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Does Psilocybin Require Psychedelic Effects to Treat Depression?

NCT05710237 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 41

Last updated 2026-05-07

No results posted yet for this study

Summary

Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of serotonin (5HT)2A receptor antagonists such as risperidone.

The purpose of this "double dummy" proof-of-concept trial is to evaluate whether psilocybin's antidepressant effects are dependent on its psychedelic effects. Sixty participants with treatment-resistant depression will be randomly assigned to one of three groups: 1) Psilocybin 25 mg plus risperidone 1 mg; 2) Psilocybin 25 mg plus placebo; and 3) Placebo plus risperidone 1 mg. The investigator's hypothesize that the combination of psilocybin and risperidone will be well tolerated, safe, and will block the psychedelic effects of psilocybin in patients diagnosed with treatment-resistant depression.

Conditions

  • Treatment-resistant Depression

Interventions

DRUG

Placebo

The placebo will be administered once during the trial in combination with either risperidone 1 mg or psilocybin 25 mg.

DRUG

Psilocybin 25 mg

The psilocybin used in this study meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The psilocybin will be administered once during the trial in combination with either risperidone 1 mg or place. It will also be administered in conjunction with supportive therapy.

DRUG

Risperidone 1 MG

The risperidone is encapsulated using a cellulose capsule and contains 1 mg of risperidone. The risperidone will be administered once during the trial in combination with either psilocybin 25 mg or placebo. It will also be administered with supportive therapy.

Sponsors & Collaborators

  • Centre for Addiction and Mental Health

    lead OTHER

Principal Investigators

  • M. Ishrat Husain, MBBS, MD · Centre for Addiction and Mental Health

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-07-01
Primary Completion
2026-04-14
Completion
2026-04-14

Countries

  • Canada

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05710237 on ClinicalTrials.gov