Serotonergic antidepressant use is associated with weaker psilocybin effects

This pre-print survey study explored the effects of using psilocybin with an antidepressant and/or within two years of discontinuing an antidepressant. In participants taking psilocybin with an antidepressant (n=595), the probability of weaker psilocybin effects was higher for SSRIs than non-serotonergic antidepressants. In terms of discontinuation (n=1,541), the weakening effect of antidepressants on psilocybin waned between 3-6 months after discontinuation.

Abstract

“Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggests 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 serotonergic antidepressants may diminish psilocybin’s effects both concurrently and after discontinuation of antidepressants.

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

Results: In reports (n=595) of taking psilocybin with an antidepressant, probabilities [95% CI] of weaker than expected psilocybin effects were 0.48 [0.41-0.54] (SSRIs), 0.56 [0.44-0.67] (SNRIs) and 0.29 [0.2-0.39] (bupropion). Following serotonergic antidepressant discontinuation (n=1,542 reports), the odds of reduced psilocybin effects were not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3-6 months OR = 0.42, 95% [0.25-0.72] p = 0.001.

Conclusions: Serotonergic antidepressants appear to weaken psilocybin’s effects relative to a non-serotonergic antidepressant. This dampening effect on psilocybin effects may last as long as 3 months following antidepressant discontinuation.”

Authors: Natalie Gukasyan, Roland R. Griffiths, David Yaden, Denis Antoine & Sandeep Nayak

Summary of Serotonergic antidepressant use is associated with weaker psilocybin effects

Introduction

Psilocybin-assisted therapy can produce rapid and robust antidepressant effects in patients with major depressive disorder and treatment-resistant depression. Still, little is known about how they interact with other psychotropic drugs.

The current standard of practice in psychedelic-assisted therapy trials is to discontinue serotonergic antidepressants and, in some cases, other psychotropic drugs for at least four to five half-lives before treatment. This is done to avoid adverse effects or reduced efficacy of psychedelics with concurrent use of antidepressants. Studies have found that fluoxetine reduces the effects of psilocybin when taken with fluoxetine, but does not affect scores on the Mystical Experience Questionnaire or self-reported subjective “good drug effects”.