Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)

This study is using brain scans to understand how psilocybin (the active compound in psychedelic mushrooms) affects the number of synapses (connections between brain cells) in people with treatment-resistant depression. It aims to understand the biological mechanism behind psilocybin's antidepressant effects. **You may be eligible if...** - You are between 18 and 65 years old - You have a primary diagnosis of major depressive disorder (MDD) that is not psychotic - Your depression has not responded to two or more antidepressant medications taken at adequate doses - Your current depression score on standard rating scales is above the threshold (HamD-17 greater than 14) - You are able to read and communicate in English well enough to understand the consent form **You may NOT be eligible if...** - You have a history of bipolar disorder or psychosis - You have active suicidal thoughts or plans - You have significant substance use disorder - You have serious heart, kidney, or liver disease - You are pregnant or breastfeeding - You are currently taking medications that interact with psilocybin Talk to your doctor to see if this trial is right for you.