Does ±3,4-methylenedioxymethamphetamine (ecstasy) induce subjective feelings of social connection in humans? A multilevel meta-analysis

This meta-analysis (2021) explored the effect MDMA has on self-reported feelings of social connection in humans by combining the data from 27 placebo-controlled studies. It was found that MDMA has a moderate-to-large effect on self-reported sociability outcomes, suggesting that MDMA may have powerful implications for a variety of social situations.

Abstract

“3,4-Methylenedioxymethamphetamine (MDMA) is a psychostimulant known for producing positive subjective effects and for enhancing social functioning and social connection in both clinical and recreational settings. Over the past two decades, scientists have begun to study the psychological effects of MDMA through rigorous placebo-controlled experimental work. However, most existing studies have small Ns, and the average sizes of the reported effects are unknown, creating uncertainty about the impact of these findings. The goal of the present study was to quantify the strength of MDMA’s effects on self-reported social connection by aggregating sociability-related outcomes across multiple placebo-controlled studies. To this end, we conducted a multilevel meta-analysis based on 27 studies, 54 effect sizes, and a total of 592 participants. The results revealed a moderate-to-large effect (d = 0.86; 95% CI [0.68, 1.04]; r = .39; 95% CI [.32, .46]) of MDMA on self-reported sociability-related outcomes (e.g., feeling loving, talkative, and friendly). Given the magnitude of its effect on felt sociability, we propose that MDMA may have powerful implications for a variety of social contexts and for clinical settings, in particular. Finally, we discuss potential mechanisms underlying the relationship between MDMA and sociability-related feelings, as well as future directions for experimental work in this area.”

Authors: Annie Regan, Seth Margolis, Harriet de Wit, & Sonja Lyubomirsky

Summary

RESEARCH ARTICLE

A multilevel meta-analysis of 27 studies found that MDMA has a moderate-to-large effect on self-reported social connection, and that this effect may have powerful implications for a variety of social contexts and for clinical settings, in particular.

MDMA, often known as Ecstasy or Molly among recreational users, was classified as a Schedule I substance in the U.S. in 1985, but has since gained popularity in therapeutic settings for treating PTSD and other psychiatric conditions.

MDMA facilitates social connection by increasing self-reports of feeling loving, sociable, and friendly, and by decreasing reactions to negative affective stimuli. These effects may affect behavior, but their exact nature is not yet fully understood.

Scientists have begun to address the subjective psychosocial effects of MDMA through rigorous placebo-controlled experimental work, but the average sizes of the reported effects are still unknown.

Experimental studies of the effects of MDMA on the subjective experience of sociability

MDMA increases self-report ratings of feeling friendly, loving, and sociable, although the boundary conditions and mechanisms behind this relationship are not yet fully known.

Most placebo-controlled MDMA studies use within-subjects designs, and participants are administered moderate doses of MDMA or an inactive placebo at successive lab sessions. Subjective drug effects are most frequently assessed with the Adjective Mood Rating Scale, the Bond and Lader Mood Rating Scale, or other visual analogue scales.

To minimize expectancy effects, researchers use an active control that has similar energizing and euphoric effects as the experimental drug. This minimizes the likelihood that participants will respond to subjective measures based on their expectations.

Researchers have found that MDMA has unique subjective effects in contrast to similar drugs, such as methylphenidate and modafinil. More research is needed to investigate the similarities and differences in the subjective experience of MDMA versus other stimulants or other mood-boosting substances.

The present research

We sought to illuminate the strength of MDMA’s effects on self-reported social connection by synthesizing self-reported sociability-related outcomes across multiple placebo-controlled MDMA studies. However, the number of controlled MDMA experiments is relatively small.

A meta-analysis was conducted to determine the average effect size of MDMA on self-reported sociability-related outcomes. A meta-regression analysis was conducted to predict the average effect size.

Literature search

We searched PsycINFO and PubMed for studies on the subjective effects of MDMA, and emailed principal investigators from laboratories and research groups that have conducted placebo-controlled experiments with MDMA asking for any other or unpublished work examining the subjective effects of MDMA.

Inclusion criteria

We included placebo-controlled human studies that measured felt sociability, but many included multiple self-report items assessing constructs such as friendliness, talkativeness, and/or extraversion, resulting in multiple effect sizes from a single study.

Selected studies

We searched for 32 studies on MDMA and included male and female healthy young adult volunteers. All studies used a double-blind design with concealed placebo conditions, and most included complete data for each participant.

We included 61 studies with effect sizes and 95% confidence intervals in our initial analysis, but excluded five studies with outliers. We used 27 studies and 54 effect sizes in our final analysis.

Calculation of effect sizes

We calculated Cohen’s d for each effect size included in our meta-analysis. The within-person correlation was assumed to be .5, but the results do not substantively change with different assumed within-person correlations.

Analytic approach

We used a multilevel model to account for dependencies among effect sizes, including variance within studies, between studies, and between participants. This resulted in an equation where djk is equal to an overall mean plus random variation.

Overall effect size and variability

The meta-analysis included 54 effect sizes from 27 studies with a total of 592 participants. The average effect size of MDMA on sociability was moderate to large.

Effect sizes predicted by outcome type

We conducted a meta-regression to determine the effect of felt sociability on extraversion, friendliness, loving, and sociability. Extraversion was coded as the reference group for pairwise comparisons.

The omnibus F-test indicated that the effect sizes did not significantly vary across outcome measures, and no statistically significant differences were detected between each category and extraversion.

Effect sizes predicted by MDMA dosage

We conducted a meta-regression to determine if the effect size of MDMA could be predicted by the maximum MDMA dosage administered to participants in each study. The results indicated that the effect size increased by .01 for each 1 mg increase in MDMA dosage.

Publication bias

A funnel plot and a rank correlation test were used to examine publication bias in the included studies. The results showed that as study variance increased, the effect size increased, indicating that nonsignificant or negative findings for particular measures of sociability were not reported in some studies.

Discussion

MDMA has a moderate-to-large effect on self-reported sociability-related outcomes, which is in line with the growing body of theory and research on MDMA’s social functioning and social connection.

Mechanisms underlying the effects of MDMA on subjective sociability

MDMA may boost felt sociability through increased empathy. MDMA increases emotional empathy but not cognitive empathy, and this may be why MDMA users express more concern for and attention toward those experiencing moods congruent to their own.

MDMA may increase felt sociability via diminished threat perception, increased reward salience from social interactions, or a combination of these mechanisms. These three processes may also account for anecdotal reports of closeness, trust, and deep connection among recreational MDMA users.

MDMA as a social catalyst

Most placebo-controlled MDMA studies have been conducted with participants isolated in a laboratory room, with no opportunity for actual social interaction beyond receiving experimental instructions. However, one study found that participants who were tested in the presence of another participant felt more positive effects.

These findings support the idea that MDMA’s effects are dependent on the specific social context, including whether another person is present and whether (and what type of) future interaction is expected. Additionally, future research should explore how beliefs about MDMA might impact subjective experiences on the drug.

Implications for clinical contexts

Researchers are currently investigating the use of MDMA to treat a variety of mental health conditions, including PTSD and social anxiety among autistic adults. However, more research is needed to determine the exact mechanisms underlying MDMA’s influence on social experience and social functioning.

MDMA’s effects on sociability could have important implications for mental health treatment, as it may help patients feel more talkative and loving, which could facilitate the therapeutic alliance.

MDMA may create and maintain therapeutic (or other social) bonds by affecting several neurotransmitter systems, including serotonin, dopamine and norepinephrine, which are involved in social processes. Alternatively, MDMA may trigger social behavior indirectly, via shifts in self-perceptions that promote felt sociability.

MDMA may trigger downstream psychological changes that lead to increased desire for social interaction, valuing social interaction more, and feeling more rewarded by social interaction.

Limitations

This meta-analysis found that MDMA makes users feel sociable, loving, and friendly, but not as sociable as other stimulants. This suggests that future research should focus on studying MDMA’s unique subjective effects in contrast to other drugs.

Researchers are encouraged to include a larger battery of validated psychological measures tapping the experience of connection in future studies of MDMA, including comparisons to other substances and a sense of true connection and openness to deep conversation.

We included placebo-controlled human studies on MDMA to minimize variance due to participant characteristics and research setting. The sample sizes were relatively small and participants were largely sampled from Western, educated, industrialized cultures, which limits generalizability to other populations.

Concluding words

The current research indicates that MDMA has moderate-to-large effects on feelings of sociability in experimental settings, despite the fact that such settings typically preclude actual socializing. MDMA may have powerful implications for a variety of social contexts, including doctor-patient interactions and therapy sessions.