What side effects are associated with this type of intervention?

Common treatments for depression, such as SSRIs and SNRIs, can cause side effects like nausea, insomnia, sexual dysfunction, and weight gain. Antipsychotics like Risperidone may lead to extrapyramidal symptoms, weight gain, metabolic syndrome, and sedation. Psilocybin, a serotonin 5HT2A receptor agonist, has shown potential side effects including transient anxiety, confusion, and perceptual changes.

What prior FDA approvals exist?

The FDA has approved several treatments for depression that involve modulation of the serotonin system. Selective serotonin reuptake inhibitors (SSRIs) like escitalopram and fluoxetine are commonly used and work by increasing serotonin levels in the brain. Additionally, atypical antipsychotics such as Risperidone, which acts as a serotonin 5HT2A receptor antagonist, have been approved for use in treatment-resistant depression. While Psilocybin, a serotonin 5HT2A receptor agonist, is not yet FDA-approved, it is currently being studied for its potential antidepressant effects in clinical trials.

What other types of research exist?

Promising novel alternatives for depression treatment in 2024 include: 1) Ayahuasca, which has shown efficacy in treatment-resistant depression in small trials; 2) Vortioxetine, an antidepressant with multimodal activity, including serotonin modulation; 3) Esketamine, a rapid-acting antidepressant administered via nasal spray; 4) Mirtazapine, particularly for patients with prominent insomnia; and 5) Cannabidiol (CBD), which has shown potential in reducing anxiety and depressive symptoms in preliminary studies.

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Psychedelic

Psilocybin for Depression (PSI-RIS Trial)

Phase 2

Recruiting

Led By M. Ishrat Husain, MBBS, MD

Research Sponsored by Centre for Addiction and Mental Health

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline (day -1) to visit 5 (day 7)

Summary

This trial uses a magic mushroom substance and therapy to treat people with depression that hasn't improved with other treatments. It aims to understand if the mind-altering effects are needed for its antidepressant benefits. Psilocybin, a compound derived from magic mushrooms, has shown potential in early trials for treating depression with relatively low side effects.

Who is the study for?

Adults aged 18-65 with treatment-resistant depression, defined as not responding to two or more antidepressants, can join this trial. They must be able to consent and communicate in English, have normal bloodwork, use effective contraception if applicable, and safely stop current medications affecting the study.

What is being tested?

The trial is testing whether psilocybin's effects on depression require its psychedelic aspect by comparing three groups: one taking psilocybin with risperidone (which may block psychedelic effects), another taking psilocybin with a placebo, and a third group receiving placebo plus risperidone.

What are the potential side effects?

Possible side effects include those related to psilocybin such as nausea, headache, increased heart rate or blood pressure changes; and for risperidone potential weight gain, fatigue or restlessness could occur.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline (day -1) to visit 5 (day 7)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline (day -1) to visit 5 (day 7)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline (day -1) to visit 5 (day 7) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Feasibility of administering psilocybin (25mg) with risperidone (1mg)

Tolerability and safety of administering psilocybin (25mg) with risperidone (1mg)

Secondary study objectives

Subjective psychedelic effects as measured by the 5-Dimensional Altered States of Consciousness (5D-ASC) Rating Scale

Other study objectives

Change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from Baseline to 1-week post-treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Risperidone 1 mg plus Psilocybin 25 mgExperimental Treatment2 Interventions

Group II: Placebo plus Psilocybin 25 mgExperimental Treatment2 Interventions

Group III: Risperidone 1 mg plus PlaceboActive Control2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for depression often target serotonin pathways, particularly the 5HT2A receptor. Psilocybin, a serotonin 5HT2A receptor agonist, stimulates these receptors and has shown significant antidepressant effects in clinical trials. Conversely, Risperidone, a serotonin 5HT2A receptor antagonist, blocks these receptors to help alleviate symptoms of depression and psychosis. These mechanisms underscore the critical role of serotonin in mood regulation, offering potential targeted therapies for effective depression management.

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