(+/-)3,4-Methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates.
(+/-)3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has been proposed to be useful as an adjunct to psychotherapy. This study assessed the neurotoxic potential of MDMA in nonhuman primates. Monkeys were repeatedly administered doses (2.50, 3.75, and 5.00 mg/kg) of MDMA subcutaneously and analyzed for regional brain content of serotonin and 5-hydroxyindoleacetic acid two weeks later. In all regions of the monkey brain examined, MDMA produced a selective dose-related depletion of serotonin and 5-hydroxyindoleacetic acid. These neurochemical deficits were associated with evidence of structural damage to serotonergic nerve fibers. In addition, MDMA produced pathological changes in nerve cell bodies in the dorsal, but not median, raphe nucleus. These results indicate that MDMA is a selective serotonergic neurotoxin in nonhuman primates and that humans using this drug may be at risk for incurring central serotonergic neuronal damage.
Ricaurte
G A
GA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Forno
L S
LS
Wilson
M A
MA
DeLanney
L E
LE
Irwin
I
I
Molliver
M E
ME
Langston
J W
JW
D015104:3,4-Methylenedioxyamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity*; D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000172:deficiency; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009412:Nerve Fibers / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011903:Raphe Nuclei / Q000187:drug effects; D012453:Saimiri; D012701:Serotonin / Q000172:deficiency*
D000662:Amphetamines; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine