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3,4-methylenedioxymethamphetamine (mdma): A review

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Abstract

This article reviews the history, pharmacology, and adverse events associated with the use of 3,4-methylenendioxymethamphetamine (MDMA), commonly known as Ecstasy. Past research describing the neurotoxic effects of MDMA in animals, current research on the neurotoxic effects of MDMA in humans, and the attendant changes in psychologic functioning will be highlighted in this review. Finally, the limitations of human research on the effects of MDMA and suggestions for future MDMA research will be discussed.

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References and Recommended Reading

  1. Zickler P: Annual Survey Finds Increasing Teen use of Ecstasy, Steroids, 2001. This survey of school age students found that from 1999 to 2000, Ecstasy use increased in eighth-graders and 12th-graders from 1.7% to 3.1% and from 3.6% to 5.6%, respectively. This annual survey examined 45,000 school age students nationwide.

  2. Shulgin A: The background and chemistry of MDMA. J Psychoactive Drugs 1986, 18:291–304.

    PubMed  CAS  Google Scholar 

  3. Greer G, Strassman R: Information on Ecstasy. Am J Psychiatry 1985, 142:1391.

    PubMed  CAS  Google Scholar 

  4. Greer G, Tolbert R: Subjective reports of the effects of MDMA in a clinical setting. J Psychoactive Drugs 1986, 18:319–327.

    PubMed  CAS  Google Scholar 

  5. Nichols D: Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J Psychoactive Drugs 1986, 18:305–313.

    PubMed  CAS  Google Scholar 

  6. Ricaurte G, Bryan G, Strauss L, et al.: Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals. Science 1985, 229:986–988.

    Article  PubMed  CAS  Google Scholar 

  7. Barnes D: Ecstasy returns to schedule I. Science 1988, 240:24.

    Article  PubMed  CAS  Google Scholar 

  8. Randall T: Ecstasy-fueled "rave" parties become dances of death for English youths. Med News Perspect 1992, 268:1505–1506.

    CAS  Google Scholar 

  9. Millman R, Beeder B: The new psychedelic culture: LSD, Ecstasy, "rave" parties and The Grateful Dead. Psychiatr Ann 1994, 24:148–150.

    Google Scholar 

  10. Weir E: Raves: a review of the culture, the drugs and the prevention of harm. CMAJ 2000, 162:1843–1848.

    PubMed  CAS  Google Scholar 

  11. Randall T: "Rave" scene, Ecstasy use, leap Atlantic. JAMA 1992, 268:1506.

    Article  PubMed  CAS  Google Scholar 

  12. Peroutka S: Incidence of recreational use of 3,4-methylenedimethoxymethamphetamine (MDMA, "Ecstasy") on an undergraduate campus. N Engl J Med 1987, 317:1542–1543.

    PubMed  CAS  Google Scholar 

  13. Riley S, James C, Gregory D, et al.: Patterns of recreational drug use at dance events in Edinburgh, Scotland. Addiction 2001, 96:1035–1047.

    Article  PubMed  CAS  Google Scholar 

  14. Schuckit M: MDMA (Ecstasy): an old drug with new tricks. Drug Abuse Alcohol Newsletter 1994, 23:1–4.

    Google Scholar 

  15. Morgan M: Ecstasy (MDMA): a review of its possible persistent psychological effects. Psychopharmacology 2000, 152:230–248.

    Article  PubMed  CAS  Google Scholar 

  16. Helmlin H-J, Bracher K, Bourquin D, et al.: Analysis of 3, 4-methylenedioxymethamphetamine (MDMA) and its metabolites in plasma and urine by HPLC-DAD and GC-MS. J Anal Toxicol 1996, 20:432–440.

    PubMed  CAS  Google Scholar 

  17. Zhao H, Brenneisen R, Scholer A, et al.: Profiles of urine samples taken from Ecstasy users at rave parties: analysis by immunoassays, HPLC, and GC-MS. J Anal Toxicol 2001, 25:258–269.

    PubMed  CAS  Google Scholar 

  18. Pacifici R, Farre M, Pichini S, et al.: Sweat testing of MDMA with the Drugwipe Analytical Device: a controlled study with two volunteers. J Anal Toxicol 2001, 25:144–146. MDMA and its metabolites are not easily detected in human bodily fluids. In this study, immunochemical strips applied to two human subjects between 2 and 12 hours after initial ingestion of MDMA were able to detect MDMA in its metabolites in their sweat, suggesting that the immunochemical strips may be an effective means of rapidly detecting this substance in humans suspected of ingesting MDMA.

    PubMed  CAS  Google Scholar 

  19. Battaglia G, Yeh S, O’Hearn E, et al.: 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetinelabeled serotonin uptake sites. J Pharmacol Exp Ther 1987, 242:911–916.

    PubMed  CAS  Google Scholar 

  20. O’Hearn E, Battaglia G, De Souza E, et al.: Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity. J Neurosci 1988, 8:2788–2803.

    PubMed  CAS  Google Scholar 

  21. Slikker W Jr, Ali S, Scallet A, et al.: Neurochemical and neurohistiological slterations in the rat and monkey produced by orally administered methylenedioxymethamphetamine (MDMA). Toxicol Appl Pharmacol 1988, 94:448–457.

    Article  PubMed  CAS  Google Scholar 

  22. McCann U, Ridenour A, Shaham Y, Ricaurte G: Serotonin neurotoxicity after (+/-) 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans. Neuropsychopharmacology 1994, 10:129–138.

    PubMed  CAS  Google Scholar 

  23. McCann U, Szabo Z, Scheffel U, et al.: Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on brain serotonin neurons in human beings. Lancet 1998, 352:1433–1437.

    Article  PubMed  CAS  Google Scholar 

  24. Stone D, Stahl D, Hanson G, Gibb J: The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3, 4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. Eur J Pharmacol 1986, 128:41–48.

    Article  PubMed  CAS  Google Scholar 

  25. Lyon R, Glennon R, Titeler M: 3,4-methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors. Psychopharmacology 1986, 88:525–526.

    Article  PubMed  CAS  Google Scholar 

  26. Steele T, Nichols D, Yim G: Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochem Pharmacol 1987, 36:2297–2303.

    Article  PubMed  CAS  Google Scholar 

  27. Schmidt C, Taylor V: Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol 1987, 36:4095–4102.

    Article  PubMed  CAS  Google Scholar 

  28. Stone D, Merchant K, Hanson G, Gibb J: Immediate and longterm effects of 3,4-methylenedioxymethamphetamine on serotonin pathways in brain of rat. Neuropharmacology 1987, 26:1677–1683.

    Article  PubMed  CAS  Google Scholar 

  29. Meltzer H, Lowy M: The serotonin hypothesis of depression. In Psychopharmacology: The Third Generation of Progress. Edited by Meltzer H. New York: Raven Press; 1987.

    Google Scholar 

  30. Davidson D, Parrott A: Ecstasy (MDMA) in recreational users: self-report psychological and physiological effects. Hum Psychopharmacol 1997, 12:221–226.

    Article  Google Scholar 

  31. Liester M, Grob C, Bravo G, Walsh R: Phenomenology and sequelae of 3,4-methylenedioxymethampethamine use. J Nerv Ment Dis 1992, 180:345–352.

    Article  PubMed  CAS  Google Scholar 

  32. Siegel R: MDMA: nonmedical use and intoxication. J Psychoactive Drugs 1986, 18:349–354.

    PubMed  CAS  Google Scholar 

  33. Solowij N, Hall W, Lee N: Recreational MDMA use in Sydney: a profile of ‘Ecstasy’ users and their experiences with the drug. Br J Psychiatry 1992, 87:1161–1172.

    CAS  Google Scholar 

  34. Dowling G, McDouough E, Bost R: "Eve" and "Ecstasy": a report of five deaths associated with the use of MDA and MDMA. JAMA 1987, 257:1615–1617.

    Article  PubMed  CAS  Google Scholar 

  35. Lukaszewski T: 3,4-methylenedioxyamphetamine overdose. Clin Toxicol 1979, 15:405–409.

    PubMed  CAS  Google Scholar 

  36. Poklis A, Mackell M, Drake W: Fatal intoxication from 3,4-methylenedioxyamphetamine. J Forensic Sci 1979, 24:70–75.

    PubMed  CAS  Google Scholar 

  37. Reed D, Cravey R, Sedgwick P: A fatal case involving methylenedioxyamphetamine. Clin Toxicol 1972, 5:3–6.

    PubMed  CAS  Google Scholar 

  38. Campkin N, Davies U: Another death from Ecstasy. J R Soc Med 1992, 85:61.

    PubMed  CAS  Google Scholar 

  39. Coore J: A fatal trip with Ecstasy: a case of 3,4-methylenedioxymethamphetamine/ 3,4-methylenedioxyamphetamine toxicity. J R Soc Med 1996, 89:51–52.

    Google Scholar 

  40. Maxwell D, Polkey M, Henry J: Hyponatraemia and catatonic stupor after taking Ecstasy. BMJ 1993, 307:1399.

    PubMed  CAS  Google Scholar 

  41. Chadwick I, Linsley A, Freemont A, et al.: Ecstasy, 3,4-methylenedioxymethamphetamine (MDMA), a fatality associated with coagulopathy and hyperthermia. J Royal Soc Med 1991, 84:371.

    CAS  Google Scholar 

  42. Dykhuizen R, Brunt P, Atkinson P, et al.: Ecstasy induced hepatitis mimicking viral hepatitis. Gut 1995, 36:939–941.

    PubMed  CAS  Google Scholar 

  43. Fidler H, Dhillon A, Gertner D, Burroughs A: Chronic Ecstasy (3,4-methylenedioxymethamphetamine) abuse: a recurrent and unpredictable cause of severe acute hepatitis. J Hepatol 1996, 25:563–566.

    Article  PubMed  CAS  Google Scholar 

  44. Khakoo S, Coles C, Armstrong J, Barry R: Hepatotoxicity and accelerated fibrosis following 3,4-methylenedioxymethamphetamine (Ecstasy) usage. J Clin Gastroenterol 1995, 20:244–247.

    Article  PubMed  CAS  Google Scholar 

  45. Gledhill J, Moore D, Bell D, Henry J: Subarachnoid hemorrhage associated with MDMA abuse. J Neurol Neurosurg Psychiatry 1993, 56:1036–1037.

    PubMed  CAS  Google Scholar 

  46. Hanyu A, Ikeguchi K, Imai H, et al.: Cerebral infarction associated with 3,4-methylenedioxymethamphetamine (Ecstasy) abuse. Eur Neurol 1995, 35:173.

    PubMed  CAS  Google Scholar 

  47. Duflou J, Mark A: Aortic dissection after ingestion of Ecstasy MDMA. Am J Forensic Med Pathol 2000, 21:261–263.

    Article  PubMed  CAS  Google Scholar 

  48. Suarez R, Riemersma R: Ecstasy and sudden cardiac death. Am J Forensic Med Pathol 1988, 9:339–341.

    PubMed  CAS  Google Scholar 

  49. Coccaro E, Siever L, Klar H, et al.: Serotonergic studies in patients with affective and personality disorders. Arch Gen Psychiatry 1989, 46:587–599.

    PubMed  CAS  Google Scholar 

  50. Benazzi F, Mazzoli M: Psychiatric illness associated with Ecstasy. Lancet 1991, 338:1520.

    Article  PubMed  CAS  Google Scholar 

  51. Curran H, Travill R: Mood and cognitive effects of +/− 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy): weekend-end "high" followed by mid-week low. Addiction 1997, 92:821–831.

    Article  PubMed  CAS  Google Scholar 

  52. Krystal J: Chronic 3,4-methylenedioxymethamphetamine (MDMA) use: effects on mood and neuropsychological function? Am J Drug Alcohol Abuse 1992, 18:331–341.

    PubMed  CAS  Google Scholar 

  53. McCann U, Ricaurte G: Lasting neuropsychiatric sequelae of (+/-) methylenedioxymethamphetamine (Ecstasy) in recreational use. J Clin Psychopharmacol 1991, 11:302–305.

    Article  PubMed  CAS  Google Scholar 

  54. McGuire P, Cope H, Fahy T: Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine (Ecstasy). Br J Psychiatry 1994, 165:391–395.

    PubMed  CAS  Google Scholar 

  55. Parrott A, Lasky J: Ecstasy (MDMA) effects on mood and cognition: before, during and after a Saturday night dance. Psychopharmacology 1998, 139:261–268.

    Article  PubMed  CAS  Google Scholar 

  56. Schifano F, Di Furia L, Minicuci N, Briolo R: MDMA (Ecstasy) consumption in the context of polydrug use: a report on 150 patients. Drug Alcohol Depend 1998, 52:85–90.

    Article  PubMed  CAS  Google Scholar 

  57. Cassidy G, Ballard C: Psychiatric sequelae of MDMA (Ecstasy) and related drugs. Ir J Psychol Med 1994, 11:132–133.

    Google Scholar 

  58. Creighton F, Black D, Hyde C: Ecstasy psychosis and flashbacks. Br J Psychiatry 1991, 159:713–715.

    PubMed  CAS  Google Scholar 

  59. McGuire P, Fahy T: Chronic paranoid psychosis after misuse of MDMA (Ecstasy). BMJ 1991, 302:697.

    PubMed  CAS  Google Scholar 

  60. Schifano F: Chronic atypical psychosis associated with MDMA (Ecstasy) abuse. Lancet 1991, 338:1335.

    Article  PubMed  CAS  Google Scholar 

  61. Vaiva G, Boss V, Bailly D, et al.: An "accidental" acute psychosis with Ecstasy use. J Psychoactive Drugs 2001, 33:95–98. This case study presented one individual who experienced an acute episode of psychosis characterized by delusions and violent behavior 12 hours after ingesting MDMA. Although he had no previously known psychiatric history, he met criteria for mild major depression with some psychotic symptoms 6 months after taking MDMA.

    PubMed  CAS  Google Scholar 

  62. Parrott A, Sisk E, Turner J: Psychobiological problems in heavy ‘Ecstasy’ (MDMA) polydrug users. Drug Alcohol Depend 2000, 60:105–110. In this study using clinical symptoms self-assessment scales to compare a group of heavy MDMA users with a non-MDMA using control group, heavy users had significantly greater levels of anxiety, paranoid ideation, anorexia, somatization, obsessionality, psychoticism, and disturbed sleep patterns than did controls. Light MDMA users had intermediate symptom on the majority of self-assessment scores when compared with controls except on measures of paranoid ideation and psychoticism. The authors suggest those early indicators (psychoticism and paranoia) of developing psychiatric disorders present in light users may continue with continued MDMA use.

    Article  PubMed  CAS  Google Scholar 

  63. Pallanti S, Mazzi D: MDMA (Ecstasy) precipitation of panic disorder. Biol Psychiatry 1992, 32:91–95.

    Article  PubMed  CAS  Google Scholar 

  64. Whitaker-Azmitia P, Aronson T: Ecstasy (MDMA)-induced panic. Am J Psychiatry 1989, 146:119.

    PubMed  CAS  Google Scholar 

  65. Morgan M: Recreational use of Ecstasy (MDMA) is associated with elevated impulsivity. Neuropsychopharmacology 1998, 19:252–264. A group of 16 MDMA users was compared with 1) a group of 12 non-MDMA users with substance use and personal histories comparable to the MDMA users, and 2) a group of 16 non-substance-using controls. Using the Impulsiveness, Venturesomeness, and Empathy Scale (IVE), a significant difference between the MDMA group and the other groups was seen on measures of impulsiveness but no significant differences were reported on other scale measures.

    Article  PubMed  CAS  Google Scholar 

  66. Commins D, Vosmer G, Virus R, et al.: Biochemical and histological evidence that methylenedioxymethamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther 1987, 241:338–345.

    PubMed  CAS  Google Scholar 

  67. Schmidt C: Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J Pharmacol Exp Ther 1987, 240:1–7.

    PubMed  CAS  Google Scholar 

  68. Ricaurte G, Forno L, Wilson M, et al.: (+/-) 3,4-methylenedioxymethamphetmine selectively damages central sertonergic neurons in nonhuman primates. JAMA 1988, 260:51–55.

    Article  PubMed  CAS  Google Scholar 

  69. Insel T, Battaglia G, Johannessen J, et al.: 3,4-methylenedioxymethamphetamine (Ecstasy) selectively destroys brain serotonin terminals in Rhesus monkeys. J Pharmacol Exp Ther 1989, 249:713–720.

    PubMed  CAS  Google Scholar 

  70. Ricaurte G, Martello A, Katz J, Martello M: Lasting effects of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: neurochemical observations. J Pharmacol Exp Ther 1992, 261:616–622.

    PubMed  CAS  Google Scholar 

  71. Peroutka S, Pascoe N, Faull K: Monoamine metabolites in the cerebrospinal fluid of recreational users of 3,4-methylenedioxymethamphetamine. Res Commun Substance Abuse 1987, 8:125–138.

    Google Scholar 

  72. Ricaurte G, Finnegan K, Irwin I, Langston J: Aminergic metabolites in cerebrospinal fluid of humans previously exposed to MDMA: preliminary observations. Ann N Y Acad Sci 1990, 600:699–710.

    Article  PubMed  CAS  Google Scholar 

  73. Price L, Ricaurte G, Krystal J, Heninger G: Neuroendocrineand mood responses to intravenous L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users. Arch Gen Psychiatry 1989, 46:20–22.

    PubMed  CAS  Google Scholar 

  74. Verkes R, Gijsman H, Pieters M, et al.: Cognitive performance and serotonergic function in users of Ecstasy. Psychopharmacology 2001, 153:196–202.

    Article  PubMed  CAS  Google Scholar 

  75. Semple D, Ebmeier K, Glabus M, et al.: Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA (Ecstasy) users. Br J Psychiatry 1999, 175:63–69. In this study, 10 long-term Ecstasy users and 10 non-Ecstasy using but substance using controls were administered a serotonin transporter ligand before undergoing neuroimaging with single photon emission computed tomography (SPECT). Diminished binding to cortical serotonin transporters was found in long-term Ecstasy users compared with controls that used substances other than Ecstasy.

    PubMed  CAS  Google Scholar 

  76. Obrocki J, Buchert R, Vaterlein O, et al.: Ecstasy-long-term effects on the human central nervous system revealed by positron emission tomography. Br J Psychiatry 1999, 175:186–188. This neuroimaging study used positron emission tomography (PET) and 2-[18F]-fluoro-2-deoxy-d-glucose to examine glucose metabolism, an indicator of neuronal activity, in seven Ecstasy users who had not used the substance for 2 to 16 months and seven non-substance using controls. Decreased glucose metabolism in the neurons of the hippocampus, amygdala, and cingulate was seen in the abstinent Ecstasy users compared with the non-substance using controls.

    Article  PubMed  CAS  Google Scholar 

  77. Buchert R, Obrocki J, Thomasius R, et al.: Long-term effects of Ecstasy abuse on the human brain studied by FDG PET. Nucl Med Commun 2001, 22:889–897. In this study using PET, 93 Ecstasy users who had taken approximately 483 Ecstasy tablets for approximately 20 years (last use 6.5 months prior to the study) demonstrated decreased FDG uptake in the striatum, cingulate, amygdala, cortex, and hippocampus, bilaterally when compared with 27 non-substance using controls. Greater reductions in 2-[18F]-fluoro-2-deoxy-d-glucose uptake were seen in those began using Ecstasy before the age of 18.

    Article  PubMed  CAS  Google Scholar 

  78. Curren H: Is MDMA neurotoxic in humans? An overview of evidence and of methodological problems in research. Neuropsychobiology 2000, 42:34–41.

    Article  Google Scholar 

  79. Baggott M, Heifets B, Jones R, et al.: Chemical analysis of Ecstasy pills. JAMA 2000, 284:2190. In this study 107 Ecstasy tablets were examined for their content by GCMS. MDMA or its analogues, MDEA and MDA, were found in 67 tablets although 31 tablets contained no MDMA, but other identifiable substances including dextromethorphan, caffeine, ephedrine, pseudoephedrine, and salicylates. Nine tablets contained no identifiable drug at all.

    Article  PubMed  CAS  Google Scholar 

  80. Sherlock K, Wolff K, Hay A, Conner M: Analysis of illicit Ecstasy tablets: implications for clinical management in the accident and emergency departments. J Accid Emerg Med 1999, 16:194–197. Twenty-five Ecstasy tablets were analyzed for content by gas chromatography. Of the 25 tablets, 12 tablets contained MDMA, four tablets contained MDEA, and the other 9 contained no MDMA, but instead contained varying amounts of caffeine, amphetamine, ephedrine, ketamine, and paracetamol.

    PubMed  CAS  Google Scholar 

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  1. Harvard Medical School, Alcohol and Drug Abuse Treatment Program, McLean Hospital, 115 Mill Street, 02478, Belmont, MA, USA

    Grace O’Leary MD, Jessica Nargiso MA & Roger D. Weiss MD

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  1. Grace O’Leary MD
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  2. Jessica Nargiso MA
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  3. Roger D. Weiss MD
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O’Leary, G., Nargiso, J. & Weiss, R.D. 3,4-methylenedioxymethamphetamine (mdma): A review. Curr Psychiatry Rep 3, 477–483 (2001). https://doi.org/10.1007/s11920-001-0041-y

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