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J Psychopharmacol. 2016 Dec;30(12):1296-1304. Epub 2016 Sep 5.

Serotonergic neurotransmission in emotional processing: New evidence from long-term recreational poly-drug ecstasy use.

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Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Center for Decision Neuroscience, Copenhagen Business School, Copenhagen, Denmark.
Singularity University, Moffett Field, CA, USA.
Neurons, Inc., Holbæk, Denmark.
Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark
Centre for Neuropsychopharmacology, Imperial College London, London, UK.


The brain's serotonergic system plays a crucial role in the processing of emotional stimuli, and several studies have shown that a reduced serotonergic neurotransmission is associated with an increase in amygdala activity during emotional face processing. Prolonged recreational use of ecstasy (3,4-methylene-dioxymethamphetamine [MDMA]) induces alterations in serotonergic neurotransmission that are comparable to those observed in a depleted state. In this functional magnetic resonance imaging (fMRI) study, we investigated the responsiveness of the amygdala to emotional face stimuli in recreational ecstasy users as a model of long-term serotonin depletion. Fourteen ecstasy users and 12 non-using controls underwent fMRI to measure the regional neural activity elicited in the amygdala by male or female faces expressing anger, disgust, fear, sadness, or no emotion. During fMRI, participants made a sex judgement on each face stimulus. Positron emission tomography with 11C-DASB was additionally performed to assess serotonin transporter (SERT) binding in the brain. In the ecstasy users, SERT binding correlated negatively with amygdala activity, and accumulated lifetime intake of ecstasy tablets was associated with an increase in amygdala activity during angry face processing. Conversely, time since the last ecstasy intake was associated with a trend toward a decrease in amygdala activity during angry and sad face processing. These results indicate that the effects of long-term serotonin depletion resulting from ecstasy use are dose-dependent, affecting the functional neural basis of emotional face processing.


MDMA; amygdala; ecstasy; emotion; fMRI; serotonin

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