Investigation to Understand and Optimize Psilocybin (OPTIMIZE)

Participants receive a single 25 mg oral dose of psilocybin within a "set and setting" framework including preparatory sessions, two facilitators during dosing and post-dose integration sessions.

After dosing, subjects are randomised to taVNS, sham taVNS, or no taVNS to evaluate effects on depressive symptoms, anxiety, well-being, functional outcomes, social behaviour and safety.

Outcomes include clinical rating scales, measures of real-world social behaviour and early behavioural responses associated with longer-term treatment outcomes.