A Study of Psychedelics in Healthy Older Adults With Low Well-being

This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being. The main questions it aims to answer are, does psilocybin: 1. Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology. 2. Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology. 3. Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI Participants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below. Researchers will compare participants who receive the following drug options: * A low-to-moderate dose of Psilocybin (5-10 mg) * A moderate-to-high dose of Psilocybin (25-30 mg) * A low-to-moderate dose of Dextromethorphan (30-60 mg) * A moderate-to-high dose of Dextromethorphan (80-90 mg)

NCT Number	NCT07386730
Lead Sponsor	Jennifer Mitchell
Conditions	Anhedonia in Healthy Volunteers, Older Adults (50-90 Years)
Enrollment	80 participants
Start Date	2026-06-01
Primary Completion	2030-02 (estimated)
Study Completion	2030-02 (estimated)
Updated on ClinicalTrials.gov	2026-06-08