Long-lasting effects of (±)3,4-methylene-dioxymethamphetamine (Ecstasy) on serotonin system function in humans

Background: Fifteen (±)3,4-Methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse, and 15 control 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 psychometric measures were evaluated 3 weeks and then 12 months after MDMA discontinuation. Results: MDMA users showed significantly reduced PRL and CORT responses in comparison with control subjects at 3 weeks (respectively, p< .001; p< .005). The responses of PRL to D-fen were unmodified at 12 months after prolonged abstinence and were significantly reduced in comparison with controls (p< .001). In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p< .05). MDMA users’ high scores on the Novelty Seeking (NS) scale on the Tridimensional Personality Questionnaire (TPQ) appeared unchanged by long-term abstinence. In contrast, Buss Durkee Hostility Inventory (BDHI) (Buss and Durkee 1957) direct and guilt scores decreased significantly after 12 months of abstinence. PRL AUCs at 12 months were inversely correlated with the measures of MDMA exposure (r = −.538). Conclusions: Our data indicate long-lasting 5-HT system impairment in abstinent MDMA users although the hypothesis of serotonergic changes attributable to a premorbid condition cannot be excluded. CORT restored responses to D-fen at 12 months, and the correlation of neuroendocrine changes with MDMA exposure suggest that the neuroendocrine impairment may be due to a partially reversible neurotoxic action of MDMA on the human brain.