3,4-methylenedioxymethamphetamine (MDMA, """"""""Ecstacy"""""""") is a synthetic amphetamine derivative used by humans for recreational purposes. Despite its illicit status and knowledge that MDMA is highly neurotoxic to brain serotonin systems in animals, reports of human MDMA use have increased. The purpose of this project is two-fold: 1) to confirm and extend data suggesting that recreational MDMA users incur damage to central serotonin neurons, and 2) to further probe for functional consequences of MDMA exposure. In particular, biochemical and functional studies will be performed in a controlled inpatient setting to address the following specific questions: 1) Biochemical Studies - a. Using cerebrospinal (CSF) measurements of monoamine metabolites can it be determined: i.whether MDMA neurotoxicity is dose related, ii. whether there are sex differences in the response to MDMA neurotoxicity; and iii. whether CSF HVA is also reduced in MDMA users with greatest exposure. b. Using neuroendocrine challenge with m-CPP, can MDMA-induced alterations in brain serotonin innervation be detected, i.e., are prolactin and/or cortisol responses altered? 2) Functional Studies - a. Do MDMA users have altered mood, anxiety, temperature, or cognitive responses to pharmacological (m-CPP) challenge? b. Can alterations in mood, anxiety, and cognition (behavioral domains that putatively involve serotonin) be detected in MDMA users in response to physiochemical challenge (tryptophan depletion)? c. Are the previously noted alterations of sleep architecture in MDMA users exacerbated following tryptophan depletion, and does m-CPP differentially affect sleep in MDMA users and controls? d. Do MDMA users have an altered response to ischemic or thermal pain, and is their analgesic response to morphine altered? e. Can differences in impulsivity and hostility that were previously observed in MDMA users be confirmed and extended using other research instruments?
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