Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin

This study is testing whether one or two doses of psilocybin (a psychedelic compound) combined with psychotherapy works better for people with treatment-resistant depression — meaning depression that hasn't improved with at least two different antidepressant medications. **You may be eligible if...** - You are between 18 and 65 years old - You have been diagnosed with moderate to severe major depressive disorder (not with psychosis) - You have tried at least two antidepressant medications without enough improvement - You can read and communicate in English - You are able to swallow oral medication - You agree to use effective contraception if applicable **You may NOT be eligible if...** - You have a history of psychosis or schizophrenia - You have had drug or alcohol dependence in the past 3 months - You are at high risk of suicide requiring immediate treatment - You have a significant neurological condition like epilepsy - You have a pacemaker, metal implants in your skull, or are unsuitable for MRI - You are pregnant Talk to your doctor to see if this trial is right for you.