Pharmacogenomics of 3,4-Methylenedioxymethamphetamine (MDMA): A Narrative Review of the Literature.
Guillaume Drevin, Maria Pena-Martin, Aurélien Bauduin, Antoine Baudriller, Marie Briet, Chadi Abbara
Pharmaceutics August 20, 2024 DOI: 10.3390/pharmaceutics16081091 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | 3,4-methylenedioxymethamphetamine Pharmacodynamics MDMA Research 3 Pharmacogenomics genetic factors Genetic variations Genetic differences Drug metabolism pharmacokinetics |
| Citations | 4 |
| Key findings | Genetic variants in MDMA metabolism and pharmacodynamic targets are under-investigated, with only a few associations such as COMT Val158Met and 5HTTLPR polymorphisms linked to specific effects. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative with notable psychoactive properties and emerging therapeutic potential, particularly for treating post-traumatic stress disorders (PTSD) and substance use disorders. However, its use remains controversial due to inter-individual variability influenced by both environmental and genetic factors. In this context, pharmacogenomics could play a crucial role in guiding MDMA treatment by identifying individuals with genetic predispositions affecting their response to MDMA. Tailoring treatment plans based on individual's genetic makeup may enhance therapeutic outcomes and minimize adverse effects, leading to safer and more effective use of MDMA in clinical settings. Literature analysis reveals that the influence of genetic variants within genes encoded for enzymes involved in MDMA metabolism and/or pharmacodynamics (PD) targets have been relatively under-investigated in humans. Some studies have pointed out associations between MDMA-induced effects and polymorphisms. For example, the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and cardiovascular MDMA-induced effects. Similarly, polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with several MDMA-induced adverse effects including mood disorders. However, despite these findings, only a few associations have been highlighted. Furthermore, some genes encoded for MDMA targets have been only poorly investigated, representing a significant research gap. These observations underscore the need for large-scale, controlled pharmacogenomics studies focusing on a broad panel of genes involved into MDMA pharmacokinetics and PD. Such studies could provide critical insights for optimizing MDMA's therapeutic use and minimizing its risks.
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 5
- Drugs Used in "Chemsex"/Sexualized Drug Behaviour-Overview of the Related Clinical Psychopharmacological Issues. Brain Sciences April 22, 2025
- Commentary on Methods for Addressing Functional Unblinding and Mechanistic Uncertainty in Clinical Trials of Psychedelic-Assisted Treatments Current Treatment Options in Psychiatry November 11, 2025
- Psychologists’ attitudes towards the use of MDMA in therapy may be shaped by personal experiences Clinical Psychologist August 13, 2026
- Applications of MDMA in Modern Medicine - A Literature Review Journal of Education, Health and Sport January 14, 2025
- Integrating Artificial Intelligence and Digital Innovations in Psychedelic and Brain Therapeutics. ACS Medicinal Chemistry Letters January 23, 2025
Cites 36
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration Social Neuroscience June 25, 2009
- Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study PLoS One May 4, 2012
- A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy Frontiers in Psychiatry March 20, 2019
and 31 more in the library