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

U D McCann, A Ridenour, Y Shaham, George A. Ricaurte

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology April 1994 DOI: 10.1038/npp.1994.15 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational case-control study Peer reviewed
Sample size 58
Population 30 MDMA users and 28 controls admitted to a controlled inpatient setting
Duration At least 2 weeks of drug abstinence
Measures cerebrospinal fluid monoamine metabolites (5-HIAA), prolactin response to L-tryptophan, nociceptive responses to ischemic pain, personality measures of impulsivity and aggression
Topics MDMA Serotonin
Key findings MDMA users had lower cerebrospinal fluid 5-HIAA levels than controls and lower scores on impulsivity and indirect hostility, while prolactin response to L-tryptophan and ischemic pain responses were similar. The authors suggest serotonin neurotoxicity may be a potential complication of MDMA use and that serotonin systems are involved in modulating impulsive and aggressive personality traits.

Abstract

(+/-)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.