Psilocybin for Cancer Pain

Recruiting at 2 trial locations

Overseen By Isabel Kristan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yvan Beaussant, MD, MSci

Must be taking: Opioids

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others

Disqualifiers: Psychotic disorder, Bipolar, Heart disease, 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: 11

Duration: 1 day

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall objective of this study is to assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy to alleviate opioid-refractory pain in patients with advanced-cancer. The name of the study intervention used in this research study is: Psilocybin (a tryptamine derivative)

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications that could interact with psilocybin, such as antidepressants, antipsychotics, and mood stabilizers. These medications will need to be tapered off appropriately to avoid withdrawal effects before participating in the study.

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

Research suggests that psilocybin may have therapeutic benefits in palliative care, which often includes managing cancer pain, although it is not yet approved for this use in the U.S. Additionally, psilocybin has shown potential in treating major depressive disorder, which can be relevant as depression often accompanies chronic pain conditions. ^{1 2 3 4 5}

Is psilocybin safe for human use?

Psilocybin is generally considered safe when used in controlled settings with proper screening and support, although it can cause challenging psychological experiences and, in rare cases, lead to risky behavior or enduring psychological distress. It is important to use it under medical supervision, especially for individuals with pre-existing mental health conditions. ^{2 6 7 8 9}

How does the drug psilocybin differ from other treatments for cancer pain?

Psilocybin is unique because it is a psychoactive compound found in certain mushrooms, known for its hallucinogenic effects, and is being explored for its potential to alleviate cancer pain by affecting the brain's perception of pain. Unlike traditional pain medications, psilocybin may offer a novel approach by potentially altering consciousness and emotional responses to pain. ^{2 4 10 11 12}

Research Team

Yvan Beaussant, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with advanced cancer experiencing pain not relieved by opioids, on a high opioid dose, and seen by palliative care recently. They must be able to take pills, consent to the study, have certain organ functions within safe ranges, and commit to lifestyle changes for the trial. Pregnant women or those who can become pregnant without effective birth control are excluded.

Inclusion Criteria

I can take care of myself and am up and about more than 50% of my waking hours.

My cancer is advanced and not likely to be cured.

I am 18 years old or older.

Exclusion Criteria

I am not on any medications that can't be stopped and would interfere with the study drugs.

I have risk factors for a specific heart rhythm condition (like heart failure or low potassium).

Participants with a history of, or a current diagnostic of primary psychotic disorder, major depressive disorder with psychotic features, bipolar affective disorder type 1 or history of or current dissociative identity disorder; and participants who have an ongoing substance use disorder (defined as active in the past year). Participants with first-degree relatives with schizophrenia or bipolar disorder may be eligible depending on their age and personal and family psychiatric history. The decision will be made by the principal investigator and study psychiatrist based on risk assessment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preparation

Participants undergo 2 preparation sessions with therapists, either in-clinic or remote

1-2 weeks

2 visits (in-person or remote)

Treatment

Participants receive a single psilocybin session in-clinic with therapists

1 day

1 visit (in-person)

Integration

Participants have integration sessions with therapists, including one the day after treatment and another one week later

1 week

2 visits (in-person or remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at weeks 2, 3, 5, 8, and 12

12 weeks

5 visits (in-person or remote)

Treatment Details

Interventions

• Psilocybin

Trial Overview The trial is testing psilocybin-assisted therapy's safety and ability to reduce pain in patients with advanced cancer whose pain isn't managed by opioids. Participants will receive doses of psilocybin under controlled conditions.

Participant Groups

Group I: Psilocybin Experimental Treatment 1 Intervention

Participants will complete study procedures as follows: * 2, in-clinic or remote, preparation sessions with therapists. * In-clinic treatment session with therapists at Dana-Farber Cancer Institute. Participants will take a predetermined amount of psilocybin once. Participants will be transported home by a friend or family member. * In-clinic integration session the day after psilocybin administration with therapists. * In-clinic or remote, integration session with therapists 1 week after psilocybin administration. * In-clinic or remote follow visits with therapists at week 2, 3, 5, 8, and 12 after psilocybin administration.

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?

Yvan Beaussant, MD, MSci

Lead Sponsor

Trials

2

Recruited

30+

Cy Biopharma

Collaborator

Trials

1

Recruited

20+

Pancreatic Cancer North America

Collaborator

Trials

1

Recruited

20+

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]

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]

This study found that the binding of serotonin 2A receptors (5-HT2AR) in the brain can predict how long the peak effects of psilocybin last and how quickly individuals return to normal consciousness after its effects wear off.

Higher levels of 5-HT2AR binding were associated with lower scores on the Mystical Experience Questionnaire, suggesting that individual differences in receptor availability may influence the subjective experience of psilocybin, which could have implications for its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. Stenbæk, DS., Madsen, MK., Ozenne, B., et al.[2022]

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 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]

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 survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

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]

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quickly and accurately measure the levels of psilocybin and psilocin in magic truffles, with high precision and reliability (r² > 0.99).

The study found that only psilocybin was present in the examined Psilocybe sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh truffles, indicating variability in psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? Pellegrini, M., Rotolo, MC., Marchei, E., et al.[2019]

Medicinal fungi and plants, such as Cordyceps and Ganoderma species, contain compounds that can trigger apoptosis (programmed cell death) in cancer cells through mitochondrial pathways.

These natural compounds show promise for development into effective anticancer drugs, highlighting the potential of traditional medicine in modern cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apoptosis and Anti-cancer Drug Discovery: The Power of Medicinal Fungi and Plants. Wong, JH., Sze, SCW., Ng, TB., et al.[2021]

Genomic analysis of five species of Psilocybe mushrooms revealed a much greater metabolic diversity than previously understood, indicating potential for discovering new compounds beyond psilocybin and psilocin.

Two species, P. cyanescens and P. mexicana, were identified as producers of aeruginascin, along with other metabolites like lumichrome and verpacamide A, which may help explain the pharmacological and toxicological effects associated with these mushrooms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Survey of Psilocybe Natural Products. Dörner, S., Rogge, K., Fricke, J., et al.[2022]

References

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

Psilocybin in Palliative Care: An Update. [2023]

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

The pharmacology of psilocybin. [2016]

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

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. [2022]

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

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

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

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

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

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

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

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

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? [2019]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Apoptosis and Anti-cancer Drug Discovery: The Power of Medicinal Fungi and Plants. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Genetic Survey of Psilocybe Natural Products. [2022]