsequences

NIDApublications,news,andevents

Resourcesforhealthcareprofessionals,educators,andpatientsand

families

InformationonNIDAresearchstudiesandclinicaltrials

Fundinginformation(includingprogramannouncementsanddeadlines)

Internationalactivities

Linkstorelatedwebsites(accesstowebsitesofmanyotherorganizationsin

thefield)

InformationinSpanish(enespañol)

NIDAwebsitesandwebpages

www.drugabuse.gov

www.teens.drugabuse.gov

www.easyread.drugabuse.gov

www.drugabuse.gov/drugs-abuse/cocaine

www.researchstudies.drugabuse.gov

www.irp.drugabuse.gov

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Forphysicianinformation

NIDAMED:www.drugabuse.gov/nidamed

Otherwebsites

InformationoncocaineabuseisalsoavailablethroughthefollowingWebsite:

SubstanceAbuseandMentalHealthServices

Administration:www.samhsa.gov

DrugEnforcementAdministration:www.dea.gov

MonitoringtheFuture:www.monitoringthefuture.org/

ThePartnershipatDrugFree.org:www.drugfree.org/drug-guide

Thispublicationisavailableforyouruseandmaybereproducedinits

entiretywithoutpermissionfromtheNIDA.Citationofthesourceis

appreciated,usingthefollowinglanguage:Source:NationalInstituteon

DrugAbuse;NationalInstitutesofHealth;U.S.DepartmentofHealthand

HumanServices.

“This course was developed from the public domain document: Cocaine – National Institute on Drug Abuse

(NIDA) - NIH (2016).”