Pilot Study of Psilocybin-Assisted Therapy for Demoralization in Patients Receiving Hospice Care

Phase 2

Active, not recruiting

Conditions: Hospice
Cancer Terminal
Psilocybin
Demoralization
Cancer-related Problem/Condition
Terminal Illness
Psychotherapy
Terminal Cancer

Interventions: Drug: Psilocybin
Behavioral: Psychotherapy

Registration Number: NCT04950608

Lead Sponsor: Yvan Beaussant, MD, MSci

Brief Summary: The overall objective of this study is to develop and pilot test a novel regimen of psilocybin-assisted psychotherapy for demoralization in patients receiving hospice care.

-The name of the study drug involved in this study is Psilocybin

Detailed Description: The purpose of this research is to understand how psilocybin-assisted therapy may be adapted in the context of hospice care, in order to test its safety in people with terminal illness who experience demoralization, and to study how well it works to lessen symptoms of psychological and existential distress.

* This research study involves a combined drug and psychotherapeutic (talk therapy) intervention. The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits.

* The treatment regimen consists of a single administration of psilocybin with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions

* The name of the study drug involved in this study is Psilocybin. Psilocybin is a naturally occurring psychedelic drug produced by more than 200 species of mushrooms, which is manufactured for medical use to control potency and purity.

* Participants will be followed for up to 24 weeks (approximately 6 months) after the study treatment. It is expected that about 15 people will take part in this research study.

* This research study is a Feasibility Study, which mean it is the first time investigators are examining psilocybin-assisted therapy in the context of hospice care. Psilocybin is an "Investigational" drug, meaning that the study drug has not been approved by the U.S. Food and Drug Administration (FDA) as a treatment for any disease. However, the FDA has granted psilocybin the status of "breakthrough therapy" in the treatment of depression and the investigators have permission from the FDA to use this drug in this research study.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 15

Inclusion Criteria

Patients enrolled in hospice care at home
Age ≥ 21 years.
Any terminal illness with respect of exclusion criteria
Palliative Performance Scale (PPS) ≥ 50 % (see Appendix A)
Moderate-to-severe demoralization as measured by Demoralization Scale-II ≥ 8
Significant other or other caregiver present at home the night of study drug administration
No driving for 24 hours following study drug administration.
English proficiency
Ability to understand and the willingness to sign a written informed consent document.
Psilocybin is very likely to have no genotoxic effects. One study that directly focused on the mutagenic potential of psilocybin did not found this type of toxicity. However, due to the lack of clinical and non-clinical studies on the effects of psilocybin on the developing human fetus, women and men of child-bearing potential and 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 on 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

Current General Inpatient (GIP) hospice status
Patients currently receiving chemotherapy
Condition impairing oral intake or digestive absorption
Presence of a delirium diagnosed by the CAM
Significant suicide risk as defined by suicidal ideation with intend and a plan as endorsed on item 5 on the C-SSRS within the past month or at V0
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
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 judged by the study psychiatrist and/or principal investigator to be incompatible with establishment of 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:
- Serotoninergic antidepressants
- Centrally-acting serotonergic agents (e.g. MAO inhibitors)
- Antipsychotics (e.g. first and second generation)
- Mood stabilizers (e.g. lithium, valproic acid)
- Aldehyde dehydrogenase inhibitors (e.g. disulfiram)
- Significant inhibitors of UGT 1A0 or UGT 1A10
Any psychiatric medication will be tapered if possible in an appropriate fashion to avoid withdrawal effects. They will be discontinued long enough before the psilocybin Session to avoid the possibility of any drug-drug interaction (the interval will be at least five times the particular drug and active metabolites' half-life).
End stage liver disease or cirrhosis as primary hospice diagnosis
Patients who have elevated AST and ALT five times above the normal laboratory limit on their last available bloodwork 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 disfunction; 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PATH	Psychotherapy	The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits. -The treatment regimen consists of a single administration of psilocybin 25 mg orally combined with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions
PATH	Psilocybin	The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits. -The treatment regimen consists of a single administration of psilocybin 25 mg orally combined with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions

Primary Outcome Measures

Name	Time	Method
Number of Participants Screened Per Study Period	Through study completion, through 22 months	This measurement will assess enrollment feasibility based on the screening log.
Eligible Population	Through study completion, over 22 months	Number of screened hospice patients who met pre-eligibility criteria and were approached for consent
Number of Participants Enrolled Over Study Period	Through study completion, over 22 months	This measurement will assess enrollment feasibility based on the screening log.
Average Time From Screening to Enrollment	From date of screening until the date of enrollment, assessed up to 12 months	This measurement will assess enrollment feasibility based on the screening log.
Number of Therapy Sessions Completed by Enrolled Participants	Through study completion, a period of 22 months	Therapy sessions included 5 sessions: 2 preparation visits (V1 and V2), dosing (V3) and 2 integration visits (V4 and V5)
Mean Score of Acceptability Ratings on Reactions to Research Participation Questionnaire Revised (RRPQR)	At Week 1 post dosing session	The RRPQ-R is a validated 23-item instrument designed to assess participants' experiences and perceptions of research participation. It comprises five subscales: participation (7 items, range 7-35), personal benefit (5 items, range 5-25), emotional reactions (6 items, range 6-30), perceived drawbacks (3 items, range 3-15), and global evaluation (2 items, range 2-10). Items are rated on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Higher scores on participation, personal benefit, and global evaluation indicate more positive perceptions, while higher scores on emotional reactions and perceived drawbacks reflect greater negative emotional or practical impact. A total score can be calculated by summing across all items (range 23-115), with higher scores reflecting more favorable overall experiences of research participation.

Secondary Outcome Measures

Name	Time	Method
Change in Global Quality Life Score as Assessed by Functional Assessment of Chronic Illness Therapy - Palliative Care 14 (FACIT-Pal 14)	At Baseline, and weeks 1, 3, and 7	The FACIT-Pal-14 is a validated 14-item measure of quality of life in palliative care populations. Items assess physical, emotional, social, and functional well-being over the past 7 days using a 5-point Likert scale (0 = not at all to 4 = very much). Scores are summed to produce a total score ranging from 0 to 56, with higher scores reflecting better quality of life. Subscale scores are not typically reported separately, but can be derived if needed by summing relevant items. The measure is widely used in palliative and supportive care research to evaluate patient-centered outcomes.
Change in Physical Domain Score as Assessed by PROMIS Pain Interference Scale (PIS)	At Baseline, and weeks 1, 3, and 7	The PROMIS Pain Interference Scale (8a) is a validated 8-item instrument assessing the extent to which pain hinders engagement in social, emotional, cognitive, and physical activities. Items are rated over the past 7 days on a 5-point Likert scale (1 = not at all to 5 = very much). Raw scores range from 8 to 40 and are converted to standardized T-scores (mean = 50, SD = 10) using PROMIS scoring manuals. Higher scores indicate greater interference of pain with daily functioning. The measure is administered only if pain is reported and allows both raw and T-score interpretations to facilitate comparison across studies.
Change in Hospital Anxiety and Depression Scale (HADS A and D) Score	At Baseline, and weeks 1, 3, and 7	It is a self-report questionnaire consisting of 14 items, and subjects rate how they felt during the previous week on a 4-point Likert scale. The HADS consists of an anxiety and depression subscale (0-21 points each), and total scores can range from 0 to 42. Higher scores indicate more severe depression and anxiety.
Change in Life Attitude Profile - Revised, Death Acceptance Subscale (LAP-R) Score	At Baseline, and weeks 1, 3, and 7	The LAP-R Death Acceptance subscale is a validated 8-item measure assessing acceptance of and anxiety about death. Items are rated on a 7-point Likert scale (1 = strongly disagree to 7 = strongly agree). Subscale scores are calculated by summing item responses, yielding a total range of 9 to 56, with higher scores reflecting greater acceptance of death and lower death-related anxiety. The measure is commonly used in palliative care and existential research to evaluate psycho-existential adjustment in serious illness.
Challenging Experience Questionnaire (CEQ) Score	Immediately after the intervention, at the end of the dosing day	The CEQ is a validated 26-item instrument assessing psychologically and somatically difficult aspects of psilocybin experiences. It consists of seven subscales: grief (3 items, range 3-15), fear (6 items, range 6-30), death (3 items, range 3-15), insanity (3 items, range 3-15), isolation (3 items, range 3-15), physical distress (3 items, range 3-15), and paranoia (5 items, range 5-25). Items are rated on a 5-point Likert scale (1 = not at all to 5 = extremely). Subscale scores are computed by summing responses within each domain, with higher scores indicating more challenging experiences. A total score (range 26-130) may also be calculated by summing across all items, providing a global index of psychological challenge.
Change in Social Isolation Scale (SIS) Score	At Baseline, and weeks 1, 3, and 7	The PROMIS Social Isolation Scale-6a is a validated 6-item short form that measures perceived social disconnection, including feelings of exclusion, detachment, and lack of belonging. Items are rated on a 5-point Likert scale (1 = never to 5 = always). Raw scores range from 6 to 30 and are converted to standardized T-scores (mean = 50, SD = 10) based on PROMIS scoring guidelines. Higher scores represent greater perceived social isolation. The measure is widely used in psychosocial and palliative care research to assess the impact of illness on social well-being.
Change in Spiritual Domain Score as Assessed by Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-sp-12)	At Baseline, and weeks 1, 3, and 7	The FACIT-Sp-12 is a validated 12-item measure widely used in cancer and palliative care to assess spiritual well-being. It includes three subscales: meaning (4 items, range 0-16), peace (4 items, range 0-16), and faith (4 items, range 0-16). Items are rated on a 5-point Likert scale (0 = not at all to 4 = very much). Subscale scores are summed, and a total score (range 0-48) is obtained by summing across all items. Higher scores indicate greater spiritual well-being. The FACIT-Sp-12 is one of the most commonly used measures of spirituality in serious illness research and has strong psychometric validity.
Change in Demoralization Scale (DS-II)	At Baseline, and weeks 1, 3, and 7	The DS-II is a validated 16-item self-report measure of demoralization, capturing experiences of disheartenment, helplessness, and loss of meaning. It comprises two subscales: meaning and purpose (8 items, range 0-16) and distress and coping ability (8 items, range 0-16). Items are rated on a 3-point scale (0 = never, 1 = sometimes, 2 = often). Subscale scores are summed, and a total score (range 0-32) is calculated by adding across all items, with higher scores indicating greater demoralization. For Version 5 (V5), items are anchored to the past week rather than the past two weeks in the original version, improving temporal sensitivity in clinical research.
Mystical Experience Questionnaire (MEQ-30)	Immediately after the intervention, at the end of the dosing day	The MEQ-30 is a validated 30-item self-report instrument assessing the phenomenological features of mystical-type experiences induced by psychedelics. It yields four subscales: mystical (15 items, range 0-75), positive mood (6 items, range 0-30), transcendence of time and space (6 items, range 0-30), and ineffability (3 items, range 0-15). Items are rated on a 6-point Likert scale (0 = none to 5 = extreme). Subscale scores are summed, and a total score (range 0-150) is calculated by summing across all items. Higher scores indicate stronger mystical-type experiences, with ≥60% of the maximum possible score on each subscale often used as a criterion for a "complete" mystical experience.