Serotonin neurotoxicity after (+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans.
(+/-)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.
McCann
U D
UD
Unit on Anxiety and Affective Disorders, National Institute of Mental Health, Bethesda, Maryland 20892.
Ridenour
A
A
Shaham
Y
Y
Ricaurte
G A
GA
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D000328:Adult; D000704:Analysis of Variance; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D013287:Illicit Drugs / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D010556:Personality Tests; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000378:metabolism*
D013287:Illicit Drugs; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D011388:Prolactin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D006719:Homovanillic Acid