Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use

This two-part online retrospective survey (n=2,153) analysed the interaction between psilocybin-containing mushrooms and common antidepressants. Participants who took psilocybin while on antidepressants (n=611) often experienced weaker effects than expected, particularly with SSRIs and SNRIs. Additionally, the survey showed that even after discontinuing SSRIs or SNRIs, the weakening effects on psilocybin might persist for up to 3 months (n=1,542). The study indicates that serotonergic antidepressants may reduce the effects of psilocybin.

Abstract of Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use

Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin’s effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period.

Aims: To learn the extent to which antidepressants may diminish the effects of psilocybin-containing mushrooms both concurrently and after discontinuation of antidepressants.

Methods: Online retrospective survey of individuals with use of psilocybin mushrooms (1) with an antidepressant and/or (2) within 2 years of discontinuing an antidepressant. Participants who took mushrooms with an antidepressant and either took the same dose pre-antidepressant or took the same dose with other people not on antidepressant reported the strength of drug effects relative to their expectation. Participants who took mushrooms following discontinuation of an antidepressant also reported the presence of weakened effects.

Results: In reports (n = 611) of taking mushrooms with an antidepressant, probabilities [95% CI] of weaker than expected drug effects were 0.47 [0.41–0.54] (selective serotonergic reuptake inhibitors, SSRIs), 0.55 [0.44–0.67] (serotonin norepinephrine reuptake inhibitors, SNRIs) and 0.29 0.2–0.39. Following SSRI/SNRI discontinuation (n = 1,542 reports), the probability of reduced drug effects was not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3–6 months, probability = 0.3 [0.20–0.46], p = 0.001. A sensitivity analysis found that removing responses involving fluoxetine, which has an especially long half-life, did not significantly alter this result.

Conclusions: SSRI/SNRIs appear to weaken psilocybin drug effects relative to a non-serotonergic antidepressant. This dampening effect may last as long as 3 months following antidepressant discontinuation.”

Authors: Natalie Gukasya, Roland R. Griffiths, David B. Yaden, Denis G. Antoine & Sandeep M. Nayak

Summary of Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use

Psilocybin-assisted therapy can potentially become a widely used treatment for major depressive disorder and treatment-resistant depression if early results are successfully and safely replicated at scale. Although psilocybin and other serotonin 2A receptor agonists may soon debut in clinical practice, relatively little is known about their interactions with other psychotropic drugs commonly used in patients with depression and other mental health conditions.

Studies of lysergic acid diethylamide (LSD), a 5HT2A agonist, suggest that patients taking monoamine oxidase inhibitors (MAOIs) may be insensitive to the effects of LSD, and conversely a potentiation of LSD effects with tricyclic antidepressants and lithium. A recent study found that psilocybin reduced negative subjective drug effects in healthy participants who had taken the SSRI escitalopram for 14 days, but did not affect total scores on the Mystical Experience Questionnaire.

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Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use

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Cite this paper (APA)

Gukasyan, N., Griffiths, R. R., Yaden, D. B., Antoine, D. G., & Nayak, S. M. (2023). Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. Journal of Psychopharmacology, 02698811231179910.

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Roland Griffiths
Roland R. Griffiths is one of the strongest voices in psychedelics research. With over 400 journal articles under his belt and as one of the first researchers in the psychedelics renaissance, he has been a vital part of the research community.