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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of psilocybin, a psychedelic compound, to help individuals with advanced cancer manage mild depression and related challenges. Participants will receive a single high dose of psilocybin during a specialized therapy session called PEARL. The trial seeks individuals in Ontario with stage IV solid tumors or certain other advanced cancers who are experiencing mild depression. Participants must be able to engage in therapy and follow the trial's instructions. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research has shown that psilocybin therapy has been tested for safety in cancer patients. In one study, patients who took psilocybin found it easy to handle, with most side effects being mild and temporary, such as headaches or slight nausea. Another study confirmed that psilocybin is safe for cancer patients and can be used in therapy settings.

Although the current trial remains in the early stages, these studies suggest that psilocybin is generally safe when used carefully. It is important to remember that while these findings are promising, each person's experience may differ. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about psilocybin therapy for cancer because it offers a novel approach to managing psychological distress often experienced by cancer patients. Unlike traditional treatments such as antidepressants or anti-anxiety medications, psilocybin is a psychedelic compound that works by targeting serotonin receptors in the brain, potentially leading to profound changes in mood and perception. This mechanism of action is believed to help patients achieve a greater sense of emotional well-being and possibly alleviate symptoms more rapidly. Additionally, psilocybin therapy could provide lasting benefits after just a few sessions, unlike daily medications that take longer to show effects.

What evidence suggests that psilocybin might be an effective treatment for cancer?

Research has shown that a single 25 mg dose of psilocybin, which participants in this trial will receive, can help cancer patients experiencing depression. In one study, more than half of the participants remained free from depression after taking psilocybin. Another study found that this 25 mg dose greatly improved depression symptoms compared to smaller doses. Early studies with cancer patients who have depression found psilocybin to be safe and effective. These results suggest that psilocybin could help boost mood in people with cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Sarah Hales, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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 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 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]

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2803623

Assessment of Psilocybin Therapy for Patients With Cancer ... Nonetheless, this study demonstrates the safety and preliminary efficacy of psilocybin treatment for patients with cancer and depression ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206443

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03866174

A Study of Psilocybin for Major Depressive Disorder (MDD) The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10102915/

Assessment of Psilocybin Therapy for Patients With Cancer ... Nonetheless, this study demonstrates the safety and preliminary efficacy of psilocybin treatment for patients with cancer and depression ...

5. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2023/Data-Demonstrating-Long-Term-Improvement-in-Depression-in-Cancer-Patients-Following-Single-Dose-of-COMP360-Psilocybin-Therapy-to-be-Presented-at-ASCO-2023/default.aspx

News Details More than half of the patients (16/28) treated with a single dose of 25mg COMP360 psilocybin with psychological support remained in remission ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05506982?term=psychedelic&cond=cancer&viewType=Table&rank=7

Study Details | NCT05506982 | Psilocybin Combined With ... This phase I trial evaluates the side effects of psilocybin and how well it works under supportive care conditions in cancer survivors living with ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0885392423005304

A Pilot Study of Psilocybin Enhanced Group Psychotherapy ... This pilot study demonstrated the safety, feasibility, and possible efficacy of psilocybin-assisted group therapy for cancer patients dealing with depressive ...