Non-randomised sequential experimental-medicine study (estimated n=200) using single oral doses of psilocybin and ketanserin to probe 5-HT2A receptor effects in healthy volunteers with PET and MRI outcomes.
This experimental medicine project compares psilocybin (5-HT2A agonist) and ketanserin (5-HT2A antagonist) effects on brain function using MRI and multiple PET tracers (CIMBI-36, UCB-J) in healthy volunteers.
Design includes sequential allocation across subprojects examining receptor occupancy, long-term effects (1 and 12 week follow-ups), and functional connectivity with single oral dosing (25 mg specified in one subproject) and repeated neuroimaging assessments.
Single oral psilocybin dose used across subprojects (25 mg specified in Subproject 2c).
25 mg specified in Subproject 2c; other subprojects use a single oral dose (unspecified).
Oral 5-HT2A antagonist used for occupancy and fMRI comparisons.
Ketanserin oral dose (unspecified) — encoded as non-listed active comparator.
Oral placebo comparator used in Subproject 2c.
Placebo oral capsule.
In healthy volunteers given medium–high doses of psilocybin, greater acute mystical-type experiences (MEQ total score)—notably the Positive Mood and Mysticality subscales—were associated with persisting positive psychological effects at three months, whereas Transcendence of Time and Space and Ineffability were not. The paper also provides the first qualitative descriptions of complete mystical experiences after oral psilocybin, emphasising themes of cosmic connection, familial love and profound beauty.