Healthy VolunteersMDMA

Acute psychological effects of 3, 4-methylenedioxymethamphetamine (MDMA,“Ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram

This study (n=16) found that the psychological effect of MDMA (105mg/70kg) was markedly reduced by citalopram, suggesting that MDMA-activity is associated with the 5-HT uptake site.

Authors

  • Matthias Liechti
  • Franz Vollenweider

Published

Neuropsychopharmacology
individual Study

Abstract

3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo-controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies.

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Research Summary of 'Acute psychological effects of 3, 4-methylenedioxymethamphetamine (MDMA,“Ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram'

Introduction

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is an amphetamine derivative known from controlled studies to produce a characteristic psychoactive profile in humans, including heightened mood, increased sociability, moderate derealization and depersonalization, cognitive disturbances, and intensified sensory awareness. Preclinical work shows that MDMA primarily releases serotonin (5-HT) and, to a lesser extent, dopamine (DA), and that selective serotonin reuptake inhibitors (SSRIs) such as citalopram block MDMA-induced 5-HT release in vitro and in animals, suggesting carrier-mediated 5-HT efflux as a mechanism. It remains unclear, however, whether this mechanism accounts for MDMA's psychological effects in humans, as prior human information consisted mainly of uncontrolled case reports with mixed findings. Liechti and colleagues set out to test whether acute pretreatment with the highly selective 5-HT uptake inhibitor citalopram would attenuate the psychological effects of orally administered MDMA in healthy volunteers. The study used psychometric rating scales in a double-blind, placebo-controlled within-subject design and hypothesised that a 40 mg intravenous infusion of citalopram would reduce the subjective effects produced by 1.5 mg/kg oral MDMA.

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Study Details

References (1)

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