NCT06341426

Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin

Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: A Randomized Phase II Clinical Trial Comparing One Versus Two Psychedelic Doses of Psilocybin (PSI-1V2)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Sponsor: University Health Network, Toronto · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to see if one or two doses of psilocybin is more effective in relieving depressive symptoms in patients with treatment-resistant depression (TRD). Researchers also want to know if a second dose of psilocybin is safe and well-tolerated. This study will see if psilocybin is effective, safe, and well-tolerated by tracking changes in depressive symptoms, suicidality, and side effects. This study will also see if a second dose of psilocybin has an effect on quality of life, functioning, cognition (thinking, reasoning, remembering), and how long depressive symptoms improve (or worsen) after psilocybin is administered.

Detailed description

During the past decade, there has been increased interest in the use of psilocybin as a novel treatment for mental health disorders, including treatment-resistant depression (TRD). Recent studies have suggested that psilocybin has the potential to relieve depressive symptoms when combined with psychotherapy (i.e., psilocybin-assisted psychotherapy \[PAP\]). Each psilocybin dosing session requires the use of extensive resources, including two specialized therapists supporting the patient for 6-8 hours per dosing session. If two doses of psilocybin prove to be more effective than a single dose of psilocybin in relieving depressive symptoms, then two doses should be the standard intervention for future trials and clinical application. However, if a second dose of psilocybin does not offer increased anti-depressant benefit from the first dose, then a second dose of psilocybin would only increase the risk of adverse side effects and cost of treatment. Therefore, the purpose of this study is to determine whether a second dose of psilocybin provides better efficacy, safety and tolerability than a single dose. The investigators hypothesize that two doses of psilocybin will be more beneficial compared to a single dose, and that there will be no significant difference between the groups (one dose versus two doses) in safety or tolerability. The primary objective of assessing antidepressant efficacy will be evaluated by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) between baseline and Week 8. Safety and tolerability will be assessed using standardized adverse effects monitoring, in addition to close participant monitoring during the dosing day (e.g., blood pressure changes, dissociative and psychotomimetic effects, treatment-emergent manic symptoms, and suicidality). Secondary objectives include evaluating the effects of one versus two psilocybin doses on suicidality, quality of life, functioning, cognition, and duration of clinical benefits during the six month observational follow-up period. Exploratory objectives include evaluating predictors of response, such as static and dynamic clinical factors and expectancy effects, and cost-effectiveness of one versus two psilocybin doses.

Conditions

• Major Depressive Disorder
• Depression
• Treatment-Resistant Depression
• Mood Disorders

Interventions

Type	Name	Description
DRUG	Single Psychedelic Dose Psilocybin	One psychedelic dose (1mg of psilocybin + 25mg of psilocybin) taken in conjunction with psilocybin-assisted psychotherapy
DRUG	Two Psychedelic Doses Psilocybin	Two psychedelic doses (25 mg of psilocybin + 25mg of psilocybin) taken in conjunction with psilocybin-assisted psychotherapy

Timeline

• Start date: 2024-02-05
• Primary completion: 2028-02-01
• Completion: 2028-08-01
• First posted: 2024-04-02
• Last updated: 2024-04-02

Locations

1 site across 1 country: Canada