Although the popular drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to damage brain serotonin (5-HT) neurons in animals, the fate and functional consequences of 5-HT neurons after MDMA injury are not known in humans. We investigated the long-term effects of MDMA use on cortical 5-HT neurons in humans and memory function, because brain 5-HT has been implicated in memory function.
Twenty-two recent MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 13 control subjects. The effects of MDMA use on cortical 5-HT neurons was studied by means of single-photon emission computed tomography with iodine 123–labeled 2β-carbomethoxy-3β-(4-iodophenyl) tropane ([123I]β-CIT) by quantification of brain 5-HT transporter densities. Verbal memory performance was assessed with the Rey Auditory Verbal Learning Test.
Mean cortical [123I]β-CIT-labeled 5-HT transporter density was significantly lower in recent MDMA users than in controls (1.17 vs 1.28 [–9%]) but not in ex-MDMA users (1.24 vs 1.28 [−3%]). Recent and ex-MDMA users recalled significantly fewer words than did controls on the immediate recall (47.0 and 48.0 vs 60.0, respectively; P = .001) as well as the delayed recall (9.8 and 10.1 vs 13.1, respectively; P = .003). Greater use of MDMA was associated with greater impairment in immediate verbal memory. However, memory performance was not associated with [123I]β-CIT binding to cortical 5-HT transporters or duration of abstinence from MDMA.
The present study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the human cortex may be reversible, the effects of MDMA on memory function may be long-lasting.