Electrophysiological evidence of serotonergic impairment in long-term MDMA("ecstasy") users

Objective: "Ecstasy," or 3,4-methylenedioxymethamphetamine (MDMA), causes l ong-term impairment to the serotonin (5-HT) system in rats, dogs, and nonhu man primates. 5-HT dysfunction has also been observed in human recreational users of the drug, but whether 5-HT dysfunction in humans is caused by MDM A has not been established, since dysfunction may have preceded MDMA exposu re This ambiguity about causation is particularly important in MDMA researc h, because 5-HT deficiency is a predictor of risky behavior. Method: The 5-HT function of 22 longterm MDMA users was compared to that of 20 drug-naive comparison subjects and 19 cannabis users. 5-HT function was assessed with the intensity dependence paradigm, a tool that measures 5-HT -related attenuation of neural response to auditory stimuli (measured with EEG). Results: Long-term MDMA users exhibited 5-HT dysfunction, relative to both cannabis users and drug-naive comparison subjects. This dysfunction was rel ated to total MDMA consumption (after removing the effect of frequency of u se) but not to frequency of use (after removing the effect of total consump tion). Conclusions: These data show that 5-HT dysfunction occurs in MDMA users, is related to users' MDMA consumption, and is independent of cannabis use. Th e results do not suggest that self-medication explains this relationship, b ecause the deficit was related to total MDMA consumption but not frequency of consumption. The results are thus consistent with the thesis that MDMA c onsumption causes 5-HT impairment in humans.