Psilocybin Therapy for Depression

(BAP Trial)

Overseen By Joshua D Woolley, MD,PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Antidepressants, Antipsychotics, Opioids, others

Disqualifiers: Bipolar I, Schizophrenia, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if psilocybin therapy, which uses a compound found in certain mushrooms, is safe and effective for individuals with Bipolar II Disorder currently experiencing depression. Participants will receive psilocybin in a controlled setting, with preparation and follow-up sessions. Suitable candidates have tried at least two other medications for their condition without success and have a support person to assist throughout the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking mental health research.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that could interact with psilocybin, such as some antidepressants, antipsychotics, stimulants, opioids, and Lithium. Bupropion is allowed, but it's best to discuss your specific medications with the study team.

Is there any evidence suggesting that psilocybin therapy is likely to be safe for humans?

Research shows that psilocybin therapy is generally safe in a controlled environment. Studies have found no serious side effects from a single dose of psilocybin, and no deaths were linked to its use. Most individuals tolerate it well, particularly under medical guidance. However, serious risks exist for some, making medical supervision crucial. Overall, the safety of psilocybin in clinical trials is reassuring, but personal health considerations are important when deciding to participate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bipolar II disorder, which often involve medications like mood stabilizers and antidepressants, psilocybin therapy uses a psychedelic compound derived from certain mushrooms. This treatment is unique because it targets the brain's serotonin receptors in a novel way, potentially leading to rapid and profound changes in mood and perception. Researchers are excited about psilocybin therapy because it might offer fast-acting relief from depressive symptoms with just one or two doses, compared to the weeks or months traditional medications can take to become effective. Additionally, the therapy sessions include preparation and integration support, which may enhance the therapeutic benefits and help patients integrate their experiences into daily life.

What evidence suggests that psilocybin therapy might be an effective treatment for Bipolar II Disorder?

Research shows that psilocybin therapy may help treat depression. Studies have found that psilocybin can greatly reduce symptoms of depression. A review of several studies reported strong positive effects both shortly after treatment and over time. Trials where participants knew they received psilocybin also showed significant decreases in depression. Additionally, past participants reported feeling more empathetic and accepting of themselves, with no serious side effects. While these findings are promising, this trial will specifically investigate the effectiveness of psilocybin therapy in treating depression in people with Bipolar II Disorder. ^{3 6 7 8 9}

Who Is on the Research Team?

Joshua D Woolley, MD,PhD

Principal Investigator

University of California, San Francisco

David Guard, PhD

Principal Investigator

San Francisco State University

Are You a Good Fit for This Trial?

Inclusion Criteria

Age 30 to 65

Comfortable speaking and writing in English

Able to attend all in-person visits at UCSF as well as virtual visits

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Sessions

Participants engage in preparatory visits with trained facilitators before psilocybin administration

1-2 weeks

2-3 visits (in-person)

Treatment

Participants receive one or two doses of psilocybin in a monitored setting, with preparation and integration sessions

6 weeks

4-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Monthly visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin Therapy

How Is the Trial Designed?

Group I: Psilocybin therapy Experimental Treatment 1 Intervention

Participants will receive one or two doses of psilocybin in a monitored setting approximately three weeks apart, with preparation sessions before and integration sessions after.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

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]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

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, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

The HOPE trial, involving 12 cancer patients, showed that psilocybin-assisted group therapy is safe, with no serious adverse events reported, and resulted in significant reductions in depression symptoms over six months.

Participants experienced substantial decreases in depression scores, with six out of twelve achieving remission at two weeks, indicating that this group therapy model could be an effective treatment for depression in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Lewis, BR., Garland, EL., Byrne, K., et al.[2023]

In a pilot study involving 15 participants, those who underwent psilocybin-facilitated smoking cessation reported significant insights into their self-identity and reasons for smoking, which contributed to their ability to quit smoking.

Participants experienced lasting positive changes beyond smoking cessation, such as increased altruism and pro-social behavior, suggesting that the therapeutic effects of psilocybin may extend beyond the immediate treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. Noorani, T., Garcia-Romeu, A., Swift, TC., et al.[2019]

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]

Citations

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sciencedirect.com

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A dose of therapy with psilocybin - A meta-analysis ...

The overall treatment effect was large both in the short-term (Cohen's d = 1.69) and long-term follow-up (Cohen's d = 2.10). However, no significant association ...

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Psychedelics Research and Psilocybin Therapy

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A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence ...

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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.

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nature.com

nature.com/articles/s41598-024-53188-9

Patient perspectives and experiences with psilocybin ...

Psilocybin treatment for major depressive disorder (MDD) and TRD has recently been awarded 'breakthrough therapy' status by the FDA. With over ...

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pubmed.ncbi.nlm.nih.gov

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The safety of psilocybin-assisted psychotherapy

Based on the available data, the safety of psilocybin-assisted psychotherapy is generally supported, and no deaths were attributed to psilocybin.

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sciencedirect.com

sciencedirect.com/science/article/pii/S277240852400125X

Safety pharmacology of acute psilocybin administration in ...

No serious adverse reactions occurred. These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical ...

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ccjm.org

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Psychedelics have a reassuring safety profile in highly controlled clinical trial settings, though they carry serious risks for some patients.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06299319

Study Details | NCT06299319 | Feasibility, Clinical Effects, ...

To assess the safety, and feasibility, of psilocybin, administered with psychological support to adult participants with TROCD. · To assess the clinical effects ...