Subjective Experience Following Psilocybin

NCT ID: NCT06768944

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2028-01-31

Brief Summary

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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

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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

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Investigating the Importance of the Subjective Psychedelic Experience

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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High-dose psilocybin + placebo

placebo + 25 mg psilocybin (+60 min)

Group Type ACTIVE_COMPARATOR

Psilocybin 25 mg

Intervention Type 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 (25mg)

Placebo

Intervention Type DRUG

inactive placebo

Low-dose psilocybin + placebo

placebo + 1 mg psilocybin (+60 min)

Group Type PLACEBO_COMPARATOR

Psilocybin 1 mg

Intervention Type 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 (1mg)

Placebo

Intervention Type DRUG

inactive placebo

High-dose psilocybin + risperidone

1 mg risperidone + 25 mg psilocybin (+60 min)

Group Type EXPERIMENTAL

Psilocybin 25 mg

Intervention Type 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 (25mg)

Risperidone 1 MG

Intervention Type DRUG

risperidone 1mg capsules

Low-dose psilocybin + risperidone

1 mg risperidone + 1 mg psilocybin (+60 min)

Group Type ACTIVE_COMPARATOR

Psilocybin 1 mg

Intervention Type 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 (1mg)

Risperidone 1 MG

Intervention Type DRUG

risperidone 1mg capsules

Interventions

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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)

Intervention Type 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)

Intervention Type DRUG

Risperidone 1 MG

risperidone 1mg capsules

Intervention Type DRUG

Placebo

inactive placebo

Intervention Type DRUG

Other Intervention Names

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PEX010 high-dose psilocybin PEX010 low-dose psilocybin Risperdal

Eligibility Criteria

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Inclusion Criteria

* 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
* At least one self-reported positive experience prior to study participation with a psychoactive substance, specifically those known for altering perception or inducing hallucinatory effects (cannabis or psychedelics, including psilocybin, LSD, DMT, mescaline) or experience with non-pharmacological altered states of consciousness (meditation, breathwork)

Exclusion Criteria

* Any notable abnormality on electrocardiogram or routine medical blood or urinalysis laboratory tests: I.e., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes, or other medical condition, as determined by the study staff, that could compromise participant safety
* Serious electrocardiogram abnormality, i.e., evidence of ischemia, myocardial infarction, QTc (Fridericia formula) prolongation (QTc \> 0.45 for men, QTc \> 0.47 for women).
* Abnormal liver enzymes (AST, ALT, GGT ≥4 times upper normal limit)
* Pre-existing low white blood cell count or a history of drug-induced leukopenia/neutropenia
* Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
* History of epilepsy or seizures, neuroleptic malignant syndrome or tardive dyskinesia
* Hypertension (\>140mmHg systolic or 90mmHg) or Tachycardia (HR \>100bpm) as measures by best result of maximum of three vital sign recordings in a supine position after a 5 min resting period. Participants with a blood pressure not higher than 165/95 or a heart rate of not higher than 110bpm can be conditionally enrolled but dosing will only happen if the vitals at the dosing sessions are in the limits outlined above for inclusion.
* 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. Medication with potential drug-drug interactions (especially uridine 5'-diphospho-glucuronosyltransferase (UGT) and ALDH inhibitors and alcohol dehydrogenase (ADH) inhibitors for psilocybin and CYP2D6- and to a lesser extend CYP3A4 modulators for risperidone) are prohibited for at least 5 half-lives of the active moiety before the dosing.
* Serotonergic psychedelic use in the past 3 months (e.g. psilocybin, LSD, DMT, mescaline)
* Serious adverse events following previous psychedelic use
* Currently pregnancy or nursing, trying to become pregnant, or unwilling to use acceptable method of contraception during the study
* Acceptable methods of contraception include oral contraceptives, barrier with spermicide, IUD, medroxyprogesterone acetate (Depo Provera), contraceptive patch, vaginal contraceptive ring, or being post-menopausal or deemed medically unable to become pregnant (i.e., due to hysterectomy)
* Current or recent (within 12 weeks) participation in a clinical trial involving medication administration
* Any sensitivity or adverse reaction to previous use of a hallucinogen or risperidone
* 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
* The participant experienced a significant life event (such as pending loss of housing, family status change, loss of a close friend or relative) that could affect stability in the past 30 days.
* Any other circumstances that, in the opinion of the investigators, compromises participant safety
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Calgary

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Leah Mayo, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

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University of Calgary

Calgary, Alberta, Canada

Site Status

Countries

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Canada

Central Contacts

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Ana Deutsch, MSc

Role: CONTACT

587-893-0257

Facility Contacts

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Ana Deutsch, MSc

Role: primary

8257341098

Other Identifiers

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REB24-1121

Identifier Type: -

Identifier Source: org_study_id