Psilocybin Therapy for Depression in Parkinson's Disease

(PDP2 Trial)

Overseen By Joshua Woolley, MD,PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joshua Woolley, MD, PhD

Must not be taking: Psilocybin interactions

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it excludes those who regularly use medications that might interact with psilocybin. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug psilocybin for depression in Parkinson's Disease?

Research shows that psilocybin has been effective in reducing symptoms of depression in several clinical trials, and it is well tolerated with limited side effects. It has shown promise in treating major depressive disorder and other psychiatric conditions, suggesting potential benefits for depression in Parkinson's Disease. ^{1 2 3 4 5}

Is psilocybin safe for use in humans?

Psilocybin has been studied in healthy adults and in people with depression and anxiety related to life-threatening diseases, showing a promising safety profile. However, some adverse reactions, such as rapid heartbeat, have been reported, possibly due to other substances in the mushrooms. Overall, recent research suggests psilocybin is generally safe when used in controlled settings. ^{3 6 7 8 9}

How is the drug psilocybin unique in treating depression in Parkinson's disease?

Psilocybin is unique because it is a psychedelic compound that can rapidly reduce depression symptoms, even in cases where other treatments have failed, and it may only require one or a few doses to have long-lasting effects. ^{1 2 6 10 11}

What is the purpose of this trial?

The purpose of this study is to understand whether people with Parkinson's Disease and depression have improvement in their symptoms after psilocybin therapy.

Research Team

Ellen Bradley, MD

Principal Investigator

University of California, San Francisco

Joshua D Woolley, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for English-speaking adults aged 40-80 with Parkinson's Disease (stages 1-3) and depression, who can attend visits at UCSF. They must have a doctor managing their condition but cannot join if they have psychotic symptoms, significant cognitive issues, or use certain medications like dopamine agonists or MAO inhibitors.

Inclusion Criteria

Comfortable speaking and writing in English

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

I have Parkinson's diagnosed by a neurologist, in early to mid-stage.

Exclusion Criteria

Psychotic symptoms involving loss of insight

I have significant memory or thinking problems.

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 and Integration

Participants undergo psychotherapy sessions before and after each psilocybin administration session

4-6 weeks

Multiple visits (in-person)

Psilocybin Administration Session 1

Participants receive one dose of psilocybin in a monitored setting with preparation and integration sessions

1 day

1 visit (in-person)

Psilocybin Administration Session 2

Participants receive a second dose of psilocybin in a monitored setting with preparation and integration sessions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study aims to see if psilocybin therapy helps improve depressive symptoms in those with Parkinson's Disease. Participants will receive psilocybin treatment and their symptom changes will be monitored.

Participant Groups

Group I: Psilocybin Administration Session 2 Experimental Treatment 1 Intervention

Participants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.

Group II: Psilocybin Administration Session 1 Experimental Treatment 1 Intervention

Participants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

Joshua Woolley, MD, PhD

Lead Sponsor

Trials

3

Recruited

100+

Findings from Research

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

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 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, derived from Psilocybe cubensis mushrooms, is being investigated as a novel treatment for major depression, with a focus on its safety and efficacy compared to traditional antidepressants.

The proposed study will include both preclinical toxicity evaluations in mice and a clinical trial assessing the safety and pharmacokinetics of psilocybin in healthy adults, followed by an open trial in patients with major depressive disorder, aiming to provide comprehensive data on its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. Escamilla, R., González-Trujano, ME., González Mariscal, JM., et al.[2023]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

This study identified phenylethylamine in Psilocybe semilanceata mushrooms, which may contribute to adverse reactions during psilocybin intoxication, as evidenced by a case involving three young men who experienced severe symptoms.

The levels of phenylethylamine in these mushrooms can vary significantly, with the highest concentration found in the case of hospitalization, suggesting that this compound could play a role in the tachycardia and other symptoms not directly linked to psilocybin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions. Beck, O., Helander, A., Karlson-Stiber, C., et al.[2019]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

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]

A single dose of psilocybin (0.5-20 mg/kg) significantly increases the expression of genes related to neuroplasticity in the prefrontal cortex and hippocampus, suggesting its potential therapeutic effects for mental health disorders.

The study highlights that psilocybin's effects on gene expression are dose-dependent and predominantly observed in the prefrontal cortex, emphasizing the need to assess both gene expression and protein translation to understand its rapid effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Jefsen, OH., Elfving, B., Wegener, G., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Assessing potential of psilocybin for depressive disorders. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. [2023]

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

The pharmacology of psilocybin. [2016]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

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

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. [2020]

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

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

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

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. [2022]