Psilocybin Therapy for Depression and Anxiety in 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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if psilocybin, a substance from mushrooms, can safely help people with early-stage Parkinson's Disease who have depression or anxiety. It works by changing how the brain processes emotions. Psilocybin has been studied for its potential to reduce anxiety and depression in patients with serious illnesses, showing significant decreases in symptoms.

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.

What data supports the effectiveness of the drug Psilocybin Therapy?

Research shows that psilocybin, a component of 'magic mushrooms', may help treat major depressive disorder and addiction, with studies indicating rapid antidepressant effects and potential for aiding smoking cessation. ^{1 2 3 4 5}

Is psilocybin therapy generally safe for humans?

Psilocybin therapy has been studied in various settings and is generally considered safe when administered in controlled environments with proper support. Some people may experience challenging psychological effects, especially at higher doses, but these are usually manageable with support. Long-term negative effects are rare, and most participants report positive experiences. ^{5 6 7 8 9}

How does Psilocybin Therapy differ from other treatments for this condition?

Psilocybin Therapy is unique because it involves the use of a psychedelic compound that can alter perception and mood, potentially offering a novel approach to mental health conditions. Unlike traditional medications, which often target specific neurotransmitters, psilocybin may work by promoting new neural connections and enhancing emotional processing. ^{10 11 12 13 14}

Research Team

Joshua Woolley, MD/PhD

Principal Investigator

University of California, San Francisco

Ellen Bradley, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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]

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]

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]

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

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

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

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. [2019]

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

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

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

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. [2023]

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

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

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. [2016]

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

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

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

Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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

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

Tetrahydrocannabinol for tremor in multiple sclerosis. [2013]

13. Australia pubmed.ncbi.nlm.nih.gov

Cannabis: are there any benefits? [2021]

14. England pubmed.ncbi.nlm.nih.gov

The California program for the investigational use of THC and marihuana in heterogeneous populations experiencing nausea and vomiting from anticancer therapy. [2019]