MDMA Dependence and Discontinuation Syndrome

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DESCRIPTION (provided by applicant): MDMA is one of the most widely abused drugs by adolescents and young adults. Recent studies suggest widespread MDMA dependence, with up to 48% of users diagnosed as dependent. These studies suggest that day-to-day problems relating to MDMA abuse and dependence may be more severe and prevalent than previously believed. Yet MDMA dependence has not been fully characterized, with signs, symptoms, risk and protective factors, and the natural history of MDMA dependence remaining largely unknown. Retrospective reports document high rates of appaxent withdrawal symptoms in MDMA users. It remains to be determined the extent to which symptoms are due to other drugs, sequelae of activities undertaken while under the influence of MDMA, reemergence of preexisting conditions, or represent a true MDMA discontinuation syndrome. We propose a series of controlled inpatient trials to characterize MDMA dependence and the MDMA-specific discontinuation syndrome. In the first experiment, MDMA users (80 dependent and 80 nondependent) will be hospitnlized and given placebo or a single nontoxic dose of MDMA in order to elicit a discontinuation syndrome. In the second experiment, 40 hospitalized dependent MDMA users will be given placebo or a single nontoxic dose of MDMA to relieve withdrawal following illicit use of MDMA. Stir-report, observer-rated, physiological, neurocognitive, hormonal, and behavioral measures will be made. Addiction to MDMA appears to be a serious risk of use; our studies will carefttlly define important clinical features of this emerging disorder.