Therapeutic Use of Psilocybin in Depression: a Systematic Review of Clinical Evidence

Psilocybin as a treatment for major depressive disorder is evaluated through a systematic review of clinical evidence, with a focus on whether serotonin 5-HT2A receptor activity mediates antidepressant effects. The review frames depression treatment as limited by effectiveness and adherence, then summarizes why psilocybin is of interest: it primarily acts at the 5-HT2A receptor while also interacting with 5-HT1A and 5-HT2C, and its precise therapeutic mechanisms are still being studied. The authors apply a structured evidence synthesis approach aimed at consolidating findings on efficacy and safety, identifying inconsistencies and limitations across the literature, and highlighting gaps to guide future research and potential clinical practice.