Pragmatic Trial of Psilocybin Therapy in Palliative Care (PT2PC)

November 21, 2025 updated by: Charles S. Grob, M.D.

Pragmatic Trial of Psilocybin Therapy in Palliative Care (PT2PC): A Multicenter Triple-blind Phase 2 Randomized Controlled Trial of Psilocybin Therapy for Demoralized Adults Near the End of Life

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

After providing written informed consent, participants deemed eligible for this trial will be randomized to a brief course of talk therapy plus 1 dose of oral psilocybin vs the same brief course of talk therapy plus 1 dose of oral ketamine (the active control). Participants' degree of demoralization and other clinical outcomes (e.g., depression, anxiety) will be assessed at 1, 2, and 5 weeks after the study drug administration. After completing the study, participants will have the option of being told which study drug they took (aka, "unblinded"); those who were randomized to the active control will be offered another brief course of talk therapy plus 1 dose of oral psilocybin, and the same sequence of outcome assessments.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Brian T Anderson, M.D.
  • Phone Number: (510) 985-3522
  • Email: pt2pc@ucsf.edu

Study Locations

  • United States
    • California
      • Greenbrae, California, United States, 94904
      • Los Angeles, California, United States, 90095
      • San Francisco, California, United States, 94518
        • Recruiting
        • University of San Francisco
        • Contact:
          • Brian T. Anderson, M.D.
          • Phone Number: 510-985-3522
          • Email: pt2pc@ucsf.edu
      • Torrance, California, United States, 90502
        • Recruiting
        • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
        • Contact:
        • Contact:
    • Maryland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Psilocybin
A single moderate-to-high dose of oral psilocybin, plus 4-5 sessions of a brief, existential psychotherapy.
Drug: Psilocybin
Psilocybin, [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate.
Other Names:
  • Hallucinogen
Active Comparator: Ketamine
A single low-to-moderate dose of oral liquid ketamine, plus 4-5 sessions of a brief, existential psychotherapy.
Drug: 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.
Other Names:
  • Ketalar

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
i) Change in clinician-rated Clinical Global Impression (CGI) for Severity of demoralization.
Time Frame: From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.
The CGI-I is a widely used and validated assessment of global clinical improvement. Possible scores range "0=Not assessed", "1=Very much improved", to "7=Very much worse." The CGI-I has been adapted here for assessing improvement in 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).
Time Frame: From Enrollment (V1) to ~14-days (V8) and ~35-days (V9) post-drug for patients treated with psilocybin therapy vs active control.
The CGI-I is a widely used and validated clinician-rated assessment of global clinical improvement. Possible scores range "0=Not assessed", "1=Very much improved", to "7=Very much worse." The CGI-I has been adapted here for assessing improvement in demoralization.
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
Time Frame: From Pre-dose V4 to ~14-days post drug (V8), and from Pre-dose V4 to ~35-days post drug (V9),
A comparison to active control using the following measures: PHQ-9, GRID-HAM-D6.compared to active control
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
Time Frame: From Enrollment (V1) to ~14-days post drug (V8), and Enrollment (V1) to ~35-days post drug (V9)
A comparison to active control, using the following measures: GAD-7, FACIT-Pal-14 FACIT-Sp-12.
From Enrollment (V1) to ~14-days post drug (V8), and Enrollment (V1) to ~35-days post drug (V9)
Change in patient-reported pain
Time Frame: From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9),
A comparison to active control, using the Brief Pain Inventory-Short Form (BPI-SF).
From Enrollment (V1) to ~14-days post drug (V8), and from Enrollment (V1) to ~35-days post drug (V9),
Associations will be explored between change in Demoralization Scale-II and other measures pre-dose and 7 days post drug
Time Frame: From Pre-dose (V4) to 7-days post-drug.
Associations will be explored between change in Demoralization Scale-II and 1) Credibility Expectancy Questionnaire (CrEQ), 2) Treatment Allocation Questionnaire, 3) Mystical Experience Questionnaire-30 (MEQ-30) and PEQ-4, 4) Challenging Experience Questionnaire (ChEQ), and 5) Change in Death Transcendence Scale-15 item (DTS-15)
From Pre-dose (V4) to 7-days post-drug.
DS-II and PHQ-9 comparison measures assessment
Time Frame: Throughout the study
Change in DS-II and PHQ-9 will be compared to assess if there is a differential response to psilocybin therapy in this population.
Throughout the study

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Treatment Allocation Questionnaire (TAQ) at Week 2.
Time Frame: Baseline and Week 2
The TAQ is a questionnaire made for this study. Participants will be asked what study drug they believed they received at their medication visit (psilocybin or ketamine). They will then be asked to rate with which certainty they believe this using a visual analog scale 0-100%.
Baseline and Week 2
Treatment Allocation Questionnaire (TAQ) at Week 5.
Time Frame: Baseline and Week 5
The TAQ is a questionnaire made for this study. Participants will be asked what study drug they believed they received at their medication visit (psilocybin or ketamine). They will then be asked to rate with which certainty they believe this using a visual analog scale 0-100%.
Baseline and Week 5
Mystical Experience Questionnaire-30 (MEQ30) at Medication Visit.
Time Frame: At the end of the Medication Visit (Visit 4 / Day 0)
The MEQ30 is a validated, patient-reported outcome assessing mystical-type experiences, derived from the earlier surveys of subjective responses to psilocybin. Scores range 0-150 with a higher score indicating a more mystical-type experience.
At the end of the Medication Visit (Visit 4 / Day 0)
Challenging Experience Questionnaire (ChEQ) at Medication Visit.
Time Frame: At the end of the Medication Visit (Visit 4 / Day 0)
The ChEQ is a validated, patient-reported outcome assessing challenging experiences with psychedelics. Possible scores range 0-130 with a higher score indicating greater psychologically adverse reactions to psilocybin.
At the end of the Medication Visit (Visit 4 / Day 0)
Change from Baseline in 15-item Death Transcendence Scale (DTS-15) at Week 1.
Time Frame: Baseline and Week 1
The DTS-15 is a validated, patient-reported outcome assessing death transcendence. Possible scores range 0-60 with a higher score indicating a higher level of death transcendence.
Baseline and Week 1
Persisting Effects Questionnaire 4-item (PEQ-4) at Week 5.
Time Frame: Week 5
The PEQ-4 is a patient-reported outcome assessing the enduring effects of psilocybin. Ratings are made with respect to other life experiences. Possible scores range 0-32 with a higher score indicating higher enduring effects of psilocybin.
Week 5
Change in patient-reported pain from Baseline in Brief Pain Inventory-Short Form (BPI-SF) at Week 5.
Time Frame: Baseline and Week 5
The BPI-SF is a validated, patient-reported outcome assessing pain over the last 24-hours, with higher scores on subscales indicating higher severity of pain, and/or higher impact on functioning. This measure will assess change in pain in the subset of patients with moderate-to-severe pain at Baseline.
Baseline and Week 5
Change in patient-reported pain from Baseline in Brief Pain Inventory-Short Form (BPI-SF) at Week 2.
Time Frame: Baseline and Week 2
The BPI-SF is a validated, patient-reported outcome assessing pain over the last 24-hours, with higher scores on subscales indicating higher severity of pain, and/or higher impact on functioning. This measure will assess change in pain in the subset of patients with moderate-to-severe pain at Baseline.
Baseline and Week 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Charles S. Grob, M.D.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of California, San Francisco

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Charles S. Grob, M.D., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 19, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 24, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 3, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 21-008459

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data from this study may be requested from other researchers 2 years after the completion of the primary endpoint by contacting the study sponsor.

IPD Sharing Time Frame

Data will become available 2 years after completion of the primary endpoint.

IPD Sharing Access Criteria

Data will be made available to qualified investigators who agree to the data sharing policies of the study.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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