Psilocybin Therapy for Clinician Burnout and Depression

Overseen By Timara Freeman-Young, PA-C

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Washington

Must not be taking: SSRIs, Neuroleptics, Tramadol, Psychedelics

Disqualifiers: Schizophrenia, Bipolar, Substance abuse, others

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

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

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. Participants must be off selective serotonin inhibitors (SSRIs) for at least five half-lives of the drug plus 2 weeks, and avoid taking any psychiatric medications during the study. If your doctor recommends starting a new psychiatric medication, you must notify the study team and may need to withdraw from the study.

What data supports the effectiveness of the drug psilocybin for clinician burnout and depression?

Research shows that psilocybin has been studied in clinical trials for depression and other psychiatric disorders, with some patients experiencing significant, long-term improvements after treatment. Although more research is needed, initial results are promising, indicating that psilocybin could be effective for conditions like depression. ^{1 2 3 4 5}

Is psilocybin generally safe for human use?

Psilocybin has been studied in healthy adults and shown to have a safety profile that supports its use under controlled conditions, although caution is advised with higher doses. It has been used in clinical trials for depression and substance use disorders, and while it can cause hallucinations and other effects, it is generally considered safe when administered in a controlled setting. ^{4 5 6 7 8}

How is psilocybin therapy different from other treatments for clinician burnout and depression?

Psilocybin therapy is unique because it uses a psychedelic compound found in certain mushrooms to potentially reduce symptoms of depression, offering long-term improvements after just one or a few sessions, unlike traditional antidepressants that require regular dosing. It is also noted for having limited side effects and no risk of addiction or overdose, which sets it apart from many other mind-altering drugs. ^{1 5 9 10 11}

What is the purpose of this trial?

This trial investigates whether a single dose of psilocybin, combined with therapy sessions, can help reduce depression and burnout in healthcare workers affected by their frontline roles during the COVID pandemic. Psilocybin may change brain activity to improve mood, especially when paired with supportive therapy. The study will compare the effects of psilocybin over time. Psilocybin has shown promise in reducing depression and anxiety in patients with life-threatening cancer, according to previous studies.

Research Team

Anthony Back, MD

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for English-speaking physicians and nurses who have faced significant stress from frontline work during the COVID pandemic, with moderate to severe depression symptoms. They must not be on SSRIs or start new psychiatric meds during the study, need a negative pregnancy test if applicable, and commit to all sessions and evaluations. A support person must be available for transportation and monitoring post-dosing.

Inclusion Criteria

I am willing to attend all sessions, take medications, and complete evaluations as required.

My depression symptoms persist despite trying at least one standard treatment.

I am not taking new psychiatric medications during the study.

Exclusion Criteria

Any use of psychedelic drugs within the prior 12 months

I am not taking tramadol due to its risks with psilocybin.

I cannot stop taking my neuroleptic or SSRI medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of psilocybin or placebo, accompanied by psychedelic-assisted psychotherapy

1 day

1 visit (in-person)

Short-term Follow-up

Participants are monitored for short-term effects on depression and burnout symptoms

1 week

1 visit (virtual)

Long-term Follow-up

Participants are monitored for longer-term effects on depression and burnout symptoms

24 weeks

Multiple visits (virtual)

Treatment Details

Interventions

• Psilocybin

Trial Overview The study tests the impact of a single dose of psilocybin combined with psychotherapy on healthcare workers' depression and burnout due to COVID-19 related stress. Participants will also receive pre- and post-dose therapy sessions to help integrate their experiences.

Participant Groups

Group I: Psilocybin arm Experimental Treatment 1 Intervention

psychedelic assisted psychotherapy + 25mg psilocybin

Group II: Placebo Active Control 1 Intervention

Psychedelic assisted psychotherapy + 250mg niacin

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

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]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

Psilocybin treatment in depressed patients leads to transient increases in brain connectivity and activation in key neural areas, which are associated with positive antidepressant responses, suggesting a 'brain reset' effect.

The review analyzed 5 studies involving neuroimaging techniques, indicating that psilocybin-assisted psychotherapy may be particularly effective in both refractory and non-refractory depression cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurobiological Correlates of Psilocybin Response in Depression. Qasim, S., Zaheer, Z., Jawad, MY., 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]

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]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

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]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

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]

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]

Recent FDA-approved clinical studies suggest that psilocybin-assisted psychotherapy may effectively treat conditions like depression, anxiety, and certain addictions, indicating its potential as a valuable therapeutic tool.

If early clinical findings are confirmed by larger studies, psilocybin could significantly influence psychiatric medicine and expand treatment options for mental health disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin: from ancient magic to modern medicine. Nichols, DE.[2021]

References

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

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

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

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

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

Neurobiological Correlates of Psilocybin Response in Depression. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

The pharmacology of psilocybin. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. [2021]

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

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

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

Assessing potential of psilocybin for depressive disorders. [2023]

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

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

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

Psilocybin: from ancient magic to modern medicine. [2021]