Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study
This prospective survey study found that people on serotonergic antidepressants reported significantly reduced acute subjective psychedelic effects—especially mystical, challenging and emotional breakthrough experiences—compared with unmedicated participants, yet both groups showed similar improvements in well‑being and depressive symptoms. The authors conclude SRIs may blunt subjective effects without diminishing short‑term antidepressant benefit, warranting controlled investigation.
Authors
- Robin Carhart-Harris
- David Nutt
- David Erritzoe
Published
Abstract
Background
There is growing evidence for the therapeutic effects of psychedelics. However, it is still uncertain how these drugs interact with serotonergic antidepressants (serotonin reuptake inhibitors (SRIs)).
Objective
This study explores the interaction between psychedelics and SRIs in terms of therapeutic effects. The objective is to compare acute psychedelic effects and subsequent changes in well-being and depressive symptoms among ‘SRI −’ individuals (not on psychiatric medication) and ‘SRI +’ individuals (undergoing SRI treatment).
Methods
Using prospective survey data, the study employs multivariate analysis of covariance (MANCOVA) and linear mixed effect models to analyse subjective differences and changes in well-being and depressive symptoms pre- and post-psychedelic experiences.
Results
Results indicate that ‘SRI −’ participants experience significantly more intense subjective effects compared to ‘SRI +’ participants ( F = 3.200, p = 0.016) in MANCOVA analysis. Further analysis reveals ‘SRI –’ individuals report stronger mystical (18.2% higher, p = 0.048), challenging (50.9% higher, p = 0.001) and emotional breakthrough experiences (31.9% higher, p = 0.02) than ‘SRI +’ individuals. No differences are observed in drug-induced visual effects ( p = 0.19). Both groups exhibited similar improvements in well-being and depressive symptoms after the psychedelic experience.
Conclusion
Individuals presumed to be on serotonergic antidepressants during psychedelic use display reduced subjective effects but similar antidepressant effects compared to those not undergoing SRI treatment. Further controlled research is needed to comprehend the interplay between serotonergic antidepressants and psychedelics, illuminating potential therapeutic benefits and limitations in clinical contexts.
Research Summary of 'Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study'
Introduction
Classic psychedelics such as psilocybin, LSD, DMT and mescaline have seen a renewed research interest because controlled administration can produce rapid and sometimes sustained symptom improvements in depression, OCD and anxiety disorders. Many clinical participants are already prescribed serotonergic antidepressants (selective serotonin reuptake inhibitors, SSRIs, and serotonin–noradrenaline reuptake inhibitors, SNRIs), and earlier case reports and observational work have suggested that chronic SRI use can attenuate the subjective effects of psychedelics. Conversely, a recent randomised trial of 14-day escitalopram pre-treatment in healthy volunteers found reduced physiological and some negative effects of psilocybin but no reduction in positive subjective effects, leaving the interaction between SRIs and psychedelics uncertain. Barbut Siva and colleagues set out to address this gap using prospectively collected survey data from naturalistic psychedelic experiences. The study compared acute subjective psychedelic effects and before–after changes in well-being and depressive symptoms between people with self-reported psychiatric diagnoses who were currently taking SRIs ('SRI +') and those who reported no lifetime psychiatric medication use ('SRI -'), aiming to inform trial design and clinical practice for psychedelic-assisted interventions.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Pro members can view the original manuscript directly in the browser.
Study Details
- Study Typeindividual
- Journal
- Topics
- Authors
- APA Citation
Barbut Siva, J., Barba, T., Kettner, H., Kuc, J., Nutt, D. J., Carhart-Harris, R., & Erritzoe, D. (2024). Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study. Journal of Psychopharmacology, 38(2), 145-155. https://doi.org/10.1177/02698811231224217
References (22)
Papers cited by this study that are also in Blossom
Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Bonson, K. R. · Neuropsychopharmacology (1996)
Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S. et al. · Journal of Psychopharmacology (2016)
Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)
Erritzoe, D., Barba, T., Spriggs, M. J. et al. · Journal of Psychopharmacology (2024)
Gashi, L., Sandberg, S., Pedersen, W. · International Journal of Drug Policy (2021)
Gonza ´lez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. · Neuron (2007)
Goodwin, G. M., Croal, M., Feifel, D. et al. · Neuropharmacology (2023)
Show all 22 referencesShow fewer
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Davis, A. K., Streeter Barrett, F., Cosimano, M. P. et al. · Journal of Psychopharmacology (2022)
Griffiths, R. R., Yaden, D. B., Nayak, S. et al. · Journal of Psychopharmacology (2023)
Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)
Kettner, H., Rosas, F. E., Timmermann, C. et al. · Frontiers in Pharmacology (2021)
Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)
Malcolm, B., Thomas, K. · Psychopharmacology (2021)
Moreno, F. A., Wiegand, C. B., Taitano, E. K. et al. · Journal of Clinical Psychiatry (2006)
Nour, M. R., Evans, J., Nutt, D. J. et al. · Frontiers in Human Neuroscience (2016)
Nutt, D. J., Erritzoe, D., Carhart-Harris, R. L. · Cell (2020)
Roseman, L., Haijen, E. C. H. M., Idialu-Ikato, K. et al. · Journal of Psychopharmacology (2019)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Cited By (5)
Papers in Blossom that reference this study
O’Mahony, B., Harrington, C., Harkin, A. et al. · Journal of Psychopharmacology (2026)
Moreno, F. A., Allen, K. E., Wiegand, C. B. et al. · Journal of Psychopharmacology (2026)
Chisamore, N., Kaczmarek, E. S., Doyle, Z. et al. · Canadian Journal of Psychiatry (2025)
Becker, A. M., Humbert-Droz, M., Mueller, L. et al. · Clinical Pharmacology and Therapeutics (2025)
Marwood, L., Croal, M., Mistry, S. et al. · Journal of Psychiatric Research (2024)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.