Exploratory Study of Low Dose Psilocybin

This parallel-group, randomized, quadruple-masked early-phase trial will evaluate feasibility, initial signals of efficacy, and mechanisms of action of once-weekly low doses of oral psilocybin (0, 1, 2.5, 5 mg) over five weekly 6-hour administration sessions in adults with moderate to severe demoralization.

Assessments include baseline medical and psychiatric evaluation, repeated self-report VAS measures during each 6-hour session, EEG tasks at peak drug effects across sessions, and brief qualitative interviews after each session; blood pressure and ECG monitoring with clinical thresholds for intervention are specified.

Primary aims are feasibility and early efficacy signals on demoralization; secondary aims include mechanistic evaluation using EEG and safety/tolerability through adverse event monitoring and vital signs.