Safety and Efficacy of Psilocybin-assisted Psychotherapy for Demoralization Syndrome in Patients Diagnosed With Advanced Stage Cancer

Safety and Efficacy of Psilocybin-assisted Psychotherapy for Demoralization Syndrome in Patients Diagnosed With Advanced Stage Cancer: a Pilot Study

Demoralization syndrome is frequently present in palliative care and oncology patients. In particular, up to a third of patients diagnosed with cancer will experience demoralization due to their illness. The relevance of demoralization syndrome in oncology is tied to this syndrome's association with other mental health ailments such as depression, anxiety, suicidal ideation, and quality of life. Unfortunately, so far no pharmacological strategy has been devised for demoralization, and only a few psychotherapeutic approaches have been trialed in this population, though no psychotherapeutic treatments have been tested for demoralization specifically. The new wave of psychedelic research has been showing encouraging results in a broad spectrum of psychiatric diagnosis, including depression and anxiety in patients diagnosed with cancer and other life-threatening diseases. To date, no clinical trials have been published in which the potential therapeutic effects of psychedelics are explored for the treatment of demoralization syndrome. The aim of this open label pilot study is to assess the safety and efficacy of psilocybin-assisted psychotherapy as a treatment for demoralization syndrome in patients diagnosed with cancer. Fifteen participants between the ages of 18 to 70 years with advanced stage cancer and demoralization syndrome will be enrolled in a treatment program which will include 6 psychotherapeutic sessions and one psilocybin (25 mg) dosing session. Our outcome of interest will be a decrease in demoralization, as measured by the Demoralization Scale at baseline and at the end of the study, and adverse events registration. Other measures of interest include Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and the Columbia Suicide Severity Rating Scale. Those patients with partial response a month after the psilocybin intervention will be offered the possibility of a second psilocybin 25 mg dosing session.

Study Overview

• Status: Recruiting
• Conditions: Safety; Demoralization
• Intervention / Treatment: Drug: Psilocybin-assisted Psychotherapy

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gustavo Vazquez, MD, PhD, FRCPC; Phone Number: 613-544-4900 x51214; Email: vazquezg@providencecare.ca

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 3N6
      • Recruiting
      • Queen's University
      • Contact: Vazquez Gustavo, MD, PhD; Phone Number: 51214 613-544-4900; Email: vazquezg@providencecare.ca
      • Sub-Investigator: Carolina Hernandorena, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with advanced stage cancer (stages 3 and 4)
• Aged between 18 and 70 years.
• Moderate-to-severe demoralization as measured by Demoralization Scale≥ 30
• English proficiency
• Ability to understand and the willingness to sign a written informed consent document.
• Individuals of child-bearing potential who are sexually active must agree to use an acceptable contraceptive method (hormonal or barrier method of birth control; abstinence) throughout their participation in the study. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled in this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of psilocybin administration.

Exclusion Criteria:

• Condition impairing oral intake or digestive absorption.
• Primary brain tumor.
• Presence of delirium.
• Significant suicide risk as defined by suicidal ideation with intent and a plan.
• Current or past history of schizophrenia, psychotic disorder, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder, as assessed by medical history.
• Patients with first-degree relatives with schizophrenia or bipolar disorder
• Previous diagnosis of epilepsy, stroke or Transient Ischemic Attack (TIA), dementia, and Parkinson's disease.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to psilocybin.
• Other personal circumstances and behavior that would limit compliance with study requirements or that are judged by the study psychiatrist and/or principal investigator to be incompatible with establishing rapport or safe exposure to psilocybin.

• Potential for adverse drug-drug interactions. Concomitant medications with significant potential to interact with study medications will be exclusionary if they cannot be tapered. These include the following:

  • MAO inhibitors
  • Patients currently on antipsychotics (e.g. first and second generation) when taken regularly (6 weeks or less prior to screening visit)
  • Mood stabilizers (e.g. lithium, valproic acid, lamotrigine)
  • Aldehyde dehydrogenase inhibitors (e.g. disulfiram)
  • Significant inhibitors of UGT 1A0 or UGT 1A10
• Patients who have elevated AST and ALT five times above the normal laboratory limit on their last available bloodwork performed at screening and patients with symptoms suggestive of liver failure including confusion, asterixis or jaundice.
• Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal condition or any other unstable condition that, in the opinion of the principal investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study. This may include but is not limited to clinical symptoms or recent history of significant tachyarrhythmias; severe angina or myocardial ischemia; poorly controlled congestive heart failure; poorly controlled hypertension; poorly controlled hypo- or hyperthyroidism; uncontrolled diabetes; severe renal or liver dysfunction; acute respiratory failure; sepsis; history of cerebral aneurysms; glaucoma; increased intracranial pressure and any intracranial mass.
• Women who are pregnant, nursing, or planning a pregnancy.
• Use of a classic psychedelic or MDMA in the last 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: advanced cancer participants

Drug: Psilocybin-assisted Psychotherapy; The intervention will be psilocybin-assisted psychotherapy. The first treatment period will include four preparation sessions with Managing Cancer and Living Meaningfully (CALM) therapy elements. The psilocybin dosing session will take place after these preparation sessions are completed. The dosing session will include an in-person visit lasting approximately 8 hours in which the participant will receive a capsule of psilocybin 25 mg under constant supervision of therapists. The following day, the first integration session will take place and two weeks later the second integration session along with CALM will be conducted. Participants who show a partial response will be offered a second dosing session, entering the second treatment period. The second treatment period includes a second dosing session using the same dose and safety measures as the first one. It will also be followed by an integration session the following day, and a second integration session with CALM two weeks later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs) and Serious Adverse Events (SAEs) register		From enrollment to the end of the follow up period at week 16 or 19
Demoralization Scale	Demoralization Scale is a 24-item Likert scale. Items are scored on a 5-point scale from 0 (never) to 4 (all the time), in which higher scores are associated with higher demoralization. Scores can range from 0 to 96. A cut-off point of ≥ 30 in this scale is considered as high demoralization and will be used for participant inclusion in the study.	From enrollment to the end of the follow up period at week 16 or 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Anxiety Rating Scale	The Hamilton Anxiety Rating Scale is a 14-item Likert scale. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56. Higher scores are associated with increased symptom severity, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	From enrollment to the end of the follow up period at week 16 or 19
Hamilton Depression Rating Scale	The Hamilton Depression Rating Scale is a 17-item Likert scale. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-68. Higher scores are associated with increased symptom severity.	From enrollment to the end of the follow up period at week 16 or 19
Columbia Suicide Severity Rating Scale	Columbia Suicide Severity Rating Scale includes ten categories, all of which maintain binary responses (yes/no) to indicate a presence or absence of suicidal behavior. Affirmative answers are associated with higher suicidality	From enrollment to the end of the follow up period at week 16 or 19

Collaborators and Investigators

• Sponsor: Gustavo Vazquez

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 5, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): February 11, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 65563

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