(+/-) 3,4-Methylenedioxymethamphetamine (MDMA, """"""""Ecstasy"""""""") is an increasingly popular psychoactive drug of abuse that has been shown to be a potent brain serotonin (5-HT) neurotoxin in animals. Growing evidence in recreational MDMA users indicates that MDMA can also lead to 5-HT damage in humans. Recent data in non-human primates suggests that some MDMA users (i.e., those who use MDMA in a """"""""binge"""""""" regimen) may also incur brain dopamine (DA) neurotoxicity, although clinical studies to test this possibility have not yet been conducted. Functional consequences of MDMA neurotoxicity in humans have been difficult to identify. However, several studies have demonstrated altered sleep patterns and endocrine function in individuals previously exposed to MDMA. Since 5-HT and DA are involved in the regulation of sleep and endocrine function, it is possible that altered sleep and endocrine function in MDMA users is related to MDMA-induced 5-HT and/or DA neurotoxicity. Further, since sleep and circadian rhythms influence hormonal secretion (and vice versa), abnormalities of sleep and endocrine function in MDMA users may be inter-related. The proposed studies are intended to extend previous studies of sleep and neuroendocrine function in MDMA users, and explore possible interrelations between sleep and nocturnal neuroendocrine function in MDMA users and matched controls.
The specific aims of the project are: 1) To analyze sleep patterns of 2 groups of MDMA users and 2 groups of matched control subjects using standard polysomnographic and spectral power methods. One group of MDMA users will be """"""""bingers,"""""""" whereas the second group will report never having taken more than dose of MDMA dose per 12-hour period. One control group will be matched with MDMA users for non-MDMA drug use (in addition to other demographic variables) whereas the second group of controls will have no history of illicit drug abuse. 2) To characterize the nocturnal secretion patterns of prolactin, growth hormone, and cortisol, three hormones that are modulated by 5-HT and/or DA influenced by sleep; and 3) To conduct 5-HT pharmacological challenges with m-chlorophenylpiperazine (m-CPP) in male and female MDMA users during sleep, when environmental and cognitive factors that can influence endocrine secretion are minimal. Results from the proposed studies will help better define the functional consequences of MDMA exposure in humans, and could shed light on the roles of 5-HT and DA in sleep and nocturnal endocrine function.
