Pragmatic Trial of Psilocybin Therapy in Palliative Care

NCT05403086 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-008459
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

This multicenter, triple-blind, phase 2, randomized controlled trial will evaluate the efficacy and safety of psilocybin therapy compared to an active control in treating demoralization in adults near the end of life (≤2 years life expectancy).

Conditions

Demoralization

Keywords

Palliative Care; Serious Medical Illness; Life-threatening Condition; Advanced and Progressive Illness

Outcome Measures

Primary Outcomes (1)

• Change in patient-reported Demoralization Scale-II..

  The DS-II is a validated, patient-reported outcome assessing demoralization with a 2-week recall period.

  From Pre-dose V4 to ~14-days post drug (V8), and from Pre-dose (V4) to ~35-days post drug (V9), compared to active control.

Secondary Outcomes (7)

• i) Change in clinician-rated Clinical Global Impression (CGI) for Severity of demoralization.

  From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.

• ii) Odds ratio of meeting criteria for demoralization on the clinician-rated Demoralization Interview Interview (DI).

  From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.

• Change in depression symptoms

  From Pre-dose V4 to ~14-days post drug (V8), and from Pre-dose V4 to ~35-days post drug (V9),

• Change in anxiety symptoms, quality of life, and spiritual well-being

  From Enrollment (V1) to ~14-days post drug (V8), and Enrollment (V1) to ~35-days post drug (V9)

• Change in patient-reported pain

  From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9),

Study Arms (2)

Psilocybin

EXPERIMENTAL

A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.

Drug: Psilocybin

Ketamine

ACTIVE COMPARATOR

A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.

Drug: Ketamine

Interventions

Psilocybin DRUG

Psilocybin, \[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate.

Also known as: Hallucinogen

Psilocybin

Ketamine DRUG

ketamine hydrochloride injection, for intravenous or intramuscular use, contains ketamine, a nonbarbiturate general anesthetic and has a molecular formula of C13H16ClNO•HCl and a molecular weight of 274.19. The chemical name for ketamine hydrochloride is (±)-2-(o-Chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride.

Also known as: Ketalar

Ketamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General
• Provision of signed and dated informed consent form and the capacity to consent to research.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Is currently a patient in a study-engaged clinical site
• Has a life-threatening illness and a life expectancy of ≤2 years
• Has moderate-to-severe demoralization
• Ability to take oral medication (capsules and liquid)

You may not qualify if:

• General
• Known allergic or severe reactions to the non-psychoactive components of psilocybin capsules or liquid ketamine
• Treatment with another investigational drug or intervention within 1 month of signing Informed Consent Form (ICF)
• If deemed by clinical judgment of the study investigators to be unsafe for undergoing the intervention
• Neurological
• Cognitive impairment sufficient to impede the ability to complete study tasks
• History of intracranial hemorrhage
• Recent embolic stroke
• Recent seizure
• Current intracranial mass
• Advanced stage of a neurologic disease that elevates risk for psychosis
• Cardiovascular
• Uncontrolled hypertension
• Clinically significant cardiac disease
• Respiratory

Sponsors & Collaborators

• Charles S. Grob, M.D.: lead
• University of California, San Francisco: collaborator

Study Sites (5)

Marin Cancer Care

Greenbrae, California, 94904, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of San Francisco

San Francisco, California, 94518, United States

RECRUITING

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

RECRUITING

Sunstone Therapies

Rockville, Maryland, 20850, United States

RECRUITING

Related Publications (11)

• Gan LL, Gong S, Kissane DW. Mental state of demoralisation across diverse clinical settings: A systematic review, meta-analysis and proposal for its use as a 'specifier' in mental illness. Aust N Z J Psychiatry. 2022 Sep;56(9):1104-1129. doi: 10.1177/00048674211060746. Epub 2021 Dec 8.

  PMID: 34879712 BACKGROUND

• Caruso R, Breitbart W. Mental health care in oncology. Contemporary perspective on the psychosocial burden of cancer and evidence-based interventions. Epidemiol Psychiatr Sci. 2020 Jan 9;29:e86. doi: 10.1017/S2045796019000866.

  PMID: 31915100 BACKGROUND

• Reiche S, Hermle L, Gutwinski S, Jungaberle H, Gasser P, Majic T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:1-10. doi: 10.1016/j.pnpbp.2017.09.012. Epub 2017 Sep 22.

  PMID: 28947181 BACKGROUND

• Ross S. Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress. Int Rev Psychiatry. 2018 Aug;30(4):317-330. doi: 10.1080/09540261.2018.1482261. Epub 2018 Aug 13.

  PMID: 30102082 BACKGROUND

• Robinson S, Kissane DW, Brooker J, Michael N, Fischer J, Franco M, Hempton C, Sulistio M, Pallant JF, Clarke DM, Burney S. Refinement and revalidation of the demoralization scale: The DS-II-internal validity. Cancer. 2016 Jul 15;122(14):2251-9. doi: 10.1002/cncr.30015. Epub 2016 May 12.

  PMID: 27171617 BACKGROUND

• Robinson S, Kissane DW, Brooker J, Hempton C, Michael N, Fischer J, Franco M, Sulistio M, Clarke DM, Ozmen M, Burney S. Refinement and revalidation of the demoralization scale: The DS-II-external validity. Cancer. 2016 Jul 15;122(14):2260-7. doi: 10.1002/cncr.30012. Epub 2016 May 12.

  PMID: 27171544 BACKGROUND

• Anderson BT, Danforth A, Daroff PR, Stauffer C, Ekman E, Agin-Liebes G, Trope A, Boden MT, Dilley PJ, Mitchell J, Woolley J. Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine. 2020 Sep 24;27:100538. doi: 10.1016/j.eclinm.2020.100538. eCollection 2020 Oct.

  PMID: 33150319 BACKGROUND

• Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer GR. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011 Jan;68(1):71-8. doi: 10.1001/archgenpsychiatry.2010.116. Epub 2010 Sep 6.

  PMID: 20819978 BACKGROUND

• Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512.

  PMID: 27909164 BACKGROUND

• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.

  PMID: 27909165 BACKGROUND

• Schipper S, Nigam K, Schmid Y, Piechotta V, Ljuslin M, Beaussant Y, Schwarzer G, Boehlke C. Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database Syst Rev. 2024 Sep 12;9(9):CD015383. doi: 10.1002/14651858.CD015383.pub2.

  PMID: 39260823 DERIVED

MeSH Terms

Interventions

Psilocybin; Hallucinogens; Ketamine

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Charles S. Grob, M.D.

  Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charles S. Grob, M.D.

CONTACT

(626) 522-8615; pt2pc@lundquist.org

Brian T Anderson, M.D.

CONTACT

(510) 985-3522; pt2pc@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A Multicenter Triple-blind Phase 2 Randomized Controlled Trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Sciences

Model Details: Parallel with optional Crossover for the control arm

Study Record Dates

• First Submitted: April 24, 2022
• First Posted: June 3, 2022
• Study Start: January 19, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will become available 2 years after completion of the primary endpoint.
• Access Criteria: Data will be made available to qualified investigators who agree to the data sharing policies of the study.

Locations

US (5)