OPEN Foundation

M. Wardle

Oxytocin receptor gene variation predicts subjective responses to MDMA

January 20, 2016 / MDMA, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , ,

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 3-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.

Bershad, A. K., Weafer, J. J., Kirkpatrick, M. G., Wardle, M. C., Miller, M. A., & de Wit, H. (2016). Oxytocin receptor gene variation predicts subjective responses to MDMA. Social neuroscience. http://dx.doi.org/10.1080/17470919.2016.1143026

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Acute effects of MDMA on autonomic cardiac activity and their relation to subjective prosocial and stimulant effects

September 10, 2014 / MDMA, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

MDMA is a stimulant with unique “prosocial” effects, the physiological and pharmacological mechanisms of which are unknown. Here, we examine the relationship of measures of parasympathetic and sympathetic nervous system activity to the prosocial effects of MDMA. Parasympathetic activity was measured using respiratory sinus arrhythmia (RSA) and sympathetic activity using pre-ejection period (PEP). Over three sessions, 33 healthy volunteers received placebo, 0.75 mg/kg, and 1.5 mg/kg MDMA under counterbalanced, double-blind conditions, while we measured subjective feelings, RSA, and PEP. RSA and PEP data were available for 26 and 21 participants, respectively. MDMA increased prosocial and stimulated feelings, decreased RSA, and decreased PEP. At 1.5 mg/kg, subjective prosocial effects correlated with stimulated feelings and PEP, but not RSA. This suggests sympathetic, rather than parasympathetic, effects relate to the prosocial effects of MDMA.

Clark, C. M., Frye, C. G., Wardle, M. C., Norman, G. J., & Wit, H. (2014). Acute effects of MDMA on autonomic cardiac activity and their relation to subjective prosocial and stimulant effects. Psychophysiology. https://dx.doi.org/10.1111/psyp.12327

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MDMA decreases the effects of simulated social rejection

February 8, 2014 / Anxiety disorders / PTSD, MDMA, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , ,

Abstract

3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6. https://dx.doi.org/10.1016/j.pbb.2013.11.030

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30 April - Q&A with Rick Strassman

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