(±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates

MDMA, also known as ecstasy, is used recreationally and has been proposed as a therapy aid. In monkeys given repeated doses of 2.50, 3.75, or 5.00 mg/kg subcutaneously, the drug caused a dose-related depletion of serotonin and its metabolite 5-hydroxyindoleacetic acid across all brain regions examined two weeks later. These chemical deficits were accompanied by structural damage to serotonergic nerve fibers and pathological changes in nerve cell bodies within the dorsal raphe nucleus, but not the median raphe nucleus. The findings indicate MDMA acts as a selective serotonergic neurotoxin in nonhuman primates, suggesting humans using the drug may risk central serotonergic neuronal damage.

Study at a glance

Abstract

(+/-)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.