Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré, Laura Xicota, E. B. de Sousa Fernandes Perna, Eef L. Theunissen, Johannes G. Ramaekers
Scientific Reports January 12, 2018 DOI: 10.1038/s41598-018-19618-1 via OpenAlex
Summary
MDMA's mood effects depend partly on a genetic variation in the serotonin transporter gene (5-HTTLPR). People with the short variant of this gene typically show more anxiety and negative mood, while those with two long alleles (l-group) tend to be less anxious. In a pooled analysis of four placebo-controlled studies with 63 polydrug ecstasy users, MDMA (75 mg) generally improved mood but also increased anxiety and confusion. Unexpectedly, the l-group reported higher anxiety regardless of MDMA or placebo. MDMA reduced depressive feelings only in females from the l-group, suggesting a sex- and genotype-dependent effect.
Study at a glance
| Characteristics | Pooled analysis of four placebo-controlled, within-subject studies Peer reviewed |
|---|---|
| Sample size | 63 |
| Population | Polydrug ecstasy users |
| Intervention | MDMA 75 mg |
| Dose | 75 mg |
| Topics | Anxiety Depression MDMA Serotonin |
| Keywords | Serotonin transporter Mood Psychology |
| Citations | 12 |
| Key finding | MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l-allele showing this beneficial effect. |
Abstract
Abstract MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant (‘ s -group’) of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a lower transcriptional efficiency compared to individuals who are homozygous for the l -allele (‘ l -group’). The present study aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood effects. Four placebo-controlled, within-subject studies were pooled, including in total 63 polydrug ecstasy users (N s-group = 48; N l-group = 15) receiving MDMA 75 mg and placebo on two test days, separated by minimally 7 days. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced –independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l -group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l -group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l -allele showing this beneficial effect.