Recruiting
Phase 2

Psilocybin Therapy

Sponsor:

Charles S. Grob, M.D.

Code:

NCT05403086

Conditions

Demoralization

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Psilocybin

Ketamine

Study Details

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

Study ID

NCT05403086

Start date

Jan 19, 2025

Status verified date

Nov, 2025

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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)

Exclusion Criteria:

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

  • Severe pulmonary disease
  • Supplemental oxygen requirement

Gastrointestinal

  • Current intractable nausea/vomiting/diarrhea
  • Recent, clinically significant GI bleed
  • Markedly abnormal liver function tests

Endocrine, Renal, and Reproductive

  • Pregnancy or lactation
  • Severe renal insufficiency
  • Unstable insulin-dependent diabetes mellitus

Prohibited Medications

  • Antipsychotics (with exceptions)
  • Antidepressants (with exceptions)
  • Dopamine agonists
  • Drugs known to have adverse interactions with psilocybin or ketamine

Study Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Psilocybin

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

active comparator: Ketamine

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

Interventions

Psilocybin

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

Ketamine

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.

Primary outcome measure

  • Change in patient-reported Demoralization Scale-II.. [ Time Frame: 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. ]

Central Contacts and Locations

Central contacts

Charles S. Grob, M.D.

(626) 522-8615pt2pc@lundquist.org

Brian T Anderson, M.D.

(510) 985-3522pt2pc@ucsf.edu

Locations

Marin Cancer Care

Recruiting

Greenbrae, California, United States, 94904

Contacts

Barbara M. Galligan, M.D.

415-925-5000pt2pc@marincancercare.com

Joshua S Biddle, M.D.

(415) 465-0481Joshua.Biddle@mymarinhealth.org

University of California, Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Contacts

Ziva M. Cooper, Ph.D.

310-983-3417ZCooper@mednet.ucla.edu

Katrina F DeBonis, M.D.

(310) 206-1596KDeBonis@mednet.ucla.edu

University of San Francisco

Recruiting

San Francisco, California, United States, 94518

Contacts

Brian T. Anderson, M.D.

510-985-3522pt2pc@ucsf.edu

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Recruiting

Torrance, California, United States, 90502

Contacts

Charles S Grob, M.D.

626-522-8615pt2pc@lundquist.org

Michael Makhinson, M.D.

(626) 522-8615pt2pc@lundquist.org

Sunstone Therapies

Recruiting

Rockville, Maryland, United States, 20850

Contacts

Manish Agrawal, M.D.

301-337-7570manish.agrawal@sunstonetherapies.com

Kimberly Roddy, MBA

(301) 750-3401kim.roddy@sunstonetherapies.com

More Information

Sponsor

Charles S. Grob, M.D.

Last update posted

Nov 25, 2025

Last verified

Nov, 2025

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Charles S. Grob, M.D. on 2025-11-25.