Subjective Experience Following Psilocybin

NCT06768944 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: REB24-1121
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Investigating the Importance of the Subjective Psychedelic Experience

Keywords

psychedelics; psilocybin; stress response; cortisol; healthy participants; risperidone; subjective effects

Outcome Measures

Primary Outcomes (1)

• Positive effects

  Persisting Effects Questionnaire (PEQ) - 145 questions rated using a 6-point Likert scale from 0 to 6. There are 12 sub-scale themes assessing positive and negative changes in Attitudes About Life, Attitudes About Self, Mood Changes, Social Effects, Behavioural Changes, and Spirituality. Higher scores in the positive sub-scales indicate a better outcome, while higher scores in the negative sub-scales indicate a worse outcome.

  One week and one month post-dosing

Secondary Outcomes (8)

• Stress reactivity

  From start of dosing session to end of dosing session

• Biomarkers of stress and plasticity

  from baseline to dosing session (one week post-baseline) to follow-up 1 (one week post doing session) to follow-up 2 (one month post dosing session)

• Mood

  from baseline to one week and one month post-dosing

• Well-being

  from baseline to one week and one month post-dosing

• Anxiety

  from baseline to one week and one month post-dosing

Study Arms (4)

High-dose psilocybin + placebo

ACTIVE COMPARATOR

placebo + psilocybin (+60 min)

Drug: Psilocybin high-dose; Drug: Placebo

Low-dose psilocybin + placebo

ACTIVE COMPARATOR

placebo + psilocybin (+60 min)

Drug: Psilocybin low-dose; Drug: Placebo

High-dose psilocybin + risperidone

EXPERIMENTAL

risperidone + psilocybin (+60 min)

Drug: Psilocybin high-dose; Drug: Risperidone 1 MG

Low-dose psilocybin + risperidone

ACTIVE COMPARATOR

risperidone + psilocybin (+60 min)

Drug: Psilocybin low-dose; Drug: Risperidone 1 MG

Interventions

Placebo DRUG

inactive placebo

High-dose psilocybin + placebo; Low-dose psilocybin + placebo

Risperidone 1 MG DRUG

risperidone 1mg capsules

Also known as: Risperdal

High-dose psilocybin + risperidone; Low-dose psilocybin + risperidone

Psilocybin high-dose DRUG

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

Also known as: PEX010, high-dose psilocybin

High-dose psilocybin + placebo; High-dose psilocybin + risperidone

Psilocybin low-dose DRUG

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.

Also known as: PEX010, low-dose psilocybin

Low-dose psilocybin + placebo; Low-dose psilocybin + risperidone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals of all sexes, gender identities, and ethnicities
• Ages 18 to 65 years of age at the time of screening
• Ability to read/write in English
• Agree not to consume psychoactive drugs 24 hours before dosing sessions or consume psychedelics during duration of study participation

You may not qualify if:

• Any notable abnormality on electrocardiogram or routine medical blood or urinalysis laboratory tests
• Current psychiatric diagnoses, such as: major depressive disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, moderate to severe substance use disorders, eating disorders, personality disorders, post-traumatic stress disorder
• Lifetime or current psychiatric diagnoses of: psychosis, schizophrenia, bipolar disorder
• Family history: a first- or second degree relative with a history of schizophrenia or other psychotic disorders, bipolar I or II
• Medication: Any medication with the potential to interact with the investigational medicinal products, especially those with serotonergic mechanisms of actions like SSRIs, SNRIs or MAO-Inhibitors as well as other antipsychotics
• Currently pregnancy or nursing, trying to become pregnant, or unwilling to use acceptable method of contraception during the study
• Current or recent (within 12 weeks) participation in a clinical trial involving medication administration
• Cognitive impairment (Folsetin Mini Mental State Exam score \< 24)
• A disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
• Suffered a traumatic brain injury with one of the following symptoms Loss of consciousness \>30min Alteration of consciousness/mental state \>24h Post-traumatic amnesia \>1 day Glasgow Coma Scale (best available score in first 24 hours) \<13
• Any other circumstances that, in the opinion of the investigators, compromises participant safety

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

Location

MeSH Terms

Conditions

Fractures, Stress

Interventions

Psilocybin; Risperidone

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Leah Mayo, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana Deutsch, MSc

CONTACT

587-893-0257; ana.deutsch@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: January 10, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)