NCT06796361

Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness

Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness (PDR-Study)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 25 Years – 75 Years
• Healthy volunteers: Accepted

Summary

Psilocybin (active compound of "magic mushrooms") is a prototypical psychedelic substance that acts via agonism on serotonin (5-HT) 2A receptors. Psilocybin is rapidly metabolized into its active metabolite psilocin. Psilocybin is currently under investigation as potential treatment for various neuropsychiatric disorders. Psilocybin is also widely used for recreational purposes and as research tool in neuroscience. Besides its current clinical development, a clear characterization of the dose-response relationship of psilocybin is lacking. With the present study the investigators aim to close this knowledge gap by administering low (5mg) to high (40mg) single doses of psilocybin to healthy participants. Besides its agonism on 5-HT2A receptors, psilocin also binds to other receptors and inhibits serotonin transporters (SERT). To this data only few studies have investigated these effects and never at a high dose.

Detailed description

Psilocybin is widely used for recreational and spiritual purposes. Additionally Psilocybin is currently reused in experimental studies with healthy subjects and in studies investigating its effects on patients suffering from anxiety, depression, addiction personality disorders and other pathological conditions. The present PDR-study will characterize the subjective effects of different doses of psilocybin using modern psychometric instruments, explore the relationship between the plasma-concentration of psilocybin and its subjective effects, and examine the contribution of the 5-HT2A receptor in the psilocybin-induced alterations of consciousness in a mechanistic study in healthy subjects. Participants will recieve doses of 5, 10, 20, and 40 mg psilocybin, 40 mg of psilocybin with pretreatment of 40 mg ketanserin, and placebo (control for psilocybin). Placebo pretreatment (control for ketanserin) will be used for all psilocybin administrations without ketanserin. Administrations will be separated by at least 10 days and are in random and counter-balanced order.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Ketanserin 40mg plus Psilocybin 40mg	40mg Ketanserin oral will be administered followed by 40mg Psilocybin.
DRUG	40mg Psilocybin	Placebo oral followed by 40mg Psilocybin one hour later.
DRUG	20mg Psilocybin	Placebo oral followed by 20mg Psilocybin one hour later.
DRUG	10mg Psilocybin	Placebo oral followed by 10mg Psilocybin oral one hour later.
DRUG	5mg Psilocybin	Placebo oral followed by 5mg Psilocybin one hour later
OTHER	Placebo	Oral Placebo followed by oral Placebo one hour later

Timeline

• Start date: 2025-04-21
• Primary completion: 2026-08-01
• Completion: 2026-08-01
• First posted: 2025-01-28
• Last updated: 2025-05-28

Locations

1 site across 1 country: Switzerland