Long-Term Neuropsychiatric Consequences of "Ecstasy" (MDMA): A Review

REFERENCES

• Christophersen AS. Amphetamine designer drugs—an overview and epidemiology. Toxicol Lett 2000;112–113:127–131.
   Google Scholar
• Steele TD, McCann UD, Ricaurte GA. 3,4-Methylenedioxy- methamphetamine (MDMA, “ecstasy”): pharmacology and toxi- cology in animals and humans. Addiction 1994;89:539–51.
   PubMed Web of Science ®Google Scholar
• Green AR, Cross AJ, Goodwin GM. Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethampheta- mine (MDMA or “ecstasy”). Psychopharmacology 1995;119:247–60.
   PubMed Web of Science ®Google Scholar
• Ricaurte GA, McCann UD. Assessing long-term effects of MDMA (ecstasy) [Letter]. Lancet 2001;358:1831–2.
   PubMed Web of Science ®Google Scholar
• Camí J, Farré M, Mas M, Roset PN, Poudevida S, Mas A, et al. Human pharmacology of 3,4-methylenedioxymethampheta- mine (“ecstasy”): psychomotor performance and subjective ef- fects. J Clin Psychopharmacol 2000;20:455–66.
   PubMed Web of Science ®Google Scholar
• Randall T. ‘Rave’ scene, ecstasy use, leap Atlantic. JAMA 1992; 268:1506.
   Google Scholar
• European Monitoring Centre for Drugs and Drug Addiction. An- nual report on the state of the drugs problem in the European Union. Luxembourg: Office for Official Publications of the Euro- pean Communities, 1998 [Available on the World Wide Web at http://www.emcdda.org/multimedia/publications/Annual_Report/ 1998/AR_98_EN.pdf].
   Google Scholar
• Massachusetts Department of Education. Illegal drug use. In: 1999 Massachusetts Youth Risk Behavior Survey [Available on the World Wide Web at http://www.doe.mass.edu/lss/yrbs99/ chapter4.html].
   Google Scholar
• Laviola G, Adriani W, Terranova ML, Gerra G. Psychobiological risk factors for vulnerability to psychostimulants in human ado- lescents and animal models. Neurosci Biobehav Rev 1999; 23:993–1010.
   PubMed Web of Science ®Google Scholar
• Pham JV, Puzantian T. Ecstasy: dangers and controversies. Pharmacotherapy 2001;21:1561–5.
   Google Scholar
• Liechti ME, Baumann C, Gamma A, Vollenweider FX. Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) are attenuated by the serotonin uptake in- hibitor citalopram. Neuropsychopharmacology 2000;22:513–21.
   PubMed Web of Science ®Google Scholar
• Vollenweider FX, Gamma A, Liechti M, Huber T. Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naive healthy volunteers. Neuropsycho- pharmacology 1998;19:241–51.
   PubMed Web of Science ®Google Scholar
• Kelly PA. Does recreational ecstasy use cause long-term cogni- tive problems? West J Med 2000;173:129–30.
   PubMedGoogle Scholar
• Martin TL. Three cases of fatal paramethoxyamphetamine over- dose. J Anal Toxicol 2001;25:649–51.
   PubMed Web of Science ®Google Scholar
• Sylvester B. Ecstacy [sic] heading for clinical trial: ‘club drug’ to be used in trauma test. HealthScout News, 14 November 2001 [Available on the World Wide Web at http://www.healthscout. com/template.asp?page=newsdetail'408&id=504729].
   Google Scholar
• Zimmerman R. FDA permits first test of ecstasy as treatment for stress disorder. Wall St J, 6 November 2001 [Available on the World Wide Web at http://www.mapinc.org/drugnews/v01/ n1894/a09.html].
   Google Scholar
• Ricaurte G, Bryan G, Strauss L, Seiden L, Shuster C. Hallucino- genic amphetamine selectively destroys brain serotonin nerve terminals. Science 1985;229:986–8.
   PubMed Web of Science ®Google Scholar
• Ricaurte GA, Martello AL, Katz JL, Martello MB. Lasting effects of (±)3,4-methylenedioxymethamphetamine (MDMA) on sero- tonergic neurons in nonhuman primates: neurochemical obser- vations. J Pharmacol Exp Ther 1992;261:616–22.
   PubMed Web of Science ®Google Scholar
• Ricaurte GA, Yuan J, McCann UD. (±)3,4-Methylene- dioxymethamphetamine (‘ecstasy’)–induced serotonin neuro- toxicity: studies in animals. Neuropsychobiology 2000;42:5–10.
   PubMed Web of Science ®Google Scholar
• Gouzoulis-Mayfrank E, Daumann J, Tuchtenhagen F, Pelz S, Becker S, Kunert HJ, et al. Impaired cognitive performance in drug free users of recreational ecstasy (MDMA). J Neurol Neu- rosurg Psychiatry 2000;68:719–25.
   PubMed Web of Science ®Google Scholar
• Burgess C, O’Donohoe A, Gill M. Agony and ecstasy: a review of MDMA effects and toxicity. Eur Psychiatry 2000;15:287–94.
   PubMed Web of Science ®Google Scholar
• McCann UD, Eligulashvili V, Ricaurte GA. (±)3,4-Methylene- dioxy-methamphetamine (‘ecstasy’)–induced serotonin neuro- toxicity: clinical studies. Neuropsychology 2000;42:11–6.
   Google Scholar
• Gerra G, Zaimovic A, Giucastro G, Maestri D, Monica C, Sar- tori R, et al. Serotonergic function after (±)3,4-methylene- dioxymethamphetamine (‘ecstasy’) in humans. Int Clin Psycho- pharmacol 1998;13:1–9.
   Google Scholar
• Verkes RJ, Gijsman HJ, Pieters MS, Schoemaker RC, De Visser S, Kuijpers M, et al. Cognitive performance and serotonergic function in users of ecstasy. Psychopharmacology 2001; 153:196–202.
   PubMed Web of Science ®Google Scholar
• Kish SJ, Furukawa Y, Ang L, Vorce SP, Kalasinsky KS. Striatial serotonin is depleted in brain of a human MDMA (ecstasy) user. Neurology 2000;55:294–6.
   PubMedGoogle Scholar
• Semple DM, Ebmeier KP, Glabus MF, O’Carroll RE, Johnstone EC. Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users. Br J Psychiatry 1999;75:63–9.
   Google Scholar
• Obrocki J, Buchert R, Väterlein O, Thomasius R, Beyer W, Schie- mann T. Ecstasy—long-term effects on the human central ner- vous system revealed by positron emission tomography. Br J Psychiatry 1999;175:186–8.
   Google Scholar
• McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA. Positron emission tomographic evidence of toxic effect of MDMA (“ecstasy”) on brain serotonin neurons in human beings. Lancet 1998;352:1433–7.
   PubMed Web of Science ®Google Scholar
• Chang L, Ernst T, Grob CS, Poland RE. Cerebral 1H MRS alter- ations in recreational 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) users. J Magn Reson Imaging 1999;10:521–6.
   PubMed Web of Science ®Google Scholar
• Reneman L, Booij J, Schmand B, Van den Brink W, Gunning B. Memory disturbances in “ecstasy” users are correlated with an altered brain serotonin neurotransmission. Psychopharmacol- ogy 2000;148:322–4.
   PubMed Web of Science ®Google Scholar
• Rodgers J. Cognitive performance amongst recreational users of “ecstasy.” Psychopharmacology 2000;151:19–24.
   PubMed Web of Science ®Google Scholar
• McGuire PK, Cope H, Fahy TA. Diversity of psychopathology as- sociated with the use of 3,4-methylenedioxymethamphetamine (‘ecstasy’). Br J Psychiatry 1994;165:391–5.
   PubMed Web of Science ®Google Scholar
• Reneman L, Booij J, De Bruin K, Reitsma JB, De Wolff FA, Gun- ning WB, et al. Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 2001;358:1864–9.
   Google Scholar
• Huether G, Zhou D, Rüther E. Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) and its congeners. J Neural Transm 1997;104:771–94.
   PubMed Web of Science ®Google Scholar
• Shulgin AT. The background and chemistry of MDMA. J Psycho- active Drugs 1986;18:291–304.
   PubMed Web of Science ®Google Scholar
• Haase J, Killian AM, Magnani F, Williams C. Regulation of the serotonin transporter by interacting proteins. Biochem Soc Trans 2001;29:722–8.
   Google Scholar
• Gudelsky GA, Nash JF. Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions. J Neurochem 1996;66:243–9.
   PubMed Web of Science ®Google Scholar
• Sprague JE, Everman SL, Nichols DE. An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylene- dioxymethamphetamine. Neurotoxicology 1998;19:427–41.
   PubMed Web of Science ®Google Scholar
• Morgan MJ. Ecstasy (MDMA): a review of its possible persistent psychological effects. Psychopharmacology 2000;152:230–48.
   PubMed Web of Science ®Google Scholar
• Schifano F, Di Furia L, Forza G, Minicuci N, Bricolo R. MDMA (‘ecstasy’) consumption in the context of polydrug abuse: a report on 150 patients. Drug Alcohol Depend 1998;52:85–90.
   Google Scholar
• Hernández-López C, Farré M, Roset PN, Menoyo E, Pizarro N, Ortuno J, et al. 3,4-Methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther 2002;300:236–44.
   PubMed Web of Science ®Google Scholar
• Gerra G, Zaimovic A, Ferri M, Zambelli U, Timpano M, Neri E, Marzocchi GF, et al. Long-lasting effects of (±)3,4-methylene- dioxymethamphetamine (ecstasy) on serotonin system function in humans. Biol Psychiatry 2000;47:127–36.
   PubMed Web of Science ®Google Scholar
• Bolla KI, McCann UD, Ricaurte GA. Memory impairment in abstinent MDMA (“ecstasy”) users. Neurology 1998;51:1532–7.
   PubMed Web of Science ®Google Scholar
• Zakzanis KK, Young DA. Memory impairment in abstinent MDMA (“ecstasy”) users: a longitudinal investigation. Neurol- ogy 2001;56:966–9.
   PubMed Web of Science ®Google Scholar
• Krystal JH, Price LH, Opsahl C, Ricaurte GA, Heninger GR. Chronic 3,4-methylenedioxymethamphetamine (MDMA) use: effects on mood and neuropsychological function? Am J Drug Al- cohol Abuse 1992;18:331–41.
   PubMed Web of Science ®Google Scholar
• Wareing M, Fisk JE, Murphy PN. Working memory deficits in current and previous users of MDMA (‘ecstasy’). Br J Psychol 2000;91:181–8.
   PubMed Web of Science ®Google Scholar
• Parrott AC. Human research on MDMA (3,4-methylene- dioxymethamphetamine) neurotoxicity: cognitive and behav- ioural indices of change. Neuropsychobiology 2000;42:17–24.
   PubMed Web of Science ®Google Scholar
• Fox HC, Parrott AC, Turner JJ. Ecstasy use: cognitive deficits re- lated to dosage rather than self-reported problematic use of the drug. J Psychopharmacol 2001;15:273–81.
   PubMed Web of Science ®Google Scholar
• Altman HJ, Normile HJ. What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile de- mentia. Neurobiol Aging 1988;9:627–38.
   PubMed Web of Science ®Google Scholar
• Colado MI, Murray TK, Green AR. 5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p- chloroamphetamine and fenfluramine administration and ef- fects of chlormethiazole and dizocilpine. Br J Pharmacol 1993; 108:583–9.
   PubMed Web of Science ®Google Scholar
• Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, et al. Association of dopamine transporter reduc- tion with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 2001;158:377–82.
   PubMed Web of Science ®Google Scholar
• Pedersen W, Skrondal A. Ecstasy and new patterns of use: a nor- mal population study. Addiction 1999;94:1695–706.
   PubMed Web of Science ®Google Scholar
• McCann UD, Ricaurte GA. Lasting neuropsychiatric sequelae of 3,4-methylenedioxymethamphetamine (“ecstasy”) in recre- ational users. J Clin Psychopharmacol 1991;11:302–5.
   PubMedGoogle Scholar
• Morland J. Toxicity of drug abuse—amphetamine designer drugs (ecstasy): mental effects consequences of single dose use. Toxicol Lett 2000;112–113:147–52.
   Google Scholar
• Bailly D. Neuropsychiatric disorders induced by MDMA [In French, with an English abstract]. Encephale 1999;25:595–602.
   Google Scholar
• McGuire P. Long term psychiatric and cognitive effects of MDMA use. Toxicol Lett; 2000;112–113:153–6.
   Google Scholar
• Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. Can Med Assoc J 2001;165:917–28.
   PubMed Web of Science ®Google Scholar
• Allen RP, McCann UD, Ricaurte GA. Persistent effects of (±)3,4 methylenedioxymethamphetamine (MDMA, “ecstasy”) on hu- man sleep. Sleep 1993;16:560–4.
   PubMed Web of Science ®Google Scholar
• Henry JA, Jeffreys KJ, Dawling S. Toxicity and deaths from 3,4- methylenedioxymethamphetamine (“ecstasy”). Lancet 1992; 340:384–7.
   PubMed Web of Science ®Google Scholar
• Teter CJ, Guthrie SK. A comprehensive review of MDMA and GHB: two common club drugs. Pharmacotherapy 2001;21:1486–513.
   PubMed Web of Science ®Google Scholar
• Holmes SB, Banerjee AK, Alexander WD. Hyponatremia and seizures after ecstasy use. Postgrad Med J 1999;75:32–43.
   PubMed Web of Science ®Google Scholar
• Reneman L, Habraken JB, Majoie CB, Booij J, Den Heeten GJ. MDMA (“ecstasy”) and its association with cerebrovascular accidents: preliminary findings. Am J Neuroradiol 2000;21:1001–7.
   PubMed Web of Science ®Google Scholar
• Harries DP, De Silva R. ‘Ecstasy’ and intracerebral haemor- rhage. Scott Med J 1992;37:150–2.
   Google Scholar
• Bitsch A, Thiel A, Rieckmann P, Prange H. Acute inflammatory CNS disease after MDMA (‘ecstasy’). Eur Neurol 1996;36:328–9.
   Google Scholar
• Bertram M, Egelhoff T, Schwarz S, Schwab S. Toxic leuken- cephalopathy following “ecstasy” ingestion [Letter]. J Neurol 1999;246:617–8.
   Google Scholar
• Gamma A, Frei E, Lehmann D, Pascual-Marqui RD, Hell D, Vol- lenweider FX. Mood state and brain electric activity in ecstasy users. Neuroreport 2000;11:157–62.
   Google Scholar
• Schreckenberger M, Gouzoulis-Mayfrank E, Sabri O, Arning C, Zimny M, Zeggel T, et al. “Ecstasy”-induced changes of cerebral glucose metabolism and their correlation to acute psychopathol- ogy: an 18FDG PET study. Eur J Nucl Med 1999;26:1572–9.
   PubMedGoogle Scholar
• Galynker II, Cai J, Ongseng F, Finestone H, Dutta E, Serseni D. Hypofrontality and negative symptoms in major depressive dis- order. J Nucl Med 1998;39:608–12.
   PubMed Web of Science ®Google Scholar
• Andreasen NC, O’Leary DS, Cizadlo T, Arndt S, Rezai K, Ponto LL, et al. Schizophrenia and cognitive dysmetria: a positron- emission tomography study of dysfunctional prefrontal- thalamic-cerebellar circuitry. Proc Natl Acad Sci USA 1996; 93:9985–90.
   PubMed Web of Science ®Google Scholar
• Schmahmann JD, Sherman JC. The cerebellar cognitive affec- tive syndrome. Brain 1998;121:561–79.
   PubMed Web of Science ®Google Scholar
• Ricaurte GA, MacCann UD, Szabo Z, Scheffel U. Toxicody- namics and long-term toxicity of the recreational drug, 3,4- methylenedioxymethamphetamine (MDMA, ‘ecstasy’). Toxicol Lett 2000;112–113:143–6.
   Google Scholar
• Graeff FG. Role of 5-HT in defensive behavior and anxiety. Rev Neurosci 1993;4:181–211.
   PubMedGoogle Scholar
• Sarter M, Markowitsch HJ. Involvement of the amygdala in learning and memory: a critical review, with emphasis on anatomical relations. Behav Neurosci 1985;99:342–80.
   PubMed Web of Science ®Google Scholar
• Aggleton JP, Brown MW. Episodic memory, amnesia, and the hippocampal–anterior thalamic axis. Behav Brain Sci 1999; 22:425–89.
   PubMed Web of Science ®Google Scholar
• Cummings JL. Frontal-subcortical circuits and human behav- ior. Arch Neurol 1993;50:873–80.
   PubMed Web of Science ®Google Scholar
• Buchert R, Obrocki J, Thomasius R, Väterlein O, Petersen K, Jenicke L, et al. Long-term effects of ‘ecstasy’ abuse on the hu- man brain studied by FDG PET. Nucl Med Commun 2001; 22:889–97.
   PubMed Web of Science ®Google Scholar
• Gruber E, DiClemente RJ, Anderson MM, Lodico M. Early drinking onset and its association with alcohol use and problem behavior in late adolescence. Prev Med 1996;25:293–300.
   PubMed Web of Science ®Google Scholar
• Robins LN, Przybeck TR. Age of onset of drug use as a factor in drug and other disorders. NIDA Res Monogr 1985;56:178–92.
   PubMedGoogle Scholar
• Chugani HT, Muller RA, Chugani DC. Functional brain re- organization in children. Brain Dev 1996;18:347–56.
   PubMed Web of Science ®Google Scholar
• Huttenlocher PR. Synaptic density in human frontal cortex— developmental changes and effects of aging. Brain Res 1979; 163:195–205.
   PubMed Web of Science ®Google Scholar
• Benes FM. Brain development, VII: Human brain growth spans decades. Am J Psychiatry 1998;155:1489.
   PubMed Web of Science ®Google Scholar
• Filley CM, Price BH, Nell V, Antoinette T, Morgan AS, Bresna- han JF, et al. Toward an understanding of violence: neurobehav- ioral aspects of unwarranted physical aggression. Neuropsychi- atry Neuropsychol Behav Neurol 2001;14:1–14.
   PubMedGoogle Scholar
• Bezard E, Dovero S, Prunier C, Ravenscroft P, Chalon S, Guil- loteau D, et al. Relationship between the appearance of symp- toms and the level of nigrostriatal degeneration in a progressive 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine–lesioned macaque model of Parkinson’s disease. J Neurosci 2001;21:6853–61.
   Google Scholar
• Scheffel U, Szabo Z, Mathews WB, Finley PA, Dannals RF, Ravert HT, et al. In vivo detection of short- and long-term MDMA neurotoxicity—a positron emission tomography study in the living baboon brain. Synapse 1998;29:183–92.
   PubMedGoogle Scholar
• Hunter AJ. Serotonergic involvement in learning and memory. Biochem Soc Trans 1998;17:79–81.
   Google Scholar
• Durig J, Hornung JP. Neonatal serotonin depletion affects de- veloping and mature mouse cortical neurons. Neuroreport 2000;11:833–7.
   Google Scholar
• Ballard PA, Tetrud JW, Langston JW. Permanent human parkinsonism due to l-methyl-4-phenyl-1,2,3,6-tetrahydropyri- dine (MTPT): seven cases. Neurology 1985;35:949–56.
   PubMed Web of Science ®Google Scholar
• Calne DB, Langston JW, Martin WR, Stoessl AJ, Ruth TJ, Adam MJ, et al. Positron emission tomography after MTPT: observa- tions relating to the cause of Parkinson’s disease. Nature 1985;317:246–8.
   PubMed Web of Science ®Google Scholar