Its precise mechanisms remain under investigation.<h4>Objectives</h4>(1) To consolidate evidence on psilocybin’s efficacy and safety for depression and the role of 5HT2a, (2) to identify limitations in the literature, and (3) to highlight areas needing further research.<h4>Methods</h4>This systematic review follows PRISMA guidelines and analyses 22 studies, including randomised controlled trials (RCTs) and open-label studies. The gene discussed is HTR2A; the disease is depressive disorder.