No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation
Open accessAbstract
The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial registration: MDMA & PSB NTR 2636.
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In MDMA users, CSF and plasma oxytocin concentrations are uncorrelated.
“or in MDMA users (92)”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [92]
The Discussion (page unavailable) says plasma and CSF oxytocin concentrations do not correlate when sampled at the same time, citing another study for that observation. But this paper measured serum oxytocin in MDMA users, not CSF oxytocin, so it does not establish that the two concentrations are uncorrelated in MDMA users. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRecent trials found no effect of intranasal oxytocin in MDMA users.
“or in MDMA users (92)”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [92]
The Abstract reports that intranasal oxytocin did not affect the study’s measures of empathy and social interaction in 20 MDMA users. But the Results (Empathy tests and questionnaires; page unavailable) report an effect on self-rated personal distress, so the unqualified claim of “no effect” is too broad. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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Pitts, E. G., Minerva, A. R., Chandler, E. B., Kohn, J. N., Logun, M. T., Sulima, A., Rice, K. C., & Howell, L. L. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.80 · Cited by 20 · see citing works
Key interindividual determinants in MDMA pharmacodynamics
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MDMA does not alter responses to the Trier Social Stress Test in humans
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LSD acutely impairs fear recognition and enhances emotional empathy and sociality
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Zusammenhang von Empathiefähigkeit und Serumoxytocinkonzentration bei 14-jährigen Jugendlichen
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The good, the bad, and the intoxicated
Mason, N. L. (2021) · doi:10.26481/dis.20210608nm
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Self-citation
- Authors
- Kuypers, K. P. C., de la Torre, R., Farre, M., Yubero-Lahoz, S., Dziobek, I., Van den Bos, W., & Ramaekers, J. G.
- Affiliations
- Maastricht University (NL)
- Freie Universität Berlin (DE)
- Corresponding author
- Kuypers, Kim P. C.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-06-27
- Volume
- 9
- Issue
- 6
- Pages
- e100719
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4074089
- OpenAlex
- W2127572868
- Cited by
- 88
- References
- 55
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 11 · 2020: 2 · 2019: 6 · 2018: 12 · 2017: 10 · 2016: 9 · 2015: 9 · 2014: 1
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (400-07-201, 400-07-2013)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- MDMA, affective empathy, cognitive empathy, oxytocin, 5-HT1A receptor, pindolol, social interaction, trust, reciprocity, 5-HT2A receptor, vasopressin 1a receptor, plasma oxytocin
- MeSH terms
- Adolescent, Adult, Emotions, Empathy, Female, Humans, Interpersonal Relations, Male, Oxytocin, Pindolol, Surveys and Questionnaires, Placebo Effect, N-Methyl-3,4-methylenedioxyamphetamine, Substance-Related Disorders, Receptor, Serotonin, 5-HT1A, Young Adult
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