Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies
Matthias E. Liechti, Franz X. Vollenweider
Human Psychopharmacology: Clinical and Experimental December 1, 2001 DOI: 10.1002/hup.348 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind placebo-controlled within-subject study Peer reviewed |
|---|---|
| Sample size | 44 |
| Population | Healthy human volunteers |
| Interventions | Citalopram Ketanserin Haloperidol MDMA |
| Dose | 1.5 mg/kg orally for MDMA; 40 mg intravenously for citalopram; 50 mg orally for ketanserin; 1.4 mg intravenously for haloperidol |
| Topics | MDMA Serotonin |
| Keywords | Ketanserin Citalopram Hallucinogen Stimulant Haloperidol Dopamine Methamphetamine Pharmacology 5-HT Receptor Anesthesia |
| Citations | 243 |
| Key points | The overall psychological effects of MDMA depend largely on carrier-mediated 5-HT release, while its euphoric mood effects relate in part to dopamine D2 receptor stimulation and its perceptual effects to 5-HT2 receptor stimulation. |
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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 116
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology 2013
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers Frontiers in Human Neuroscience May 27, 2014
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
and 111 more in the library
Cites 28
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin Synapse 2000
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
and 23 more in the library