**Psilocybin Therapy for Depression in Parkinson's Disease** This study aims to see if psilocybin, a substance found in some mushrooms, can help people with Parkinson's Disease (PD) feel less depressed. PD is a brain disorder that causes shaking, stiffness, and difficulty with walking and balance. This study involves 60 people aged 40 to 80 with early to moderate PD and depression. Participants will try two doses of psilocybin in a safe setting and have therapy sessions before and after taking the drug. They will also have tests like brain scans and blood draws to see if their symptoms improve. The entire study, including follow-ups, lasts about 3 months after the second drug session. **Key Points:** - **Study Length:** About 3 months, including follow-up visits. - **Participation:** Includes taking oral psilocybin, therapy sessions, and tests. - **Eligibility:** Adults aged 40-80 with PD and depression who can attend visits at UCSF. Participants need to speak English, have a doctor for PD, and cannot take certain medications or have severe mental health issues. The results will help understand if psilocybin is safe and effective for treating depression in PD patients.