Oxytocin receptor gene variation predicts subjective responses to MDMA

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.

Keywords: MDMA; OXTR; oxytocin; social behavior.

Figure 1

Subjective responses to single oral doses of MDMA (0.75 and 1.5 mg/kg) and placebo on four factors summarizing the effects of the drug. The subjective factors were derived from a principal component analysis of drug-related visual analogue scales, and AUC was calculated using the change from precapsule. Bars depict mean ± SEM. * indicates significant difference from placebo, p < 0.05; ** indicates significant difference from placebo, p < 0.01.

Figure 2

Mean ratings of euphoria, anxiety, dizziness, and sociability after MDMA or placebo, by genotype (AA: N = 10; AG: N = 30, GG: N = 28). AUC was calculated using the change from precapsule. Bars depict mean ± SEM. * indicates significant difference between A/A and A/G; # indicates significant difference between A/A and G/G, p < 0.05.