Neural and cardiac toxicities associated with 3,4-methylenedioxymethamphetamine (MDMA).
Michael H. Baumann, Richard B Rothman
International review of neurobiology 2009 DOI: 10.1016/s0074-7742(09)88010-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA |
| Key findings | Argues that MDMA's pharmacological effects occur at the same doses in rats and humans; high doses depleting serotonin are associated with tolerance and impaired release, while non-depleting doses can cause persistent behavioral dysfunction. Proposes that the metabolite MDA, a potent 5-HT(2B) agonist, may contribute to valvular heart disease risk in heavy users. |
Abstract
(+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is a commonly abused illicit drug which affects multiple organ systems. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been viewed as neurotoxicity. Recent data implicate MDMA in the development of valvular heart disease (VHD). The present paper reviews several issues related to MDMA-associated neural and cardiac toxicities. The hypothesis of MDMA neurotoxicity in rats is evaluated in terms of the effects of MDMA on monoamine neurons, the use of scaling methods to extrapolate MDMA doses across species, and functional consequences of MDMA exposure. A potential treatment regimen (l-5-hydroxytryptophan plus carbidopa) for MDMA-associated neural deficits is discussed. The pathogenesis of MDMA-associated VHD is reviewed with specific reference to the role of valvular 5-HT(2B) receptors. We conclude that pharmacological effects of MDMA occur at the same doses in rats and humans. High doses of MDMA that produce 5-HT depletions in rats are associated with tolerance and impaired 5-HT release. Doses of MDMA that fail to deplete 5-HT in rats can cause persistent behavioral dysfunction, suggesting even moderate doses may pose risks. Finally, the MDMA metabolite, 3,4-methylenedioxyamphetamine (MDA), is a potent 5-HT(2B) agonist which could contribute to the increased risk of VHD observed in heavy MDMA users.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 25
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- 3,4-methylenedioxymethamphetamine (MDMA): current perspectives Substance Abuse and Rehabilitation November 1, 2013
- Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use Journal of Neuroscience June 4, 2014
- Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy Journal of Psychopharmacology September 10, 2020
- The risk of chronic psychedelic and MDMA microdosing for valvular heart disease Journal of Psychopharmacology August 12, 2023
and 20 more in the library
Cites 61
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and 56 more in the library