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NationalInstituteonDrugAbuse(NIDA)TheNeurobiologyofEcstasy(MDMA)LastUpdatedJanuary2007https://www.drugabuse.gov

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TableofContentsTheNeurobiologyofEcstasy(MDMA)

SectionI

SectionII

SectionIII

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SectionI

1:Introduction:long-termeffectsofecstasy

Aneffectivewayofstartingapresentationistopresentsomethinginterestingorprovocative.Thisfirstimageshowssectionstakenfromtheneocortexofmonkeysthatweregivenecstasytwiceadayfor4days(controlmonkeysweregivensaline).Thesectionontheleft,takenfromthebrainofacontrolmonkey,showsthepresenceofalotofserotonin.Themiddlesectionshowsasectionfromamonkeytwoweeksafterreceivingecstasy.Pointoutthatmostoftheserotoninisgone.Thesectionontherightshowsasectionfromamonkeysevenyearsafterreceivingecstasy.Pointoutthatalthoughtherehasbeensomerecoveryofserotonin,thebrainstillhasnotreturnedtonormal.Indicatethatyouwilldiscussthisinyourtalkinmoredetail.Introduce

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thepurposeofyourpresentation.Indicatethatyouwillexplainhowecstasyinteractswithspecifictargetsinthebrainandwhatcanhappenafterrepeatedorlong-termuse.Tellthestudentsthatyouwillreviewhowneuronscommunicatewitheachotherandhowecstasyaltersthiscommunication,resultinginchangesinmood,behavior,andmemory.

2:Defineecstasy

Ecstasyisaderivativeofamphetamine(showninpurpleontheimage).Itschemicalnameis3,4-methylenedioxymethamphetamine(MDMA)andithasasimilarstructuretomethamphetamine.ecstasyhasavarietyofstreetnamesincluding,XTC,Adam,M&M,E,andessence.Explaintostudentsthatecstasyisunlikeotherdrugsofabuse,whichareoftenderivedfromplants(e.g.,cocaine,morphine,nicotine).Incontrast,ecstasyissynthesizedinclandestinelaboratories--infact,thereareseveral"designerdrugs"thataremade(inclandestinelaboratories)byalteringthestructureofthe

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amphetaminemolecule.Becauseecstasyissynthesizedinlaboratories,itspuritycanvarysubstantiallyfromlabtolab,andothercompoundsareeasilycombinedintothesametablet(contaminantsoftenincludecaffeine,ephedrine,ketamine-amildhallucinogenandmethamphetamine).

3:Ecstasygetsintothebraineasily

Thechemicalstructureofecstasyallowsittoreachthebrainquicklyafteringestion.Usetheimagetoillustratetothestudentsthepathwaythatecstasyfollowsfromthemouthtothebrain.First,thepillisingestedanditdisintegratesquicklyinthestomachcontents.Oncedissolved,someecstasymoleculesareabsorbedfromthestomachintothebloodstream,butmostoftheecstasymoleculesmovefromthestomachintothesmallintestine.There,theyareabsorbedintothebloodstreamveryeasily.

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Thefollowingexplanationisoptionalandmaybedesirableforpresentationtostudentswhohavehadsomechemistry:ecstasyisaweakbase--thismeansthatecstasyislikelyto"pickup"oracceptahydrogenion(H+)fromthesurroundingmedium(thegastricacidinthestomachisloadedwithH+).AftertheecstasyhasacceptedaH+,ithasacharged(orpolar)character,whichmakesitdifficulttocrossabiologicalmembrane.Biologicalmembraneshaveanonpolarcore,socompoundshavinganonpolarnaturearemorelikelytodiffuseacrossthemembrane(passivediffusion).Therefore,mostoftheecstasyisnotabsorbedfromthestomachintothebloodstream.Rather,theecstasymoleculesgetemptiedfromthestomachintothesmallintestine.InthesmallintestinethemorealkalineenvironmentcausesecstasytogiveupitsH+,becomingmorenonpolar.Thelargesurfaceareaandthemorealkalineenvironmentenabletheecstasymoleculestodiffuseacrossthemembraneintothebloodcapillariesveryquickly.

Ecstasymoleculesthathaveenteredthebloodstreamfromthestomachandsmallintestinesthentraveltotheliver(shownbythebottombluearrows).Intheliver,someoftheecstasyismetabolizedtoinactivecompoundsandtherestiscarriedthroughtheveinstotheheart(bluearrow).Onceintheheart,theecstasyispumpedtothelungsalongwiththeblood,whichbecomesoxygenatedandthenreturnstotheheart(redarrow).Now,oxygenatedbloodcarriestheecstasyfromthehearttothebrain(redarrow)andtootherorgansinbodythathaveahighbloodflow.Normallythereisabarrierbetweenthebloodvesselsinthebrainandbrainmatter,whichexcludesmanydrugsfromenteringthebrain.However,ecstasyispredominantlyinitsnonpolarforminbloodandthereforeitcrossesthebarrierintothebrainveryeasily.Itwilltakeabout15minutesforecstasytoreachthebrainiftakenonanemptystomach.

4:Whatweknowaboutecstasy

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Inrecentyears,therehasbeenalotofresearchcarriedouttounderstandhowecstasyaffectsthebrain.Scientistshavemadealotofprogressinidentifyinghowecstasychangesmoodandbehavior.Indicatetostudentsthatecstasyhasshort-termandlong-termeffectsonthebrain.Theshort-termeffectsofecstasyincludechangesinbrainchemistryandbehavior.Thelong-termeffectsincludechangesinbrainstructure(basedmainlyonanimalstudies)andbehavior.Tellthemthatyouwilltrytoillustratehowthesechangestakeplace.Youcouldaskstudentsiftheyhaveanyknowledgeoftheshort-termorlong-termeffectsofecstasyonthebrain.Iftheyvolunteersomeanswers,listthemontheboard;indicatethatyouwilldiscusshowsomeoftheseeffectsareproduced.

5:Howdoweknow?Researchinanimalsandhumans

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Bringuptheimportanceofanimalsinresearch.Researchinanimalshasprovideduswithadetailedunderstandingabouttheactionsofecstasyinthebrain.Infact,manyoftheresearchfindingsobtainedfromanimals,suchasratsandmonkeys,havenowbeenreplicatedinhumans.Indicatetothestudentsthatanotherimportantaspectofusinganimalsinresearchistounderstandmechanismsfortoxicityproducedbycompounds.ecstasyisaclassicexampleofadrugthatproducestoxicity(inthebrain)anditwouldbeimpossibletostudythisinlivinghumans.Inthefollowingsetofimages,theinformationhighlightinghowecstasyworkswasobtainedfromresearchusinganimals.

6:Brainareassensitivetoecstasy

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Beforeexplaininghowecstasyworks,itmaybehelpfultopointouttheareasofthebrainthataresensitivetotheeffectsofecstasy.ecstasyaffectscognition(thinking),mood,andmemory.Italsocancauseanxietyandalteredperceptions(similartobutnotquitethesameashallucinations).Themostdesirableeffectofecstasyisitsabilitytoprovidefeelingsofwarmthandempathy.Tellstudentsthatyouwilltalkabouttheeffectsofecstasyinmoredetailinafewminutes.Thereareseveralpartsofthebrainthatareimportantintheseactionsofecstasy.Pointtotheneocortex(inyellow),whichisimportantincognition,memory,andalteredperceptions.Pointtotheseveralstructuresdeepinthebrainthatmakeupthelimbicsystem(e.g.,theamygdala(red),hippocampus(blue),basalganglia(purple),andhypothalamus(green),whichisinvolvedinchangesinmood,emotions,andtheproductionofanxiety(thehippocampusisalsoinvolvedinmemory).Scientistsdonotknowyetwhichareaofthebrainisinvolvedintheabilityofecstasytogeneratefeelingsofempathy(youcouldaskstudentstosuggestwheretheythinkecstasymightdothis-limbicareasareagoodguess).

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7:Anatomyofaneuron

Nowthatthestudentsknowthattherearespecificregionsofthebrainaffectedbyecstasy,youwillneedtodescribehowitworks.First,indicatethatthedifferentregionsofthebrainareconnectedbynervecellsorneuronsviapathways.Thesepathwaysofneuronssendandintegrateinformation(electricalandchemical).Describetheneuronusingtheschematicinthisimage.Thecellbody,whichcontainsthenucleus,isthecenterofactivity.Dendritesreceivechemicalinformationfromotherneuronsthatisconvertedtoelectricalsignalswhichtraveltowardthecellbody.Whenthecellbodyreceivesenoughelectricalsignalstoexciteit,alargeelectricalimpulseisgeneratedandittravelsdowntheaxontowardtheterminal.Intheterminalarea,chemicalscalledneurotransmittersarereleasedfromtheneuroninresponsetothearrivalofanelectricalsignal.Tellthestudentsthatyouwillexplainthisinmoredetail,usingtheneurochemicalserotoninasanexample.

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SectionII

1:Howdoesecstasywork:serotoninpathwaysinthebrain

Thenervepathwaythatispredominantlyaffectedbyecstasyiscalledtheserotoninpathway.Serotoninisaneurotransmitterthatissynthesized,stored,andreleasedbyspecificneuronsinthispathway.Itisinvolvedintheregulationofseveralprocesseswithinthebrain,includingmood,emotions,aggression,sleep,appetite,anxiety,memory,andperceptions.Tellthestudentsthatyouwillshowthemhowachemicallikeserotonincanregulatetheseprocesses.First,describehowserotoninpathwaysinnervate(connectto)differentbrainregions.Pointtothecellbodiesoftheserotoninpathwaythatarelocatedinthebrainstemarea"theRaphenucleus"inpink).Showstudentshowtheseneuronssendlongaxonstohighercentersinthe

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brainincludingtheneocortex(yellow)andthelimbicsystem(e.g.,theamygdala--redandhippocampus--blue).Pointtoasecondpathwayforserotoninneuronsthatdescendsdownthespinalcord;theseneuronscontrolmuscleactivity;tellthestudentsthatyouwilltalkaboutthisinmoredetailinafewminutes.Indicatethatthefunctionofserotonindependsontheregionofthebrainintowhichitisreleased(italsodependsonthetypeofserotoninreceptorpresentinthatregion--seediscussioninimage9).Forexample,theserotoninneuronsintheneocortexinthefrontofthebrain(frontalcortex)regulatecognition,memory,andperceptions.Theserotoninneuronsinthehippocampusregulatememory.Theserotoninneuronsinotherlimbicareassuchastheamygdalaalsoregulatemood.

2:Theserotoninneuron:themajortargetofecstasy

Inordertohelpstudentsunderstandhowecstasyaffectsthefunction

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ofserotoninneurons,itwillbeusefultoreviewhowneurotransmissiontakesplaceinalittlemoredetail.Youcanexplainserotoninneurotransmissionasanexample(serotoninisoneofmanyneurotransmitters).Thisimageshowstheconnectionbetweentwoneurons(the"synapse").Serotoninisstoredinsmallvesicleswithinthenerveterminalofaneuron.Electricalimpulses(arisingintheRaphenucleus,forexample)travelingdowntheaxontowardtheterminalcausethereleaseofserotoninfromsmallvesiclesintothesynapticspace.Pointtothespacebetweentheterminalandtheneighboringneuron.Wheninthesynapticspace,theserotoninbindstospecialproteins,calledreceptors,onthemembraneofaneighboringneuron(thisisusuallyatadendriteorcellbody).Whenserotoninbindstoserotoninreceptors(thereareactuallyatleast14typesofserotoninreceptors),itcausesachangeintheelectricalpropertiesofthereceivingneuronthatgenerallyresultsinadecreaseinitsfiringrate.Gotothenextimagetoexplainhowtheactionofserotoninisterminated.

3:Serotonintransporters

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Serotonin(inpink)ispresentinthesynapticspaceonlyforalimitedamountoftime.Ifitisnotboundtotheserotoninreceptor,serotoninisremovedfromthesynapticspaceviaspecialproteinscalledtransporters(ingreen).Theserotonintransportersareproteinslocatedontheserotoninneuronterminalsandtheyareinauniquepositiontotransportserotoninfromthesynapticspacebackintotheneuronwhereitcanbemetabolizedbyenzymes.Explaintoyourstudentsthattheserotonintransportersaretheprimarytargetsforecstasy.

4:Ecstasyandserotonintransporters

Whenecstasybindstotheserotonintransporters,moreserotoninendsupinthesynapticspace.Thisoccursfortworeasons.First,ecstasycanpreventthetransportersfromcarryingserotoninbackintotheterminal.Second,ecstasycancausethetransporterstoworkin

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reversemode--theyactuallybringserotoninfromtheterminalintothesynapticspace.So,moreserotoninispresentinthesynapticspaceandmoreserotoninreceptorsbecomeactivated.Thisisthemajorshort-termeffectofecstasythataltersbrainchemistry.Althoughtheserotoninsystemistheprimarytargetforecstasy,ecstasyhassimilareffectsonthedopamine(anotherneurotranmsitter)systemaswell.ecstasycaninhibitdopaminetransportersandcauseanincreaseindopaminelevelsinthesynapticspace(notshownhere).Tohelpstudentsunderstandhowthealterationinbrainchemistryresultsinpsychologicalchanges,gotothenextimage.

5:Short-term(acute)effectsofecstasy

Explainthatwhenapersonusesecstasy,theincreaseinserotoninindifferentbrainregions(i.e.,theareaswhereserotoninneuronstravelingfromtheraphenucleusterminate)causespsychological

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effects.Theseincludeelevatedmoodandfeelingsofempathy.Theecstasyisalsoreinforcing,whichmeansthatitspleasurablepropertiesincreasethelikelihoodthatthepersonwilltakeitagain.Tellthestudentsthatdrugsthatarereinforcingareusuallyaddictive.

Studentsmightaskyouifecstasyisaddictive.Scientistsandhealthprofessionalsdon'thaveadefinitiveansweryet.Fornowthereareseveralpiecesofevidencethatsuggestthatecstasyhasthepotentialtobeaddictive.Inonestudyofecstasyusers,43%ofrespondentsmetcriteriathatarecommonlyusedtodeterminedependenceforotherdrugsofabuse.Thisincludedsymptomssuchascontinuingtousethedrugdespiteknowledgeofphysicalorpsychologicalharm,experiencingwithdrawaleffects,andtolerance(ordiminishedresponse)torepeateduseofecstasy.Inaresearchsetting,monkeyswilladministerecstasytothemselves(theyactuallypressalevertoobtainaninjection),justastheydoforotheraddictivedrugs.Monkeyswillnotself-administerdrugsthatarenotaddictive.Inaddition,thereisemergingresearchtoshowthatecstasyhasactionsinaspecificpathwaywithinthelimbicsystemcalledthe"rewardpathway",whichcanexplainit'sreinforcingeffects.Infact,alladdictivedrugsactinsomewaywithinthe"rewardpathway".Formoreinformationonthis,seetheNIDATeachingPacketreferencedattheend.

Manyofthepsychologicaleffectsofecstasyareduetoitsactionswithinthelimbicsystem(theamygdala,inred,andhippocampus,inblue,especially).Theabilityofecstasytoproducemildstimulationisduetoitsactionsinanotherpartofthelimbicsystem--thebasalganglia(inpurple).Itisherewhereecstasy'seffectsonthedopaminesystemmaybeimportant.Theheightenedperceptionsinvolvetheactionsofecstasyintheneocotex(inyellow).ecstasycanalsoreducetheappetite,becauseitactsinthehypothalamus(ingreen),whichcontrolsfeedingbehavior.

6:Short-termadverseeffects

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Peoplewhotakeecstasydesireitspleasurableorreinforcingeffects(justdescribedinthelastimage).However,fewdrugsareabletoproducedesirableeffectswithoutalsoproducingsideeffects.ecstasyisnoexception,andthereareseveralsideeffectsoradverseeffectsthatcanoccur,especiallyathighdoses.However,somepeoplewhotakeonlyoneecstasypillmayhavenegativepsychologicaleffectssuchascloudedthinking,agitation,anddisturbedbehavior.Pointtoareasofthebrainwhereecstasymayproducetheseadverseeffects(theneocortex,inyellowandlimbicstructures,inredandblue).Otheradverseeffectscanoccuraswell.Theseincludesweating,drymouth(thirsty),increasedheartrate,fatigue,musclespasms(especiallyjaw-clenching)andhyperthermia.Inthelattercase,ecstasycandisrupttheabilityofthebraintoregulatebodytemperature.Thisusuallyresultsinhyperthermia,especiallywhentheuserisinahotenvironmentand/orengaginginintensephysicalactivitysuchasfastdancingat"rave"parties.Youcanprovidesomeexamplestoshowwhereecstasyproducesthesesideeffects.Forexample,thedevelopmentofthirstandthehyperthermiaareduetoactionsofecstasyinthehypothalamus(green),whichcontrolsdrinkingbehaviorandbody

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temperature.Youmightpointoutthattheeffectofecstasyonthehypothalamuscausesmultipleeffectsinthebody,andinsomecasestheyareverydangerous(seethenextimage).Themusclespasmsandjaw-clenchingareduetoecstasy'sactionatthemotorneuronsinthespinalcord(inyellow)(remindthestudentsthatamajorserotoninpathwaydescendsdownthespinalcord).Themotorneuronssendsignalstothemusclestocontract.

7:Life-threateningeffectsaftermultipledosesor"stacking"

Somepeopletakemultipledosesofecstasyinonenight("stacking").Thismightbeduetothereinforcingeffectofthedrugwearingoffovertime.Often,ifsomethingfeelsgood,onewantstodoitagain!Unfortunately,increaseddosesalsoincreasetheadverseeffects,andsomeofthesecanbecomelife-threatening.Forexample,repeateddosesorahighdoseofecstasycancauseheatinjurydueto

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hyperthermia,hypertension(highbloodpressure),cardiacarrhythmias(irregularheartbeat),musclebreakdownandrenalfailureduetosaltandfluiddepletion.Indicatethatthesedangerouseffectscanbeproducedbyecstasyactinginthebrain.Again,thehypothalamusisveryimportant,becauseitregulatesheartrateandbloodpressure,fluidretentionandkidneyfunctionand,ofcourse,bodytemperature.Ifthebodytemperaturegetstoohigh,itcancausebraindamageorevenkillaperson.

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SectionIII

1:Short-termeffectsafterecstasyisgonefromthebody

Ecstasyisanunusualdrugbecauseithaseffectsonthebrainthatdevelopandpersistforashorttimeafterthedrugiseliminatedfromthebody.Theseoftenincludethedevelopmentofdepression-likefeelings,anxiety,restlessness,irritability,andsleepdisturbances.These"aftereffects"occurbecauseofachemicalchangethattakesplaceattheserotoninsynapse.Toillustratehowthisoccurs,thisimageshowstheserotoninsynapseduringandaftertakingecstasy.Threeconditionsareillustrated:ontheleft,neuronsnormallyreleaseserotonininresponsetoelectricalimpulses(basicallythereleaseisin"spurts").Thisresultsinthenormalactivationofserotoninreceptors,whichkeepsourpsychologicalandphysiologicalfunctiononaneven

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keel.So,forexample,wehaveanormalmoodandwearecalm.Inthemiddle,ecstasycausesasustainedincreaseintheamountofserotonininthesynapticspace,leadingtosustainedactivationofmoreserotoninreceptors.Thiscanproduceanelevatedmood(oreuphoria).Eventually,theserotoninneuronscan'tmakeserotoninfastenoughtoreplacethatwhichwaslost,soonceEcstasyisgonefromthebody(ontheright),lessserotoninisreleasedwitheachelectricalimpulseandfewerserotoninreceptorsareactivated,producingdepression-likefeelingsandanxiety.Anotherimportanteffectthatmayemergeaftertakingecstasyismemorydisruption.(Askstudentsiftheycanfigureoutwhichareaofthebrainisaffectedhere;theanswershouldincludethecerebralcortexandthehippocampus).Thisisanadverseeffectthatmaypersistwithrepeatedorlong-termuseofecstasy.Indicatetostudentsthatthereissomeevidenceforthisobtainedfromhumanstudies.

2:Long-termeffectsofecstasy:neurotoxic?

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WhenpeopleuseEcstasyrepeatedlyorlongterm,theremaybechangesintheirbrainchemistrythatsuggestthattheserotoninneuronsaredamaged.Onemajorclueisthatserotoninitselfanditsmetabolites(remindstudentsthatserotoninthatistakenbackupintotheterminalismetabolizedbyenzymes)arediminishedinthebrainsofanimalstreatedwithecstasy.Moreover,thebestevidencethatwehavesofaristhatevensevenyearsafterabriefexposuretoecstasy,serotoninlevelsinmonkeybrainshavenotfullyreturnedtonormal.Thisisdescribedinthenextimage.

3:Long-termeffectsinmonkeys

Averyimportantexperimentwasperformedinmonkeystodetermineifecstasycanactuallydamageneurons.Monkeysweregivenecstasytwiceadayforfourdays(controlmonkeysweregivensaline).One

ImagecourtesyofDr.GARicaurte,JohnsHopkinsUniversitySchoolofMedicine.

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groupofmonkeys'brainswereremovedtwoweekslaterforanalysisandanothergroupofmonkeyslivedforanadditionalsevenyearsbeforetheirbrainswereremoved.Scientistsexaminedthebrainsforthepresenceofserotonin.Thisimageshowsthepresenceofserotonininneuronsoftheneocortexfromthreetypicalmonkeys.Ontheleft,themonkeywhodidnotreceiveanyecstasyhadalotofserotonin(inpink)intheneocortex.Twoweeksafteramonkeyreceivedecstasy,mostoftheserotoninwasgone(pointtothemiddlepanel),suggestingthattheserotoninneuronterminalsweredestroyed(therewasnodestructionoftheserotonincellbodiesarisingbackinthebrainstem).Pointtotheright-handpanelandshowstudentsthatthisdamageappearedtobelong-termbecausesevenyearslatertherewassomerecovery,butitwasnotcomplete.Scientistsfoundsimilarchangesinlimbicareasofthebrainsuchasthehippocampusandamygdala.Themonkeyexperimentsareanimportantreminderthathumansmaysufferthesamefate,althoughthisstillremainstobedemonstrated.Tellthestudentshowdifficultitistodothissamekindofexperimentinhumans,becauseitrequiresremovingpiecesofthebraintolookforthelossoftheserotoninneurons.

4:Ecstasycausesdegenerationofserotoninnerveterminals

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Thisimageillustratesthedegenerationofserotoninnerveterminalsafterlong-termorrepeateduseofecstasy(youcanreferbacktoimage9tocomparethisdegeneratingterminaltoahealthyterminal).Remindstudentsthatwehaveseveralpiecesofevidencethatsupportthiseffectofecstasy.Experimentsinanimalsgivenecstasyindicatethatthiskindofdegenerationoccurs.Moreover,somestudiesofhumanecstasyusersreportlessserotoninandserotoninmetabolitesinthecerebrospinalfluid(whichsurroundsandbathesthebrainandspinalcord)comparedwithnonusers.Incontrast,theanimalstudiesindicatethattheserotonincellbodiesarestillintactbutthegeneticinstructionsfromthenucleusforanyregrowthoftheterminalsmaybeabnormal.

Althoughscientistsdonotyetknowforcertainhowecstasydamagestheserotoninterminalsintheseanimalstudies,someprogresshasbeenmadeinunderstandingthisprocess.Onemechanismisdamagethatinvolvestheproductionofoxygenradicals(unstableformsofoxygen),whichareverydestructivetoproteins,lipids,andDNA.Therichsupplyofmitochondria(whichareamajorsourceofoxygenradical

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formation)foundintheterminalsmaycausetheterminalstobeespeciallysensitivetodrugslikeecstasy.

5:Long-termecstasyusemayimpairmemory

Itisnotpossibletolookdirectlyatdamagedserotoninterminalsinlivinghumans.Thebestevidencefordamagetoserotoninneuronsafterlong-termorrepeatedEcstasyuseinhumansistheassociationbetweentheneurochemicalandbehavioralchanges.AlthoughmanybehavioralmeasureshavebeenassessedinEcstasyusers(thelistisextensive),themostconsistentfindingsarethatsomechronicEcstasyusershaveverbalandvisualmemoryimpairments.Researchisongoingtodetermineifthinkingabilityisdisruptedaswell.However,itisimportanttokeepinmindthatmanyusersofEcstasymayunknowinglybetakingotherdrugsthataresoldasEcstasy,and/ortheymayintentionallyuseotherdrugs,suchasmarijuana,whichmay

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contributetotheobserveddeficitsinmemory.Additionally,moststudiesinpeopledonothavemeasuresofmemoryabilityinEcstasyusersbeforetheybegantakingdrugs.Therefore,itisdifficulttoruleoutpre-existingmemorydeficitsinEcstasyuserscomparedtononusers.Nevertheless,insomestudiesEcstasyuserswhohadmemoryimpairmentsalsohadlessserotoninmetabolitesorchangesinothermarkersofserotoninfunction.Infact,severalstudieshaveshownthatthedegreeofimpairmentorthechangesinmarkersofserotoninfunctionwererelatedtotheextentofEcstasyuseoverthelifetime.Ontheimage,pointtothebrainareasthatareinvolvedinthememoryimpairment-theneocortex(yellow)andthehippocampus(blue).[Asanaside,youcantellstudentsaninterestinglinkbetweenlowserotoninandmemoryimpairment:normalpeoplewhoarefedadietthatcausesthemtosynthesizelessserotoninalsohavememoryimpairment.]