Oxytocin receptor gene variation predicts subjective responses to MDMA

Anya K. Bershad, Jessica J. Weafer, Matthew G. Kirkpatrick, Margaret C. Wardle, Melissa A. Miller, Harriet de Wit

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish
Pages (from-to)592-599
Number of pages8
JournalSocial Neuroscience
Issue number6
StatePublished - Nov 1 2016

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute on Drug Abuse [grant numbers R01 DA002182 and R21 DA026570] to H. de Wit. Anya K. Bershad was supported by a grant from the National Institute of General Medical Sciences [2T32GM007281].

Publisher Copyright:
© 2016 Taylor & Francis.


  • MDMA
  • OXTR
  • oxytocin
  • social behavior

ASJC Scopus subject areas

  • Social Psychology
  • Development
  • Behavioral Neuroscience


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