Psilocybin-Assisted Therapy for Depression

(PAT-BD-01 Trial)

Recruiting at 3 trial locations

Overseen By Vy Ngo, B.Sc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Lakshmi N Yatham

Must not be taking: Psychedelics, others

Disqualifiers: Rapid cycling, Psychotic disorder, Substance use, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 11

Duration: 12 weeks

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications at least 2 weeks before the dosing visit and throughout the study, but lamotrigine, valproate, lithium, and lorazepam (up to 2 mg/day) are allowed. The protocol does not specify all prohibited medications, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug psilocybin for depression?

Research suggests that psilocybin, when used with therapeutic support, can quickly and significantly reduce symptoms of depression, with effects lasting from just one or two doses. Studies have shown that psilocybin affects brain activity in ways that may help alleviate depression. ^{1 2 3 4 5}

Is psilocybin-assisted therapy generally safe for humans?

Psilocybin-assisted therapy is generally considered safe when administered under supervision, with most side effects being mild and temporary. Serious adverse events are uncommon, but there have been reports of increased suicidal thoughts and behaviors in some cases, so further research is needed to understand who might be at risk. ^{6 7 8 9 10}

How is the drug psilocybin different from other depression treatments?

Psilocybin is unique because it can produce rapid and lasting antidepressant effects with just one or two doses, unlike traditional antidepressants that often require daily use. It works by activating serotonin 2A receptors in the brain, which is different from how most standard depression medications function. ^{1 3 6 11 12}

What is the purpose of this trial?

This study is a 12-week (in addition to up to 30 days of screening) randomized, double-blind, placebo-controlled, parallel-group trial. The primary objective of this study is to assess the effectiveness, safety, and tolerability of single-dose psilocybin (25 mg)-assisted therapy in comparison to active placebo (1 mg micro-dose) psilocybin-assisted therapy in patients with bipolar II depression who have not responded to adequate trials with at least two first or second-line treatments for bipolar II depression (i.e. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy). The active placebo is a substance that looks identical to the study medication but contains less therapeutic ingredients, and thus is less capable of producing the transformative and meaningful aspects of psychedelic experience compared to the 25 mg dose. Participants will have a total of 11 study visits over a period of up to 16 weeks, which includes 5 therapy sessions from trained study therapists.

Research Team

Dr. Lakshmi N Yatham

Principal Investigator

UBC Department of Psychiatry

Eligibility Criteria

This trial is for individuals with bipolar II depression who haven't improved after trying at least two different treatments, such as quetiapine, lithium, or sertraline. Participants should be stable and have no other psychological conditions that could interfere with the study.

Inclusion Criteria

Sufficient English language skills to understand and comply with study requirements

Willing to practice highly effective contraception methods or abstain from heterosexual intercourse

I have bipolar type II and am currently experiencing a major depressive episode.

Exclusion Criteria

History of rapid cycling (4 or more mood episodes in the preceding 12 months)

Lifetime history of a primary psychotic disorder

History of psychotic symptoms

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of psilocybin (25 mg) or active placebo (1 mg) with therapy sessions

12 weeks

11 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests if a single high dose of psilocybin (25 mg) in therapy sessions helps more than a very low dose (1mg), which serves as an active placebo. The trial lasts up to 16 weeks and includes double-blind testing where neither doctors nor patients know who gets what treatment.

Participant Groups

Group I: Active Experimental Treatment 1 Intervention

25 mg psilocybin.

Group II: Placebo Placebo Group 1 Intervention

1 mg psilocybin (micro-dose)

Who Is Running the Clinical Trial?

Lakshmi N Yatham

Lead Sponsor

Trials

2

Recruited

100+

Findings from Research

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

In a placebo-controlled study involving individuals with moderate to severe major depressive disorder, psilocybin (0.3 mg/kg) showed larger antidepressant effect sizes compared to placebo, with 66.7% of participants responding and 46.7% achieving remission after treatment.

The antidepressant effects of psilocybin persisted for an average of 2 months, indicating its potential as a long-lasting treatment option for depression, although the strength of the mystical experience during dosing did not correlate with these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. Sloshower, J., Skosnik, PD., Safi-Aghdam, H., et al.[2023]

In a study using the Flinders Sensitive Line rat model of depression, neither psilocin nor psilocybin demonstrated an antidepressant-like effect, as measured by the forced swim test, which assesses immobility and swimming behavior.

Despite previous positive results in humans, this study suggests that the Flinders Sensitive Line model may not be suitable for testing the effects of psilocybin, indicating a need for alternative animal models or behavioral tests in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. Jefsen, O., Højgaard, K., Christiansen, SL., et al.[2020]

In a phase 2 trial with 104 participants, a single dose of psilocybin significantly reduced depression scores compared to a niacin placebo, showing a mean difference of -12.3 points on the MADRS scale by day 43, indicating strong efficacy.

Psilocybin treatment led to a significant reduction in functional disability as measured by the Sheehan Disability Scale, with no serious adverse events reported, suggesting it is a safe option when combined with psychological support for treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. Raison, CL., Sanacora, G., Woolley, J., et al.[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]

In a phase II study involving 19 adults with treatment-resistant depression, a single 25 mg dose of synthetic psilocybin (COMP360) showed a significant reduction in depression scores, with a mean change of -14.9 on the MADRS scale after 3 weeks.

The treatment was generally safe, with 63.2% of participants experiencing mild treatment-emergent adverse events, but no serious adverse events or increased suicidal thoughts were reported, indicating a favorable safety profile for psilocybin in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Goodwin, GM., Croal, M., Feifel, D., et al.[2023]

Psilocybin, a psychedelic drug, shows promising safety and efficacy in treating major depression and treatment-resistant depression (TRD), with initial phase 2 trials indicating positive outcomes when combined with psychological support.

The first international randomized controlled trial in 2022 found that a 25 mg dose of psilocybin was effective compared to an active placebo, and phase 3 trials are set to begin in 2023, suggesting a growing interest in psilocybin as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of psilocybin therapy for treatment-resistant depression: an update. Borissova, A., Rucker, JJ.[2023]

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 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 proof-of-concept randomized controlled trial is being conducted with 60 adults suffering from treatment-resistant depression (TRD) to assess the feasibility and safety of combining psilocybin with risperidone, which is expected to block the psychedelic effects of psilocybin.

The study aims to provide pilot data on the antidepressant effects of this combination compared to psilocybin alone, potentially allowing for psilocybin to be used as a treatment for TRD without the need for a psychedelic experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial. Husain, MI., Blumberger, DM., Castle, DJ., et al.[2023]

References

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

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Psilocybin for the Treatment of Depression: A Promising New Pharmacotherapy Approach. [2023]

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

Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat. [2020]

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

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. [2023]

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

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

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

Psilocybin history, action and reaction: A narrative clinical review. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. [2023]

9. England pubmed.ncbi.nlm.nih.gov

The development of psilocybin therapy for treatment-resistant depression: an update. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial. [2023]