The effect of MDMA administration on oxytocin concentration levels: systematic review and a multilevel meta-analysis in humans

3,4-Methylenedioxmethamphetamine (MDMA) has been shown to enhance social cognition, partly through its effects on oxytocin, a neuropeptide involved in social cognition. Despite growing evidence linking MDMA to increased oxytocin levels, no study has systematically examined this relationship across different doses, times, and participant characteristics. This systematic review and meta-analysis evaluates the effects of MDMA administration on peripheral oxytocin levels in humans. A systematic search identified ten studies, comprising 39 effect size estimates. Multilevel meta-analyses were conducted using Hedge's g as the primary outcome, with dose, time of measurement, and sex as moderators. Results revealed that oxytocin levels increased over time, peaking between 150 and 200 min, before declining. The dose did not significantly predict oxytocin changes, and a trend suggested that samples with a higher proportion of female participants exhibited smaller increases in oxytocin levels. These findings suggest that MDMA transiently elevates oxytocin levels in a time-dependent manner, potentially contributing to its prosocial effects. Importantly, these findings may guide oxytocin-informed timing of MDMA-assisted psychotherapy sessions. Standardization of methods and larger sample sizes are needed to clarify these effects and optimize the therapeutic benefits of MDMA.