Serotonin neurotoxicity after (+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans

Neuropsychopharmacology. 1994 Apr;10(2):129-38. doi: 10.1038/npp.1994.15.


(+/-)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 neuropsychiatric disease states.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives*
  • 3,4-Methylenedioxyamphetamine / toxicity
  • Adult
  • Analysis of Variance
  • Female
  • Homovanillic Acid / cerebrospinal fluid
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Illicit Drugs / toxicity*
  • Male
  • Middle Aged
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Pain / physiopathology
  • Pain Measurement
  • Personality Tests
  • Prolactin / blood
  • Serotonin / metabolism*


  • Illicit Drugs
  • Serotonin
  • 3,4-Methylenedioxyamphetamine
  • Hydroxyindoleacetic Acid
  • Prolactin
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Homovanillic Acid