Oxytocin receptor gene variation predicts subjective responses to MDMA
Anya K. Bershad, Jessica Weafer, Matthew G. Kirkpatrick, Margaret C. Wardle, Melissa A. Miller, Harriet de Wit
Social Neuroscience January 20, 2016 DOI: 10.1080/17470919.2016.1143026 via OpenAlex
Summary
AI-generated from the abstractMDMA (ecstasy) increases sociability and empathy, likely through the release of oxytocin. A single-letter variation in the oxytocin receptor gene (OXTR rs53576) influences how people respond to the drug. In a double-blind, within-subjects study, 68 healthy volunteers with past MDMA experience received placebo, 0.75 mg/kg, or 1.5 mg/kg of MDMA. At the higher dose, individuals with the A/A genotype did not show the increase in sociability seen in G allele carriers. No genotypic differences appeared at the lower dose or in cardiovascular or other subjective effects. The results suggest MDMA-induced sociability depends on oxytocin signaling and that genetic variation in the oxytocin receptor modulates the drug's social effects.
Study at a glance
| Characteristics | Within-subjects, double-blind, placebo-controlled experiment Peer reviewed |
|---|---|
| Sample size | 68 |
| Population | Healthy volunteers with past MDMA experience |
| Intervention | MDMA |
| Dose | 0, 0.75 mg/kg, and 1.5 mg/kg |
| Duration | Three sessions |
| Topics | MDMA |
| Keywords | Oxytocin receptor Single-nucleotide polymorphism Genotype |
| Citations | 35 |
| Key finding | MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype of the OXTR rs53576 polymorphism, whereas it did in G allele carriers. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here, we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this three-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg, and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.