(+)3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative used recreationally by humans. 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 twofold; 1) to confirm and extend data suggesting that recreational MDMA use have increased. The purpose of this project is twofold: 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 in-patient setting to address the following specific questions; 1. Biochemical Studies a. Using CSF measurements of monoamine metabolites, can it be determined: 1) Whether MDMA neurotoxicity is dose (exposure) related; 2) Whether there are sex differences in the response to MDMA neurotoxicity; and 3) Whether CSF HVA is also reduced in MDMA users with the 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 physicochemical 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 difference in impulsivity and hostility that were previously observed in MDMA users be confirmed and extended using other research instruments? By addressing these questions, this research will test the hypothesis that MDMA neurotoxicity generalizes to humans, and that the toxicity has functional consequences. The long-term goals of this project are to better delineate the public health risks of recreational MDMA use, and to utilize this unique population of individuals to further elucidate the role of brain serotonin systems in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA005938-08
Application #
2882574
Study Section
Special Emphasis Panel (SRCD)
Project Start
1991-08-01
Project End
2002-02-28
Budget Start
1999-03-01
Budget End
2002-02-28
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Yuan, Jie; Darvas, Martin; Sotak, Bethany et al. (2010) Dopamine is not essential for the development of methamphetamine-induced neurotoxicity. J Neurochem 114:1135-42
McCann, Una D; Wilson, Michael J; Sgambati, Francis P et al. (2009) Sleep deprivation differentially impairs cognitive performance in abstinent methylenedioxymethamphetamine (""Ecstasy"") users. J Neurosci 29:14050-6
McCann, Una D; Sgambati, Francis P; Schwartz, Alan R et al. (2009) Sleep apnea in young abstinent recreational MDMA (""ecstasy"") consumers. Neurology 73:2011-7
McCann, Una D; Szabo, Zsolt; Vranesic, Melin et al. (2008) Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxymethamphetamine (""ecstasy"") users: relationship to cognitive performance. Psychopharmacology (Berl) 200:439-50
McCann, U D; Ridenour, A; Shaham, Y et al. (1994) Serotonin neurotoxicity after (+/-)3,4-methylenedioxymethamphetamine (MDMA;""Ecstasy""): a controlled study in humans. Neuropsychopharmacology 10:129-38