ORIGINAL INVESTIGATION Memory-related hippocampal functioning in ecstasy and amphetamine users A prospective fMRI study Benjamin Becker & Daniel Wagner & Philip Koester & Katja Bender & Christoph Kabbasch & Euphrosyne Gouzoulis-Mayfrank & Jörg Daumann Received: 31 December 2011 / Accepted: 5 September 2012 / Published online: 23 September 2012 # Springer-Verlag 2012 Abstract Rationale Recreational use of ecstasy (3,4-methylenediox- ymethamphetamine [MDMA]) has been associated with memory impairments. Functional neuroimaging studies with cross-sectional designs reported altered memory-related hip- pocampal functioning in ecstasy-polydrug users. However, differences might be pre-existing or related to the concom- itant use of amphetamine. Objective To prospectively investigate the specific effects of ecstasy on memory-related hippocampal functioning. Methods We used an associative memory task and function- al magnetic resonance imaging (fMRI) in 40 ecstasy and/or amphetamine users at baseline (t1) and after 12 months (t2). At t1, all subjects had very limited amphetamine and/or ecstasy experience (less than 5 units lifetime dose). Based on the reported drug use at t2, subjects with continued ecstasy and/or amphetamine use (n 0 17) were compared to subjects who stopped use after t1 (n 0 12). Results Analysis of repeated measures revealed that encoding- related activity in the left parahippocampal gyrus changed differentially between the groups. Activity in this region in- creased in abstinent subjects from t1 to t2, however, decreased in subjects with continued use. Decreases within the left para- hippocampal gyrus were associated with the use of ecstasy, but not amphetamine, during the follow-up period. However, there were no significant differences in memory performance. Conclusions The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning. However, alternative explanations such as (sub-)acute can- nabis effects are conceivable. Keywords Amphetamine . Cognition . Ecstasy . fMRI . Hippocampus . Longitudinal design Introduction The popular recreational drug “ecstasy” (3,4-methylene- dioxymethamphetamine [MDMA]) causes selective and persistent lesions to central serotonergic nerve terminals in laboratory animals (Fischer et al. 1995; Green et al. 2003; Hatzidimitriou et al. 1999). Although these data cannot be extrapolated directly to human recreational users, a growing number of studies suggest that MDMA might be harmful to the serotonergic system in humans. Several studies reported subtle abnormalities in psychological and neurocognitive functioning in MDMA users that might reflect functional sequelae of long-lasting alterations in serotonergic systems (Gouzoulis-Mayfrank and Daumann 2006a; Green et al. 2003; Parrott 2000; Reneman et al. 2006; Schilt et al. 2007). Recent reviews and well-controlled studies suggest ecstasy-specific impairments in learning and memory (Fox et al. 2002; Gouzoulis-Mayfrank and Daumann 2009; Electronic supplementary material The online version of this article (doi:10.1007/s00213-012-2873-z) contains supplementary material, which is available to authorized users. B. Becker (*) : D. Wagner : P. Koester : E. Gouzoulis-Mayfrank : J. Daumann Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany e-mail: ben_becker@gmx.de K. Bender Institute of Legal Medicine, University of Cologne, Cologne, Germany C. Kabbasch Department of Neuroradiology, University of Cologne, Cologne, Germany Psychopharmacology (2013) 225:923–934 DOI 10.1007/s00213-012-2873-z