Long-lasting effects of (+/-)3,4-methylene-dioxymethamphetamine (ecstasy) on serotonin system function in humans

Background: Fifteen (+/-)3,4-Methylenedioxymethamphetamine (MDMA) users, wh o did not show other drug dependencies or prolonged alcohol abuse, and 15 c ontrol subjects were included in the study. Methods: Prolactin (PRL) and cortisol (CORT) responses to the serotonergic agonist d-fenfluramine (D-fen), clinical psychobehavioral changes, and psyc hometric measures were evaluated 3 weeks and then 12 months after MDMA disc ontinuation. Results: MDMA users showed significantly reduced PRL and CORT responses in comparison with control subjects at 3 weeks (respectively, p < .001; p < .0 05). The responses of PRL to D-fen were unmodified at 12 months after prolo nged abstinence and were significantly reduced in comparison with controls (p < .001). In contrast, CORT responses in MDMA users were restored after 1 2 months of abstinence, with significantly higher responses to D-fen, in co mparison with 3-week responses (p < .05). MDMA risers' high scores on the N ovelty Seeking (NS)scale on the Tridimensional Personality Questionnaire (T PQ) appeared unchanged by long-term abstinence. In contrast, Buss Durkee Ho stility Inventory (BDHI) (Buss and Durkee 1957) direct and guilt scores dec reased significantly after 12 months of abstinence. PRL AUCs at 12 months w ere inversely correlated with the measures of MDMA expo sure (r = -.538). Conclusions: Our data indicate long-lasting 5-HT system impairment in absti nent MDMA users although the hypothesis of serotonergic changes attribute t o a premorbid condition cannot be excluded CORT restored responses to D-fen at 12 months, and the correlation of neuroendocrine changes with MDMA expo sure suggest that the neuroendocrine impairment may be due to a partially r eversible neurotoxic action of MDMA on the human brain. (C) 2000 Society of Biological Psychiatry.