Serotonin neurotoxicity after (±)3,4-methylenedioxymethamphetamine (MDMA "Ecstasy"): A controlled study in humans

Una D. McCann, Alison Ridenour, Yavin Shaham, George A. Ricaurte

Research output: Contribution to journalArticlepeer-review

286 Scopus citations


(±)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular recreational drug, is known to damage brain serotonin 5-hydroxytryptamine (5-HT) neurons in experimental animals. Whether MDMA is neurotoxic in humans has not been established. Thirty MDMA users and 28 controls were admitted to a controlled inpatient setting for measurement of biologic and behavioral indexes of central 5-HT function. Outcome measures obtained after at least 2 weeks of drug abstinence included concentrations of monoamine metabolites in cerebrospinal fluid (CSF), prolactin responses to L-tryptophan, nociceptive responses to ischemic pain, and personality characteristics in which 5-HT has been implicated (i.e., impulsivity and aggression). Subjects with a history of MDMA exposure had lower levels of CSF 5-hydroxyindoleacetic acid (the major metabolite of 5-HT) than controls (p =.001). Although they resembled controls in their prolactin response to L-tryptophan and their response to ischemic pain, MDMA users had lower scores on personality measures of impulsivity (p =.004) and indirect hostility (p =.009). The CSF findings suggest that 5-HT neurotoxicity may be a potential complication of MDMA use. Further, differences in personality support the view that 5-HT systems are involved in modulating impulsive and aggressive personality traits. Additional studies of MDMA-exposed individuals are needed to confirm and extend the present findings. Such studies could help elucidate the role of 5-HT in normal brain function as well as in neurovsvchiatric disease states.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
Issue number2
StatePublished - Apr 1994


  • Amphetamine
  • Drug abuse
  • Neurotoxicity
  • Personality
  • Prolactin
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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