3,4-Methylenedioxymethamphetamine (MDMA or """"""""ecstasy"""""""") use represents one of the most rapidly growing forms of illicit drug abuse in the United States in the last decade. This trend is of serious concern, given evidence that ecstasy may produce substantial and possibly irreversible neurotoxicity - as shown by 1) pre-clinical studies in animals; 2) clinical reports of persistent adverse psychiatric effects in human ecstasy users; and particularly 3) neuropsychological studies of ecstasy users showing long-lasting residual cognitive deficits. Available neuropsychological studies, however, are subject to methodological limitations, including 1) limited sample size; 2) use of comparison subjects not matched for exposure to all-night dancing in the """"""""rave"""""""" subculture; 3) limitation in control for possible premorbid differences in cognitive ability between ecstasy users and non-users; 4) limited screening for recent drug use at the time of testing; and perhaps most importantly, 5) testing of ecstasy users who reported substantial lifetime use of other illicit drugs making it difficult to exclude the potentially confounding residual cognitive effects of other drug exposure. In a recently completed pilot study, now in press, we have attempted to address each of these limitations, but have nevertheless still found important residual cognitive deficits in young heavy ecstasy users. The proposed study builds on this pilot study to examine a larger sample of 140 ecstasy users and 70 comparison subjects, with particular care to address the 5 potential limitations above. First, all subjects in both groups will be recruited from the rave subculture. Second, we will obtain and adjust for numerous measures of subjects' premorbid status, including several family-of-origin variables, history of attention deficit hyperactivity disorder and conduct disorder, and other attributes. Third, we will screen subjects at the time of testing for MDMA, other illicit drugs, and alcohol; and by hair analysis for drug use during the past 90 days. Fourth and most importantly, we have access to a unique population of nearly """"""""pure"""""""" ecstasy users, with minimal exposure to other drugs or alcohol, thus greatly reducing the problem of dealing with this confounding variable. Our pilot study with this population shows that the proposed study is feasible. The primary specific aim of the study is to assess the residual neuropsychological effects of ecstasy by comparing ecstasy users to well-matched non-users, with exceptional control for potentially confounding factors. The secondary specific aim is to assess the contributions of a) total lifetime ecstasy use and b) time since last ecstasy use to cognitive function. The results of this study will improve our understanding of the nature, extent, and correlates of ecstasy-associated residual cognitive deficits.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA017953-05
Application #
7488415
Study Section
Special Emphasis Panel (ZRG1-HOP-C (02))
Program Officer
Grant, Steven J
Project Start
2004-09-30
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
5
Fiscal Year
2008
Total Cost
$336,608
Indirect Cost
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Halpern, John H; Sherwood, Andrea R; Hudson, James I et al. (2011) Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs. Addiction 106:777-86
Krebs, T S; Johansen, P-Ø; Jerome, L et al. (2009) Importance of psychiatric confounding in non-randomized studies of heavy ecstasy users. Psychol Med 39:876-8