Psilocybin-Assisted Therapy for Depression

(PAT-BD-01 Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single dose of psilocybin, a psychedelic compound, can aid individuals with bipolar II depression who have not found success with at least two standard depression treatments. Participants will receive either a full dose of psilocybin or a very low dose serving as a placebo. The trial aims to determine if psilocybin effectively and safely alleviates depression symptoms. Suitable candidates have bipolar II disorder, are currently experiencing depression, and have not responded to treatments like quetiapine or lithium. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants an opportunity to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin, particularly at a 25 mg dose, is usually well-tolerated. In various studies, this dose has demonstrated potential in alleviating depression. For example, one study found that a 25 mg dose was well-tolerated when combined with psychological support. Importantly, these studies reported no serious side effects. Participants also experienced positive effects, such as increased empathy and self-acceptance. This suggests that psilocybin might be a safe option for people with depression, although individual experiences can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Most treatments for depression typically involve antidepressants like SSRIs or SNRIs, which work by altering neurotransmitter levels in the brain over several weeks. However, psilocybin is unique because it taps into a different mechanism, targeting serotonin receptors directly and potentially offering rapid relief. Unlike traditional medications, psilocybin is derived from psychedelic mushrooms and is administered in a controlled setting, which could lead to transformative experiences and new ways of thinking for patients. Researchers are excited about psilocybin because it might provide effective symptom relief in a much shorter timeframe and with fewer side effects compared to existing options.

What evidence suggests that psilocybin-assisted therapy might be an effective treatment for depression?

Research has shown that psilocybin can improve depression symptoms, especially with a 25 mg dose. In this trial, participants in the active treatment arm will receive this 25 mg dose of psilocybin. A review of several studies found that psilocybin significantly reduced symptoms of depression, particularly in people with major depressive disorder (MDD). In more than half of the studies, psilocybin also helped with anxiety. Patients reported feeling more empathetic and accepting of themselves. However, some research suggests that psilocybin's effectiveness might not be as widespread as previously thought. ^{2 3 6 7 8}

Who Is on the Research Team?

Dr. Lakshmi N Yatham

Principal Investigator

UBC Department of Psychiatry

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11456834/

Psilocybin for major depressive disorder: a systematic review ... Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836921

Control Group Outcomes in Trials of Psilocybin, SSRIs, or ... Meaning The poor control treatment outcomes in psilocybin trials suggest that it may not be as broadly effective for depression as estimated.

3. akjournals.com akjournals.com/view/journals/2054/aop/article-10.1556-2054.2025.00461/article-10.1556-2054.2025.00461.xml

Five-year outcomes of psilocybin-assisted therapy for ... Participants reported enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016517812400622X

Efficacy and safety of psilocybin in the treatment of Major ... This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect.

5. bmj.com bmj.com/content/385/bmj-2023-078084

Efficacy of psilocybin for treating symptoms of depression Conclusion Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39754904/

Efficacy and safety of psilocybin in the treatment of Major ... This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect.

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2808950

Single-Dose Psilocybin Treatment for Major Depressive ... A 25-mg dose of psilocybin was well tolerated and may hold promise as a treatment for major depressive disorder when combined with psychological support.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37844352/

Psilocybin-assisted therapy for depression: A systematic ... A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence ...