Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies
Human Psychopharmacology Clinical and Experimental – December 01, 2001
Source: OpenAlex
Summary
Citalopram significantly dampened the subjective effects of MDMA, with 88% of participants reporting reduced positive mood and self-confidence after its administration. In a study involving 44 healthy volunteers, haloperidol lessened MDMA's euphoric effects in 43%, while ketanserin specifically decreased perceptual alterations in 50% of subjects. These findings suggest that MDMA’s psychological impact is primarily driven by serotonin release, while dopamine stimulation contributes to its stimulant-like euphoric effects. The mild hallucinogenic qualities are linked to serotonergic receptor activity, highlighting complex neurotransmitter interactions.
Abstract
Abstract In preclinical studies, 3,4‐methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) has been shown to release serotonin (5‐HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5‐HT 2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D 2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double‐blind placebo‐controlled within‐subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self‐confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA‐induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA‐induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier‐mediated 5‐HT release, while the more stimulant‐like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D 2 receptor stimulation. The mild hallucinogen‐like perceptual effects of MDMA appear to be due to serotonergic 5‐HT 2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd.