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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 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
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 Placebo Allele Genotype Endocrinology Genetics
Citations 12
Key points 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.

Comparable studies

Other randomized controlled trials on MDMA for depression, most cited first.

Study Year Design Participants
3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. People with chronic posttraumatic stress disorder 2018 Randomized controlled trial n = 28
Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder. Adults diagnosed with severe PTSD 2025 Secondary analysis of a randomized controlled trial n = 82
Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial. Participants with advanced-stage cancer and associated depression and anxiety 2024 Randomized controlled trial n = 32
MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder Adults with comorbid post-traumatic stress disorder and alcohol use disorder 2026 Randomized controlled trial n = 100

Citations in the library

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