Research Confirms That Serotonergic Antidepressants Like SSRIs, SNRIs Can Decrease Psilocybin’s Effects

Research Confirms That Serotonergic Antidepressants Like SSRIs, SNRIs Can Decrease Psilocybin's Effects


A new study published in the Journal of Psychopharmacology found that serotonergic antidepressants like SSRIs and SNRIs can decrease psilocybin’s effects, Psychedelic Spotlight reports. Serotonergic antidepressants are often the first avenue for treating depression and include household names such as Prozac and Zoloft. 

The research, published in June of 2023, comes from an online retrospective survey involving 2,153 people who had taken psilocybin mushrooms while also using an antidepressant and individuals who had used psilocybin within two years after stopping their antidepressants. The 611 respondents who had taken mushrooms alongside an antidepressant reported weaker-than-expected psilocybin effects, as did the 1,542 participants who had ceased their SSRI/SNRI medication. However, what’s notable is that the probability of weakened results was not significantly different between those who had discontinued antidepressants a week before taking shrooms and those who ceased taking their meds three to six months prior. 

The study demonstrates that SNRI/SSRI antidepressants reduce the effects of psilocybin compared to non-serotonergic antidepressants—and that individuals who have stopped antidepressants may experience weaker effects up to three months after discontinuing their medication.

People who take psilocybin, the compound responsible for the hallucinogenic properties of magic mushrooms, have been talking about how antidepressants diminish the experience for years. However, what was, for so long, a discussion kept to music festivals and Reddit boards now has scientific backing. The confirmation comes at a time when psilocybin itself gains traction in the treatment of depression. Back in 2022, COMPASS Pathways unveiled the “largest randomized, controlled, double-blind study of psilocybin therapy ever completed,” which shows “significant” improvements to treatment-resistant depression (TRD) symptoms.

And recently, doctors from the University of Texas MD Anderson Cancer Center in Houston began a trial for psilocybin therapy to treat cancer-related anxiety and depression in patients by “examining the effects of psilocybin for patients with controlled advanced cancer on maintenance therapy experiencing challenges with mental health.” 

While this is applaudable, as too many readers know, one does not need a cancer diagnosis to benefit from taking psilocybin for depression. While depressants like SSRIs can take up to six weeks to start working, psychedelics, such as psilocybin (not to mention ketamine), can reverse the effects of depression quickly and, hopefully, more effectively. As a 2020 study suggests, traditional antidepressants improve symptoms in about an extra 20 out of 100 people. Another study published in 2020 indicates that psilocybin can not only be an effective and quick-acting treatment for major depressive disorder, but more than half of the study’s participants stayed in remission from depression four weeks after treatment. 

As a result, looking at statistics alone, many folks currently taking serotonergic antidepressants may be considering swapping out their Lexapro for psilocybin (which may also be more cost-effective in treating depression). So does one need to wean off their current medication before embarking on a psychedelic healing journey? When one takes two drugs together that both increase serotonin levels, such as an SSRI and MDMA, there is always the risk for serotonin toxicity, or serotonin syndrome, which can happen when drugs increase levels of the neurotransmitter serotonin between nerve cells past a safe level, leading to anything from nausea and anxiety to in rare cases coma and death. The latter, as so many people reading this who have taken psychedelics while on antidepressants can confirm, is pretty unheard of. 

The research on antidepressants lowering the effects of psilocybin says that it’s generally safe to use serotonergic antidepressants pre-psilocybin treatment. However, be aware that SSRIs and SNRIs may not only diminish psilocybin’s effects but can do so for up to three months after stopping the antidepressant medication. So, if you’re on an SSRI or SSNI, it’s okay to try psilocybin for depression, but be aware that you may need three months to experience the full effect of your new medicine. 


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