Psilocybin Therapy for Cancer-related Chronic Pain

Recruiting at 1 trial location

Overseen By Ali J. Zarrabi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Serotonergic drugs, MAOIs, others

Disqualifiers: Pregnancy, Psychotic disorder, Hypertension, others

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

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

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

11 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if psilocybin can safely help cancer survivors who feel hopeless and have chronic pain. Psilocybin changes brain perception to improve mood and reduce pain. Psilocybin has been studied since the 1960s for its potential to treat cancer-related psychiatric distress, showing promise in improving depression and anxiety.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications that interact with psilocybin, such as probenecid, diclofenac, and consistent use of serotonergic drugs like SSRIs and SNRIs. If you are on other antidepressants, stimulants, or antipsychotics, you may need to taper off these medications under medical supervision before starting the trial.

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

Research suggests that psilocybin may help reduce symptoms of depression and anxiety in cancer patients, which could indirectly alleviate chronic pain by improving overall mental well-being. Studies have shown that psilocybin can have lasting positive effects on mood and anxiety, which are often linked to the experience of chronic pain. ^{1 2 3 4 5}

Is psilocybin safe for use in humans?

Psilocybin is generally considered safe when used in controlled settings with screened and supported participants, although it can cause challenging psychological experiences and, in rare cases, enduring psychological symptoms. It is important to use it under medical supervision, especially for individuals with pre-existing health conditions. ^{5 6 7 8 9}

How is psilocybin therapy different from other treatments for cancer-related chronic pain?

Psilocybin therapy is unique because it uses a psychedelic compound found in certain mushrooms to potentially alter perception and mood, which may help manage chronic pain differently than traditional pain medications that typically target physical pain pathways. ^{10 11 12 13 14}

Research Team

Ali J. Zarrabi, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for cancer survivors aged 26-85 with a life expectancy over six months, experiencing chronic pain and demoralization. They must have been diagnosed at least a year ago and have someone to care for them post-treatment. Exclusions include non-English speakers, substance abuse, certain medical conditions like seizures or severe heart disease, BMI <=18, renal insufficiency, use of specific drugs including SSRIs/SNRIs/MAOIs or efavirenz.

Inclusion Criteria

I am between 26 and 85 years old.

Signed informed consent form (ICF)

Prognosis of greater than six months as determined by their primary oncologist

Exclusion Criteria

Current substance use disorder of greater than mild severity

Personal history of a psychotic disorder or Bipolar disorder type I/II

I am younger than 26 or older than 85.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single administration of 25 mg psilocybin and undergo observation for up to 8 hours on day 14

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for changes in demoralization, anxiety, depression, quality of life, and other symptoms

3.5 months

5 visits (in-person)

Treatment Details

Interventions

• Psilocybin

Trial Overview The trial tests the effects of psilocybin in combination with palliative psychotherapy on demoralized cancer survivors with chronic pain. It aims to see if this treatment can alleviate anxiety, depression and improve quality of life.

Participant Groups

Group I: Supportive care (psilocybin, observation) Experimental Treatment 4 Interventions

Patients receive psilocybin PO and undergo observation for up to 24 hours on day 14.

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Psilocybin has shown promise in reducing symptoms of depression and anxiety, particularly in cancer patients, with effects lasting for at least six months after a single treatment, based on three controlled studies.

In small pilot studies, psilocybin has also demonstrated potential effectiveness in treating addiction to alcohol and cigarettes, suggesting its versatility as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Therapeutic Effects of Psilocybin: A Systematic Review. Goel, DB., Zilate, S.[2022]

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]

A single dose of psilocybin (0.5-20 mg/kg) significantly increases the expression of genes related to neuroplasticity in the prefrontal cortex and hippocampus, suggesting its potential therapeutic effects for mental health disorders.

The study highlights that psilocybin's effects on gene expression are dose-dependent and predominantly observed in the prefrontal cortex, emphasizing the need to assess both gene expression and protein translation to understand its rapid effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Jefsen, OH., Elfving, B., Wegener, G., et al.[2022]

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]

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]

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]

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]

References

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

Potential Therapeutic Effects of Psilocybin: A Systematic Review. [2022]

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

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

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

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. [2022]

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

Psilocybin in Palliative Care: An Update. [2023]

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

The pharmacology of psilocybin. [2016]

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

[Hallucinogenic mushrooms]. [2018]

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

Intravenous mushroom poisoning. [2019]

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

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

9. 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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Si(IV)-methoxyethylene-glycol-naphthalocyanine: synthesis and pharmacokinetic and photosensitizing properties in different tumour models. [2019]

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

Ring-Fused Diphenylchlorins as Potent Photosensitizers for Photodynamic Therapy Applications: In Vitro Tumor Cell Biology and in Vivo Chick Embryo Chorioallantoic Membrane Studies. [2020]

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

The Photosensitizer Temoporfin (mTHPC) - Chemical, Pre-clinical and Clinical Developments in the Last Decade. [2023]

13. Germany pubmed.ncbi.nlm.nih.gov

Conjugation of chlorin p(6) to histamine enhances its cellular uptake and phototoxicity in oral cancer cells. [2013]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy. [2018]