Psilocybin as an alternative to conventional treatments: A systematic review

Psilocybin-assisted therapy shows promise for treating depression and anxiety, especially in cases resistant to conventional treatments. A systematic review of controlled clinical trials from 2020 to 2025, following PRISMA guidelines, included adults aged 18-65 with DSM-5 diagnoses of depression or anxiety who received psilocybin with psychotherapeutic support. Due to methodological differences across studies, a qualitative narrative synthesis was conducted. The review highlights psilocybin's effects on neuroplasticity and brain networks as a potential therapeutic mechanism, but the heterogeneity of the studies prevents a quantitative meta-analysis.

Study at a glance

Abstract

Introduction. Limitations of conventional treatments for depression and anxiety, particularly in treatment-resistant cases, have driven interest in alternative therapeutic approaches. Psilocybin, a serotonergic agonist with demonstrated effects on neuroplasticity and large-scale brain networks, has emerged as a promising therapeutic option. Materials and methods: A systematic review of controlled clinical trials published between 2020 and 2025 was conducted in accordance with PRISMA guidelines. Searches were performed in PubMed/MEDLINE, Scopus, PsycINFO, Web of Science, and the Cochrane Library. Eligible studies included adults aged 18-65 years with DSM-5 diagnoses of depression and/or anxiety who received psilocybin-assisted therapy with psychotherapeutic support. Risk of bias was assessed using RoB 2, the Jadad scale, and the Newcastle–Ottawa Scale. Due to methodological heterogeneity, a qualitative narrative synthesis was performed.