Psilocybin-Assisted Therapy in Treatment-Resistant Depression

This study tests psilocybin-assisted therapy — a single or small number of guided psychedelic sessions using psilocybin (the active compound in 'magic mushrooms') — as a treatment for people with severe depression that has not responded to at least two different antidepressant medications. Therapy sessions are led by trained guides. **You may be eligible if...** - You are an adult with a confirmed diagnosis of major depressive disorder - You are currently in a depressive episode lasting at least 3 months - You have tried at least 2 antidepressant medications from different drug classes without adequate relief - You are in generally good health based on medical history and basic lab tests - You have no significant cognitive impairment - You have a support person who can accompany you home after sessions **You may NOT be eligible if...** - You have a history of psychosis, schizophrenia, or bipolar disorder type I - You have serious heart, liver, or seizure conditions - You are currently taking medications that interact with psilocybin (such as lithium or certain antidepressants) - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.