Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects

PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018.


Methylenedioxymethamphetamine (MDMA) increases oxytocin, empathy, and prosociality. Oxytocin plays a critical role in emotion processing and social behavior and has been shown to mediate the prosocial effects of MDMA in animals. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the oxytocin receptor (OXTR) may influence the emotional and social effects of MDMA in humans. The effects of common genetic variants of the OXTR (rs53576, rs1042778, and rs2254298 SNPs) on the emotional, empathogenic, and prosocial effects of MDMA were characterized in up to 132 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. In a subset of 53 subjects, MDMA produced significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. The rs53576 and rs225498 SNPs did not moderate the subjective effects of MDMA in up to 132 subjects. None of the SNPs moderated MDMA-induced impairments in negative facial emotion recognition or enhancements in emotional empathy in the Multifaceted Empathy Test in 69 subjects. MDMA significantly increased plasma oxytocin concentrations. MDMA and oxytocin concentrations did not differ between OXTR gene variants. The present results provide preliminary evidence that OXTR gene variations may modulate aspects of the prosocial subjective effects of MDMA in humans. However, interpretation should be cautious due to the small sample size. Additionally, OXTR SNPs did not moderate the subjective overall effect of MDMA (any drug effect) or feelings of "closeness to others".

Trial registration: ClinicalTrials.gov: http://www.clinicaltrials.gov, No: NCT00886886, NCT00990067, NCT01136278, NCT01270672, NCT01386177, NCT01465685, NCT01771874, and NCT01951508.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Empathy / drug effects
  • Empathy / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • N-Methyl-3,4-methylenedioxyamphetamine / adverse effects
  • Oxytocin / antagonists & inhibitors
  • Oxytocin / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Oxytocin / genetics*
  • Social Behavior
  • Social Behavior Disorders / drug therapy*
  • Social Behavior Disorders / genetics
  • Social Behavior Disorders / pathology
  • Young Adult


  • OXTR protein, human
  • Receptors, Oxytocin
  • Oxytocin
  • N-Methyl-3,4-methylenedioxyamphetamine

Associated data

  • ClinicalTrials.gov/NCT00886886
  • ClinicalTrials.gov/NCT01386177
  • ClinicalTrials.gov/NCT01951508
  • ClinicalTrials.gov/NCT00990067
  • ClinicalTrials.gov/NCT01270672
  • ClinicalTrials.gov/NCT01465685
  • ClinicalTrials.gov/NCT01771874
  • ClinicalTrials.gov/NCT01136278

Grant support

This study was supported by the Swiss National Science Foundation (grant no. 320030_149493 and 320030_170249 to MEL). http://www.snf.ch. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.