Role of Serotonin Transporter and Receptor Gene Variations in the Acute Effects of MDMA in Healthy Subjects
Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
ACS Chemical Neuroscience December 27, 2018 DOI: 10.1021/acschemneuro.8b00590 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pooled analysis of randomized, double-blind, placebo-controlled studies Peer reviewed |
|---|---|
| Sample size | 124 |
| Population | Healthy subjects |
| Intervention | MDMA |
| Dose | 125 mg |
| Topics | MDMA Serotonin |
| Keywords | Tph2 Serotonin transporter Tryptophan hydroxylase Single-nucleotide polymorphism Pharmacology Receptor Endocrinology Genetics Genotype |
| Citations | 13 |
| Key points | None of the tested genetic polymorphisms in serotonin-system genes significantly influenced the response to MDMA after correction for multiple comparisons. |
Abstract
Methylenedioxymethamphetamine (MDMA; ecstasy) is used recreationally and has been investigated as an adjunct to psychotherapy. Most acute effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine [5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms (SNPs) and polymorphic regions in 5-HT system genes, may contribute to interindividual differences in the acute effects of MDMA. We characterized the effects of common genetic variants within selected genes that encode the 5-HT system (TPH1 [tryptophan 5-hydroxylase 1] rs1800532 and rs1799913, TPH2 [tryptophan 5-hydroxylase 2] rs7305115, HTR1A [5-HT1A receptor] rs6295, HTR1B [5-HT1B receptor] rs6296, HTR2A [5-HT2A receptor] rs6313, and SLC6A4 [serotonin transporter] 5-HTTLPR and rs25531) on the physiological and subjective response to 125 mg of MDMA compared with placebo in 124 healthy subjects. Data were pooled from eight randomized, double-blind, placebo-controlled studies that were conducted in the same laboratory. TPH2 rs7305115, HTR2A rs6313, and SLC6A4 5-HTTLPR polymorphisms tended to moderately alter some effects of MDMA. However, after correcting for multiple comparisons, none of the tested genetic polymorphisms significantly influenced the response to MDMA. Variations in genes that encode key targets in the 5-HT system did not significantly influence the effects of MDMA in healthy subjects. Interindividual differences in the 5-HT system may thus play a marginal role when MDMA is used recreationally or therapeutically.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 11
- Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies Journal of Psychopharmacology March 30, 2021
- Dosing Psychedelics and MDMA. Current Topics in Behavioral Neurosciences 2022
- MDMA interactions with pharmaceuticals and drugs of abuse Expert Opinion on Drug Metabolism & Toxicology March 31, 2020
- Cellular Uptake of Psychostimulants – Are High- and Low-Affinity Organic Cation Transporters Drug Traffickers? Frontiers in Pharmacology January 20, 2021
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
and 6 more in the library
Cites 38
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and 33 more in the library