Antidepressants may diminish psilocybin's effects even after discontinuation

SSRIs and SNRIs can weaken psilocybin's acute subjective effects in some people, and the blunting may persist after stopping the antidepressant. A retrospective survey study collected 2,625 responses from individuals who used psilocybin while taking an antidepressant or within two years after discontinuation. About half of participants on an SSRI or SNRI reported lower than expected psilocybin effects when taken together. The probability of reduced effects decreases over time, but may remain significant for 1 to 3 months after discontinuing SSRIs or SNRIs. The pattern was not strongly tied to fluoxetine, suggesting longer-term brain changes rather than just current drug levels, possibly involving serotonin receptor density. Adverse events from the combination were rare, but the findings need confirmation in larger, controlled studies.