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Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs pp 161–172Cite as

Pharmacokinetics of MDMA

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Abstract

Effects of MDMA usually begin 30–45 min after oral administration of a 75–150 mg dose with peak effects occurring 60–90 min after ingestion, which start to diminish after 2 h, however lasting up to 8 h (Table 3). The time to maximum concentration (Tmax) is 2 h after oral ingestion of MDMA 50, 75, or 125 mg. The half-life shows little variation after a wide range of doses. After a 50-, 75-, or 125-mg dose, the half-life is 8 h [49]. Other studies found the half-life to be 9.53 h after a 75-mg dose and 9.12 h after a 125-mg dose [50]. The maximum concentration (Cmax) after oral ingestion appears to be dose dependent. A Cmax of 105.6 ng/ml was reported in a single subject who took a 50-mg dose [51], whereas a Cmax of 330 ng/ml was found in another subject who took MDMA 135 mg [52]. In a group of eight subjects, the Cmax values after ingestion of MDMA 75 mg and 125 mg were 126.5 and 226.3 ng/ml, respectively [50], whereas in another group of eight subjects, Cmax values of 130.9 and 236.4 ng/ml were obtained after ingestion of MDMA 75 mg and 125 mg, respectively [49]. These studies indicate, that the Cmax exhibits a slightly greater-than-expected increase compared with the increase in dose. According to these observations, and following a usual recreational dose of 100–150 mg, the Cmax should be in the range of 200–300 ng/ml. The area under the concentration-time curve (AUC) data from these studies also suggests nonlinearity. The AUC measured over 24 h after ingestion of a 125-mg dose (2,235.9 µg/l/h) is more than twice the AUC after ingestion of a 75-mg dose (995.4 µg/l/h [50]. Nonlinearity is further supported by other evidence, in which the dose ratio of MDMA was 1:3 (50 mg and 150 mg), whereas the AUC ratio over 24 h after ingestion was greater than 1:10. The authors suggested that the non-renal clearance of MDMA is dose dependent.

Keywords

  • Disseminate Intravascular Coagulation
  • Disseminate Intravascular Coagulation
  • Neuroleptic Malignant Syndrome
  • Malignant Hyperthermia
  • MDMA User

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Hiramatsu M, Kumagai Y, Unger SE, Cho AK. Metabolism of methylenedioxymethamphetamine: formation of dihydroxy-methamphetamine and a quinone identified as its glutathione adduct. J Pharmacol Exp Ther. 1990;25:521–527.

    Google Scholar 

  2. Tucker GT, Lennard MS, Ellis SW, et al. The demethylenation of methylenedioxymethamphetamine (“Ecstasy”) by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol. 1994;47:1151–1156.

    CrossRef  PubMed  CAS  Google Scholar 

  3. Mas M, Farre M, de la Torre R, et al. Cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther. 1999;290:136–145.

    PubMed  CAS  Google Scholar 

  4. Cami J, de la Torre R, Ortuno J, et al. Pharmacokinetics of ecstasy (MDMA) in healthy subjects . Eur J Clin Pharmacol. 1997;52:A168.

    Google Scholar 

  5. Verebey K, Alrazi J, Jaffee JH. The complications of ‘Ecstasy’ (MDMA). JAMA. 1988;259:1649–1650.

    CrossRef  PubMed  CAS  Google Scholar 

  6. Helmlin HJ, Bracher K, Bourquin D, Vonlanthen D, Brenneisen R. Analysis of 3,4-methylenedioxymeth-amphetamine (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 

  7. Hiramatsu M, DiStefano EW, Cho AK. Stereochemical differences in the in vivo and in vitro metabolism of MDMA . FASEB. 1989;3:A1035.

    Google Scholar 

  8. Lin LY, Kumagai Y, Cho AK. Enzymatic and chemical demethylenation of (methylenedioxy)amphetamine and (methylenedioxy)methamphetamine by rat brain microsomes. Chem Res Toxicol. 1992;5:401–406.

    CrossRef  PubMed  CAS  Google Scholar 

  9. de la Torre R, Farré M, Ortuno J, Mas M, Brenneisen R, Roset PN, et al. Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol. 2000;49:104–109.

    CrossRef  PubMed  CAS  Google Scholar 

  10. Lin LY, DiStefano EW, Schmitz DA, et al. Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos. 1997;25:1059–1064.

    PubMed  CAS  Google Scholar 

  11. Kreth KP, Kovar KA, Schwab M, Zanger UM. Identification of the human cytochrome P450 involved in the oxidative metabolism of “Ecstasy”-related designer drugs. Biochem Pharmacol. 2000;59:1563–1571.

    CrossRef  PubMed  CAS  Google Scholar 

  12. Schwab M, Seyringe RE, Brauer RB, Hellinger A, Griese EU. Fatal MDMA intoxication. Lancet. 1999;353:593–594.

    CrossRef  PubMed  CAS  Google Scholar 

  13. Saunders N. Ecstasy. In: Walder P, editor. Ecstasy und verwandte Designerdrogen. Zürich: Ricco Bilger; 1994. pp. 26–42.

    Google Scholar 

  14. Henry JA, Hill IR. Fatal interaction between ritonavir and MDMA. Lancet. 1998;352:1751–1752.

    CrossRef  PubMed  CAS  Google Scholar 

  15. Kreth K, Kovar K, Schwab M, Zanger UM. Identification of the human cytochromes P450 involved in the oxidative metabolism of “Ecstasy” – related drugs. Biochem Pharmacol. 2000;69:1563–1571.

    CrossRef  Google Scholar 

  16. Demirkiran M, Jankovic J, Dean JM. Ecstasy intoxication: an overlap between serotonin syndrome and neuroleptic malignant syndrome. Clin Neuropharmacol. 1996;19:157–164.

    CrossRef  PubMed  CAS  Google Scholar 

  17. Dar KJ, McBrien ME. MDMA-induced hyperthermia: report of a fatality and review of current therapy. Inten Care Med. 1996;22:995–996.

    CrossRef  CAS  Google Scholar 

  18. Henry JA, Jeffreys KJ, Dawling S. Toxicity and deaths from 3,4-methylene-dioxymethamphetamine. Lancet. 1992;340:384–387.

    CrossRef  PubMed  CAS  Google Scholar 

  19. Benowitz NL. Amphetamines. In: Olson KR, editor. Poisoning and drug overdose. Stamford, CT: Appleton & Lange; 1999. pp. 68–70.

    Google Scholar 

  20. Singarajah C, Lavies NG. An overdose of ecstasy: a role for dantrolene. Anaesthesia. 1992;47:686–687.

    CrossRef  PubMed  CAS  Google Scholar 

  21. Mallick A, Bodenham AR. MDMA-induced hyperthermia: a survivor with an initial body temperature of 42.9°C. J Accid Emerg Med. 1997;14:336–338.

    CrossRef  PubMed  CAS  Google Scholar 

  22. Murthy BVS, Wilkes RG, Roberts NB. Creatine kinase isoform changes following ecstasy overdose. Anaesth Inten Care. 1997;25:156–159.

    CAS  Google Scholar 

  23. Hall AP, Lyburn ID, Spears FD, Riley B. An unusual case of Ecstasy poisoning. Inten Care Med. 1996;22:670–671.

    CrossRef  CAS  Google Scholar 

  24. Vollenweider FX, Gamma A, Liechti M, Huber T. Psychological and cardiovascular effects and short-term sequelae of MDMA (“Ecstasy”) in MDMA-naïve healthy volunteers. Neuropsychopharmacology. 1998;19:241–251.

    PubMed  CAS  Google Scholar 

  25. Hall AP. “Ecstasy” and the anaesthetist. Br J Anaesth. 1997;79:697–698.

    CrossRef  PubMed  CAS  Google Scholar 

  26. Schmidt CJ, Black CK, Abbate GM, Taylor VL. MDMA-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors. Brain Res. 1990;529:85–90.

    CrossRef  PubMed  CAS  Google Scholar 

  27. Olson KR. Comprehensive evaluation and treatment. In: Olson KR, editor. Poisoning and drug overdose. Stamford, CT: Appleton & Lange; 1999. pp. 1–61.

    Google Scholar 

  28. Ghuran A, Nolan J. Recreational drug misuse: issues for the cardiologist. Heart. 2000;83:627–633.

    CrossRef  PubMed  CAS  Google Scholar 

  29. Qasim A, Townend J, Davies MK. Ecstasy induced acute myocardial infarction. Heart. 2001;85:E10.

    CrossRef  PubMed  CAS  Google Scholar 

  30. Milroy CM, Clark JC, Forrest ARW. Pathology of deaths associated with “Ecstasy” and “Eve” misuse. J Clin Pathol. 1996;49:149–153.

    CrossRef  PubMed  CAS  Google Scholar 

  31. McEvoy AW, Kitchen ND, Thomas DG. Intracerebral haemorrhage and drug abuse in young adults. Br J Neurosurg. 2000;14:449–454.

    CrossRef  PubMed  CAS  Google Scholar 

  32. Reneman L, Habraken JB, Majoie CB, Booij J, den Heeten GJ. MDMA (“Ecstasy”) and its association with cerebrovascular accidents: preliminary findings. Am J Neuroradiol. 2002;21:1001–1007.

    Google Scholar 

  33. McCann U, Slate SO, Ricaurte GA. Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’). Drug Saf. 1996;15:107–115.

    CrossRef  PubMed  CAS  Google Scholar 

  34. Ranalli E, Bouton R. Intracerebral haemorrhage associated with ingestion of “Ecstasy” . Eur Neuropsychopharmacol. 1997;7:S263.

    CrossRef  Google Scholar 

  35. Maxwell DL, Polkey MI, Henry JA. Hyponatraemia and catatonic stupor after taking “Ecstasy”. BMJ. 1993;307:1399.

    CrossRef  PubMed  CAS  Google Scholar 

  36. Kessel B. Hyponatraemia after ingestion of “Ecstasy” BMJ. 1994;308:414.

    CrossRef  PubMed  CAS  Google Scholar 

  37. Holden R, Jackson MA. Near-fatal hyponatraemic coma due to vasopressin over-secretion after “Ecstasy” (3,4-MDMA) . Lancet. 1996;347:1052.

    CrossRef  PubMed  CAS  Google Scholar 

  38. Matthai SM, Davidson DC. Cerebral oedema after ingestion of MDMA (“Ecstasy”) and unrestricted intake of water . BMJ. 1996;312:1359.

    CrossRef  PubMed  CAS  Google Scholar 

  39. Henry JA, Fallon JK, Kicman AT, et al. Low-dose MDMA (“Ecstasy”) induces vasopressin secretion . Lancet. 1998;351:1784.

    CrossRef  PubMed  CAS  Google Scholar 

  40. Wilkins B. Cerebral oedema after MDMA (“Ecstasy”) and unrestricted water intake: hyponatraemia must be treated with low water input. BMJ. 1999;313:689–690.

    CrossRef  Google Scholar 

  41. Parr MJA, Low HM, Botterill P. Hyponatremia and death after “Ecstasy” ingestion. Med J Aust. 1997;166:136–137.

    PubMed  CAS  Google Scholar 

  42. Finch E, Sell L, Arnold D. Cerebral oedema after MDMA (“Ecstasy”) and unrestricted water intake: drug workers emphasize that water is not an antidote to drug . BMJ. 1996;313:690.

    CrossRef  PubMed  CAS  Google Scholar 

  43. Forsling ML, Fallon JK, Shah D, Tilbrook GS, Cowan DA, Kicman AT, et al. The effect of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus. Br J Pharmacol. 2002;135:649–656.

    CrossRef  PubMed  CAS  Google Scholar 

  44. Henry JA, Jeffreys KJ, Dawling S. Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ectasy”). Lancet. 1992;340:384–387.

    CrossRef  PubMed  CAS  Google Scholar 

  45. Ellis AJ, Wendon JA, Portmann B, Williams R. Acute liver damage and ecstasy ingestion. Gut. 1996;38:454–458.

    CrossRef  PubMed  CAS  Google Scholar 

  46. Jones AL, Simpson KJ. Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications. Aliment Pharmacol Ther. 1999;13:129–133.

    CrossRef  PubMed  CAS  Google Scholar 

  47. McGuire PK, Cope H, Fahy TA. Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine (‘Ecstasy’). Br J Psychiatr. 1994;165:391–395.

    CrossRef  CAS  Google Scholar 

  48. Hayner GN, McKinney H. MDMA: the dark side of ecstasy. J Psychoactive Drugs. 1986;18:341–347.

    CrossRef  PubMed  CAS  Google Scholar 

  49. Parrott AC, Sisk E, Turner JJ. Psychobiological problems in heavy ‘Ecstasy’ (MDMA) polydrug users. Drug Alcohol Depend. 2000;60:105–110.

    PubMed  CAS  Google Scholar 

  50. Dowling GP, McDonough ET, Bost RO. ‘Eve’ and ‘Ecstasy’: a report of five deaths associated with the use of MDEA and MDMA. JAMA. 1987;257:1615–1617.

    CrossRef  PubMed  CAS  Google Scholar 

  51. Perrone J. Amphetamines. In: Viccellio P, editor. Emergency toxicology. Philadelphia: Lippincott-Raven; 1998. pp. 899–902.

    Google Scholar 

  52. Rochester JA, Kirchner JT. Ecstasy (3,4-methylene-dioxymethamphetamine): history, neurochemistry, and toxicology. J Am Board Fam Pract. 1999;12:137–142.

    PubMed  CAS  Google Scholar 

  53. Screaton GR, Singer M, Cairns HS, Thrasher A, Sarne RM, Cohen SL. Hyperpyrexia and rhabdomyolysis after MDMA (“Ecstasy”) abuse . Lancet. 1992;339:677–678.

    CrossRef  PubMed  CAS  Google Scholar 

  54. McKinney PE. Designer drugs. In: Haddad LM, Shannon MW, Winchester JF, editors. Poisoning and drug overdose. Philadelphia: WB Saunders; 1998. pp. 569–580.

    Google Scholar 

  55. Ames D, Wirshing WC. Ecstasy, the serotonin syndrome, and neuroleptic malignant syndrome – a possible link. J Am Med Assoc. 1992;268:1505–1506.

    CrossRef  Google Scholar 

  56. Tehan B. Tehan B. Ecstasy and dantrolene . BMJ. 1993;306:146.

    CrossRef  PubMed  CAS  Google Scholar 

  57. Logan AS, Stickle B, O’Keefe N. Survival following “Ecstasy” ingestion with a peak temperature of 42 degrees. Anaesthesia. 1993;48:1017–1018.

    CrossRef  PubMed  CAS  Google Scholar 

  58. Larner AJ. Dantrolene and ‘Ecstasy’ overdose. Anaesthesia. 1993;38:179–180.

    Google Scholar 

  59. Singarajah C, Lavies NG. An overdose of ectasay. A role for dantrolene. Anaesthesia. 1992;47:686–687.

    CrossRef  PubMed  CAS  Google Scholar 

  60. Campkin NTA, Davies UM. Treatment of ‘Ecstasy’ overdose with dantrolene . Anaesthesia. 1993;48:82–83.

    CrossRef  PubMed  CAS  Google Scholar 

  61. Watson JD, Ferguson C, Hinds CJ, Skinner R, Coakley JH. Exceptional heatstroke induced by amphetamine analogues - does dantrolene have a place. Anaesthesia. 1993;48:542–543.

    Google Scholar 

  62. Dowsett RP. Deaths attributed to “Ecstasy” overdose . Med J Aust. 1996;164:700.

    PubMed  CAS  Google Scholar 

  63. Chadwick IS, Curry PD, Linsley A, Freemont AJ, Doran B. Ecstasy, 3,4-methylenendioxyamphetamine (MDMA), a fatality associated with coagulopathy and hyperthermia . J R Soc Med. 1991;84:371.

    PubMed  CAS  Google Scholar 

  64. Hopkins PM, Ellis FR, Halsall PJ. Evidence for related myopathies in exertional heat stroke and malignant hyperthermia. Lancet. 1991;338:1491–1492.

    CrossRef  PubMed  CAS  Google Scholar 

  65. Hollander JE. The management of cocaine-associated myocardial ischemia. N Engl J Med. 1995;333:1267–1272.

    CrossRef  PubMed  CAS  Google Scholar 

  66. Sandyk R. L-dopa induced ‘serotonin syndrome’ in a parkinsonian patient on bromocriptine. J Clin Psychopharmacol. 1986;6:194–195.

    CrossRef  PubMed  CAS  Google Scholar 

  67. Guze BH, Baxter LRJ. The serotonin syndrome: case responsive to propranolol . J Clin Psychopharmacol. 1986;6:119–120.

    CrossRef  PubMed  CAS  Google Scholar 

  68. McDowell DM. MDMA, ketamine, GHB, and the “club drug” scene. In: Galanter M, Kleber HD, editors. Textbook of substance abuse treatment. Washington, DC: American Psychiatric Press; 1999. pp. 295–305.

    Google Scholar 

  69. Green AR, Cross AJ, Goodwin GM. Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”). Psychopharmacology. 1995;119:247–60.

    CrossRef  PubMed  CAS  Google Scholar 

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    Enno Freye MD, PhD

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Freye, E. (2009). Pharmacokinetics of MDMA. In: Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2448-0_25

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