[Clinical application and mechanistic studies of psychedelics for treatment of depression: progress and future challenges].
Nan fang yi ke da xue xue bao = Journal of Southern Medical University January 20, 2026 Ke Xia, Tianming Gao
Classic psychedelics, especially psilocybin, show promise for treating depression, with several randomized controlled trials indicating that one or a few sessions of psychedelic-assisted psychotherapy can produce rapid and lasting antidepressant effects in patients with treatment-resistant depression. Mechanistically, these substances quickly increase neurotrophic factors, enhance neuroplasticity, and reorganize brain networks, creating a window for psychotherapy. However, the specific molecular and circuit-level mechanisms remain unclear, with debate between the 5-HT2A receptor-dependent hypothesis and the TrkB neurotrophic pathway-dependent hypothesis. Key challenges include psychedelic-related risks, incomplete mechanistic understanding, lack of standardized protocols, and insufficient long-term safety data.