This interventional, randomised, double-blind, triple-masked crossover study (n=16) will assess dose-response and the role of 5-HT2A receptors on psilocybin effects using single oral doses (5, 10, 20, 40 mg), a 40 mg ketanserin pretreatment condition, and placebo.
Randomised, placebo-controlled, double-blind, triple-masked six-period crossover in healthy adults to characterise subjective dose–response to single oral doses of psilocybin (5–40 mg).
A mechanistic arm uses 40 mg ketanserin pretreatment to probe the contribution of 5‑HT2A receptor antagonism to psilocybin-induced alterations of consciousness.
Primary assessments include modern psychometric instruments of altered states and safety; pharmacokinetic sampling will relate plasma concentrations to subjective effects. Sessions are separated by at least 10 days.
40 mg ketanserin oral followed 1 h later by 40 mg psilocybin oral (single session).
Psilocybin 40 mg given 1 h after pretreatment.
Ketanserin 40 mg oral given 1 h before psilocybin (encoded as non-psilocybin comparator).
Placebo pretreatment followed by 40 mg psilocybin oral (single session).
Placebo pretreatment 1 h before psilocybin.
Placebo pretreatment.
Placebo pretreatment followed by 20 mg psilocybin oral.
Placebo pretreatment.
Placebo pretreatment followed by 10 mg psilocybin oral.
Placebo pretreatment.
Placebo pretreatment followed by 5 mg psilocybin oral.
Placebo pretreatment.
Placebo pretreatment followed by placebo oral (control).
Placebo followed by placebo 1 h later.