NCT06768944

Subjective Experience Following Psilocybin

The Role of the Subjective Experience in Supporting Positive Effects Following Psilocybin: a Randomized, Controlled Clinical Trial Using Risperidone in Healthy Adults

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 128 (estimated)
• Sponsor: University of Calgary · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to determine the importance of the acute subjective experience induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with either a placebo or risperidone, an atypical antipsychotic that block the subjective effects of psilocybin.

Detailed description

The overall goal of this clinical trial is to systematically explore the relationship between the subjective psychedelic experience, improvements in well-being, and the stress response following psilocybin administration. The investigators aim to determine whether blocking the acute subjective effects (via risperidone) will influence the acute or protracted effects of psilocybin as measured via self-report, biochemical, or psychophysiological measures. The study also aims to determine if individual variability in stress reactivity or regulation predicts acute (day of dosing) or protracted (1-week later) effects of psilocybin. A single site will recruit 128 participants aged 18 to 65 who do not meet criteria for any psychiatric diagnoses. A series of questionnaires, blood labs, and medical exams including electrocardiogram will determine inclusion into the study. Once accepted into the study, participants will complete baseline measures assessing cortisol and brain-derived neurotrophic factor (BDNF) levels, cognitive flexibility, mood, well-being, personality traits, and anxiety levels. Participants will then be randomly assigned into one of the following groups: i) high dose psilocybin (25mg; "active dose") in combination with placebo pretreatment ii) high dose psilocybin (25mg; "active dose") in combination with risperidone pretreatment (1mg) iii) low dose psilocybin (1mg "active control") in combination with placebo pretreatment, iv) low dose psilocybin (1mg "active control") in combination with risperidone pretreatment (1mg). Outcome measures will be assessed at 1-week and 1-month after each dosing session.

Conditions

• Investigating the Importance of the Subjective Psychedelic Experience

Interventions

Type	Name	Description
DRUG	Psilocybin 25 mg	The drug product (DP) PEX010 is a capsule for oral administration and is manufactured with DS PYEX (12.5-14.0% psilocybin), excipients, and HPMC capsules. The product is manufactured in two product strengths, and this represents the high-dose (25mg)
DRUG	Psilocybin 1 mg	The drug product (DP) PEX010 is a capsule for oral administration and is manufactured with DS PYEX (12.5-14.0% psilocybin), excipients, and HPMC capsules. The product is manufactured in two product strengths, and this represents the low-dose (1mg)
DRUG	Risperidone 1 MG	risperidone 1mg capsules
DRUG	Placebo	inactive placebo

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-12-01
• Completion: 2028-01-01
• First posted: 2025-01-10
• Last updated: 2026-02-06

Locations

1 site across 1 country: Canada