Abstract
3,4‐Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a psychostimulant drug producing heightened mood and facilitated social communication. In animal studies, MDMA effects are primarily mediated by serotonin (5‐HT), but also by dopamine (DA) and possibly noradrenaline (NA). In humans, however, the neurochemical and neurophysiological basis of acute MDMA effects remains unknown. The distribution of active neuronal populations after administration of a single dose of MDMA (1.7 mg/kg) or placebo was studied in 16 healthy, MDMA‐naïve volunteers. Thirty‐one‐channel scalp EEGs during resting with open and closed eyes was analyzed in the different EEG frequency bands. Scalp maps of power showed significant, global differences between MDMA and placebo in both eye conditions and all frequency bands. Low resolution brain electromagnetic tomography (LORETA) was used to compute 3D, functional images of electric neuronal activity from the scalp EEG data. MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion. This activation of frontotemporal areas indicates that the observed enhancement of mood and possibly the increased extroversion rely on modulation of limbic orbitofrontal and anterotemporal structures known to be involved in emotional processes. Comparison of the MDMA‐specific EEG pattern with that of various 5‐HT, DA, and NA agonists indicates that serotonin, noradrenaline, and, to a lesser degree, dopamine, contribute to the effects of MDMA on EEG, and possibly also on mood and behavior. Hum. Brain Mapping 14:152–165, 2001. © 2001 Wiley‐Liss, Inc.