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 (n=161) examines the interactions between psychedelics and serotonergic antidepressants (SRIs), focusing on their effects on well-being and depressive symptoms. Utilizing multivariate analysis and linear mixed effect models, it compares subjective psychedelic experiences and post-use well-being between individuals on SRIs (‘SRI +’) and those not (‘SRI −’). Findings indicate ‘SRI −’ participants experience more intense mystical, challenging, and emotional breakthroughs, while ‘SRI +’ participants have less intense experiences but similar improvements in well-being and depressive symptoms.

Abstract of Interactions between classic psychedelics and serotonergic antidepressants

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.”

Authors: Jessica B. Siv, Tommaso Barba, Hannes Kettner, Joanna Kuc, David J. Nutt, Robin L. Carhart-Harris, & David Erritzoe

Summary of Interactions between classic psychedelics and serotonergic antidepressants

There is a resurgence of research into the use of psychedelic compounds in clinical settings, with promising results in treating depression, obsessive-compulsive disorder and anxiety disorders.

Many subjects in clinical studies involving psychedelic drugs have been using SSRIs and SNRIs (here SRIs to capture both) for extended periods. These drugs block serotonin reuptake and enhance the serotonin 1A receptor signalling pathway, which fosters stress tolerance and resilience.

Patients are typically required to stop taking SRIs for at least two weeks before the start of the trial, due to the lack of established safety data for combined psilocybin and SRIs, and to previous case reports suggesting chronic use of SRIs can reduce the therapeutically important subjective effects of psychedelics.

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Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study

https://doi.org/10.1177/02698811231224217

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Cite this paper (APA)

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, 02698811231224217.

Study details

Participants
161 Humans

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