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Original Article
June 6, 2011

In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users

Author Affiliations

Author Affiliations: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet (Drs Erritzoe, Frokjaer, Svarer, and Knudsen and Ms Christoffersen), Center for Integrated Molecular Brain Imaging (Drs Erritzoe, Frokjaer, Svarer, Ramsøy, Jernigan, and Knudsen; Mr Holst; and Ms Christoffersen), Department of Biostatistics (Mr Holst) and Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences (Dr Johansen), University of Copenhagen, and Positron Emission Tomography and Cyclotron Unit, University Hospital Rigshospitalet (Dr Madsen), Copenhagen, Denmark; DTU Informatics, Technical University of Denmark, Lyngby (Mr Rasmussen); Neuropsychopharmacology Unit, Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Imperial College, London, England (Dr Erritzoe); Danish Center for Magnetic Resonance Imaging, Hvidovre University Hospital, Hvidovre (Drs Ramsøy and Jernigan); and Department of Psychiatry, University of California San Diego, La Jolla (Dr Jernigan).

Arch Gen Psychiatry. 2011;68(6):562-576. doi:10.1001/archgenpsychiatry.2011.56

Context  Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) have direct agonistic effects on postsynaptic serotonin2A receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.

Objective  To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin2A receptor binding.

Design  A positron emission tomography study of 24 young adult drug users and 21 nonusing control participants performed with carbon 11 (11C)–labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile (DASB) and fluorine 18 (18F)–labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14).

Participants  Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls.

Main Outcome Measures  In vivo cerebral SERT and serotonin2A receptor binding.

Results  Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, −56%; pallidostriatum, −19%; and amygdala, −32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of lifetime MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin2A receptor binding in the serotonin2A receptor agonist users (both user groups) was also detected.

Conclusions  We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin2A receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin2A agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.