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 via OpenAlex
Summary
AI-generated from the abstractA pooled analysis of eight placebo-controlled studies in 124 healthy subjects tested whether common genetic variants in serotonin-system genes influence the physiological and subjective effects of 125 mg of MDMA. Variants in TPH2, HTR2A, and the serotonin-transporter gene showed only modest, non-significant associations after correction for multiple comparisons. No tested genetic polymorphism significantly altered the response to MDMA. The results suggest that interindividual differences in serotonin-system genes play a marginal role in MDMA's effects, whether used recreationally or therapeutically.
Study at a glance
| 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 |
| Citations | 13 |
| Key finding | 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.