Oxytocin receptor gene variation predicts subjective responses to MDMA

Introduction

MDMA (3,4-methylenedioxymethamphetamine) produces distinct prosocial effects such as increased empathy and sociability, which distinguish it from other stimulant drugs and contribute both to its recreational use and its potential as an adjunct to psychotherapy. Previous research indicates that MDMA increases oxytocin release via actions in hypothalamic nuclei, and that oxytocin administration in humans can produce prosocial effects; however, some studies have questioned whether peripheral oxytocin changes fully account for MDMA's empathogenic actions. Neuroimaging and behavioural work has also implicated altered processing of emotional faces and reward-related circuitry following MDMA, but the specific role of oxytocinergic signalling in these effects remains uncertain. Bershad and colleagues set out to test whether common variation in the oxytocin receptor gene (OXTR), specifically the rs53576 single nucleotide polymorphism (A/G), influences subjective responses to MDMA. Prior studies have associated the G/G genotype with higher empathy and sociability and greater sensitivity to intranasal oxytocin, whereas A-allele carriers show relative deficits in social processing. The investigators hypothesised that individuals homozygous for A (A/A) would show reduced prosocial responses to MDMA—particularly sociability—compared with G-allele carriers, when tested under controlled, double-blind conditions using two active oral MDMA doses and placebo.