MDMA alters emotional processing and facilitates positive social interaction

Wardle, Margaret C.; de Wit, Harriet

doi:10.1007/s00213-014-3570-x

Cited by 96Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorForensic Toxicology and Drug Analysis

MDMA alters emotional processing and facilitates positive social interaction

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Wardle, Margaret C., de Wit, Harriet·2014·Psychopharmacology

DOI 10.1007/s00213-014-3570-xPMC PMC4194242

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Abstract

Background ±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") produces "prosocial" effects, such as feelings of empathy and closeness, thought to be important to its abuse and its value in psychotherapy. However, it is not fully understood how MDMA alters basic emotional processes to produce these effects, or whether it produces corresponding changes in actual social behavior. Here, we examined how MDMA affects perceptions of and responses to emotional expressions, and tested its effects on behavior during a social interaction. We also examined whether MDMA's prosocial effects related to a measure of abuse liability.Methods Over three sessions, 36 healthy volunteers with previous ecstasy use received MDMA (0.75, 1.5 mg/kg) and placebo under double-blind conditions. We measured (i) mood and cardiovascular effects, (ii) perception of and psychophysiological responses to emotional expressions, (iii) use of positive and negative words in a social interaction, and (iv) perceptions of an interaction partner. We then tested whether these effects predicted desire to take the drug again.Results MDMA slowed perception of angry expressions, increased psychophysiological responses to happy expressions, and increased positive word use and perceptions of partner empathy and regard in a social interaction. These effects were not strongly related to desire to take the drug again.Conclusions MDMA alters basic emotional processes by slowing identification of negative emotions and increasing responses to positive emotions in others. Further, it positively affects behavior and perceptions during actual social interaction. These effects may contribute to the efficacy of MDMA in psychotherapy, but appear less closely related to its abuse potential.

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MDMA enhances positive emotional experiences while blunting negative ones.
“Additionally, MDMA enhances positive emotional experiences while blunting negative ones, potentially reducing defensive responses and increasing emotional flexibility (79, 150).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [150]
The Results and Discussion (page numbers unavailable) report stronger positive responses to happy expressions and slower identification of anger under MDMA. They do not establish a general blunting of negative emotional experiences: identification of fear and other emotions was unaffected, and the measured effects concern responses to and perception of expressions rather than emotional experience broadly. (LLM, conf=0.86)
Experimental — accuracy not yet measured
MDMA at 1.5 mg/kg reduced corrugator muscle activity to happy facial expressions in female participants and increased zygomatic muscle activity to happy facial expressions in all participants, with no effects while viewing negative emotions.
“In the same study, MDMA (1.5 mg/kg) reduced corrugator (“frown”) muscle activity to happy facial expressions in female participants and increased zygomatic (“smile”) muscle activity to happy facial expressions in all participants. No effects were found while viewing negative emotions (56).”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [56]
Wardle and de Wit reported that MDMA at 1.5 mg/kg increased the intensity required to identify anger, with no effects found for a lower dose or other emotions including fearful facial expressions.
“Furthermore, Wardle and de Wit (56) reported that MDMA (1.5 mg/kg) increased the intensity required to identify anger. No effects were found for a lower dose (0.75 mg/kg) or other emotions including fearful facial expressions.”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [56]

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Sessa, B. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2016.07.004 · Cited by 97 · see citing works
MDMA-assisted therapy significantly reduces eating disorder symptoms in a randomized placebo-controlled trial of adults with severe PTSD
Brewerton, T. D., Wang, J. B., Lafrance, A., Pamplin, C., Mithoefer, M., Yazar-Klosinki, B., Emerson, A., & Doblin, R. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.03.008 · Cited by 86 · see citing works
Prosocial effects of MDMA: A measure of generosity
Kirkpatrick, M. G., Delton, A. W., Robertson, T. E., & de Wit, H. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115573806 · Cited by 85 · see citing works
The Psychedelic Future of Post-Traumatic Stress Disorder Treatment
Zaretsky, T. G., Jagodnik, K. M., Barsic, R., Antonio, J. H., Bonanno, P. A., MacLeod, C., Pierce, C., Carney, H., Morrison, M. T., Saylor, C. F., et al. (2024) · Current Neuropharmacology · doi:10.2174/1570159x22666231027111147 · Cited by 85 · see citing works
Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting
Baggott, M. J., Coyle, J. R., Siegrist, J. D., Garrison, K. J., Galloway, G. P., & Mendelson, J. E. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881115626348 · Cited by 79 · see citing works
Modulation of Social Cognition via Hallucinogens and “Entactogens”
Preller, K. H., & Vollenweider, F. X. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00881 · Cited by 71 · see citing works
“Furthermore, Wardle and de Wit (56) reported that MDMA (1.5 mg/kg) increased the intensity required to identify anger.”
BackgroundInfluential
Effects of MDMA on attention to positive social cues and pleasantness of affective touch
Bershad, A. K., Mayo, L. M., Hedger, K. V., McGlone, F. P., Walker, S. C., & de Wit, H. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0402-z · Cited by 73 · see citing works
Positive psychology in the investigation of psychedelics and entactogens: a critical review
Jungaberle, H., Thal, S., Zeuch, A., Rougemont-Bücking, A., von Heyden, M., Aicher, H., & Scheidegger, M. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.06.034 · Cited by 70 · see citing works
Pharmacological Challenge Studies with Acute Psychosocial Stress
van Hedger, K., Bershad, A., & de Wit, H. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.08.020 · Cited by 67 · see citing works
Psychological mechanisms and functions of 5-HT and SSRIs in potential therapeutic change: Lessons from the serotonergic modulation of action selection, learning, affect, and social cognition
Roberts, C., Sahakian, B. J., & Robbins, T. W. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.09.001 · Cited by 61 · see citing works
MDMA and MDMA-assisted therapy
Wolfgang, A. S., Fonzo, G. A., Gray, J. C., Krystal, J. H., Grzenda, A., Widge, A. S., Kraguljac, N. V., McDonald, W. M., Rodriguez, C. I., & Nemeroff, C. B. (2025) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20230681 · Cited by 62 · see citing works
The Emerging Field of Psychedelic Psychotherapy
Barber, G., & Aaronson, S. T. (2022) · Current Psychiatry Reports · doi:10.1007/s11920-022-01363-y · Cited by 59 · see citing works
Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin
Varker, T., Watson, L., Gibson, K., Forbes, D., & O'Donnell, M. L. (2020) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2020.1817639 · Cited by 58 · see citing works
“…emotional and cognitive processes by increasing cognitive flexibility (Wagner et al. 2019), diminishing responses to negative stimuli, enhancing responses to positive emotions, and positively affecting behavior and perceptions during social interactions (Bedi et al. 2009; Wardle and de Wit 2014).”
Background
Naltrexone alters the processing of social and emotional stimuli in healthy adults
Wardle, M. C., Bershad, A. K., & de Wit, H. (2015) · Social Neuroscience · doi:10.1080/17470919.2015.1136355 · Cited by 52 · see citing works
MDMA: a social drug in a social context
Kirkpatrick, M. G., & de Wit, H. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3752-6 · Cited by 42 · see citing works
Oxytocin and MDMA (‘Ecstasy’) enhance social reward in rats
Ramos, L., Hicks, C., Caminer, A., Goodwin, J., & McGregor, I. S. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3899-9 · Cited by 40 · see citing works
Considering the context: social factors in responses to drugs in humans
de Wit, H., & Sayette, M. A. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4854-3 · Cited by 39 · see citing works
“MDMA also changes the content of speech, increasing the use of sexual, social, and emotional, especially positive emotional, words (Baggott et al. 2015; Wardle and deWit 2014).”
Background
Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment
Borissova, A., Ferguson, B., Wall, M. B., Morgan, C. J. A., Carhart-Harris, R. L., Bolstridge, M., Bloomfield, M., Williams, T. M., Feilding, A., Murphy, K., et al. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120926673 · Cited by 38 · see citing works
“For cognitive empathy, MDMA may impair accurate recognition of negative emotions (Dolder et al., 2018; Hysek et al., 2012; Hysek et al., 2014; Wardle and de Wit, 2014; Bedi et al., 2010).”
Background
Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder
Zeifman, R. J., Kettner, H., Ross, S., Weiss, B., Mithoefer, M. C., Mithoefer, A. T., & Wagner, A. C. (2024) · European Journal of Psychotraumatology · doi:10.1080/20008066.2023.2297536 · Cited by 37 · see citing works
“…of physiological and behavioural responses to social stimuli (Bedi et al., 2009; Bershad et al., 2019; Molla et al., 2023; Schmid et al., 2014; Wardle & de Wit, 2014; Zeifman, Kettner et al., 2023), larger studies that measure therapeutic alliance at each session (including during MDMA…”
Background
Making a medicine out of MDMA
Sessa, B., & Nutt, D. (2015) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.152751 · Cited by 37 · see citing works
Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects
Vizeli, P., & Liechti, M. E. (2018) · PLoS ONE · doi:10.1371/journal.pone.0199384 · Cited by 36 · see citing works
Oxytocin receptor gene variation predicts subjective responses to MDMA
Bershad, A. K., Weafer, J. J., Kirkpatrick, M. G., Wardle, M. C., Miller, M. A., & de Wit, H. (2016) · Social Neuroscience · doi:10.1080/17470919.2016.1143026 · Cited by 34 · see citing works
A review of the effects of nicotine on social functioning.
Martin, L. M., & Sayette, M. A. (2018) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000208 · Cited by 37 · see citing works
In the face of stress: Interpreting individual differences in stress-induced facial expressions
Mayo, L. M., & Heilig, M. A. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100166 · Cited by 33 · see citing works
Detection of acute 3,4-methylenedioxymethamphetamine (MDMA) effects across protocols using automated natural language processing
Agurto, C., Cecchi, G., Norel, R., Ostrand, R., Kirkpatrick, M. G., Baggott, M. J., Wardle, M. C., de Wit, H., & Bedi, G. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0620-4 · Cited by 31 · see citing works
Analysis of recreational psychedelic substance use experiences classified by substance
Hase, A., Erdmann, M., Limbach, V., & Hasler, G. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06062-3 · Cited by 31 · see citing works
“2014; Wardle & de Wit 2014).”
Result
Drug effects on responses to emotional facial expressions
Miller, M. A., Bershad, A. K., & de Wit, H. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000164 · Cited by 31 · see citing works
“…several prosocial effects, including increased desire to socialize, heightened feelings of empathy, and enhanced recognition of positive emotions (Ter Bogt and Engels, 2005; Sumnall et al., 2006; Hysek et al., 2012, 2013; Kirkpatrick et al., 2014; Schmid et al., 2014; Wardle and deWit, 2014).”
Background
Drug-induced social connection: both MDMA and methamphetamine increase feelings of connectedness during controlled dyadic conversations
Molla, H. M., Lee, R., Lyubomirsky, S., & de Wit, H. (2023) · Scientific Reports · doi:10.1038/s41598-023-43156-0 · Cited by 30 · see citing works
“The doses used here have been administered in previous studies without problems, and reliably produce subjective effects in healthy volunteers 9,29,30 .”
Method
Toward a New Science of Psychedelic Social Psychology: The Effects of MDMA (Ecstasy) on Social Connection
Lyubomirsky, S. (2022) · Perspectives on Psychological Science · doi:10.1177/17456916211055369 · Cited by 30 · see citing works
“…benefit relationships (e.g., responses to rejection [Frye et al., 2014], pleasure of social touch [Bershad et al., 2019], and use of positive words [Wardle & de Wit, 2014])—albeit found in the absence of an interaction partner—future studies should aim to test whether MDMA affects relationships…”
Background
Can psychedelics enhance group psychotherapy? A discussion on the therapeutic factors
Ponomarenko, P., Seragnoli, F., Calder, A. E., Oehen, P., & Hasler, G. (2023) · Journal of Psychopharmacology · doi:10.1177/02698811231155117 · Cited by 27 · see citing works
“…tend to enhance positive mood, as well as reduce the response to negative facial expressions and increase goaldirected behaviour towards positive compared to negative cues (Kometer et al., 2012; Preller and Vollenweider, 2019; Rocha et al., 2019; Roseman et al., 2018a; Wardle and de Wit, 2014).”
Background
MDMA ('Ecstasy'), oxytocin and vasopressin modulate social preference in rats: a role for handling and oxytocin receptors
Ramos, L., Hicks, C., Caminer, A., Couto, K., Narlawar, R., Kassiou, M., & McGregor, I. S. (2016) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2016.10.002 · Cited by 25 · see citing works
Potential processes of change in MDMA‐Assisted therapy for social anxiety disorder: Enhanced memory reconsolidation, self‐transcendence, and therapeutic relationships
Luoma, J. B., Shahar, B., Lear, M. K., Pilecki, B. C., & Wagner, A. (2021) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2824 · Cited by 27 · see citing works
“…situations and emotional expressions of others (Bedi et al., 2009; Hysek et al., 2014; Jungaberle et al., 2018; Kuypers et al., 2017; Wardle & De Wit, 2014; Wardle et al., 2014) may make therapist expressions of positive emotion such as compassion and liking more salient at both a…”
Background
Supportive Touch in Psychedelic Assisted Therapy
Neitzke‐Spruill, L., Beit, C. S., Averill, L. A., & McGuire, A. L. (2025) · The American Journal of Bioethics · doi:10.1080/15265161.2024.2433428 · Cited by 23 · see citing works
“…prosocial effects and facilitate feelings of openness, connection and intimacy with others, euphoric and loving feelings, increased sexual arousal, an increased threshold for anger, and fear responses (Baylen and Rosenberg 2006; Greer and Tolbert 1986; Liester et al. 1992; Wardle and de Wit 2014).”
Psychedelics and Psychedelic-Assisted Psychotherapy
Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodríguez, C. I., Kalin, N. H., & McDonald, W. M. (2021) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.19104 · Cited by 21 · see citing works
Greater empathy in MDMA users
Carlyle, M., Stevens, T., Fawaz, L., Marsh, B., Kosmider, S., & Morgan, C. J. A. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119826594 · Cited by 21 · see citing works
Methylenedioxymethamphetamine is a connectogen with empathogenic, entactogenic, and still further connective properties: It is time to reconcile “the great entactogen-empathogen debate
Stocker, K., & Liechti, M. E. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811241265352 · Cited by 19 · see citing works
“…random mentioning of the other term) (e.g., Hysek et al., 2014; Molla et al., 2023; Monson et al., 2020; Schmid et al., 2014; Straumann et al., 2023; Wardle and de Wit, 2014), some “entactogen” only (e.g., Adam et al., 2024; Feduccia and Mithoefer, 2018; Mitchell et al., 2023; Oehen and Gasser,…”
BackgroundInfluential
MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy
Sarmanlu, M., Kuypers, K. P. C., Vizeli, P., & Kvamme, T. L. (2023) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110843 · Cited by 19 · see citing works
“…bias as manifested by increased recognition of positive information (e.g. happy countenances) and/or decreased recognition of negative information (e.g. angry or fearful countenances) (e.g. Bedi et al., 2010; Bedi et al., 2009; Dolder et al., 2018; Hysek et al., 2012b; Wardle and de Wit, 2014).”
Does ±3,4-methylenedioxymethamphetamine (ecstasy) induce subjective feelings of social connection in humans? A multilevel meta-analysis
Regan, A., Margolis, S., de Wit, H., & Lyubomirsky, S. (2021) · PLoS ONE · doi:10.1371/journal.pone.0258849 · Cited by 19 · see citing works
MDMA for the treatment of mood disorder: all talk no substance?
Patel, R., & Titheradge, D. (2015) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125315583786 · Cited by 16 · see citing works
Couple Therapy With MDMA—Proposed Pathways of Action
Wagner, A. C. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.733456 · Cited by 15 · see citing works
Therapeutic role of psilocybin and 3,4-methylenedioxymethamphetamine in trauma: A literature review
Fonseka, L. N., & Woo, B. K. P. (2023) · World Journal of Psychiatry · doi:10.5498/wjp.v13.i5.182 · Cited by 13 · see citing works
Effects of d-amphetamine upon psychosocial stress responses
Childs, E., Bershad, A. K., & de Wit, H. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116650388 · Cited by 13 · see citing works
Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder
Agin-Liebes, G., Zeifman, R. J., & Mitchell, J. (2025) · European Journal of Psychotraumatology · doi:10.1080/20008066.2025.2485513 · Cited by 12 · see citing works
“Additionally, MDMA’s social bonding effects – including increased feelings of closeness and empathy (Wardle & de Wit, 2014) may parallel the acceptance-of-self that is central to self-compassion.”
Altered States and Social Bonds: Effects of MDMA and Serotonergic Psychedelics on Social Behavior as a Mechanism Underlying Substance-Assisted Therapy
Schmid, Y., & Bershad, A. K. (2024) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2024.02.001 · Cited by 14 · see citing works
“During the presentation of socially rewarding stimuli, MDMA increased positive affective responses to emotional faces as measured by facial electromyography (25) and increased ventral striatal responses to images of happy faces (29).”
Background
Chemical cousins with contrasting behavioural profiles: MDMA users and methamphetamine users differ in social-cognitive functions and aggression
Zacher, A., Zimmermann, J., Cole, D. M., Friedli, N., Opitz, A., Baumgartner, M. R., Steuer, A. E., Verdejo‐García, A., Stock, A., Beste, C., et al. (2024) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2024.04.010 · Cited by 12 · see citing works
Social Psychopharmacology: Novel Approaches to Treat Deficits in Social Motivation in Schizophrenia
Bershad, A. K., & de Wit, H. (2023) · Schizophrenia Bulletin · doi:10.1093/schbul/sbad094 · Cited by 12 · see citing works
MDMA does not alter responses to the Trier Social Stress Test in humans
Bershad, A. K., Miller, M. A., & de Wit, H. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4621-x · Cited by 12 · see citing works
“Cortisol Introduction ±3,4-Methylenedioxymethamphetamine (MDMA, Becstasy^) is a widely used stimulant-psychedelic drug that produces unique prosocial effects.”
Background
LSD acutely impairs fear recognition and enhances emotional empathy and sociality
Dolder, P. C. (2016) · doi:10.26226/morressier.5785edc6d462b80296c9935b · Cited by 12 · see citing works
Negative Affect Circuit Subtypes and Neural, Behavioral, and Affective Responses to MDMA
Zhang, X., Hack, L. M., Bertrand, C., Hilton, R. A., Gray, N. J., Boyar, L., Laudie, J., Heifets, B. D., Suppes, T. M., van Roessel, P., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.7803 · Cited by 11 · see citing works
Challenges in translational research: MDMA in the laboratory versus therapeutic settings
de Wit, H., Bershad, A. K., & Grob, C. S. (2021) · Journal of Psychopharmacology · doi:10.1177/02698811211015221 · Cited by 11 · see citing works
“…to social threat (Bedi et al., 2009), it increases social feelings and dampens identification of negative emotions in others (Bedi et al., 2009; Wardle and de Wit, 2014; Wardle et al., 2014), it increases generosity toward others (Kirkpatrick et al., 2015), alters how people talk about…”
BackgroundResultInfluential
MDMA enhances positive affective responses to social feedback
Bershad, A. K., Hsu, D. T., & de Wit, H. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811231224153 · Cited by 9 · see citing works
“Beyond subjective ratings, MDMA selectively facilitated visual attention and psychophysiological responses to faces expressing positive emotions, suggesting increased salience of these positive social cues (Bershad et al., 2019; Wardle and de Wit, 2014).”
BackgroundInfluential
Will MDMA-assisted psychotherapy become a breakthrough in treatment-resistant post-traumatic stress disorder? A critical narrative review.
Szafoni, S., Więckiewicz, G., Pudło, R., Gorczyca, P. W., & Piegza, M. J. (2021) · Psychiatria Polska · doi:10.12740/pp/onlinefirst/133919 · Cited by 9 · see citing works
“Considering their importance, as well as the existence of completely different deviations in activity in PTSD patients, this seems to be another valuable therapeutic effect [12–14].”
Psychedelics and Eating Disorders: Exploring the Therapeutic Potential for Anorexia Nervosa and Beyond
Hu, S., Lin, C., Wang, H., & Wang, X. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00094 · Cited by 8 · see citing works
Substance use to enhance occupational performance and experience: a critical interpretive synthesis
Kiepek, N. C., Beagan, B. L., & Phelan, S. (2019) · Cadernos Brasileiros de Terapia Ocupacional · doi:10.4322/2526-8910.ctoar1926 · Cited by 8 · see citing works
Lack of evidence for positive reinforcing and prosocial effects of MDMA in pair-housed male and female rats
Smith, M. A., Schmidt, K. T., Sharp, J. L., Pearson, T., Davis, A. L., Gibson, A. N., & Potter, K. M. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174646 · Cited by 8 · see citing works
A Systematic Review of the MDMA Model to Address Social Impairment in Autism
Chaliha, D. R., Mamo, J. C. L., Albrecht, M. A., Lam, V., Takechi, R., & Vaccarezza, M. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210101130258 · Cited by 7 · see citing works
“(2014) found decreased frowns in response to others’ happy faces only in women [116].”
BackgroundInfluential
Psychedelics and Suicide-Related Outcomes: A Systematic Review
Meshkat, S., Malik, T., Zeifman, R. J., Swainson, J., Zhang, Y., Burback, L., Winkler, O., Greenshaw, A. J., Reichelt, A. C., Vermetten, E. H. G. J. M., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14051416 · Cited by 7 · see citing works
Facial mimicry is not modulated by dopamine D2/3 and opioid receptor antagonism
Korb, S., Clarke, A. D. F., Massaccesi, C., Willeit, M., & Silani, G. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06426-3 · Cited by 7 · see citing works
Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach
Albert, A. E., & Back, A. L. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1529427 · Cited by 6 · see citing works
“Additionally, MDMA enhances positive emotional experiences while blunting negative ones, potentially reducing defensive responses and increasing emotional ﬂ exibility (79, 150).”
Putting the MD back into MDMA
Nutt, D., & de Wit, H. (2021) · Nature Medicine · doi:10.1038/s41591-021-01385-8 · Cited by 6 · see citing works
MDMA for the treatment of misophonia, a proposal
Webb, J., & Keane, S. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.983285 · Cited by 6 · see citing works
Regular MDMA use is associated with decreased risk of drug injection among street-involved youth who use illicit drugs
Gaddis, A., Lake, S., Tupper, K. W., Nosova, E., Blommaert, K., Wood, E., & DeBeck, K. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.07.035 · Cited by 6 · see citing works
Psychostimulants and social behaviors
Cid-Jofré, V., Bahamondes, T., Correa, A. Z., Arias, I. A., Reyes-Parada, M. I., & Renard, G. M. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1364630 · Cited by 5 · see citing works
“For instance, Wardle and de Wit (Wardle and de Wit, 2014) analyzed the effects of MDMA using a three-session within-subjects design over 36 healthy volunteers of both sexes.”
BackgroundMethodInfluential
Quantitative natural language processing markers of psychoactive drug effects: A pre-registered systematic review
Ahuja, S., Zaher, F., & Palaniyappan, L. K. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251319455 · Cited by 5 · see citing works
“…an important person in the participant’s life (significant other) (Agurto et al., 2020; Baggott et al., 2015; Bedi et al., 2014; Wardle et al., 2012; Wardle and De Wit, 2014), three studies collecting free monologues (Agurto et al., 2020; Vogel et al., 2021; Zeidenberg et al., 1973), three studies…”
Influential
Comparing Mental Health across Distinct Groups of Users of Psychedelics, MDMA, Psychostimulants, and Cannabis
Rougemont-Bücking, A., Jungaberle, H., Scheidegger, M., Merlo, M. C. G., Grazioli, V. S., Daeppen, J., Gmel, G. E., & Studer, J. (2019) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2019.1571258 · Cited by 5 · see citing works
“However, because MDMA generally has mood-elevating properties (Patel and Titheradge 2015; Wardle and de Wit 2014) and it has been shown that its use is the result of psychic suffering rather than its cause (Lieb et al. 2002), the association between MDMA use and poor MHmight best be explained by…”
Background
From antidepressants and psychotherapy to oxytocin, vagus nerve stimulation, ketamine and psychedelics: how established and novel treatments can improve social functioning in major depression
Kupferberg, A., & Hasler, G. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1372650 · Cited by 4 · see citing works
Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model
Maciąg, M., Doszyn, O., Wnorowski, A., Zmorzyńska, J., & Budzyńska, B. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251324596 · Cited by 4 · see citing works
“It has been shown that MDMA enhances sociability (Wardle and De Wit, 2014) and reduces anxiety (Wolfson et al., 2020) in humans as well as in rodent models (Thompson et al., 2009).”
Practices in Religious Naturalism
Steinhart, E. C. (2018) · Routledge eBooks · doi:10.4324/9781315228907-30 · Cited by 4 · see citing works
Trip sitting or just sitting? Session facilitators substantially influence psychedelic experiences in clinical trials but not in healthy ones
Goldy, S. P., Sepeda, N. D., Hilbert, S. N., Bari, B. A., Garcia‐Romeu, A., Gukasyan, N., Barrett, F. S., Yaden, D. B., & Nayak, S. M. (2026) · Psychiatry Research · doi:10.1016/j.psychres.2026.117010 · Cited by 4 · see citing works
The 3,4‐methylenedioxymethamphetamine enhances early visual processing for salient socio‐emotional stimuli
Haggarty, C. J., Bershad, A. K., Kumar, M. K., Lee, R., & de Wit, H. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16346 · Cited by 3 · see citing works
“This effect on N170 suggests that MDMA affects early visual processing of socially salient stimuli, before it produces other cognitive or emotional processes (Bershad et al., 2016; Hysek et al., 2014; Kirkpatrick et al., 2014; Wardle & de Wit, 2014).”
Background
Social Homeostasis and Psychoactive Drugs: What Can We Learn From Opioid and Amphetamine Drug Challenge Studies in Humans?
Bershad, A. K., & de Wit, H. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.09.006 · Cited by 3 · see citing works
Post-traumatic stress disorder in psychedelic research
Bostoen, T., Tap, S. C., Breeksema, J. J., & Schoevers, R. A. (2025) · International review of neurobiology · doi:10.1016/bs.irn.2025.02.004 · Cited by 2 · see citing works
Case Report: Amplified psychoanalysis? Psychoanalysis, OCD and MDMA in a clinical case study
Dellanoce, F. (2026) · Frontiers in Psychology · doi:10.3389/fpsyg.2026.1617428 · Cited by 2 · see citing works
“3,4-Methylenedioxymethamphetamine facilitates therapeutic processes through several mechanisms that enhance emotional processing, interpersonal connections, and the overall therapeutic experience (Wardle and de Wit, 2014).”
LSD acutely impairs fear recognition and enhances emotional empathy and sociality
Dolder, P. C., Schmid, Y., Müller, F., Borgwardt, S., & Liechti, M. E. (2016) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(16)31139-7 · Cited by 2 · see citing works
MDMA for treatment of PTSD and neurorehabilitation in military populations
Dunn, W., Bershad, A. K., Krantz, D. E., & Vermetten, E. H. G. J. M. (2024) · Neurorehabilitation · doi:10.3233/nre-230270 · Cited by 2 · see citing works
“MDMA has been shown to enhance the experience of social reward across multiple dimensions including time spent socializing with a confederate, and responses to social images, attention to positive facial expressions, and social touch (Bedi et al., 2009; Bershad et al., 2019; Wardle & de Wit, 2014).”
Biochemical contributions to interpersonal emotion dynamics
Way, B. M., & Keaveney, A. (2018) · Cambridge University Press eBooks · doi:10.1017/9781316822944.007 · Cited by 2 · see citing works
Ventral striatum regulates behavioral response to ethanol and MDMA combination
Hamida, S. B., Lecourtier, L., Loureiro, M., Cosquer, B., Tracqui, A., Simmoneaux, V., Nehlig, A., Jones, B. C., de Vasconcelos, A. P., & Cassel, J. (2020) · Addiction Biology · doi:10.1111/adb.12938 · Cited by 2 · see citing works
“which include amphetamine-like stimulant actions, in parallel with enhanced feelings of empathy and social connection.(1,2) In rodents, MDMA acts as an indirect monoaminergic agonist(3,4) that induces the release of dopamine (DA) and serotonin (5-HT)(5,6) in several brain regions including the nucleus accumbens (NAc).”
Background
MDMA as well as amphetamine and alcohol increase feelings of social closeness in healthy adults
de Wit, H., Hahn, E., Smadi, S., Li, T., & Molla, H. M. (2024) · Scientific Reports · doi:10.1038/s41598-024-82632-z · Cited by 2 · see citing works
The empathogen 3,4-methylenedioxymethamphetamine, but not methamphetamine, increases feelings of global trust
Martinez, R. L., Radošić, N., Molla, H. M., de Wit, H., & Lyubomirsky, S. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251370999 · Cited by 1 · see citing works
“The doses were selected based on prior research that produced reliable subjective effects without adverse side effects (Hysek et al., 2014; Mayo et al., 2013; Wardle and de Wit, 2014).”
Psychedelic Use and Intimacy: A Systematic Review of Experimental and Naturalistic Research.
Bradford, A., Freedman, E., & Dinero, R. E. (2025) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2025.2577311 · Cited by 1 · see citing works
Shifting Patterns in Ecstasy Use: Increasing Detection of MDA in Forensic Seizures and Toxicological Cases in Southern Brazil
dos Santos, B. P., Pôrto, V. C., Birk, L., Nascimento, S., Sebben, V. C., Eller, S. C. W. D. S., & de Oliveira, T. F. (2026) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2026.2686365 · Cited by 1 · see citing works
Seeking Happiness: Understanding the Mechanisms of Mixing Music and Drugs
Lam, K., & Jadavji, N. M. (2018) · doi:10.22186/jyi.34.5.31-38 · Cited by 1 · see citing works
Trauma Innovations: MDMA as a Treatment Intervention for PTSD
Christian, A., Grey, A. E., & Sorg, T. (2015) · UST Research Online (University of St. Thomas - Minnesota)
MDMA enhances early visual processing for salient socio-emotional stimuli.Preprint
Haggarty, C. J., Bershad, A. K., Kumar, M., Lee, R., & de Wit, H. (2024) · doi:10.22541/au.171117634.48543663/v1
Addiction and Substance Use
Durrant, R. (2024) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780197544754.013.61
Quantitative Natural Language Processing Markers of Psychoactive Drug Effects: A Pre-Registered Systematic ReviewPreprint
Ahuja, S., Zaher, F., & Palaniyappan, L. K. (2024) · Research Square · doi:10.21203/rs.3.rs-4534997/v1
Two years on from Australia’s bold psychedelic experiment, here are our concerns
Rudge, C., & McClelland, R. (2025) · doi:10.64628/aa.d3hppu7em
Psychedelics and Sexual Trauma: Effects on Communication and Emotional Connection
Levey, M., Bonenti, B., Piatkowski, T. M., Ferris, J., Frankovitch, A., Barratt, M. J., Davies, E., WINSTOCK, A. R., & Puljević, C. (2026) · The Journal of Sex Research · doi:10.1080/00224499.2025.2601165
“While some smaller studies and anecdotal reports suggest that women may experience heightened emotional and prosocial responses to substances like MDMA and classic psychedelics (Kruger, Aday, et al., 2025; Wardle & de Wit, 2014), broader empirical evidence presents a more complex picture.”
Distinct Modulatory Effects on Affective Biases by Different Serotonergic Psychedelics and MDMA in Male Rats: Possible Implications for Antidepressant EffectsPreprint
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Is Ecstasy an “Empathogen”? Effects of +/- 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others
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Effects of ±3,4-Methylenedioxymethamphetamine (MDMA) Administration on Social Emotional Processing in Humans
Bedi, G. (2011) · The Open Addiction Journal · doi:10.2174/1874941001104010008 · Cited by 1 · see citing works
MDMA enhances pleasantness of affective touch
de Wit, H., & Bershad, A. K. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0473-x · Cited by 15 · see citing works
MDMA enhances emotional empathy and prosocial behavior
Hysek, C. M., Schmid, Y., Simmler, L. D., Domes, G., Heinrichs, M., Eisenegger, C., Preller, K. H., Quednow, B. B., & Liechti, M. E. (2014) · Zurich Open Repository and Archive (University of Zurich) · doi:10.5167/uzh-90165
‘Ecstasy’ as a social drug: MDMA preferentially affects responses to emotional stimuli with social content
Wardle, M. C., Kirkpatrick, M. G., & de Wit, H. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu035 · Cited by 52 · see citing works

Authors: Wardle, M. C., & de Wit, H.
Affiliations: The University of Texas Health Science Center at Houston (US)
Corresponding author: Wardle, Margaret C.
ORCID: Wardle, Margaret C.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2014-04-12
Volume: 231
Issue: 21
Pages: 4219-4229
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-014-3570-x
PMC: PMC4194242
OpenAlex: W2034187022
Cited by: 96
References: 45
Citations by year: 2026: 5 · 2025: 13 · 2024: 16 · 2023: 7 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 2 · 2016: 10 · 2015: 8 · 2014: 1
FWCI: 8.26
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: University of Chicago
National Institute on Drug Abuse (R01DA002812, T32DA007255)
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
Keywords: MDMA, ecstasy, emotional processing, prosocial effects, emotional expression perception, social interaction, empathy, abuse liability, mood, cardiovascular response, MDMA-assisted psychotherapy
MeSH terms: Adolescent, Adult, Affect, Blood Pressure, Double-Blind Method, Emotions, Empathy, Female, Hallucinogens, Heart Rate, Humans, Interpersonal Relations, Male, Social Behavior, N-Methyl-3,4-methylenedioxyamphetamine, Young Adult

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MDMA alters emotional processing and facilitates positive social interaction

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