(plus minus)3,4 methylenedioxymethamphetamine (MDMA) and fenfluramine are ring-substituted amphetamine analogs which damage serotonin (5-HT) neurons in experimental animals, including non-human primates. Both of these drugs are also used by humans, MDMA as a recreational drug of abuse, fenfluramine as a clinically prescribed appetite suppressant. MDMA and fenfluramine-induced 5-HT neurotoxicity persists for greater than 12 months in non-human primates, and has been documented using neurochemical and anatomical methods. Human MDMA users have biochemical and functional evidence of central serotonin dysfunction. Specifically, MDMA-exposed subjects have significant decreases in cerebrospinal fluid concentrations of 5-HIAA, the major metabolite of serotonin, when compared to age and sex matched control subjects. Further, MDMA subjects had alterations in sleep and impulsivity, two behavioral domains in which serotonin has been implicated.
