MDMA decreases the effects of simulated social rejection

This placebo-controlled study (n=36) investigated the effects of MDMA (52.5mg & 105mg/70kg) on social rejection, as measured by self-reported ratings of positive mood and self-esteem in response to being excluded during a virtual ball-toss game. MDMA increased subjective pro-social feelings of lovingness and reduced the impact of simulated social rejection on mood and self-esteem in a dose-dependent manner.

Abstract

“Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.”

Authors: Charles G. Frye, Margaret C. Wardle, Greg J. Norman & Harriet de Wit

Summary

MDMA is a popular recreational drug that has been shown to enhance social engagement and feelings of empathy. However, it is unclear by which neurocognitive mechanisms MDMA produces these effects.

MDMA increases subjective reports of feelings of lovingness, insight, and sociability, and decreases amygdalar activation in response to images of angry faces. It also hampers accurate identification of fearful faces, and biases emotional identification of faces towards positive emotions and away from negative ones.

MDMA reduces perception of negative social cues in tasks involving cognitive judgments of social information, and in the Cyberball task, a virtual ball-toss game drawn from ostracism research, where participants are either ‘accepted’ or ‘rejected’ by others.

We examined the effect of MDMA on the parasympathetic nervous system by measuring high-frequency heart rate variability, which tracks vagal activity, and found that the effect was similar to the effect observed under MDMA administration, i.e. positive social emotions, desire to socialize, and reduced responses to negative social stimuli. Previous studies have found that experiencing rejection during Cyberball decreases RSA, so we examined whether self-esteem, mood, and RSA were related during Cyberball under placebo and MDMA administration conditions.

2.1. Study design

Participants received placebo, 0.75, and 1.5 mg/kg MDMA across three sessions under double-blind conditions, and filled out subjective effects questionnaires at regular intervals during each session.

2.2. Participants

Healthy participants in their 20s with some college education and light to moderate drug use were recruited through flyers and online advertisements and completed a 2-h screening that included a physical examination, ECG, modified structured clinical interview for DSM-IV (SCID) and self-reported health and drug use history.

Participants were required to refrain from recreational drugs for 48 h before sessions and from alcohol and over-the-counter drugs for 24 h before sessions. They received any of the following kinds of drugs: a stimulant, a tranquilizer, a marijuana-like drug, or a placebo.

2.3. Procedure

Participants first attended a 1-h orientation, then completed three 5-h individual study sessions, completed compliance checks, had their baseline blood pressure and heart rate measured, and filled out subjective effects questionnaires. Subjective drug effects, blood pressure and heart rate were assessed at 9:30 am, 10:00 am, 11:30 am, and 12:15 pm, respectively. At 12:15 pm, participants played two Cyberball games while their ECG was recorded, and answered mood and self-esteem questionnaires immediately after each game.

2.4.1. Subjective drug effects

Subjective drug effects on social emotions were measured using single-item visual analog scales (VAS) and the drug effects questionnaire (DEQ), and the ‘Loving’ measure was found to be sensitive to the pro-social subjective effects of MDMA.

2.4.2. Cardiovascular drug effects

Cardiovascular effects were measured using disposable self-adhesive electrodes arranged in the standard Lead II configuration. The RSA was calculated using a fast Fourier transform and integrated over the respiratory frequency band (0.12 to 0.40 Hz) during the Cyberball games.

2.5. Cyberball task

Social acceptance and rejection were simulated using the widely-implemented “Cyberball” virtual ball-toss game. Participants played two games per session, one to simulate acceptance and the other to simulate rejection. Participants played two kinds of games, one against a computer, and one against another person. They answered questions about how they felt during the games, and were asked to rate their agreement on a seven-point scale with statements like “I felt sad”, “I felt somewhat inadequate”, and “I felt like an outsider”.

2.6. Statistical analyses

We analyzed our data using a planned contrast approach to repeated measures analysis of variance (RMANOVA), and compared the subjective drug effects (DEQ Feel High and VAS Loving) using a one-way (Drug) RMANOVA. We then conducted post-hoc tests on individual time points using the non-parametric Wilcoxon signed-rank test.

3.1. Typical MDMA effects

MDMA increased area-under-the-curve scores for both the DEQ ‘Feel High’ and VAS ‘Loving’ tasks. These effects were present at the time points before and after the Cyberball task.

3.2. Cyberball results

Rejection decreased self-reported mood and self-esteem when compared to the same values after acceptance, and MDMA reduced this effect. MDMA also increased the perceived percentage of throws received selectively under the rejection condition.

3.3. RSA results

High doses of MDMA decreased RSA area-under-the-curve scores, though RSA still increased over the course of the session. Simulated rejection had no significant effect on RSA.

4. Discussion

MDMA increased subjective feelings of lovingness and decreased the impact of simulated social rejection on mood and self-esteem. It also decreased the perceived objective level of rejection and decreased a cardiac index of vagal activity.

MDMA decreased perceived intensity of rejection, and increased mood and self-esteem at lower doses than it affected perception of rejection. This suggests that MDMA affects social processing and behavior in more ways than just impairing perception.

We found no effect of MDMA on the processing of social information during simulated social acceptance, suggesting that the most prominent effect of MDMA on the processing of social information is impairment of the perception of rejection and responses to rejection, rather than an introduction of positivity bias.

These findings also have implications for the pharmacological mechanisms of MDMA’s pro-social effects, as oxytocin blockade in rats results in the elimination of MDMA’s pro-social effects, and MDMA increases release of both serotonin and norepinephrine, which may explain the lower subjective responses to Cyberball during MDMA administration. Lowered levels of vagal activity are typically associated with decreased social engagement and less effective emotional regulation, but MDMA increased participants’ self-reported feelings of lovingness.

We found no effect of the Cyberball simulated social situations on RSA in a mixed-gender population, in contrast to Murray-Close (2011), which was conducted with an exclusively female subject pool.

This study has a number of limitations, such as not eliciting any autonomic response and not reflecting all aspects of social rejection in the real world. Further studies should use more complex simulations and administer the drug to dyads to examine subjective and autonomic responses. The results presented here were gathered as part of a larger study, and the Cyberball task was performed after peak drug effect.

This study indicates that MDMA induces a pro-social drug state, which may have a role in MDMA-assisted psychotherapy, where the drug may encourage patients to speak openly about their issues and reduce the negative effects of difficult psychotherapy sessions on their mood and self-esteem.

Acknowledgements

The authors thank Celina Joos, Lindsey Davis, and Michael Helzer for aiding in data collection and scoring.