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NationalInstituteonDrugAbuse(NIDA) MDMA(Ecstasy)Abuse LastUpdatedMarch2006 https://www.drugabuse.gov 1 TableofContents MDMA(Ecstasy)Abuse LetterfromtheDirector WhatisMDMA? ABriefHistoryofMDMA WhatisthescopeofMDMAabuseintheU.S.? WhoisabusingMDMA? WhataretheeffectsofMDMA? WhatdoesMDMAdotothebrain? IsMDMAAddictive? WhatdoweknowaboutpreventingMDMAabuse? ArethereeffectivetreatmentsforMDMAabuse? WherecanIgetmorescientificinformationaboutMDMA? Glossary References 2 LetterfromtheDirector Theso-called"clubdrug"MDMAcontinuestobeusedbymillionsofAmericans acrossthecountry,despiteevidenceofitspotentialharmfuleffects.3,4methylenedioxymethamphetamine(MDMA,orecstasy)hasgainedadeceptive reputationasa"safe"drugamongitsusers.Thisillegaldrug,whichhasboth stimulantandpsychedelicproperties,isoftentakenforthefeelingsofwellbeing,stimulation,andthedistortionsintimeandsensoryperceptionsthatit produces.MDMAfirstbecamepopularinthe"rave"andall-nightpartyscene, butitsusehasnowspreadtoawiderangeofsettingsanddemographic subgroups.Accordingtothe2004NationalSurveyonDrugUseandHealth, morethan11millionpeoplehavetriedMDMAatleastonce. Mythsaboundaboutboththeacuteeffectsandlong-termconsequencesofthis drug,oftencalledecstasyor"X".Indeed,onereasonfortherapidriseinthe drug’spopularityisthatmanyyoungpeoplebelievethatMDMAisanewsafe drug.ButMDMAisnotnewtothescientificcommunity,asmanylaboratories beganinvestigatingthisdruginthe1980s,andthepictureemergingfromtheir effortsisofadrugthatisfarfrombenign.Forexample,MDMAcancausea dangerousincreaseinbodytemperaturethatcanleadtokidneyfailure.MDMA canalsoincreaseheartrate,bloodpressure,andheartwallstress.Animal studiesshowthatMDMAcandamagespecificneuronsinthebrain.Inhumans, theresearchisnotconclusiveatthistime;however,anumberofstudiesshow thatlong-term,heavyMDMAuserssuffercognitivedeficits,includingproblems withmemory. NIDA-supportedresearchisdevelopingaclearerpictureofthepotential dangersofMDMA,andthisResearchReportsummarizesthelatestfindings. Wehopethatthiscompilationofscientificinformationwillinformreadersand helpthepublicrecognizetherisksofMDMAuse. NoraD.Volkow,M.D. Director NationalInstituteonDrugAbuse 3 WhatisMDMA? MDMAisanillegaldrugthatactsasbothastimulantandpsychedelic, producinganenergizingeffect,aswellasdistortionsintimeandperceptionand enhancedenjoymentfromtactileexperiences.1,2Typically,MDMA(anacronym foritschemicalname3,4-methylenedioxymethamphetamine)istakenorally, usuallyinatabletorcapsule,anditseffectslastapproximately3to6hours.The averagereporteddoseisonetotwotablets,witheachtablettypicallycontaining between60and120milligramsofMDMA.1Itisnotuncommonforuserstotake aseconddoseofthedrugastheeffectsofthefirstdosebegintofade. MDMAcanaffectthebrainbyalteringtheactivityofchemicalmessengers,or neuro-transmitters,whichenablenervecellsinthebraintocommunicatewith oneanother.ResearchinanimalshasshownthatMDMAinmoderatetohigh dosescanbetoxictonervecellsthatcontainserotoninandcancauselonglastingdamagetothem.1,3Furthermore,MDMAraisesbodytemperature.On rarebutlargelyunpredictableoccasions,thishasledtoseveremedical consequences,includingdeath.3,4Also,MDMAcausesthereleaseofanother neurotransmitter,norepinephrine,whichislikelythecauseoftheincreasein heartrateandbloodpressurethatoftenaccompaniesMDMAuse.5,6 4 AlthoughMDMAisknownuniversallyamongusersasecstasy,researchers havedeterminedthatmanyecstasytabletscontainnotonlyMDMAbutalsoa numberofotherdrugsordrugcombinationsthatcanbeharmfulaswell. AdulterantsfoundinMDMAtabletspurchasedonthestreetinclude methamphetamine,caffeine,theover-the-countercoughsuppressant dextromethorphan,thedietdrugephedrine,andcocaine.7,8Also,aswithmany otherdrugsofabuse,MDMAisrarelyusedalone.Itisnotuncommonforusers tomixMDMAwithothersubstances,suchasalcoholandmarijuana. 5 ABriefHistoryofMDMA MDMAwasdevelopedinGermanyintheearly1900sasaparentcompoundto beusedtosynthesizeotherpharmaceuticals.Duringthe1970s,intheUnited States,somepsychiatristsbeganusingMDMAasapsychotherapeutictool, despitethefactthatthedrughadneverundergoneformalclinicaltrialsnor receivedapprovalfromtheU.S.FoodandDrugAdministration(FDA)forusein humans.Infact,itwasonlyinlate2000thattheFDAapprovedthefirstsmall clinicaltrialforMDMAthatwilldetermineifthedrugcanbeusedsafelywith2 sessionsofongoingpsychotherapyundercarefullymonitoredconditionsto treatpost-traumaticstressdisorder.Nevertheless,thedruggainedasmall followingamongpsychiatristsinthelate1970sandearly1980s,withsome evencallingit"penicillinforthesoul"becauseitwasperceivedtoenhance communicationinpatientsessionsandreportedlyalloweduserstoachieve insightsabouttheirproblems.ItwasalsoduringthistimethatMDMAfirststarted becomingavailableonthestreet.In1985,theU.S.DrugEnforcement Administration(DEA)bannedthedrug,placingitonitslistofScheduleIdrugs, correspondingtothosesubstanceswithnoproventherapeuticvalue.2 6 SerotoninPresentinCerebralCortexNeuronsLong-termeffectsinmonkeys.Theleft panelisbraintissuefromanormalmonkey.Themiddleandrightpanelsillustratethe lossofserotonin-containingnerveendingsfollowingMDMAexposure. 7 WhatisthescopeofMDMAabusein theU.S.? ItisdifficulttodeterminetheexactscopeofthisproblembecauseMDMAis oftenusedincombinationwithothersubstances,anddoesnotappearinsome traditionaldatasources,suchastreatmentadmissionrates. Morethan11millionpersonsaged12orolderreportedusingecstasyatleast onceintheirlifetimes,accordingtothe2004NationalSurveyonDrugUseand Health.Thenumberofcurrent(useinpastmonth)usersin2004wasestimated tobe450,000.9 MonitoringtheFutureSurvey*-TrendsinMDMA Prevalance,2002-2004 Note:Thesedataarefromthe2005MonitoringtheFuturesurvey,fundedbythe NationalInstituteonDrugAbuse,NationalInstitutesofHealth,DHHS,andconducted annuallybytheUniversityofMichigan'sInstituteforSocialResearch."Annual"refers touseatleastonceduringtheyearprecedinganindividual'sresponsetothesurvey. "30-day"referstouseatleastonceduringthe30daysprecedinganindividual's responsetothesurvey. TheDrugAbuseWarningNetwork,maintainedbytheSubstanceAbuseand MentalHealthServicesAdministration,reportedthatmentionsofMDMAindrug 8 abuse-relatedcasesinhospitalemergencydepartmentswere2,221forthe thirdandfourthquartersof2003.Themajorityofpatientswhocameto emergencydepartmentsmentioningMDMAasafactorintheiradmissions duringthattimewereaged18–20.10 TrendsinPerceivedHarmfulnessofMDMAUse Thereis,however,someencouragingnewsfromNIDA’sMonitoringtheFuture (MTF)survey,anannualsurveyusedtotrackdrugabusetrendsamong adolescentsinmiddleandhighschoolsacrossthecountry.Between2001and 2005,annualecstasyusedecreasedby52percentin8th-graders,58percent in10th-graders,and67percentin12th-graders.RatesoflifetimeMDMAuse decreasedsignificantlyfrom2004to2005among12thgraders. In2005,8th-gradersreportedasignificantdecreaseinperceivedharmfulness inusingMDMAoccasionally.TheMTFdataalsoshowthatMDMAuseextends acrossmanydemographicsubgroups.Among12th-gradersin2005,for example,3.9percentofWhites,3.0percentofHispanicstudents,and1.4 percentofAfrican-AmericansreportedusingMDMAintheyearpriortothe 9 11 survey.11 10 WhoisabusingMDMA? MDMAfirstgainedpopularityamongadolescentsandyoungadultsinthe nightclubsceneorweekendlongdancepartiesknownasraves.However,the profileofthetypicalMDMAuserhasbeenchanging.Community-leveldatafrom NIDA'sCommunityEpidemiologyWorkGroup(CEWG),continuedtoreportthat useofMDMAhasspreadamongpopulationsoutsidethenightclubscene. ReportsalsoindicatethatuseisspreadingbeyondpredominantlyWhiteyouth toabroaderrangeofethnicgroups.InChicago,thedrugcontinuestobe predominantlyusedbyWhiteyouth,butthereareincreasingreportsofitsuse byAfrican-Americanadultsintheirtwentiesandthirties.Also,indicatorsinNew Yorksuggestthatboththedistributionanduseofclubdrugsarebecoming morecommoninnon-Whitecommunities.12 11 WhataretheeffectsofMDMA? MDMAhasbecomeapopulardrug,inpartbecauseofthepositiveeffectsthata personmayexperiencewithinanhourorsoaftertakingasingledose.Those effectsincludefeelingsofmentalstimulation,emotionalwarmth,empathy towardothers,ageneralsenseofwellbeing,anddecreasedanxiety.In addition,usersreportenhancedsensoryperceptionasahallmarkoftheMDMA experience.1,2 EffectsofMDMA ReportedUndesirableEffectsEffects(upto1weekpostMMDA,orlonger): Anxiety Restlessness Irritability Sadness Impulsiveness Aggression SleepDisturbances Lackofappetite Thirst Reducedinterestinandpleasurefromsex Significantreductionsinmentalabilities PotentialAdverseHealthEffects: Nausea 12 Chills Sweating Involuntaryjawclenchingandteethgrinding Musclecramping Blurredvision Markedriseinbodytemperature(hyperthermia) Dehydration HighBloodPressure Heartfailure Kidneyfailure Arrythmia SymptomsofMDMAOverdose: HighBloodPressure Faintness Panicattacks Lossofconsciousness Seizures Asnoted,MDMAisnotabenigndrug.MDMAcanproduceavarietyofadverse healtheffects,includingnausea,chills,sweating,involuntaryteethclenching, musclecramping,andblurredvision.2MDMAoverdosecanalsooccur—the symptomscanincludehighbloodpressure,faintness,panicattacks,andin severecases,alossofconsciousnessandseizures.1 Becauseofitsstimulantpropertiesandtheenvironmentsinwhichitisoften 13 taken,MDMAisassociatedwithvigorousphysicalactivityforextended periods.2Thiscanleadtooneofthemostsignificant,althoughrare,acute adverseeffects—amarkedriseinbodytemperature(hyperthermia).3,4 Treatmentofhyperthermiarequirespromptmedicalattention,asitcanrapidly leadtomusclebreakdown,whichcaninturnresultinkidneyfailure.Inaddition, dehydration,hypertension,andheartfailuremayoccurinsusceptible individuals.MDMAcanalsoreducethepumpingefficiencyoftheheart,6of particularconcernduringperiodsofincreasedphysicalactivity,further complicatingtheseproblems. MDMAisrapidlyabsorbedintothehumanbloodstream,butonceinthebody, MDMAmetabolitesinterferewiththebody'sabilitytometabolize,orbreakdown, thedrug.8Asaresult,additionaldosesofMDMAcanproduceunexpectedly highbloodlevels,whichcouldworsenthecardiovascularandothertoxiceffects ofthisdrug.MDMAalsointerfereswiththemetabolismofotherdrugs,including someoftheadulterantsthatmaybefoundinMDMAtablets. Inthehoursaftertakingthedrug,MDMAproducessignificantreductionsin mentalabilities.Thesechanges,particularlythoseaffectingmemory,canlastfor uptoaweek,andpossiblylongerinregularusers.ThefactthatMDMA markedlyimpairsinformationprocessingemphasizesthepotentialdangersof performingcomplexorskilledactivities,suchasdrivingacar,whileunderthe influenceofthisdrug 2,13. TheNeurobiologyofEcstasy(MDMA) 14 MDMAaltersbrainchemistrybybindingtoserotonintransporters. Overthecourseofaweekfollowingmoderateuseofthedrug,manyMDMA usersreportfeelingarangeofemotions,includinganxiety,restlessness, irritability,andsadnessthatinsomeindividualscanbeassevereastrue clinicaldepression.14Similarly,elevatedanxiety,impulsiveness,and aggression,aswellassleepdisturbances,lackofappetite,andreduced interestinandpleasurefromsexhavebeenobservedinregularMDMA users.15,16Someofthesedisturbancesmaynotbedirectlyattributableto MDMA,butmayberelatedtosomeoftheotherdrugsoftenusedincombination withMDMA,suchascocaineormarijuana,ortoadulterantscommonlyfoundin MDMAtablets. 15 WhatdoesMDMAdotothebrain? MDMAaffectsthebrainbyincreasingtheactivityofatleastthree neurotransmitters(thechemicalmessengersofbraincells):serotonin, dopamine,andnorepinephrine.5Likeotheramphetamines,MDMAcauses theseneurotransmitterstobereleasedfromtheirstoragesitesinneurons, resultinginincreasedneurotransmitteractivity.Comparedtotheverypotent stimulant,methamphetamine,MDMAcausesgreaterserotoninreleaseand somewhatlesserdopaminerelease.17Serotoninisaneurotransmitterthatplays animportantroleintheregulationofmood,sleep,pain,appetite,andother behaviors.TheexcessreleaseofserotoninbyMDMAlikelycausesthemood elevatingeffectsexperiencedbyMDMAusers.However,byreleasinglarge amountsofserotonin,MDMAcausesthebraintobecomesignificantlydepleted ofthisimportantneurotransmitter,contributingtothenegativebehavioral aftereffectsthatusersoftenexperienceforseveraldaysaftertakingMDMA.18 NumerousstudiesinanimalshavedemonstratedthatMDMAcandamage serotonin-containingneurons;1,3someofthesestudieshaveshownthese effectstobelonglasting.Thissuggeststhatsuchdamagemayoccurinhumans aswell;however,measuringserotonindamageinhumansismoredifficult. StudieshaveshownthatsomeheavyMDMAusersexperiencelonglasting confusion,depression,andselectiveimpairmentofworkingmemoryand attentionprocesses.19,20,21,22,23Suchmemoryimpairmentshavebeen associatedwithadecreaseinserotoninmetabolitesorothermarkersof serotoninfunction.ImagingstudiesinMDMAusers19,21,24haveshownchanges inbrainactivityinregionsinvolvedincognition,emotion,andmotor function.25,26,27However,improvedimagingtechnologiesandmoreresearch areneededtoconfirmthesefindingsandtoelucidatetheexactnatureofthe effectsofMDMAonthehumanbrain. Itisalsoimportanttokeepinmindthatmanyusersofecstasymayunknowingly betakingotherdrugsthataresoldasecstasy,and/ortheymayintentionallyuse otherdrugs,suchasmarijuana,whichcouldcontributetothesebehavioral effects.Additionally,moststudiesinpeopledonothavebehavioralmeasures frombeforetheusersbegantakingdrugs,makingitdifficulttoruleoutpreexistingconditions.20,28,29Factorssuchasgender,dosage,frequencyand 16 intensityofuse,ageatwhichusebegan,theuseofotherdrugs,aswellas geneticandenvironmentalfactorsallmayplayaroleinsomeofthecognitive deficitsthatresultfromMDMAuseandshouldbetakenintoconsiderationwhen studyingtheeffectsofMDMAinhumans. GiventhatmostMDMAusersareyoungandintheirreproductiveyears,itis possiblethatsomefemaleusersmaybepregnantwhentheytakeMDMA,either inadvertentlyorintentionallybecauseofthemisperceptionthatitisasafedrug. ThepotentialadverseeffectsofMDMAonthedevelopingfetusareofgreat concern.Behavioralstudiesinanimalshavefoundsignificantadverseeffects ontestsoflearningandmemoryfromexposuretoMDMAduringa developmentalperiodequivalenttothethirdtrimesterinhumans.30However, theeffectsofMDMAonanimalsearlierindevelopmentareunclear;31,32 therefore,moreresearchisneededtodeterminewhattheeffectsofMDMAare onthedevelopinghumannervoussystem. LifeThreateningEffects 17 IsMDMAAddictive? MDMAaffectsmanyofthesameneurotransmittersystemsinthebrainthatare targetedbyotheraddictivedrugs.Experimentshaveshownthatanimalswill selfadministerMDMA—animportantindicatorofadrug’sdependencypotential —althoughthedegreeofself-administrationislessthansomeotherdrugsof abusesuchascocaine.34 FewstudieshaveattemptedtoassessMDMAdependencyamongusersinthe generalpopulation,andthosethathavebeenconductedhaveshownwidely varyingresults,likelybecauseofthedifferentpopulationsamplesanddifferent typesofmeasuresused.WedoknowthatsomeMDMAusersreportsymptoms including:continuedusedespiteknowledgeofphysicalorpsychologicalharm; tolerance(ordiminishedresponse);andwithdrawaleffects,suchasfatigue, lossofappetite,depressedfeelings,andtroubleconcentrating. 18 Whatdoweknowaboutpreventing MDMAabuse? Becausesocialcontextandnetworksseemtobeanimportantcomponentof MDMAuse,theuseofpeer-ledadvocacyanddrugpreventionprogramsmay beapromisingapproachtoreduceMDMAuseamongadolescentsandyoung adults.Highschoolsandcollegescanserveasimportantvenuesfordelivering messagesabouttheeffectsofMDMAuse.Providingaccuratescientific informationregardingtheeffectsofMDMAisimportantifwehopetoreducethe damagingeffectsofthisdrug.Educationisoneofthemostimportanttoolsfor useinpreventingMDMAabuse. 19 Arethereeffectivetreatmentsfor MDMAabuse? TherearenospecifictreatmentsforMDMAabuse.Themosteffectivetreatments fordrugabuseandaddictionarecognitivebehavioralinterventionsthatare designedtohelpmodifythepatient'sthinking,expectancies,andbehaviors, andtoincreaseskillsincopingwithlife'sstressors.Drugabuserecovery supportgroupsmaybeeffectiveincombinationwithbehavioralinterventionsto supportlong-term,drug-freerecovery.Therearecurrentlynopharmacological treatmentsfordependenceonMDMA. 20 WherecanIgetmorescientific informationaboutMDMA? TolearnmoreaboutMDMAandotherdrugsofabuse,gotoourDrugSummary pages. 21 Glossary Addiction:Achronic,relapsingdiseasecharacterizedbycompulsivedrug seekinganduse. Adulterant:Asubstance,eitherabiologicallyactivematerialsuchasanother drugoraninertmaterial,addedtoadrugwhenitisformedintoatabletor capsule. Cardiovascularsystem:Theheartandbloodvessels. Dopamine:Aneurotransmitterpresentinregionsofthebrainthatregulate movement,emotion,motivation,andthefeelingofpleasure. Ecstasy:CommonstreetnameforMDMA. Gastrointestinalsystem:Thestomachandintestines. Hyperthermia:Apotentiallydangerousriseinbodytemperature. MDMA:Commonchemicalnamefor3,4-methlyenedioxymethamphetamine. Neurotransmitter:Achemicalthatactsasamessengertocarrysignalsor informationfromonenervecelltoanother. Norepinephrine:Aneurotransmitterpresentinregionsofthebrainthataffect heartrateandbloodpressure. Serotonin:Aneurotransmitterusedinwidespreadpartsofthebrain,whichis involvedinsleep,movementandemotions Tolerance:Adecreaseintheeffectofadrugthatoccurswithrepeated 22 administration. 23 References 1. Morgan,M.J.Ecstasy(MDMA):areviewofitspossiblepersistent psychologicaleffects.Psychopharmacology152:230-248(2000). 2. ParrottAC.HumanpsychopharmacologyofEcstasy(MDMA):areviewof15 yearsofempiricalresearch.HumanPsychopharmacolClinExp16:557-577 (2001). 3. Lyles,J.;andCadet,J.L.Methylenedioxymethamphetamine(MDMA, Ecstasy)neurotoxicity:cellularandmolecularmechanisms.BrainResearch Reviews42:155-168(2003). 4. 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KishSJ.Howstrongistheevidencethatbrainserotoninneuronsare damagedinhumanusersofecstasy?PharmacologyBiochemistryBehavior 71:845-855(2002). 20. Morgan,M.J.Memorydeficitsassociatedwithrecreationaluseof"ecstasy" 25 (MDMA).Psychopharmacology141:30-36(1999). 21. SoarK,TurnerJJD,andParrottAC.PsychiatricdisordersinEcstasy (MDMA)users:aliteraturereviewfocusingonpersonalpredispositionand drughistory.HumanPsychopharmacology16:641-645. 22. Verkes,R.J.;Gijsman,H.J.;Pieters,M.S.M.;Schoemaker,R.C.;deVisser,S.; Kuijpers,M.;Pennings,E.J.M.;deBruin,D.;VandeWijngaart,G.;Van Gerven,J.M.A.;andCohen,A.F.Cognitiveperformanceandserotonergic functioninusersofecstasy.Psychopharmacology153:196-202(2001). 23. Wareing,M.;Fisk,J.E.;andMurphy,P.N.Workingmemorydeficitsincurrent andprevioususersofMDMA('ecstasy').BritishJournalofPsychology 91:181-188(2000). 24. Reneman,L.;Booij,J.;Schmand,B.;vandenBrink,W.;andGunning,B. 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Degenhardt,L.;Bruno,R.;andTopp,L.Isecstasyadrugofdependence? DrugandAlcoholDependence107:1-10(2010). 35. Schenk,S.;Gittings,D.;Johnstone,M.;andDaniela,E.Development, maintenanceandtemporalpatternofself-administrationmaintainedby ecstasy(MDMA)inrats.Psychopharmacology169:21-27(2003).(23) Wareing,M.;Fisk,J.E.;andMurphy,P.N.Workingmemorydeficitsincurrent andprevioususersofMDMA('ecstasy').BritishJournalofPsychology 91:181-188(2000). 27