This Phase I, randomised, double-blind, parallel trial (n=20) will study the effects of intermittent psilocybin microdosing on mood, cognition, subjective well‑being and brain structure/function in healthy adults with no history of psychedelic use aged 21–40. The primary aim is basic science: to evaluate whether 30 days of intermittent microdosed psilocybin produces measurable changes on psychological, cognitive and neuroimaging outcomes compared with placebo, in the presumed absence of overt psychedelic experiences. Participants will be randomised to receive either 2 mg powdered psilocybin (from Psilocybe cubensis) in capsules or matching 0 mg placebo capsules three times weekly for four weeks, with weekly assessments and re‑assessment after 30 days of steady dosing; primary outcome measures are assessed from enrolment to end of treatment (8 weeks). Outcomes include task‑based fMRI (Complex Working Memory Span task), structural and diffusion imaging (including NODDI), neuropsychological batteries (NIH Toolbox, Switching Stroop, Flanker, Penn Conditional Exclusion, Face‑Name Associative Memory, 9‑hole pegboard), personality and symptom scales (NEO‑FFI, Beck Depression and Anxiety Inventories, Harvard Flourishing), and ecological momentary assessments via MindLamp. Key eligibility features are no prior psychedelic use, ability to consent, effective contraception for women of childbearing potential, and exclusion for current mood/psychotic disorders, substance use disorders, significant medical/neurological illness or MRI contraindications.
This study is being conducted to evaluate how of 30 days of intermittently microdosed psilocybin affects mood, cognition, subjective well-being and structural/functional MRI results compared to a placebo. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences.
An imperceptible dose of psilocybin in capsules will be administered to subjects three times weekly for four weeks. Assessments will be conducted once weekly. After 30 days of a steady dose of psilocybin, subjects will be re-assessed with baseline measures.
Unmatched intervention: Psliocybin
An dose of placebo in capsules, identical to the active, will be administered to subjects three times weekly for four weeks. Assessments will be conducted once weekly. After 30 days of a steady dose of psilocybin, subjects will be re-assessed with baseline measures.