Psilocybin Therapy for Cancer

Overseen By Sarah Hales, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Benzodiazepines, SSRIs, MAO inhibitors, others

Disqualifiers: Brain cancer, Psychosis, Bipolar, 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: 1

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The PEARL Pilot is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

Will I have to stop taking my current medications?

You might need to stop or adjust some of your current medications if you join this trial. The study team will decide which medications need to be paused or tapered off safely before the psilocybin session. However, you can continue taking your prescribed opioids for pain relief.

What data supports the effectiveness of the drug psilocybin for cancer patients?

Research shows that psilocybin-assisted psychotherapy can improve psychiatric and existential distress, quality of life, and spiritual well-being in cancer patients, with 60-80% of participants experiencing significant antidepressant or anxiety-reducing effects up to 6.5 months after treatment. ^{1 2 3 4 5}

Is psilocybin therapy generally safe for humans?

Psilocybin has been studied for its safety in humans, showing that it can be used safely under controlled conditions, although caution is advised with higher doses. Some studies suggest it does not worsen certain heart conditions and may protect against cell injury, but it can cause side effects like vomiting and hallucinations. ^{4 6 7 8 9}

How is psilocybin therapy different from other cancer treatments?

Psilocybin therapy is unique because it involves a psychedelic substance that can alter perception and mood, potentially helping with the emotional and psychological challenges faced by cancer patients, especially in palliative care. Unlike traditional cancer treatments that focus on directly targeting cancer cells, psilocybin may help improve quality of life by addressing mental health aspects. ^{1 3 4 10 11}

Research Team

Sarah Hales, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 with stage IV solid tumor cancers, sarcoma, endocrine, melanoma cancers, or stage 4 lymphoma who have a life expectancy of more than 6 months. They must have mild depressive symptoms and be able to use birth control if sexually active. Exclusions include severe hypertension, certain cardiovascular conditions, past intolerances to psychedelics like psilocybin, specific psychiatric diagnoses or substance abuse issues.

Inclusion Criteria

Sexually active participants must use effective birth control

Negative serum pregnancy test result at screening for participants of child-bearing potential

My kidney function is normal.

Exclusion Criteria

Severe hypertension (systolic blood pressure >140/or diastolic pressure >90)

History of past intolerability of psilocybin or other psychedelics

Past/present psychiatric diagnoses including bipolar disorder, psychotic disorders, active substance use disorders or suicidality

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Therapy Sessions

Participants undergo preparatory therapy sessions as part of the PEARL therapy

2-4 weeks

Psilocybin Session

Participants receive a single high-dose (25 mg) of psilocybin in a monitored therapeutic setting

1 day

1 visit (in-person)

Integration Sessions

Participants attend integration sessions to process the psilocybin experience

2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Psilocybin

Trial Overview The PEARL Pilot study tests the effects of a single high-dose (25 mg) of psilocybin in combination with Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy on patients with advanced cancer. It aims to explore how this treatment can help manage existential distress associated with their condition.

Participant Groups

Group I: Psilocybin Experimental Treatment 1 Intervention

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 Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

A long-term follow-up of 15 participants from a previous trial showed that psilocybin-assisted psychotherapy led to sustained reductions in anxiety, depression, and other distressing symptoms, with 60-80% of participants still experiencing significant improvements 3.2 to 4.5 years later.

Participants reported that the psilocybin therapy was among the most meaningful experiences of their lives, indicating its potential to enhance psychological and spiritual well-being in patients facing life-threatening cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Agin-Liebes, GI., Malone, T., Yalch, MM., et al.[2023]

Medicinal mushrooms like Shiitake, Turkey Tail, and Scaly Wood show promise in cancer treatment by potentially preventing lymph node metastasis, prolonging survival, and reducing side effects from chemotherapy, based on a review of nine studies.

The review highlights the need for more rigorous research, including randomized controlled trials with larger sample sizes, to confirm these benefits and determine the most effective dosages for patients with high-mortality cancers such as gastric, breast, and colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review. Dan, A., Swain, R., Belonce, S., 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]

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-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]

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]

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 systematic review of 39 clinical studies on mushroom supplements in cancer care found that certain mushrooms, like Huaier granules and polysaccharide-K, may provide survival benefits and improve quality of life for patients with specific cancers, such as hepatocellular carcinoma and gastric cancer.

Most studies reported mild adverse effects, such as nausea and diarrhea, indicating that mushroom supplements are generally safe, but the evidence is still inconclusive for routine use, highlighting the need for more rigorous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies. Narayanan, S., de Mores, AR., Cohen, L., et al.[2023]

The review highlights that five major mushrooms—Agaricus blazei, Cordyceps sinensis, Grifola frondosa, Ganoderma lucidum, and Trametes versicolor—can modify cytokine levels in cancer models, potentially influencing the disease process and immune response.

In addition to their immunological roles, these mushrooms may enhance the efficacy of chemotherapy and mitigate myelosuppression, with promising preliminary research suggesting their potential as adjunct treatments in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. Guggenheim, AG., Wright, KM., Zwickey, HL.[2020]

References

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

Psilocybin in Palliative Care: An Update. [2023]

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

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. [2023]

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

Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review. [2023]

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

The pharmacology of psilocybin. [2016]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Intravenous mushroom poisoning. [2019]

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

Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies. [2023]

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

Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. [2020]