Psilocybin Comparable to Escitalopram in the Treatment of Depression

March 2, 2022 · Posted in Peer-Reviewed Published Data, Potential Treatments 
ingredient in magic mushrooms may treat depression

Four randomized, controlled clinical trials have established that psilocybin, the hallucinogenic compound in “magic mushrooms,” has anti-depressant effects. Recently, a phase 2 clinical trial compared the effects of psilocybin to a US Food and Drug Administration (FDA)–approved treatment for depression, the selective serotonin-reuptake inhibitor (SSRI) escitalopram. The study by Robin Carhart-Harris and colleagues was published in the New England Journal of Medicine in 2021.

The 59 participants in the 6-week study, which took place in the United Kingdom, had longstanding moderate-to-severe major depressive disorder. They were randomized to two groups. The psilocybin group received two separate doses of 25 mg of psilocybin 3 weeks apart, plus 6 weeks of daily placebo. The escitalopram group received two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram. (The small doses of psilocybin administered to the escitalopram group were assumed to have negligible psychiatric effects.) All participants were told they would receive psilocybin (though not the dose) in order to standardize their expectations.

In addition to the drug treatments, all participants also received psychological support, which consisted of monitoring immediately after the administration of the drugs (given the expectation that the 25mg dose of psilocybin would produce an “altered quality of conscious experience”), psychological debriefings, and an active listening session.

Psilocybin improved depression symptoms to a greater extent than escitalopram did. Among the participants, 70% of the psilocybin group responded to the treatment, compared with 48% of the escitalopram group. Remission occurred in 57% of the psilocybin group compared with 28% of the escitalopram group. These differences in the outcomes for the two groups were not statistically significant.

The FDA has designated psilocybin a “Breakthrough Therapy” for severe depression, which indicates that the therapy may be a substantial improvement over existing therapies for a serious condition. The designation is intended to speed up the drug development and review process.

The state of Oregon legalized psilocybin-assisted therapy in 2020.

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