Psilocybin for Psychological Distress in Pancreatic and Biliary Tract Cancer

Overseen By Taylor A Johnson, BS, MA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Nebraska

Must not be taking: MAOIs, Lithium, Antipsychotics, others

Disqualifiers: Schizophrenia, Bipolar, Seizures, 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: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single session of psilocybin (a compound found in certain mushrooms) can reduce psychological distress in individuals with advanced pancreatic or biliary tract cancer. Participants will undergo one monitored session with supportive counseling before and after. Eligible participants include adults with stage IV or inoperable gastrointestinal cancer who live within 170 miles of Omaha, NE, and have a family member willing to participate in some observations. The trial aims to determine if this treatment can ease distress and study the family member's experience. 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 therapy.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, especially psychotropic drugs like MAOIs, lithium, or anti-psychotics, and potent metabolic inducers or inhibitors. If you're on these medications, you may need to stop them to participate.

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

Research has shown that psilocybin, the substance under study, is usually well-tolerated by cancer patients. Some studies have explored its use to alleviate anxiety and depression in these patients. In these studies, patients often experienced significant mood improvement after just one dose of psilocybin.

Most participants did not encounter serious side effects. However, some reported mild to moderate effects, such as temporary changes in mood or perception, which typically resolved quickly. One study found that a single 25 mg dose of psilocybin had positive effects lasting several weeks without major safety issues.

This study is in its early stages, focusing on the treatment's safety. Previous research suggests that psilocybin can be used safely under medical supervision. Since individual experiences may vary, discussing any concerns with the study team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for psychological distress in pancreatic and biliary tract cancer, which often include medications like antidepressants and anti-anxiety drugs, psilocybin is derived from psychedelic mushrooms and targets the brain's serotonin receptors. This unique mechanism may lead to profound changes in mood and perception, potentially offering faster and more effective relief than traditional medications. Researchers are excited about psilocybin because it could provide significant psychological benefits in just a single, monitored session, reducing the burden of ongoing medication and improving the quality of life for patients facing severe distress.

What evidence suggests that psilocybin might be an effective treatment for psychological distress in pancreatic and biliary tract cancer?

Research shows that psilocybin can significantly reduce feelings of depression, anxiety, and distress about life. In cancer patients, studies have found that psilocybin therapy often leads to lasting improvements in mood and mental health. For instance, one study discovered that a single 25 mg dose of psilocybin provided relief from depression for up to a year in people who had not responded to other treatments. In this trial, participants with pancreatic and biliary tract cancers will receive a 25 mg dose of psilocybin in a monitored session, suggesting that psilocybin could help reduce emotional distress in these patients. These findings offer hope that psilocybin might effectively address emotional challenges in these patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Lou Lukas, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults aged 19-85 with inoperable pancreatic or biliary tract cancer experiencing distress. They must speak English, have a life expectancy of at least 8 weeks, and be able to consent to the study. A family member must also participate. Exclusions include severe depression/anxiety, substance abuse, certain medical conditions like CNS metastases or major organ dysfunction, and those on specific medications.

Inclusion Criteria

Participant must have a life expectancy ≥ 8 weeks as determined by referring oncologist

I am under 55, had a menstrual cycle in the last 2 years, and agree to use birth control during the study.

I can care for myself but may not be able to do heavy physical work.

Exclusion Criteria

You have a problem with alcohol or using drugs for fun, except for caffeine and nicotine.

I have heart or blood circulation problems.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Sessions

Preparatory sessions in outpatient palliative care clinic or by telehealth (2-4 sessions lasting 60-90 minutes each)

2-4 weeks

2-4 visits (in-person or virtual)

Psilocybin Treatment

Participants receive 25mg of psilocybin in one 8-hour monitored session with supportive counseling

1 day

1 visit (in-person)

Integration Sessions

Integration sessions (2-3 sessions lasting up to 90 minutes each) in outpatient palliative care clinic or by phone or tele-health

1-2 weeks

2-3 visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with exploratory measures collected up to 12 months post baseline

12 months

Multiple visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial tests psilocybin's effect on psychological distress in patients with inoperable pancreatobiliary cancer. It aims to recruit participants and their family members (observational arm) to measure changes in distress levels before and after treatment over time.

How Is the Trial Designed?

Group I: Psilocybin Treatment Arm Experimental Treatment 1 Intervention

Participant with pancreatobilliary cancer will receive 25mg of psilocybin in one 8-hour monitored session with supportive counseling before and after session.

Group II: Family Observation Group Active Control 1 Intervention

The study participant will select a family member who will provide parallel data regarding distress related to pancreatobiliary cancer.

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 of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Lou Lukas

Lead Sponsor

Trials

1

Recruited

20+

Nebraska University Foundation

Collaborator

Trials

1

Recruited

20+

Jim Young Pancreatic Cancer Research Memorial Fund

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a double-blind, placebo-controlled trial with 29 cancer patients, a single dose of psilocybin (0.3 mg/kg) combined with psychotherapy led to significant and lasting reductions in anxiety and depression, with 60-80% of participants showing sustained improvements at a 6.5-month follow-up.

The positive effects of psilocybin were linked to the mystical experiences it induced, which helped improve patients' quality of life, reduce existential distress, and foster better attitudes towards death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Ross, S., Bossis, A., Guss, J., et al.[2022]

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]

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 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]

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]

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 phase 2 trial with patients suffering from major depressive disorder, psilocybin therapy (PT) led to significant improvements in personality traits associated with mental health, such as decreased neuroticism and increased openness, after 6 weeks.

Both psilocybin and escitalopram treatments resulted in positive changes in personality, but no significant differences were found between the two treatments, suggesting that both may be effective in improving mental health through similar mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression. Weiss, B., Ginige, I., Shannon, L., 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]

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]

The HOPE trial, involving 12 cancer patients, showed that psilocybin-assisted group therapy is safe, with no serious adverse events reported, and resulted in significant reductions in depression symptoms over six months.

Participants experienced substantial decreases in depression scores, with six out of twelve achieving remission at two weeks, indicating that this group therapy model could be an effective treatment for depression in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Lewis, BR., Garland, EL., Byrne, K., et al.[2023]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

Citations

1. withpower.com withpower.com/clinical-trials/using-psilocybin

Top Treatment for Psilocybin Clinical Trials | Power This trial is testing a psilocybin-based treatment to help patients with inoperable pancreas or biliary tract cancers feel less distressed. Psilocybin, found in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40259688/

Evaluating the effectiveness of psilocybin in alleviating ... Psilocybin therapy consistently showed significant reductions in depression, anxiety, and existential distress, with improvements sustained over ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/articlepdf/2803623/jamaoncology_agrawal_2023_ld_230005_1720027260.78237.pdf?resultClick=24

Assessment of Psilocybin Therapy for Patients With Cancer ... safety and preliminary efficacy of psilocybin treatment for pa- tients with cancer and depression using a scalable model with a 1-to-1 ...

4. withpower.com withpower.com/trial/phase-1-psychological-distress-4-2022-b7e6f

Psilocybin for Psychological Distress in Pancreatic and ... This trial is testing a psilocybin-based treatment to help patients with inoperable pancreas or biliary tract cancers feel less distressed.

5. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Announces-Publication-of-Results-from-COMP004-Study-on-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

Compass Pathways Announces Publication of Results from ... The COMP004 study's findings suggest that over a 52-week period, a single administration of 25 mg COMP360 psilocybin demonstrated a longer maintenance of ...

6. 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 ...

7. 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.

8. cancernetwork.com cancernetwork.com/view/psilocybin-therapy-in-cancer-yields-meaningful-improvement-in-depression

Psilocybin Therapy in Cancer Yields Meaningful ... Patients with curable metastatic cancer appear to have long-lasting improvements in depression symptoms 8 weeks after a single treatment with psilocybin ...