How Can Intranasal Oxytocin Research Be Trusted? A Systematic Review of the Interactive Effects of Intranasal Oxytocin on Psychosocial Outcomes
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Over the past two decades, research about the role of oxytocin (OT) in human behavior has grown exponentially. However, a unified theory of OT effects has yet to be developed. Relatedly, growing concerns about the robustness of conclusions drawn in the field have been raised. The current article contributes to this debate by reporting on and discussing key conclusions from a systematic review of published studies addressing the interactive effects of intranasal OT (IN-OT) administration on psychosocial outcomes in a healthy population. The review indicates that (a) tested interactive IN-OT effects were highly heterogeneous; (b) for most published interactions, no replication was attempted; (c) when attempted, replications were largely unsuccessful; (d) significance was unrelated to sample size; (e) statistical power was critically low and unrelated to the rate of significant results; and (f) research practices were characteristic of an exploratory approach. This concerning state of affairs makes it virtually impossible to tease apart true from false interactive IN-OT effects. We provide constructive directions on the basis of this observation and positive predictive value simulations for future research that should help extract true effects from noise and move the IN-OT field forward.
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Intranasal oxytocin's effects on both social and addictive behaviors in clinical studies are inconsistent and impacted by various methodological differences.
“intranasal oxytocin's effects on both social and addictive behaviors in clinical studies are inconsistent and impacted by various methodological differences emerging in this rapidly proliferating literature.”
From Results of a Randomized Controlled Trial Examining the Efficacy of Intranasal Oxytocin to Enhance Alcohol Behavioral Couple Therapy (2025) · cites this paper as [14]
Factors such as small sample sizes, underpowered and exploratory designs, measurement inconsistencies in laboratory versus naturalistic trials, and wide variability in dosing potency and strategy have shaped the complexity of the clinical oxytocin literature.
“Factors such as small sample sizes, underpowered and exploratory designs, measurement inconsistencies in laboratory versus naturalistic trials, and wide variability in dosing potency and strategy have all shaped the complexity of the clinical oxytocin literature to date13–15.”
From Results of a Randomized Controlled Trial Examining the Efficacy of Intranasal Oxytocin to Enhance Alcohol Behavioral Couple Therapy (2025) · cites this paper as [14]
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Manzato, M., Hamidabad, N. M., Clark, M. M., Pardo, L. S., Montone, R. A., Lerman, L. O., & Lerman, A. (2026) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2026.01.007 · Cited by 2 · see citing works
The pandemic should catalyze research on social pain: Examining oxytocin administration studies
Tabak, B. A. (2022) · Biological Psychology · doi:10.1016/j.biopsycho.2022.108315 · Cited by 2 · see citing works
Grebe, N. M., Sheikh, A., Ohannessian, L., & Drea, C. M. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106044 · Cited by 2 · see citing works
Bowden, S., Becker, K. D., Luxhoj, A., Grinevich, V., Lee, J. D. A., & Veenema, A. H. (2026) · Hormones and Behavior · doi:10.1016/j.yhbeh.2026.105949 · Cited by 1 · see citing works
Kroll, C., Schruers, K. R. J., Viechtbauer, W., Vingerhoets, C., Seidel, L., Riedl, A. M., & Hernaus, D. (2026) · Cortex · doi:10.1016/j.cortex.2026.03.006 · Cited by 1 · see citing works
Mentalization, Oxytocin, and Cortisol in the General Population
Török, E., Kelemen, O., & Kéri, S. (2023) · Life · doi:10.3390/life13061329 · Cited by 1 · see citing works
“These results led researchers to question the utility of the intranasal oxytocin administration paradigm and required improving the accuracy and reliability of the oxytocin level evaluation following the administration [35,36].”
BackgroundInfluentialOxytocin receptor epigenetics: from biomarker to potential therapeutic target
Burris, H. H., White, L. K., Waller, R. E., & Chaiyachati, B. H. (2024) · Pediatric Research · doi:10.1038/s41390-024-03686-3 · Cited by 1 · see citing works
No association between genetic variants in MAOA, OXTR, and AVPR1a and cooperative strategies
Rivera-Hechem, M. I., Rodríguez‐Sickert, C., Guzmán, R. A., Ramírez-Parada, T., Benavides, F., Landaeta, V., Aspé-Sánchez, M., & Repetto, G. M. (2020) · PLoS ONE · doi:10.1371/journal.pone.0244189 · Cited by 1 · see citing works
“For instance, the association between exogenous intranasal oxytocin and higher levels of trust [54, 63] and the correlation between trust and oxytocin plasma levels [64] has been poorly replicated [60, 65].”
BackgroundOxytocin increases trust in humans with a low disposition to trustPreprint
Vogt, B., Bengart, P., Declerck, C., & Fehr, E. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.01.679711 · Cited by 1 · see citing works
“Mierop et al. 3 estimate that up to 90% of reported OT interaction effects may be false positives, while the intended main effects remain undetectable due to small sample sizes.”
Grebe, N. M., Sheikh, A., Ohannessian, L., & Drea, C. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.14.507945
Better safe than sorry: Oxytocin shifts the regulatory focus
Pfundmair, M. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106361
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Deilhaug, E., Moerkerke, M., Sartorius, A. M., Kang, H., Kildal, E. S.-M., Walle, K. M., Elvsåshagen, T., Westlye, L. T., Nærland, T., Andreassen, O. A., et al. (2026) · Psychophysiology · doi:10.1111/psyp.70334
“The research on oxytocin administration has produced mixed results, and this heterogeneity extends across several domains (Audunsdottir et al. 2024; Kang et al. 2025; Keech et al. 2018; Mierop et al. 2020; Quintana et al. 2021; Winterton et al. 2021).”
Oxytocin increases trust in men low in dispositional trust
Vogt, B., Bengart, P., Declerck, C. H., & Fehr, E. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2602655123
Oxytocin as regulator of stress and inflammation in aging
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Neurobiology of Pet Loss Grief: A Review from a One Health Perspective
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“Yet, recent meta-analyses and methodological reviews have raised serious concerns about the reproducibility of intranasal oxytocin effects on human social and emotional outcomes [93,94].”
- Authors
- Mierop, A., Mikolajczak, M., Stahl, C., Béna, J., Luminet, O., Lane, A., & Corneille, O.
- Affiliations
- UCLouvain (BE)
- University of Cologne (DE)
- Centre National de la Recherche Scientifique (FR)
- Fund for Scientific Research (BE)
- Corresponding author
- Mierop, A.
- Venue
- Perspectives on Psychological Science
- Publisher
- SAGE Publications
- Published
- 2020-07-07
- Volume
- 15
- Issue
- 5
- Pages
- 1228-1242
- ISSN
- 1745-6916 (ISSN-L)
- 1745-6924
- OpenAlex
- W3039842734
- Semantic Scholar
- 23c2ca6eb84165e12da858981b2ad236997c3f16
- Cited by
- 53
- References
- 46
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 3
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Perspectives on Psychological Science (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- HAL (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- OSF Preprints (OSF Preprints) (submittedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Psychology Research and Bibliometrics
- Keywords
- intranasal oxytocin, interaction effects, psychosocial outcomes, research reproducibility, replication failure, statistical power, sample size, positive predictive value, healthy population
- MeSH terms
- Social Cognition, Psychosocial Functioning, Administration, Intranasal, Humans, Oxytocin
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