Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug–drug interactions
Saskia J. Rietjens, Laura Hondebrink, Remco H S Westerink, Jan Meulenbelt
Critical Reviews in Toxicology October 3, 2012 DOI: 10.3109/10408444.2012.725029 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA Serotonin |
| Keywords | Pharmacology Citalopram Ketanserin Serotonin syndrome Reuptake inhibitor Pharmacodynamics Pharmacokinetics |
| Citations | 51 |
| Key findings | Genetic polymorphisms and drug interactions modulate MDMA's effects, and carvedilol, ketanserin, and haloperidol may be useful treatments for MDMA intoxication. |
Abstract
Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates the triage and treatment of MDMA users needing medical care. The user's genetic profile and interactions resulting from polydrug use are key factors that modulate the individual response to MDMA and influence MDMA pharmacokinetics and dynamics, and thus clinical outcome. Polymorphisms in CYP2D6, resulting in poor metabolism status, as well as co-exposure of MDMA with specific substances (e.g. selective serotonin reuptake inhibitors (SSRIs)) can increase MDMA plasma levels, but can also decrease the formation of toxic metabolites and subsequent cellular damage. While pre-exposure to e.g. SSRIs can increase MDMA plasma levels, clinical effects (e.g. blood pressure, heart rate, body temperature) can be reduced, possibly due to a pharmacodynamic interaction at the serotonin reuptake transporter (SERT). Pretreatment with inhibitors of the dopamine or norepinephrine reuptake transporter (DAT or NET), 5-HT(2A) or α-β adrenergic receptor antagonists or antipsychotics prior to MDMA exposure can also decrease one or more MDMA-induced physiological and/or subjective effects. Carvedilol, ketanserin and haloperidol can reduce multiple MDMA-induced clinical and neurotoxic effects. Thus besides supportive care, i.e. sedation using benzodiazepines, intravenous hydration, aggressive cooling and correction of electrolytes, it is worthwhile to investigate the usefulness of carvedilol, ketanserin and haloperidol in the treatment of MDMA-intoxicated patients.
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 20
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay. Toxicology in Vitro December 1, 2017
- How MDMA's Pharmacology and Pharmacokinetics Drive Desired Effects and Harms The Journal of Clinical Pharmacology January 16, 2014
- CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4-methylene-dioxymethamphetamine in a controlled study in healthy individuals Pharmacogenetics and Genomics June 2, 2016
- MDMA Use by Paris Medical Students: Prevalence and Characteristics Substance Use & Misuse October 24, 2020
and 15 more in the library
Cites 84
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- 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
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacology March 3, 2006
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and 79 more in the library