Research confirms that serotonergic antidepressants such as SSRIs and SNRIs can decrease the effects of psilocybin

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

The study, published in June 2023, is based on an online retrospective survey of 2,153 people who had ingested psilocybin mushrooms while taking an antidepressant, and people who had taken psilocybin within two years of stopping their antidepressant medication. The 611 respondents who had taken mushrooms with an antidepressant reported less than expected psilocybin effects, as did the 1,542 participants who had stopped their SSRI/SNRI medications. It is worth noting, however, that the likelihood of mitigated outcomes was not significantly different between those who stopped their antidepressants a week before taking magic mushrooms and those who stopped their medications three to six months earlier.

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

People who take psilocybin, the compound responsible for magic mushrooms’ hallucinogenic properties, have talked about how antidepressants diminish the experience for years. However, what has long been a discussion confined to music festivals and Reddit forums now has scholarly support. The confirmation comes at a time when psilocybin itself is gaining traction in the treatment of depression. Back in 2022, COMPASS Pathways unveiled the “largest double-blind, randomized, controlled study ever completed on psilocybin therapy” showing “significant” improvements in treatment-resistant depression (TRD) symptoms.

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

While this is commendable, as too many readers know, you don’t need a cancer diagnosis to benefit from taking psilocybin for depression. While depressants like SSRIs can take up to six weeks to work, psychedelics like psilocybin (not to mention ketamine) can reverse the effects of depression quickly and hopefully more effectively. A 2020 study found that traditional antidepressants improve symptoms in about 20 out of 100 people. Another study published in 2020 indicates that not only can psilocybin be an effective and fast-acting treatment for major depressive disorder, more than half of the study participants remained in remission from their depression four weeks after treatment.

Just looking at the stats, many people currently taking serotonergic antidepressants may be considering swapping their Lexapro for psilocybin (which may also be more cost-effective in treating depression). So, do you have to stop your current medications before embarking on a psychedelic healing journey? When taking two drugs together that both increase serotonin levels, such as SSRI and MDMA, there is always a risk of serotonin toxicity or serotonin syndrome, which can occur when drugs increase levels of the neurotransmitter serotonin between nerve cells beyond safe levels, leading to nausea and anxiety, coma and death. The latter, as so many people reading this and who have taken psychedelics while on antidepressants can attest, is fairly unknown.

Research on antidepressants that blunt the effects of psilocybin shows that it is generally safe to use serotonergic antidepressants prior to treatment with psilocybin. Note, however, that SSRIs and SNRIs may not only reduce the effects of psilocybin, but may continue to do so for up to three months after antidepressant discontinuation. So if you’re taking an SSRI or SSNI, it’s okay to try psilocybin for depression. However, be aware that it may take up to three months before you feel the full effects of your new medicine.