Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of NeuropsychopharmacologyApr 16, 2024

Current knowledge about psilocybin for major depression based on clinical trials

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 1, 2026

Abstract

Eleven clinical trials examined psilocybin's effects on depression, with notable improvements in symptoms reported.

Psilocybin may reduce depressive symptoms significantly after two treatment sessions in patients with .
In open-label studies, high remission rates and sustained improvements were observed following psilocybin treatment.
Among double-blinded randomized clinical trials, psilocybin resulted in significant reductions in anxiety and depression in cancer patients, lasting over six months.
In major depressive disorder, psilocybin showed faster reductions in depression compared to the standard medication escitalopram.
A single dose of 25 mg psilocybin produced a greater antidepressant effect than 1 mg in treatment-resistant depression patients.
Psilocybin is associated with a promising safety profile, warranting further exploration of optimal dosages and long-term effects.

Simplified

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HTreceptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects. 2A

Key numbers

67%

Remission Rate

Percentage of patients achieving remission one week after psilocybin treatment.

57% vs. 28%

Higher Remission Rate

Remission rates for psilocybin vs. escitalopram after six weeks.

25 mg vs. 1 mg

Superior Antidepressant Effect

Comparison of psilocybin doses showing superior effect in patients.

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Competing interests

Conflicts of Interest . No potential conflict of interest relevant to this article was reported.

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Current knowledge about psilocybin for major depression based on clinical trials

Abstract

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Abstract

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Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the psychedelic science brief