This quadruple-blind, placebo-controlled trial (n=36) will investigate the role of stress response in shaping the positive effects of psilocybin (25mg or 1mg) by using metyrapone (750mg) to suppress cortisol production.
The study tests whether blocking the glucocorticoid stress response with metyrapone alters the acute and protracted effects of psilocybin in healthy participants.
Thirty-six psychiatrically healthy adults (22–65) will complete four randomized crossover dosing sessions: 25 mg psilocybin ± metyrapone and 1 mg psilocybin ± metyrapone; outcomes include self-report, biochemical (cortisol, ACTH, BDNF), and psychophysiological measures at acute and 1-week/1-month follow-ups.
Psilocybin is administered as oral PEX010 capsules; metyrapone is given as two 750 mg oral doses to achieve cortisol suppression.
25 mg psilocybin with oral placebo (crossover condition).
PEX010 capsule (high-dose).
Oral inactive placebo.
1 mg psilocybin (active control) with oral placebo.
PEX010 capsule (low-dose).
Oral inactive placebo.
25 mg psilocybin with metyrapone (cortisol suppression).
PEX010 capsule (high-dose).
Metyrapone 750 mg administered in 2 doses (not a listed compound reference).
1 mg psilocybin with metyrapone (cortisol suppression).
PEX010 capsule (low-dose).
Metyrapone 750 mg administered in 2 doses (not a listed compound reference).