The neurotoxic effects of the drug methylene-dioxymethamphetamine (MDMA), popularly known as """"""""ecstasy"""""""", have been conclusively shown in animals. Human studies on the long-term effects of MDMA have been hampered by the confounding issue that other drugs are often sold as MDMA, and the fact that MDMA users tend to use other drugs of abuse. Thus, it has been questioned whether the neurobehavioral deficits seen in MDMA users are specifically due to MDMA. Taken together, these key issues justify the need to conduct more systematic, rigorous examination of neurobehavioral effects of MDMA use in humans. Likewise, the more clear evidence that MDMA causes detrimental effects on the brain and behavior, the more likely MDMA users will consider substance abuse treatment. Since the United States has recently seen a dramatic increase in the use of MDMA, primarily by young adults, the significance of the neurotoxic effects of MDMA in humans is clear. A further understanding of the long-term neurobehavioral effects of MDMA in humans will have a direct and significant effect on treatment development. This resubmission will use multi-modal neurobehavioral measures including behavioral laboratory measures of impulsivity and functional magnetic resonance imaging to answer three key questions regarding MDMA use in humans. First, what are the specific effects of MDMA use on mood, impulsivity, memory, and brain function? Second, how are these deficits related to quantity and frequency of MDMA use? Third, are these deficits related to serotonin function in MDMA users? The Specific Aims of this proposal are:
Specific Aim 1 : To compare neurobehavioral measures of mood, memory, impulsivity and functional magnetic resonance imaging between heavy MDMA using subjects, matched non-MDMA using drug users, and healthy controls.
Specific Aim 2 : To determine whether the quantity and frequency of MDMA use are related to the neurobehavioral deficits seen in heavy MDMA users.
Specific Aim 3 : To determine whether neurobehavioral deficits seen in heavy MDMA users are related to serotonergic function as measured by a mCPP neuroendocrine challenge in these subjects.
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| Moeller, F Gerard; Steinberg, Joel L; Lane, Scott D et al. (2007) Diffusion tensor imaging in MDMA users and controls: association with decision making. Am J Drug Alcohol Abuse 33:777-89 |
| Valdes, Ignacio H; Steinberg, Joel L; Narayana, Ponnada A et al. (2006) Impulsivity and BOLD fMRI activation in MDMA users and healthy control subjects. Psychiatry Res 147:239-42 |
| Moeller, Frederick Gerard; Hasan, Khader M; Steinberg, Joel L et al. (2005) Reduced anterior corpus callosum white matter integrity is related to increased impulsivity and reduced discriminability in cocaine-dependent subjects: diffusion tensor imaging. Neuropsychopharmacology 30:610-7 |
| Moeller, F Gerard; Steinberg, Joel L; Dougherty, Donald M et al. (2004) Functional MRI study of working memory in MDMA users. Psychopharmacology (Berl) 177:185-94 |
