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

NCT06768944•University of Calgary

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - 65 years

Sex

ALL

Healthy Volunteers

Yes

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
+16 more criteria

Locations (1)

University of Calgary

Calgary, Alberta, Canada

Key Dates

Start Date

April 1, 2026

Primary Completion Date

December 1, 2027

Completion Date

January 1, 2028

Last Updated

February 6, 2026

Enrollment

128

ESTIMATED participants

Conditions

Investigating the Importance of the Subjective Psychedelic Experience

Interventions

Psilocybin 25 mg

DRUG

Psilocybin 1 mg

DRUG

Risperidone 1 MG

DRUG

Placebo

DRUG

Contacts

Ana Deutsch, MSc

CONTACT

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