Psilocybin mushrooms (Psilocybe spp.) produced strong antidepressant effects across 7 clinical trials involving 522 people, with symptom relief close to a full standard-deviation improvement compared to controls. Treatments worked best when doses were adjusted to body weight and paired with longer psychological support, especially 8–10 hours of preparation and dosing plus 4 or more hours of integration. Programs that allowed more time and flexibility delivered about 2× greater mood improvement than shorter, tightly scripted therapy models.