Psilocybin Therapy for Parkinson's Disease

(PDP1 Trial)

Overseen By Zach Busby

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joshua Woolley, MD, PhD

Must not be taking: Dopamine agonists, MAO inhibitors

Disqualifiers: Psychosis, Cognitive impairment, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin therapy can safely alleviate depression and anxiety in people with Parkinson's disease. Participants will receive psilocybin, a compound found in certain mushrooms, in a controlled setting to assess its impact on mental health. It suits those with early-stage Parkinson's who currently experience depression or anxiety and have a support person available. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications that could interact with psilocybin, such as dopamine agonists, MAO inhibitors, NMDAR antagonists, antipsychotics, and stimulants. It's best to discuss your current medications with the study team to see if any changes are needed.

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

Research shows that psilocybin therapy is generally safe, though some side effects may occur. Studies have found common side effects such as headaches, nausea, dizziness, and increased anxiety. Some individuals also experience higher blood pressure during sessions.

Importantly, studies with a single dose of psilocybin have reported no serious harmful reactions. This suggests that psilocybin, when used in controlled settings, is well-tolerated by most participants. However, awareness of these possible side effects remains important when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression and anxiety in Parkinson's disease?

Unlike the standard of care for depression and anxiety in Parkinson's disease, which often involves antidepressants and cognitive-behavioral therapy, psilocybin therapy uses a naturally occurring psychedelic compound. Researchers are excited about psilocybin because it targets serotonin receptors in the brain, potentially leading to rapid and lasting changes in mood and perception. This treatment offers a unique approach by providing therapeutic effects after just one or two doses, whereas traditional medications often require daily use and can take weeks to become effective.

What evidence suggests that psilocybin therapy might be an effective treatment for depression and anxiety in Parkinson's disease?

Research has shown that psilocybin therapy might help with depression and anxiety. In studies involving individuals with major depression, psilocybin had lasting effects for up to a year. Another study found that it improved quality of life and reduced anxiety in cancer patients. Psilocybin may work by increasing the brain's adaptability, potentially aiding emotional healing. This trial will evaluate the effectiveness of psilocybin therapy in treating depression and anxiety in individuals with Parkinson's. ^{6 7 8 9 10}

Who Is on the Research Team?

Joshua Woolley, MD/PhD

Principal Investigator

University of California, San Francisco

Ellen Bradley, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 40-75 with early-stage Parkinson's Disease (stages 1-3) who are experiencing depression or anxiety. Participants must be able to attend visits at UCSF, have a support person, and an established healthcare provider. Those with severe health conditions, cognitive impairments, psychotic symptoms, or on certain medications like dopamine agonists and MAO inhibitors cannot join.

Inclusion Criteria

I can go to UCSF for visits and also do virtual ones.

Have a care partner/support person available throughout the study

I am currently feeling depressed or anxious.

Exclusion Criteria

Psychotic symptoms involving loss of insight

I am not taking medication that interacts badly with psilocybin.

A health condition that makes this study unsafe or unfeasible, determined by study physicians

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation

Participants complete preparation sessions to provide information about the psilocybin experience and build rapport with the study team

1-2 weeks

Psilocybin Administration Session 1

Participants receive a low-moderate dose of 10 mg oral psilocybin in a supervised setting with safety monitoring

1 day

1 visit (in-person)

Psilocybin Administration Session 2

Participants receive a moderate-high dose of 25 mg oral psilocybin in a supervised setting with safety monitoring

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up sessions to assess PD and psychiatric symptoms

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin Therapy

Trial Overview The study is examining the safety and effectiveness of psilocybin therapy as a treatment for depression and anxiety in individuals with Parkinson's disease. It aims to understand if this therapy can be tolerated well by patients and how feasible it is as a treatment option.

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 two weeks apart, with preparation sessions before and integration sessions after.

Who Is Running the Clinical Trial?

Joshua Woolley, MD, PhD

Lead Sponsor

Trials

3

Recruited

100+

Joshua Woolley, MD/PhD

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

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, 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]

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 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]

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 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]

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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Psychedelic-assisted therapy: An overview for the internist For weeks after treatment, psychedelics appear to reopen critical periods for social learning and enhance neuroplasticity. This provides a ...

2. hopkinsmedicine.org hopkinsmedicine.org/psychiatry/research/psychedelics-research

Psychedelics Research and Psilocybin Therapy 2022 Psilocybin Treatment for Major Depression May be Effective for Up to a Year. Previous studies by Johns Hopkins Medicine researchers showed that ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0163834325001562

A dose of therapy with psilocybin - A meta-analysis ... Psilocybin-assisted therapy (PAT) has shown promising effects in treating depressive symptoms, but the role of the therapeutic component remains unclear.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11271737/

Investigating the therapeutic efficacy of psilocybin in advanced ... Psilocybin-assisted therapy shows promising results in improving quality of life, pain control, and anxiety relief for patients with advanced cancer.

5. nature.com nature.com/articles/s41514-025-00244-x

Psilocybin treatment extends cellular lifespan and ... Psilocybin treatment promotes increased longevity in aged mice, suggesting that psilocybin may be a potent geroprotective agent.

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The safety of psilocybin-assisted psychotherapy The most common adverse events during and after sessions included elevated blood pressure, headaches, nausea, vomiting, fatigue and anxiety. In addition, both ...

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A systematic review to guide clinical and research protocol ... There are several safety considerations with psilocybin use. The principal physical risks include, headaches/migraines, tachycardia, ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2817352

Acute Adverse Effects of Therapeutic Doses of Psilocybin The results overall suggest a statistically significant incidence of headache, nausea, anxiety, dizziness, and elevated blood pressure. However, ...

9. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-06303-z

Prolonged adverse effects from repeated psilocybin use in an ... We present the case of a psychologist who underwent psychedelic therapy training that involved repeated high doses of psilocybin-containing mushrooms.

10. 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 ...