Psilocybin-Assisted Psychotherapy for Depression

(PSI-1V2 Trial)

Overseen By Zoe Doyle, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others

Disqualifiers: Mania, Psychosis, Substance use disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

92 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications like antidepressants, antipsychotics, mood stabilizers, and stimulants at least one month before starting the trial, if your doctor says it's safe.

Is psilocybin safe for use in humans?

Psilocybin has been studied in clinical trials and is generally considered safe when used under medical supervision, although it can cause temporary side effects like hallucinations and changes in perception. A study on healthy adults showed that escalating doses of psilocybin were well-tolerated, and research on depression and anxiety suggests it may be safe for these conditions as well. ^{1 2 3 4 5}

How is psilocybin different from other depression drugs?

Psilocybin is unique because it is a natural compound found in 'magic mushrooms' and is used in a novel, rapid-acting therapy for depression, often requiring only one or two doses combined with psychotherapy, unlike traditional antidepressants that are taken daily and can have significant side effects. ^{4 6 7 8 9}

Research Team

Joshua Rosenblat, MD, MSc

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for individuals with treatment-resistant depression, meaning they haven't responded well to standard treatments. Participants must be adults who can safely receive psilocybin and are willing to undergo psychotherapy sessions.

Inclusion Criteria

Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation in addition to monthly check-ins by study staff to determine the first day of their last menstrual period

Current MDE must be moderate to severe, as determined by a MADRS score greater than 21

I will use condoms or other methods to prevent pregnancy during the study.

Exclusion Criteria

Major neurocognitive disorder, as determined by clinical assessment, including administration of the Montreal Cognitive Assessment (MoCA)

Lifetime history of mania, hypomania or psychosis as determined by clinical psychiatric assessment and the MINI

Treatment with another investigational drug or other intervention within 30 days of Baseline (V2)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one or two doses of psilocybin in conjunction with psilocybin-assisted psychotherapy

8 weeks

2-4 visits (in-person) for dosing sessions

Follow-up

Participants are monitored for safety, effectiveness, and various secondary outcomes such as quality of life and cognitive function

6 months

Regular follow-up visits (in-person or virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study is testing the effectiveness of one versus two doses of psilocybin in conjunction with psychotherapy on relieving symptoms of depression. It aims to determine which dosage level improves quality of life and cognitive functions more effectively.

Participant Groups

Group I: Two Doses of Psilocybin Active Control 1 Intervention

Two psychedelic doses (25mg of psilocybin + 25mg of psilocybin) taken in conjunction with psilocybin-assisted psychotherapy

Group II: Single Dose of Psilocybin Placebo Group 1 Intervention

One psychedelic dose (1mg of psilocybin + 25mg of psilocybin) taken in conjunction with psilocybin-assisted psychotherapy

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Findings from Research

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[2022]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

Psilocybin has shown promise in clinical trials for reducing symptoms of depression, indicating its potential as a novel treatment option.

Patients with treatment-resistant depression (TRD) may benefit the most from psilocybin therapy, although the risks associated with its use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. Kozak, Z., Johnson, MW., Aaronson, ST.[2023]

A single, moderate dose of psilocybin significantly reduced depressive symptoms in 52 participants with major depressive disorder, showing a decrease of 13.0 points on the MADRS scale compared to baseline, which was significantly greater than the placebo group.

54% of participants in the psilocybin group met the criteria for remission of depression 14 days after treatment, and no serious adverse events were reported, indicating a favorable safety profile for this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. von Rotz, R., Schindowski, EM., Jungwirth, J., et al.[2023]

Psilocybin, derived from Psilocybe cubensis mushrooms, is being investigated as a novel treatment for major depression, with a focus on its safety and efficacy compared to traditional antidepressants.

The proposed study will include both preclinical toxicity evaluations in mice and a clinical trial assessing the safety and pharmacokinetics of psilocybin in healthy adults, followed by an open trial in patients with major depressive disorder, aiming to provide comprehensive data on its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. Escamilla, R., González-Trujano, ME., González Mariscal, JM., et al.[2023]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]