title: Oxytocin receptor gene variation predicts subjective responses to MDMA.
abstract: 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.
authors.affiliation: a Department of Psychiatry and Behavioral Neuroscience , University of Chicago , Chicago , IL , USA.|b Interdisciplinary Scientist Training Program , University of Chicago , Chicago , IL , USA.
authors.forename: Anya K
authors.initials: AK
authors.lastname: Bershad
authors.affiliation: a Department of Psychiatry and Behavioral Neuroscience , University of Chicago , Chicago , IL , USA.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Weafer
authors.affiliation: c Department of Preventive Medicine , University of Southern California , Los Angeles , CA , USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Kirkpatrick
authors.affiliation: d Department of Psychiatry and Behavioral Science , University of Texas Health Science Center at Houston , Houston , TX , USA.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Wardle
authors.affiliation: a Department of Psychiatry and Behavioral Neuroscience , University of Chicago , Chicago , IL , USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Miller
authors.affiliation: a Department of Psychiatry and Behavioral Neuroscience , University of Chicago , Chicago , IL , USA.
authors.forename: Harriet
authors.initials: H
authors.lastname: de Wit
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D060005:Genotyping Techniques; D006213:Hallucinogens / Q000494:pharmacology*; D006579:Heterozygote; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D018045:Receptors, Oxytocin / Q000235:genetics*; D057566:Self Report; D019966:Substance-Related Disorders / Q000235:genetics; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D013287:Illicit Drugs; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: MDMA; OXTR; oxytocin; social behavior