This review in Nature Medicine outlines the science behind psychedelic medicine. It integrates mechanistic knowledge with clinical evidence across neuropsychiatric indications. It highlights the challenges, controversies and opportunities in this area. The article was published online on 6 February 2026 with doi:10.1038/s41591-025-04194-5. Psychedelics are being studied for depression, PTSD, and addictions. Mechanisms include neuroplasticity and psychological effects. Research shows their potential in the treatment of mental disorders.