Psilocybin Therapy for Cancer-related Chronic Pain

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin, a compound found in certain mushrooms, can help reduce chronic pain and feelings of hopelessness in cancer survivors. Researchers aim to determine how effectively psilocybin eases anxiety, depression, and pain under supportive care conditions. Participants must be cancer survivors who have experienced chronic pain for over three months and feel significantly demoralized. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

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

Research has shown that psilocybin, when combined with therapy, might be safe and helpful for cancer patients dealing with long-term pain. Other studies have found that psilocybin can lessen symptoms like anxiety and depression, suggesting it could be well-tolerated. However, since this is an early-stage trial, the main goal is to learn about side effects and ensure the treatment's safety. This means some reactions may still be unknown. Overall, early evidence suggests psilocybin might be a promising option for those suffering from cancer-related pain and emotional distress. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin is unique because it offers a completely different approach to managing cancer-related chronic pain compared to traditional pain medications like opioids or NSAIDs. Unlike these standard treatments, which work by blocking pain signals or reducing inflammation, psilocybin is a psychedelic compound that may change the way the brain perceives pain. Researchers are excited because it could provide relief without the risk of addiction or severe side effects associated with conventional painkillers. Additionally, psilocybin may also help improve mood and emotional well-being, which can be particularly beneficial for people dealing with the psychological toll of chronic pain.

What evidence suggests that psilocybin might be an effective treatment for cancer-related chronic pain?

Research has shown that psilocybin therapy can reduce chronic pain and improve the quality of life for cancer patients. In this trial, participants will receive psilocybin as part of supportive care, with observation for up to 24 hours. Studies indicate that psilocybin therapy can manage pain and reduce anxiety and depression related to cancer. Psilocybin sessions, combined with psychological support, are generally well-tolerated, meaning patients usually handle the treatment well. Another study found that psilocybin greatly improved symptoms of depression and anxiety in cancer patients. These findings suggest that psilocybin might relieve the emotional and physical pain experienced by cancer survivors. ^{1 3 6 7 8}

Who Is on the Research Team?

Ali J. Zarrabi, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06001749

NCT06001749 | Psilocybin in Cancer Pain Study The overall objective of this study is to assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy to alleviate ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06827054

Psilocybin With Psychotherapy for Improving Chronic Pain ... This phase II trial studies whether psilocybin with psychotherapy is safe and if it works for improving chronic pain in cancer patients who require opioids ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11271737/

Investigating the therapeutic efficacy of psilocybin in advanced ... Psilocybin-assisted therapy shows promising results in improving quality of life, pain control, and anxiety relief for patients with advanced cancer.

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/02698811251362390

Investigating the safety and tolerability of single-dose ... In this trial, COMP360 psilocybin administered in a single session with psychological support was found to be generally well-tolerated and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11886891/

Psychedelics for Cancer Pain and Associated Psychological ... A double‐blind randomized control trial analyzed the effects of psilocybin in 51 patients with cancer with symptoms of depression and/or anxiety ...

6. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-First-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

News Details A single administration of COMP360 demonstrated a highly statistically significant and clinically meaningful reduction in symptom severity ...

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

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Its potential antidepressant efficacy was suggested by preliminary studies involving patients with life-threatening cancer.

8. empr.com empr.com/news/synthetic-psilocybin-reduces-symptom-severity-in-treatment-resistant-depression/

Synthetic Psilocybin Reduces Symptom Severity in ... Findings showed COMP360 psilocybin statistically significantly reduced symptom severity compared with placebo, as measured by MADRS (mean ...