Oxytocin receptor gene variation predicts subjective responses to MDMA
Bershad, A. K., de Wit, H., Kirkpatrick, M. G., Miller, M. A., Wardle, M. C., Weafer, J. J.
This double-blind, placebo-controlled within-subjects study (n=68) investigated the subjective effects of MDMA (52.5mg and 105 mg/70kg) in relation to genetic variation of oxytocin receptors of healthy participants. Results indicated that a single nucleotide polymorphism in the oxytocin receptor gene-mediated differences in sociability and euphoria in response to the higher dose, thus providing further evidence that oxytocin mediates the distinct social effects of MDMA.
Abstract
Introduction: 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) enhances the 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.Methods: 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 behaviour, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability.Results: 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.Discussion: 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.