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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a single dose of psilocybin, a psychedelic compound, combined with therapy, can alleviate depression and burnout in healthcare workers who served on the front lines during the COVID pandemic. The trial focuses on individuals who have struggled with depression despite standard treatments. Participants will receive either psilocybin or a placebo to determine any differences in improvement. This trial suits doctors and nurses who have experienced significant stress and depression related to their pandemic work. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that psilocybin, a substance found in certain mushrooms, has been studied for its effects on mental health issues like depression. In earlier studies, most participants tolerated psilocybin well. Common side effects are usually mild to moderate and can include temporary mood or perception changes, headaches, or nausea. These effects typically resolve on their own without causing long-term problems.

In this trial, psilocybin is used alongside therapy, with mental health professionals supporting participants before and after taking the dose. This support may help manage any side effects more effectively. While the FDA has not yet approved psilocybin for treating depression, research so far suggests it is safe when used carefully in clinical settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin therapy is unique because it utilizes a psychedelic-assisted approach to tackle clinician burnout and depression. Unlike traditional antidepressants that often take weeks to work and focus on neurotransmitter modulation, psilocybin acts quickly and offers the potential for profound, lasting effects after just a single session. This treatment is particularly exciting because it targets the brain's neural pathways in a novel way, potentially offering a rapid and transformative experience that standard therapies can't match. Researchers are hopeful that this could provide a new, effective option for those who haven't found relief with existing treatments.

What evidence suggests that psilocybin might be an effective treatment for depression and burnout?

Research has shown that psilocybin, which participants in this trial may receive, may help treat depression. Studies have found that psilocybin can greatly reduce depression symptoms. This effect might occur because psilocybin influences parts of the brain related to mood and emotions. Early results suggest that even one dose, when used with therapy, can lead to noticeable improvements. While more data is needed, there is hope that psilocybin could help people with depression, including healthcare workers experiencing burnout. ^{1 2 3 4 5}

Who Is on the Research Team?

Anthony Back, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

2. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic ...

3. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.

4. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Psilocybine's formula is C12H17N2O4P, molecular weight is 284.2481, CAS number is 520-52-5, and also known as Psilocybin.

5. zfin.org zfin.org/CHEBI:8614

ZFIN ChEBI: psilocybin A tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic alkaloid isolated ...