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Halpern JH, Pope HG Jr, Sherwood AR, Barry S, Hudson JI, Yurgelun-Todd D. 
“Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs”. 
Drug Alcohol Depend. 2004 Aug 16;75(2):135-47.

BACKGROUND: A substantial literature suggests that users of illicit 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") display residual cognitive deficits. Most MDMA users, however, use other illicit drugs as well, so it is difficult to be certain that these deficits are due to MDMA, as opposed to other drug use or additional confounding factors.

METHODS: We administered a battery of neuropsychological tests to 23 young MDMA users who reported minimal exposure to any other drugs, including alcohol, and to 16 comparison individuals equally involved with the rave subculture, but reporting no MDMA use. We compared the groups by regression analyses adjusting for numerous potentially confounding variables. To test for a possible dose-response effect, we also performed a median split of 12 moderate MDMA users (22-50 lifetime uses) and 11 heavy users (60-450 uses), and compared these subgroups with non-users.

RESULTS: MDMA users as a whole performed worse than non-users on most test measures, but these comparisons rarely reached statistical significance. This picture changed markedly in the subgroup analysis: although moderate users displayed virtually no differences from non-users on any measures, the heavy users displayed significant deficits on many measures, particularly those associated with mental processing speed and impulsivity. These differences did not appear explainable by differences in family-of-origin variables, verbal IQ, levels of depression, or time since last MDMA use. CONCLUSIONS: The presence of residual cognitive deficits, even among unusually "pure" frequent users of illicit MDMA, analyzed with adjustment for confounding variables, augments the evidence that MDMA itself, rather than some associated factor, is responsible for the deficits observed.
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