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Although 3,4-methylenedioxymethamphetamine MDMA, ecstasy is a known serotonergic neurotoxin in different animal species, there is to date no conclusive evidence of its neurotoxicity in humans. MDMA use was associated with impairments of psychological well-being, verbal memory and altered serotonergic functioning in a number of cross-sectional studies. Due to inherent methodological limitations, such as the notorious polydrug use of ecstasy users and lack of control of possible pre-existing differences between ecstasy users and control participants, researchers have called for well-controlled, prospective longitudinal studies to shed more light on the issue of MDMA neurotoxicity to the human brain. This longitudinal study investigated whether mood, cognition and central serotonin transporters SERT would deteriorate with continued MDMA use and whether or not they would recover over increasing periods of MDMA abstinence. In a repeated-measures design, 11 current and ten ex-ecstasy users, and 11 polydrug but not MDMA and 15 drug-naive controls participated three times within approximately two years. Both ecstasy user groups reported a polydrug use pattern besides heavy ecstasy use. Subjective reports of ecstasy use or abstinence were verified by toxicological analyses. On each trial, the participants underwent a cognitive test battery and filled in the Symptom Check List. The availability of central SERT was assessed with positron emission tomography using the McN ligand for all groups at t1, and only for the ecstasy user groups on follow-ups. There were significant Group effects in all measures of verbal memory, with the lowest performance in the group of ex-ecstasy users. The repeated-measures analyses yielded no significant Group x Time interactions in any SCL scales or measures of memory performance, with the exception of AVLT 1 immediate recall. However, this measure may not necessarily be a valid indicator of the number or integrity of serotonergic neurons. However, alternative causes such as pre-existing group differences cannot be completely ruled out in spite of the longitudinal design. Abstract Although 3,4-methylenedioxymethamphetamine MDMA, ecstasy is a known serotonergic neurotoxin in different animal species, there is to date no conclusive evidence of its neurotoxicity in humans. Publication types Research Support, Non-U.

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