Palliadelic Treatment to Reduce Psychological Distress in Persons With Advanced Gastrointestinal Cancers

An Exploratory Pilot Study of Palliadelic Treatment to Reduce Psychological Distress in People With Pancreatobiliary and Other Advanced Gastrointestinal Cancers

The primary objective of this study is to evaluate the ability to recruit and retain participants, and to successfully conduct a psilocybin-based protocol, for a study of the treatment of distress related to stage IV or inoperable gastrointestinal cancers. Secondary objectives include pre/post, and longitudinal measurement of distress in intervention participants and a paired family member who is in an observational arm.

Study Overview

• Status: Completed
• Conditions: Psychological Distress; Pancreas Cancer; Gastrointestinal Cancer; Biliary Tract Cancer
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

Participants with stage IV or inoperable gastrointestinal cancers are eligible for intervention, paired family member recruited for observational arm. Following preparatory sessions in outpatient palliative care clinic or by telehealth (2-4 sessions lasting 60-90 minutes each), psilocybin will be administered as a 25mg capsule during an 8-hour monitored session. Integration sessions (2-3 sessions lasting up to 90 minutes each) will take place in the outpatient palliative care clinic or by phone or tele-heath. Primary and secondary objectives are complete at one-week post treatment, longitudinal exploratory measures collected up to 12 months post baseline.

Parallel assessment of health care utilization, including choices regarding anti-cancer treatment and resource utilization, and family member distress, family communication, well-being and bereavement will be conducted at concurrent time points.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Between the ages of 19 and 85
• Has stage IV or unresectable GI malignancy
• Resides within a 170-mile radius of Omaha, NE
• Speaks English
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Life expectancy ≥ 8 weeks as determined by referring oncologist
• Ability to provide written informed consent and comply with study procedures
• Awareness of the neoplastic and likely incurable nature of his/her disease
• Has one family member willing to participate in measures
• Agreeable to using an adequate method of contraception or birth control from the time of enrollment to 24 hours following the psilocybin session (male and female participant of childbearing potential, defined as age <55 and menses within the prior 2 years with intact ovaries and uterus)
• Negative pregnancy test result (female participants)

Exclusion Criteria:

• Long-term or unstable psychiatric illness that would prevent safe cessation of psychotropic drugs including MAOIs, lithium, or anti-psychotics
• Severe symptoms of depression or anxiety warranting immediate impatient evaluation or treatment
• High-risk of suicide, as measured by Columbia Suicide Severity rating Scale
• Current or prior history of schizophrenia, psychotic disorder (unless substance induced or due to medical condition) or bipolar I or II disorder
• First-degree family member with schizophrenia, psychotic disorder (unless substance induced or due to medical condition) or bipolar I or II disorder
• Conditions known to be incompatible with establishment of rapport or safe exposure to psilocybin including dissociative disorder, borderline personality, traumatic brain injury, obsessive compulsive disorder, anorexia nervosa, or bulimia nervosa
• Alcohol or recreational drug abuse disorder, excluding caffeine and nicotine
• Known CNS metastases or other major CNS disease such as seizure disorder, dementia, Parkinson's disease, multiple sclerosis
• Receive treatment in another clinical trial involving an investigational product for the treatment of cancer during the interventional stage of the protocol
• Advanced hepatic dysfunction as indicated by a Child-Pugh Score of C
• Renal dysfunction as indicated by creatinine clearance <40 ml/min using the Cockroft-Gault equation
• Cardiac or circulatory dysfunction defined as uncontrolled hypertension (systolic blood pressure > 140 or diastolic blood pressure >90 mmHg on three separate readings), angina, stroke or myocardial infarction in the prior 6 months, or claudication
• History of seizures
• Unable to skip a meal (lunch), or have diabetes which requires administration of medication more than twice daily, or with symptomatic hypoglycemia within the prior 30 days
• Pregnant or breastfeeding

• Currently using any of the following potent metabolic inducers or inhibitors

  • Inducers: rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, St. Johns Wort, or Paclitaxel and dexamethasone (latter two permitted if 5 half-lives have passed between last dose and psilocybin session)
  • Inhibitors: All HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin
• Metal in body (i.e. hearing aid, cardiac pacemaker, bone plates, braces, non-removeable piercings/implants, etc.) claustrophobia, inability to lay still for one-hour, or any other condition that would preclude MRI scanning

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin Treatment Arm; Participant with pancreatobilliary cancer will receive 25mg of psilocybin in one 8-hour monitored session with supportive counseling before and after session.	Drug: Psilocybin; Psilocybin, 25mg administered orally drug during an 8-hour monitored session with supportive pre- and post- session counseling; Other Names: mushroom
No Intervention: Family Observation Group; The study participant will select a family member who will provide parallel data regarding distress related to pancreatobiliary cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	Number of participants enrolled/ number approached.	18 months
Retention Rate	Number of participants who complete the psilocybin session and the assessments at 8-12 days post-psilocybin session/ total enrolled	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient Health Questionnaire-9 (PHQ-9) Depression Scale total score from Baseline to 1 week post-dose	Patient Health Questionnaire-9 (PHQ-9) is a nine-item, 32 point scale of frequency of common depressive symptoms. Higher score indicates worse depression.	Baseline; Day 8-11 post-dose
Change in General Anxiety DIsorder-7 (GAD-7) total score from Baseline to 1 week post-dose	Change in General Anxiety DIsorder-7 (GAD-7) is a 7 item, 21 scale to measure frequency of common symptoms of anxiety with higher score indicating higher severity.	Baseline; Day 8-11 post-dose
Change in Demoralization Scale (D-II) total score from Baseline to 1 week post-dose	Change in Demoralization Scale (D-II) is a 16 item, 32 point scale with two factors, meaning & purpose and distress & coping, that measures frequency of symptoms of demoralization and existential distress, with higher score indicating higher severity.	Baseline; Day 8-11 post-dose

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: Nebraska University Foundation
• Investigators: Principal Investigator: Lou Lukas, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2023
• Primary Completion (Actual): November 17, 2025
• Study Completion (Actual): November 17, 2025

Study Registration Dates

• First Submitted: January 15, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: inoperable; unresectable; stage IV
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; Pancreatic Neoplasms; Gastrointestinal Neoplasms; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: 0860-21-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No