SSRIs and psilocybin — the washout period question
74 replies · Harm Reduction
I've been on 20mg escitalopram for two years. I'm considering stopping to eventually explore psilocybin therapy. How long after stopping SSRIs is it safe to try psilocybin, and is there risk during the washout period from the SSRI interaction?
I know I should talk to a doctor — and I am — but I want to understand the pharmacology before that conversation.
The standard recommendation from the clinical trial literature is a minimum 2-week washout for SSRIs before psilocybin. This is because SSRIs downregulate 5-HT2A receptors, which psilocybin acts on — taking psilocybin while on SSRIs dramatically blunts or eliminates the effects, and there are theoretical interaction risks at the receptor level. Some clinicians prefer 4 weeks. Fluoxetine (Prozac) has a 5-week half-life and requires 5+ weeks.
Do NOT stop your SSRI without working with your prescriber. Abrupt SSRI discontinuation causes discontinuation syndrome (dizziness, 'brain zaps,' flu-like symptoms, emotional instability) that is distinct from withdrawal and can be severe. Taper slowly under supervision. The washout period starts after the final dose of a proper taper, not after abrupt stopping.
Important: Tramadol, lithium, and MAOIs have more serious interaction risks with psilocybin than SSRIs. If you're on any of these, the calculus is different and the risks are more severe. The LearnShrooms drug interaction checker covers most combinations. See also the SSRI tapering guide in the therapy section.
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