Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

Background 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons hav e not been studied, and sex differences and the longterm effects of MDMA us e on serotonin neurons have not been identified. We investigated the effect s of moderate and heavy MDMA use, sex differences, and long-term effects of MDMA use on serotonin neurons in different brain regions. Methods By means of flyers posted in "rave" venues in Amsterdam, the Nether lands, we recruited 15 moderate MDMA users, 23 heavy MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 15 controls who claimed never to have used MDMA. We studied the effects of MDMA on brain s erotonin neurons using (123)iodine-2 beta -carbomethoxy-3 beta-(4-iodopheny l) tropane ([I-123][beta -CIT)-a radioligand that binds with high affinity to serotonin transporters. Density of binding (expressed as a ratio of regi on-of-interest binding over binding in the cerebellum) was calculated by si ngle-photon-emission computed tomography (SPELT). Findings We saw significant effects of group and group by sex (p=0.041 and p=0.022, respectively) on overall [I-123])beta -CIT binding ratios. In heav y MDMA users, significant decreases in overall binding ratios were seen in women (p<0.01) but not men (p=0.587). In female ex-MDMA users, overall dens ities of serotonin transporters were significantly higher than in heavy MDM A users (p=0.004), but not higher than in controls (p=0.524). Interpretation Our results indicate that heavy use of MDMA is associated wi th neurotoxic effects on serotonin neurons, that women might be more suscep tible than men, and that MDMA-induced neurotoxic changes in several brain r egions of female ex-MDMA users are reversible.