This triple-blind, randomised, placebo-controlled trial (n=60) will study the role of neuroplasticity in the behavioural effects of psilocybin in individuals with mild declines in emotional wellbeing. Participants will receive one of four medication combinations (25 mg or 1 mg psilocybin with IV midazolam or IV saline).
The study randomises 60 participants to one of four parallel arms combining higher- or very-low-dose psilocybin (25 mg or 1 mg, oral) with either IV midazolam or IV saline; the primary aim is to probe neuroplasticity mechanisms underlying behavioural effects.
Assessments include MRI, TMS, EEG and questionnaires to measure neural and behavioural markers of wellbeing; midazolam is used to induce amnesia of the psychedelic experience without oversedation.
Psilocybin (25 mg) + IV midazolam
IV midazolam to induce amnesia; dosing per protocol
Psilocybin (25 mg) + IV saline (placebo for midazolam)
IV saline (placebo for midazolam)
Psilocybin (1 mg/control) + IV midazolam
IV midazolam to induce amnesia; dosing per protocol
Psilocybin (1 mg/control) + IV saline
IV saline (placebo for midazolam)