MDMA's immediate effects on empathy and recognizing emotions in people: a combined analysis

From inception up to April 2025, a search for relevant articles was conducted in the PubMed (Medline), PsycINFO, and Scopus bibliographic databases using specific keywords: "mdma" OR "ecstasy" OR "3,4-methylenedioxymethamphetamine" AND "empathy" OR "emotion" OR "social cognition" OR "emotion recognition" OR "facial emotion recognition" OR "emotional empathy" OR "cognitive empathy" OR "social". After a full text review, if a study was deemed eligible, its reference list was manually scrutinized for other relevant studies.

P The meta-analyses were conducted using the 'metafor'packagein RStudio version 2022.07.2, and Comprehensive Meta-Analysis (Version 3.3.070). Hedges'g was utilized as the measure of effect size. Hedges'g corrects for sample size bias and is interpreted according to Cohen's guidelines (0.2 for small effect, 0.5 for medium effect, and 0.8 for large effect). To evaluate heterogeneity across studies, Q statistics were used based on the random effects model, as significant heterogeneity is expected in meta-analyses of observational studies. Q assesses the amount of observed dispersion, and a statistically significant Q suggests that the studies do not share a common true effect size. The I2 index was used to assess the proportion of total variability in effect size estimates, with I2 values of approximately 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively. Publication bias due to small study bias was quantitatively tested using Egger's regression testfor each outcome. An Egger's test with avalue less than 0.05 was indicative of small study bias. Outlier and influence diagnostics were conducted to determine the impact of any outliers, and sensitivity re-analyses were performed without any identified outliers. Par12

We gathered data for the MET task, which involved obtaining means and standard deviations for three variables: (1) cognitive empathy, which measured the accuracy in discerning emotions portrayed in the photos; (2) explicit emotional empathy, reflecting the participants'ratings indicating their level of empathy towards the person in the photo; and (3) implicit emotional empathy, indicating the arousal levels experienced while viewing the photos. As for the FERT task, we focused on accuracy rates in recognizing emotions such as happiness, sadness, fear, and anger. We conducted analyses to determine whether MDMA led to an increase or decrease in accuracy or ratings for each respective variable.

, Several included studies used within-subject (crossover) designs, resulting in correlated observations between MDMA and placebo conditions. When available, within-subject statistics (means, standard deviations, and correlations) were used to compute standardized mean differences. When correlations were unreported, we used a conservative assumed correlation (r = 0.5) following recommendations for meta-analyses of psychopharmacological crossover studies. Par14

n p p MDMA did not affect cognitive empathy compared to placebo (studies: n = 4, combined overall sample: = 102, Hedges'g = 0.089, 95% CI from − 0.11 to 0.289, = 0.381). Between studies heterogeneity was non-significant (Q = 0.473 [df = 3], I2 = 0, = 0.924), thus meta-regressions were not performed. Par15

p p MDMA was found to improve explicit emotional empathy compared to placebo (N = 4, overall sample = 102, Hedge's g = 0.288, 95% CI from 0.094 to 0.481, = 0.003). Between studies heterogeneity was non-significant (Q = 1.599 [df = 3], I2 = 0, = 0.6595), thus meta-regressions were not performed. Par17

P Egger's regression test ( = 0.438) found no significant publication bias due to small study effects. Par18

p p MDMA was found to improve implicit emotional empathy compared to placebo (N = 3, overall sample = 82, Hedge's g = 0.228, 95% CI from 0.015 to 0.442, = 0.035). Between studies heterogeneity was non-significant (Q = 0.599 [df = 2], I2 = 0, = 0.741), thus meta-regressions were not performed. Par20

P Egger's regression test ( = 0.759) was conducted, and it found no significant publication bias due to small study effects. Par21

p p MDMA did not affect recognition of happy facial expressions compared to placebo (n = 9, overall sample = 294, Hedges'g = -0.035, 95% CI from − 0.614 to 0.076, = 0.536). Between studies heterogeneity was non-significant (Q = 2.872 [df = 8], I2 = 0, = 0.9421), thus meta-regressions were not performed. Par23

p p Initially, MDMA was not found to affect recognition of sad facial expressions compared to placebo (n = 9, overall sample = 294, Hedges'g = − 0.104, 95% CI from − 0.228 to 0.0192, = 0.097). Between studies heterogeneity was non-significant (Q = 8.005 [df = 8], I2 = 14.12%, = 0.432), thus meta-regressions were not performed. Par25

P p p Egger's regression test was conducted ( = 0.231) and demonstrated no significant publication bias due to small study effects. A trim-and-fill analysis identified two studies as potentially affecting the findings and imputation of these studies resulted in an adjusted effect size of − 0.058, = 0.338 (observed effect size = − 0.104, = 0.09). Influence diagnostics identified one potential outlier. Par26

p p MDMA decreased recognition of fearful facial expressions compared to placebo (N = 9, overall sample = 294, Hedge's g = − 0.239, 95% CI from − 0.402 to − 0.077, = 0.0038). Between studies heterogeneity was non-significant (Q = 14.817 [df = 8], I2 = 0, = 0.0628), thus meta-regressions were not performed. Par28

P Egger's regression test was conducted and resulted in avalue of 0.189 demonstrating no significant publication bias due to small study effects. Par29

p p MDMA decreased recognition of angry facial expressions compared to placebo (n = 9, overall sample = 294, Hedges'g = − 0.227, 95% CI from − 1.189 to 0.141, < 0.001). Between studies heterogeneity was significant and high (Q = 45.439 [df = 8], I2 = 96.59%, < 0.0001). Par31

p Egger's regression test was found to be significant ( < 0.0001) demonstrating significant publication bias due to small study effects. Par32

MDMA was found to increase emotional empathy but not cognitive empathy. Our findings are consistent with and extend prior work by Kuypers et al., who conducted a pooled subjects study to examine the effect of MDMA on empathy in this group. Our meta-analysis extends upon their earlier work by incorporating a new study published in 2019. Moreover, our meta analysis is different from a pooled subjects study since in a pooled study, researchers combine individual participant data from multiple studies into a single dataset, allowing for the analysis of larger sample sizes and enhancing statistical power. On the other hand, a meta-analysis such as we did involves the systematic review and statistical synthesis of results from multiple independent studies. This enabled us to draw more generalized conclusions, increasing the robustness of the findings and identifying patterns across different studies. The effect of MDMA on emotional empathy is believed to be primarily attributed to the substance's ability to augment the release of oxytocin, yet this conception is complex. Par36

– , , Oxytocin is a hormone that acts as a neuromodulator and plays a role in social behaviors in both animals and humans. Some studies indicate that oxytocin can promote affiliative behaviors such as generosity, empathy, and altruism. It has been observed that MDMA increases oxytocin levels. As a result, the elevation of emotional empathy associated with MDMA use might be attributed to the rise in oxytocin levels, which in turn facilitates prosocial behaviors. However, did not find significant increases in peripheral oxytocin levels following MDMA administration. Furthermore, their study indicated that increased peripheral oxytocin levels did not enhance emotional empathy, nor did it correlate with the increase in emotional empathy following MDMA use. Additionally, contrary to the belief that oxytocin exclusively promotes positive social emotions, evidence suggests that oxytocin can also enhance negative social emotions, such as aggression towards rival out-group membersand envy. Consequently, an alternative hypothesis has been proposed, suggesting that oxytocin amplifies the salience of social cues, and its effects are contingent upon individual characteristics and the specific situation in which it is administered. This perspective shares similarities with the set and setting hypothesisof psychedelic therapies, which posits that the effects of psychedelic substances are heavily influenced by the mindset of the individual and the contextual setting in which they are taken). Future research should elucidate the right set and setting for the safe use of MDMA. Par37

This is the first meta analysis to explore the effect of MDMA on facial emotion recognition. Overall, our results suggest that MDMA acutely reduces the ability to identify sad, fearful and angry facial expressions. These results could be explained by the effects of MDMA on amygdala activity. In an fMRI study by, acute MDMA administration led to a reduction in amygdala reactivity specifically towards angry facial expressions relative to neutral faces. Additionally, a meta-analysis investigating long-term MDMA users revealed significant reductions in serotonin transporter density in the amygdala. Another study utilizing 18FFlourodeoxyglucose PET to examine resting brain metabolism found pronounced reductions in left amygdala as well as the caudate and putamen in MDMA users compared to controls. Collectively, these findings suggest that MDMA administration is associated with diminished amygdala activity, potentially contributing to the altered emotional processing and recognition of negative facial expressions seen in the literature. Par38

It has been suggested that MDMA-induced-decreases in recognizing negative emotions may at least partly explain the enhanced inclination for social interaction typically seen after ingestion of MDMA. People in the user's surroundings become less scary or even just less negative, therefore this can facilitate approach behaviors. This effect could also play a role in strengthening the therapeutic alliance between a patient and therapist during psychotherapy since the patient is more interested and open to social interaction. Moreover, it could be that by attenuating the perception of potentially or seemingly negative emotions that may be conveyed through the therapist's facial expressions during psychotherapy, MDMA may promote a more positive and possibly safer space for the patient to address challenging emotions, such as the ones that may arise when talking about past traumatic events. Even if therapists do not actually express these negative facial expressions, patients can often project feelings of anger, fear and sadness onto the therapistsand with the influence of MDMA this could be lowered to enable a safer space. Therefore, future studies should examine the specific interaction between therapist and patient in an MDMA assisted psychotherapy session to examine these hypotheses. Par39

Firstly, the analysis of implicit emotional empathy included only three available studies, while other domains included 4 to 9 available studies. Secondly, this meta-analysis focused on studies in healthy volunteers, as there are no current studies investigating the effects of MDMA on these social functions in psychiatric populations. Acquiring this knowledge would enhance our comprehension of how MDMA influences individuals with psychiatric conditions, enabling us to tailor therapy more effectively, provide recommendations on who would benefit from it, and identify those who may be at risk of negative outcomes in therapeutic contexts.

It is important to note that these results point to a potential risk in using MDMA. When under the influence of MDMA, individuals may find themselves exceptionally open and responsive to the emotions and needs of others, often to the point of feeling highly connected. While this heightened empathic state may be therapeutic in a controlled setting, it also renders individuals potentially vulnerable to exploitation or abuse. The profound emotional openness induced by MDMA may lead individuals to trust and connect with others more readily, sometimes without appropriate discernment. This could be further exacerbated by a diminished ability to recognize and respond to negative emotions or potentially harmful situations, as MDMA can temporarily impair one's ability to accurately interpret and act upon cues that signal danger such as an angry face. This heightened susceptibility highlights the critical importance of conducting MDMA-assisted therapy within a controlled and secure environment, under the guidance of trained professionals, who can provide the necessary support and ensure the safety and well-being of individuals undergoing this form of treatment. Additionally, comprehensive education and preparatory sessions for individuals participating in MDMA-assisted therapy can help them understand and navigate the potential risks associated with heightened empathy.

Unfortunately, the available data on mistakes made in the Facial Emotion Recognition Task (FERT) is notably lacking, which represents a significant gap in our understanding. This missing information is crucial, as it could have provided valuable insights into whether the decrease in accuracy when identifying negative emotions under the influence of MDMA may be attributed to a misattribution of these emotions as positive. Such an analysis would have offered another layer of insight into the underlying mechanisms contributing to these observed decreases in accuracy, shedding light on the specific cognitive processes affected by MDMA.

Another key limitation involves potential challenges with maintaining effective blinding. MDMA produces distinctive physiological and psychological effects including elevated heart rate, pupil dilation, and marked changes in mood and sociability that are often recognizable to both participants and experimenters. Even under double-blind conditions, these overt cues can lead to partial unblinding and expectancy effects, potentially influencing both participants'performance on social-cognitive tasks and experimenters'subtle cues or interpretations. Several included studies attempted to mitigate this through active placebo controls (e.g., low-dose stimulants) or standardized instructions. Par43

Additional limitation concerns heterogeneity in the measurement instruments and implementation of social-cognition tasks. While we restricted inclusion to studies using two well-validated paradigms—the Multifaceted Empathy Test (MET) and the Facial Emotion Recognition Task (FERT)—small procedural differences remained. These included variations in image sets, stimulus intensity gradients, rating scales, and whether arousal and concern ratings were analyzed separately or combined. Such differences can introduce subtle variability in task sensitivity and outcome comparability, which may contribute to between-study variance that is not fully captured by conventional heterogeneity statistics.

acute Finally, the current meta-analysis focuses exclusively on theeffects of single-session MDMA administration. Although this design enhances experimental control and internal validity, it limits conclusions about the duration and functional significance of these effects. Longitudinal or follow-up data examining whether changes in empathy or emotion recognition persist after drug clearance remain sparse. Distinguishing between transient pharmacological modulation and longer-lasting neuropsychological change is critical, particularly for understanding MDMA's potential role as an adjunct in psychotherapy. Future studies should therefore include repeated assessments to determine whether acute effects on social cognition translate into enduring therapeutic or behavioral outcomes. Par45

This meta-analysis is composed solely of randomized controlled trials that provide evidence for the effects of MDMA on certain social cognition functions. Statistical analyses revealed no publication bias and almost no heterogeneity in the studies included here, which has important implications for the interpretation and reliability of the findings. The observed lack of heterogeneity suggests that the studies included in this meta-analysis are consistent with each other and yield similar results or effect sizes. This was likely achieved here by focusing on single tasks for each construct of social cognition. These findings further suggest that any variability observed across the studies is likely due to random sampling error rather than differences in study characteristics or underlying population effects. The absence of heterogeneity strengthens the overall validity and generalizability of the meta-analytic results, suggesting that the findings are robust and that the effect being examined is relatively stable across the included studies.

We also did not rely on survey data in this meta-analysis and focused exclusively on behavioral data collected through the use of comparable computerized tasks (MET or FERT). There are several advantages to this approach. First, behavioral tasks provide objective and standardized measurements of participants'performance. Unlike self-report surveys, which rely on participants'subjective perceptions and interpretations, computerized tasks directly assess participants'behavior and responses. This objectivity reduces potential biases associated with self-reporting, leading to more accurate and reliable data. Second, computerized tasks lead to reduced demand characteristics as participants may consciously or unconsciously alter their responses in surveys based on social desirability or perceived expectations. In behavioral tasks, participants are typically less aware of the specific hypotheses being tested, which reduces demand characteristics, and increases the likelihood of natural and unbiased responses. This enables researchers to capture more objective effects of MDMA in a standardized controlled environment. This is particularly valuable for studying sensitive topics such as early or recent trauma or exploring unconscious processes that occur with psychoactive substances. Lastly, computerized tasks enable replicability and standardization as they can be easily replicated and standardized across different research settings and populations. Ultimately, all of these factors contribute to enhancing the generalizability of our findings.

The studies examined in this meta-analysis focused exclusively on a young participant cohort (all age ranges were between 18 and 38), underscoring the need for future research to expand its scope and investigate the effects of MDMA on a wider range of age groups. While our findings provide valuable insights into the impact of MDMA on empathy and emotion recognition in young individuals, extending these investigations to encompass children, adolescents, and middle-aged to elderly adults is essential. Such comprehensive studies would contribute to a more comprehensive understanding of the potential age-related nuances in the effects of MDMA on these crucial socioemotional domains. Moreover, while the current studies analyzed in this meta analysis did not reveal any significant sex differences in the effects of MDMA on empathy and emotion recognition, a closer examination of each sex individually was hindered by the limited sample sizes of each sex in each study (women: 9–16, men: 8–40). In order to comprehensively investigate the potential impact of MDMA on empathy and emotion recognition according to sex, it is imperative that future research endeavors prioritize larger and more balanced sample sizes for both genders.

Understanding and alleviating social cognition difficulties, particularly empathy and emotion recognition, holds significant importance in the context of psychiatric disorders. Empathy deficits are commonly observed in various psychiatric conditions such as depression, addiction, borderline personality disorder, bipolar disorderand psychopathy. These disorders are broadly characterized by impaired interpersonal functioning and difficulties in relating to others. By investigating the effects of interventions like MDMA on empathy and facial expression recognition, we can gain valuable insights into potential therapeutic avenues for addressing these deficits. Enhancing social cognition abilities has the potential to improve interpersonal relationships, communication skills, and overall quality of life for individuals affected by these disorders. Moreover, it can contribute to the development of targeted interventions that focus on restoring and promoting empathic abilities in clinical populations. Therefore, acquiring a deeper understanding of the mechanisms underlying the enhancement of empathy is important for advancing the field of mental health and developing novel interventions for psychiatric disorders. Par49