Pilot Study of Psilocybin-Assisted Therapy for Demoralization in Patients Receiving Hospice Care - PATH Study
Phase: PHASE2
Conditions: Hospice, Psilocybin, Demoralization, Terminal Illness, Cancer-related Problem/Condition, Psychotherapy, Terminal Cancer, Cancer Terminal
Sponsor: Yvan Beaussant, MD, MSci

1
DF/HCC Protocol #: 21-202
TITLE:  
Pilot study of Psilocybin-Assisted Therapy for demoralization in patients 
receiving Hospice care – PATH study
Coordinating Center:
Dana-Farber Cancer Institute
Study site: 
Care Dimensions hospice
*Principal Investigator (PI): 
Yvan Beaussant, MD, MSc
Dana-Farber Cancer Institute (DFCI)
yvan_beaussant@dfci.harvard.edu
Other Investigators:
Zachary Sager, MD – Study psychiatrist
Dana-Farber Cancer Institute – Care Dimensions
zacharys_sager@dfci.harvard.edu
Roxanne Sholevar, MD – Study psychiatrist
Dana-Farber Cancer Institute
roxanne_sholevar@dfci.harvard.edu
Ilana M Braun, MD
Dana-Farber Cancer Institute
ibraun@partners.org
Caitlin Brennan, PhD
Care Dimensions
cbrennan@caredimensions.org
Alden Rinaldi, MD
Care Dimensions
arinaldi@caredimensions.org
Justin Sanders, MD, MSc
Dana-Farber Cancer Institute 
justin_sanders@dfci.harvard.edu
James A. Tulsky, MD
Dana-Farber Cancer Institute (DFCI)
jamesa_tulsky@dfci.harvard.edu
Alifia Waliji-Banglawala, PharmD – Study pharmacist
Care Dimensions
awaliji-banglawala@caredimensions.org
Statistician:
     Emanuele Mazzola, PhD
Dana-Farber Cancer Institute
emanuele_mazzola@dfci.harvard.edu
 

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NCI-Supplied Agent(s): None
Other Agent(s): psilocybin, Usona Institute
IND #:  154113
IND Sponsor:  Yvan Beaussant, MD, MSc  
Protocol Type / Version 26 / Version Date: April 18, 2023
Summary of changes April 18, 2023
1.
Section 5.1.1 Pre-Screening pg. 15 to include option for the Hospice Interdisciplinary Team to 
provide the Study Information flyer by email or paper to potentially eligible and interested study 
participants. 
2.
Protocol scheduled allowable window of time for psilocybin administration updated from “9am +/- 
15 minutes” to “as soon as possible – typically between 9 and 9:30am” in section 5.1.2 Visit V3: 
psilocybin session pg. 17.
3.
Protocol scheduled window of allowable time for patient and caregiver post-intervention qualitative 
interviews updated from “after V5 +/- 3 days” to “after V5” in section 5.1.4 Post-Intervention 
Assessments – Qualitative Assessment pg. 19 and Semi-Structured Interview Guides – patient and 
caregiver pg. 23.
4.
Scheduled duration after which recorded content will be destroyed “10 years” removed from section 
5.1.6 Recorded Content pg. 24.  
5.
Anticipation of incomplete intervention assessments for participants throughout intervention given 
their terminal condition indicated in section 11. Study Calendar, footnote (8).
6.
Protocol scheduled window of allowable time for V1 updated to “</=3 weeks prior to Day 0” instead 
of “2 weeks” in section 11. Study Calendar – V1.
7.
Protocol scheduled window of allowable time for V2 updated to “</= 7 days prior to Day 0” instead 
of “3 days” in section 11. Study Calendar – V2.
8.
Protocol scheduled window of allowable time for V5 updated to “Up to day 14” instead of “Day 10” 
in section 11. Study Calendar – V5.
9.
Protocol scheduled window of allowable time for Follow Up visits updated from “Week 3 +/- 3 days” 
to “Week 3 +/- 14 days” (post-dosing) in section 11. Study Calendar – F/U.
10. Protocol Version and Version Date updated accordingly.

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SCHEMA

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TABLE OF CONTENTS
SCHEMA
3
1.
OBJECTIVES9
1.1
Study Design............................................................................................................9
1.2
Primary Objectives...................................................................................................9
1.3
Secondary Objectives...............................................................................................9
2.
BACKGROUND .................................................................................................................9
2.1
Study Disease(s).......................................................................................................9
2.2
IND Agent................................................................................................................9
2.3
Rationale ................................................................................................................11
3.
PARTICIPANT SELECTION...........................................................................................12
3.1
Eligibility Criteria..................................................................................................12
3.2
Exclusion Criteria ..................................................................................................13
3.3
Inclusion of Women and Minorities ......................................................................14
3.4
Caregivers’ Inclusion/Exclusion criteria................................................................15
4
REGISTRATION PROCEDURES ...................................................................................15
4.1
General Guidelines for DF/HCC Institutions ........................................................15
4.2
Registration Process for DF/HCC Institutions.......................................................15
4.3
General Guidelines for Other Investigative Sites ..................................................15
4.4
Registration Process for Other Investigative Sites.................................................15
4.5
Initiation of Therapy ..............................................................................................16
5.
TREATMENT PLAN........................................................................................................16
5.1.
Treatment Regimen................................................................................................16
5.2.
Pre-Treatment Criteria ...........................................................................................25
5.3.
Agent Administration.............................................................................................25
5.4.
General Concomitant Medication and Supportive Care Guidelines......................26
5.5.
Criteria for Taking a Participant Off Protocol Therapy.........................................27
5.6.
Duration of Follow Up...........................................................................................27
5.7.
Criteria for Taking a Participant Off Study ...........................................................27
6.
DOSING DELAYS/DOSE MODIFICATIONS ...............................................................28
7.
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................28
7.1.
Adverse Events and Potential Risks ......................................................................29
7.2.
Adverse Events list for psilocybin.........................................................................33
7.3.
Adverse Event Characteristics...............................................................................34
7.4.
Adverse Event Reporting.......................................................................................34
7.5.
Reporting to the Food and Drug Administration (FDA) .......................................36
7.6.
Reporting to Local Risk Management...................................................................37
7.7.
Routine Adverse Event Reporting .........................................................................37
7.8.
Reporting to drug manufacturer.............................................................................37

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8.
PHARMACEUTICAL INFORMATION OF PSILOCYBIN...........................................39
8.1.
Psilocybin background...........................................................................................39
8.2.
Importance of a Supportive Set and Setting Protocol............................................40
8.3.
Description.............................................................................................................40
8.4.
Form.......................................................................................................................41
8.5.
Storage and Stability..............................................................................................41
8.6.
Compatibility .........................................................................................................42
8.7.
Handling.................................................................................................................42
8.8.
Availability ............................................................................................................42
8.9.
Preparation.............................................................................................................42
8.10.
Administration .......................................................................................................42
8.11.
Ordering.................................................................................................................42
8.12.
Accountability........................................................................................................43
8.13.
Destruction and Return ..........................................................................................43
9.
CONCOMITANT MEDICATIONS AND TAPERING INSTRUCTIONS.....................43
10.
RISKS AND MITIGATION STRATEGY IN RESPONSE TO THE 
SARS-COV2 pandemic .....................................................................................................45
11.
STUDY CALENDAR .......................................................................................................47
12.
DATA REPORTING / REGULATORY REQUIREMENTS...........................................50
12.1.
Data Reporting.......................................................................................................50
12.2.
Data Safety Monitoring..........................................................................................50
13.
STATISTICAL CONSIDERATIONS...............................................................................50
13.1.
Primary outcome variables ....................................................................................50
13.2.
Secondary outcome variables ................................................................................51
13.3.
Sample size and statistical plan..............................................................................52
14.
PUBLICATION PLAN .....................................................................................................53
REFERENCES
54
APPENDIX A
STUDY MEASUREMENT SCALES.......................................................59
A1 – Patient demographic data..........................................................................................59
A2 – Family caregiver demographic data..........................................................................60
A3 – Palliative Performance Scale ....................................................................................62
A4 – Demoralization Scale – II (DS-II).............................................................................63
A5 – Hospital Anxiety and Depression Scale....................................................................64
A6 – Functional Assessment of Chronic Illness Therapy - Palliative Care 14..................65
A8 – PROMIS Pain Interference Scale ..........................................................................66
A9 – Life Attitude Profile – revised, Death acceptance subscale......................................67
A10 – Social Isolation Scale-6a.........................................................................................69
A11 – Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12........70
A12 – Mystical Experience Questionnaire ........................................................................71

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A13 – Challenging Experience Questionnaire...................................................................72
A14 – Schedule of Attitudes toward Hastened Death .......................................................73
A15 – Columbia-Suicide Severity Rating Scale................................................................74
A16 – Confusion Assessment Method...............................................................................75
A17 – Reactions to Research Participation Questionnaire Revised ..................................76
A18 – CareGiver Oncology Quality of Life questionnaire................................................78

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1.
OBJECTIVES
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. 
1.1
Study Design
Open label, single center, concurrent mixed-methods phase 2 pilot trial of a single dose of 
psilocybin for demoralization in patients receiving hospice care. 
1.2
Primary Objectives
To assess, using quantitative and qualitative measures, the feasibility of delivering a single dose 
of psilocybin 25 mg under supportive psychotherapeutic conditions to patients with moderate-to-
severe demoralization (Demoralization Scale-II ≥ 8) who receive hospice care at home. 
Hypothesis: 
Treatment and week 1 assessments will be successfully completed in at least 60% of recruited 
subjects, and  80% of subjects who completed Week 1 assessment will evaluate favorably 
acceptability.
1.3
Secondary Objectives
To explore the safety of psilocybin-assisted therapy in this population and its preliminary 
efficacy on demoralization and other patient-reported and family caregiver-reported outcomes. 
Hypotheses: 
No serious adverse-event related to the intervention will occur and week 1 outcomes assessment 
will show improvement in demoralization. 
2.
BACKGROUND
2.1
Study Disease(s)
Terminal illness related to cancer and non-cancer diagnoses. 
2.2
IND Agent
The IND agent, psilocybin, is manufactured by Usona Institute, a 501(c)(3) non-profit medical 
research organization that obtained Breakthrough therapy status from the Federal Drug 
Administration (FDA) for its Current Good Manufacturing Practice (cGMP) psilocybin in the 
treatment of Major Depressive Disorders (IND  129532). 
Psilocybin   (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl]   dihydrogen   phosphate)   is   a   
natural   product  produced  by  numerous  species  of  Psilocybe mushrooms,  which  is  

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manufactured  for  clinical  use  to  control  potency  and  purity.  It  is  a  tryptamine  derivative,  
and  in  humans  the  phosphate group is rapidly enzymatically cleaved in the body to produce 
psilocin, an agonist at a variety of serotonin receptors, the most important of which in this setting 
is the 5-HT2A receptor.1,2  Oral psilocybin has about a 50% bioavailability and psilocin  is  
detectable  in  plasma  within  20  minutes  of  administration  of  the  parent  compound.3,4 The 
half-life of psilocin in blood is 2-3 hours. Onset of noticeable psychoactive effects occurs within 
one hour, peaks at about two hours after a dose, and loss occurs typically around six hours after 
the dose. Based  on  this  time  course,  in  the  clinical  trial  setting,  protocols  mandate  
observation  until  approximately 8 hours after dosing. 
Psilocybin reliably induces profound changes in sensory perception, emotion, thought, and sense 
of self, characterized by marked alterations in all mental functions, including perception, mood, 
volition, cognition and self-experience.5,6 These profound changes are often referred to as 
mystical-type experiences. Measures of mystical-type experience occurring during psilocybin 
treatment have been repeatedly observed to predict later effects on behavior and emotions, 
including reductions in depressive and anxious symptoms.7–9 
Non-clinical in vivo and in vitro studies, found via literature searches, demonstrate that similar to 
humans, when psilocybin is administered orally to rats it is rapidly dephosphorylated to psilocin 
in the intestinal mucosa by alkaline phosphatase and a nonspecific esterase, with approximately 
50%  of  the  total  volume  of  psilocin  absorbed  from  the  digestive  tract. Maximum plasma 
levels are achieved after approximately 90 minutes.10 When administered systemically (i.e., 
bypassing the gut), initial psilocybin metabolism is performed by tissue  phosphatases, with in 
vitro studies indicating the kidneys as being among the most active metabolic  organs.11 Across  
species  tested,  the  highest  levels  of  psilocin  were found in the neocortex, hippocampus, and 
thalamus.12 
Recent clinical studies utilizing pharmaceutical-grade oral psilocybin under controlled conditions 
have been performed upon healthy participants and various subpopulations in order to gauge 
safety events and preliminary clinical efficacy. Though the safety reporting criteria and the level 
of data verification varied greatly between studies, including many participant-reported 
outcomes, these data  have  been  utilized  to  elucidate  the  expected  adverse  event  (AE)  
profile  of  psilocybin.  The clinical studies summarized in the investigator brochure present 
similar safety profiles, with both psychological and physical adverse events reported. The most 
common adverse psychological events included transient anxiety, negative emotional states and 
paranoid/delusional thinking during dosing sessions, and the most common physical effects were 
increased blood pressure (BP) and heart rate, mild nausea, and mild headache.
Preliminary efficacy of psilocybin in these studies showed a substantial and sustained decrease in 
symptomatic response in indications including obsessive compulsive disorder (OCD), substance 
use disorder, depression, anxiety, and psychological and existential distress in patients with 
serious illness (e.g. cancer). Overall, psilocybin has been well-tolerated at the doses examined in 
the clinic. Due to the psychoactive nature of the compound, it should only be administered in a 
controlled setting and per the accompanying clinical protocol.

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Psilocybin is currently under phase 2b of drug development in patients with depression and 
treatment-resistant depression (NCT03866174 and NCT03775200 respectively), and if the 
outcomes are positive, then it seems plausible that psilocybin will become a licensed medicine 
for a range of indications in psychiatry and serious illness care when used in an approved 
treatment model.13 In the past few years, many renowned academic medical centers in the United 
States have (re)started investigating the clinical applications of psilocybin, among which John 
Hopkins University School of Medicine, New York University, Harbor-UCLA, and more 
recently Yale, Mass General Hospital and Berkley.
2.3
Rationale
More than 1.4 million Americans receive hospice care each year, of whom 30% have a principal 
diagnosis of cancer. For most of these patients and families, emotions such as fear, anger or 
sadness are common and normal. However, 38 to 50% of patients experience clinically relevant 
anxiety and/or depression that significantly impacts their and their caregivers quality of life 
(QOL).14,15 High quality hospice care ought to seek, as a fundamental goal, to address this 
psychological distress. Yet, symptoms such as depression are often underrecognized and 
undertreated in this population.16 This may be due to clinicians or patients not recognizing 
depressive symptoms in the context of serious illness,17–19 to the lack of effective treatment,20–22 
or both. In addition, existential suffering, commonly experienced at the end of life and 
manifested through demoralization syndrome, exacerbates anxiety and depression.23–26 
Improving the management of these symptoms would benefit healthcare outcomes of millions of 
patients and family caregivers, and society at large. 
Psilocybin-assisted therapy presents a novel potential therapeutic modality for hospice patients, 
as preliminary evidence suggests its safety and efficacy to treat psychosocial distress in people 
with serious illness.8,9,27–30 Psilocybin is a serotoninergic psychedelic derived from a class of 
fungi. Based on therapeutic models developed in the 1960s, this drug-facilitated psychotherapy 
combines an inner-directed psychotherapy to the consciousness-expanding properties of 
psilocybin, by agonism of the serotonin receptor 5HT2A, to facilitate the processing and 
resolution of psychological and existential issues.1,31–34 In patients with cancer, recent double-
blind, randomized controlled trials of psilocybin-assisted therapy showed pronounced and 
prolonged reductions in depression and anxiety, as well as sustained benefits in existential 
distress, spiritual well-being and quality of life.8,9,27 
Grob et al.’s study included 12 patients and demonstrated the safety and feasibility of 
administering psilocybin-assisted therapy within cross-over randomized controlled trials in this 
setting.27 Using similar designs in larger sample sizes, Griffith et al.’s and Ross et al.’s studies 
further documented safety and feasibility, and demonstrated rapid, robust and sustained 
improvements of depression and existential distress in cancer patients. In particular, Griffith et 
al.’s study found sustained remission of depression symptoms at 6 months in 70% of patients 
(n=51)8 and Ross et al.’s study found enduring antidepressant and anxiolytic effect following 
psilocybin administration in 80 and 60% of patients respectively (n=29).9  In the latter study, 3.2 
and 4.5 years follow-up showed continued reductions in depression or anxiety, sustained benefits 
in existential distress and quality of life, and improved attitudes towards death anxiety in most 

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patients.28 Following these results, the FDA approved two large multicenter confirmatory trials 
in non-cancer patients with MDD and treatment resistant depression (TRD) respectively.35,36
Another study conducted by Anderson et al. and recently published in EClinicalMedicine 
provides useful background for our study.37 This open-label study assessed the safety and 
feasibility of psilocybin-assisted group therapy for demoralization in 18 older long-term AIDS 
survivor (OLTAS) men, a population of patients with serious illness with particularly complex 
medical and psychiatric needs. Findings demonstrated a clinically meaningful change in 
demoralization from baseline to 3-month follow-up. Zero serious adverse reactions and two 
unexpected adverse reactions to psilocybin were detected, and seven participants experienced 
self-limited, severe expected adverse reactions (see adverse events table in section 7.1). 
Psychedelic-assisted therapies raise both excitement and concern among key stakeholders in 
serious illness care.38,39 Our group conducted in-depth interviews of experts involved in serious 
illness care and/or psychedelic research that highlighted the need to conduct rigorous psilocybin 
trials in the context of interdisciplinary psychosocial and palliative care.39 Rapid evolution in the 
legal and regulatory status of psychedelics has heightened the urgency of obtaining scientific 
evidence to inform future standards of care for psychedelic-assisted therapies.13,40,41 This is 
particularly true for patients with cancer receiving hospice care, who may derive substantial 
benefit and yet may have particular vulnerabilities. 
To date, no study has assessed the safety and efficacy of psilocybin-assisted therapy to address 
psychosocial, existential, or spiritual distress in patients with a terminal illness receiving hospice 
care. Defining relevant eligibility criteria and treatment regimen is critical for patient safety. 
Conducting rigorous randomized controlled studies in this population presents unique 
challenges, warranting feasibility studies that carefully prepare larger confirmatory trials. To 
bridge this gap, our Department has partnered with Care Dimensions, a non-profit leader in 
hospice care and the largest hospice organization in Massachusetts. Our group is uniquely 
equipped and positioned to deliver, assess and refine this novel intervention. This study, by pilot-
testing a new model of psilocybin-assisted therapy in patients receiving hospice care, will 
facilitate the success of future randomized multi-center trials necessary to confirm the 
intervention’s efficacy in this patient population and shape the therapeutic model. Given the 
unmet need in this large population of patients and family caregivers, the potential to positively 
impact healthcare outcomes in the field is high. 

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3.
PARTICIPANT SELECTION
3.1
Eligibility Criteria 
3.1.1
Patients enrolled in hospice care at home
3.1.2
Age  21 years.  
3.1.3
Any terminal illness with respect of exclusion criteria
3.1.4
Palliative Performance Scale (PPS)  40 % (see Appendix A)
3.1.5
Moderate-to-severe demoralization as measured by Demoralization Scale-II ≥ 8 (see 
Appendix A)
3.1.6
Significant other or other caregiver present at home the night of study drug 
administration
3.1.7
No driving for 24 hours following study drug administration.
3.1.8
English proficiency
3.1.9
Ability to understand and the willingness to sign a written informed consent document.
3.1.10 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.42 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.
3.1.11 Patients with first-degree relatives with schizophrenia or bipolar disorder may be eligible 
depending on their age and personal and family psychiatric history. The decision will be 
made by the principal investigator and study psychiatrist based on risk assessment. 

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3.2
Exclusion Criteria
3.2.1
Current General Inpatient (GIP) hospice status
3.2.2
Patients currently receiving chemotherapy 
3.2.3
Condition impairing oral intake or digestive absorption
3.2.4
Presence of a delirium diagnosed by the CAM (see Appendix A)
3.2.5
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 (see Appendix A)
3.2.6
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 
3.2.7
History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to psilocybin 
3.2.8
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 
3.2.9
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). See section 9 of the protocol 
for concomitant medications and tapering instructions. 
3.2.10 End stage liver disease or cirrhosis as primary hospice diagnosis

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3.2.11 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. 
3.2.12 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.
3.2.13 Women who are pregnant, nursing, or planning a pregnancy. 
3.3
Inclusion of Women and Minorities
Both men and women of all races and ethnic groups are eligible for this trial.
3.4
Caregivers’ Inclusion/Exclusion criteria 
Inclusion Criteria
Exclusion Criteria
Individual identified as a support person by a 
patient enrolled in the PATH study
Unable to participate
18 years of age and older
Deemed inappropriate for the study by the 
patient’s clinician
English proficiency
Unable to respond in or read English 
Ability to understand and the willingness to  sign 
a written informed consent document
Unable to obtain informed consent due to 
cognitive or emotional status
4
REGISTRATION PROCEDURES 
4.1
General Guidelines for DF/HCC Institutions
Institutions will register eligible participants in the Clinical Trials Management System (CTMS) 
OnCore. Registrations must occur prior to the initiation of any protocol-specific therapy or 
intervention. Any participant not registered to the protocol before protocol-specific therapy or 
intervention begins will be considered ineligible and registration will be denied.
An investigator will confirm eligibility criteria and a member of the study team will complete the 
protocol-specific eligibility checklist.
Following registration, participants may begin protocol-specific therapy and/or intervention. 
Issues that would cause treatment delays should be discussed with the Principal Investigator (PI) 
of the registering site. If the subject does not receive protocol therapy following registration, the 

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subject must be taken off study in the CTMS (OnCore) with an appropriate date and reason 
entered.  
4.2
Registration Process for DF/HCC Institutions
Applicable DF/HCC policy (REGIST-101) must be followed.  
4.3
General Guidelines for Other Investigative Sites
Eligible participants will be entered on study centrally at Dana-Farber Cancer Institute by the 
Study Coordinator. All sites should email the Sponsor (yvan_beaussant@dfci.harvard.edu) to 
confirm and plan intervention. The required forms can be found in Appendices. 
Following registration, participants should begin intervention within 7 days. Issues that would 
cause intervention delays should be discussed with the Principal Investigator.  If the subject does 
not receive protocol therapy following registration, the subject must be taken off study in the 
CTMS (OnCore) with an appropriate date and reason entered.  
4.4
Registration Process for Other Investigative Sites
To register a participant, the following documents should be completed by the participating site 
and e-mailed (yvan_beaussant@dfci.harvard.edu and isabel_kristan@dfci.harvard.edu) to the 
Study Coordinator:

Signed participant consent form

HIPAA authorization form

Eligibility check-list

Copy of demoralization scale, PPS score, C-SSRS, CAM scores
The participating site will then call (857-272-5830) or e-mail 
(yvan_beaussant@dfci.harvard.edu) the Study Coordinator to verify eligibility. The Study 
Coordinator will follow DF/HCC policy (REGIST-101) and register the participant on the 
protocol.  The Study Coordinator will fax or e-mail the participant study number, and if 
applicable the dose treatment level, to the participating site.  The Study Coordinator will also 
contact the participating site and verbally confirm registration.
4.5
Initiation of Therapy
 
Participants must be registered with the DF/HCC CTMS before the initiation of treatment or 
other protocol-specific interventions. Care Dimension’s pharmacy must confirm registration is 
complete prior to dispensing study drug. Treatment and other protocol-specific interventions may 
not be initiated until the External Site receives confirmation of the participant’s registration from 
the Coordinating Center. The DF/HCC Sponsor and IRB of record must be notified of any 
violations to this policy.
5.
TREATMENT PLAN

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5.1.
Treatment Regimen
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. 
 
The study schema is the following: 
5.1.1
Enrollment and study entry
Consent process flowchart
Pre-screening (remote)
The study population will include 15 adult patients, 21 years or older, who receive hospice care 
at home from Care Dimensions hospice in Massachusetts. The study team will screen potential 
participants by reviewing new admissions and reviewing the current census on a reoccurring 
basis. For potentially eligible patients, the study team will contact a referent hospice clinician 
(nurse case manager or physician) to discuss the patient case and confirm the possibility to 
further the consent process. A member of the interdisciplinary team will provide an information 
flyer (paper or electronic via email) to the potentially eligible patients. Patients can reach out to 

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the study team via the contact indicated on the flyer or a member of the study team will reach out 
to them to assess further interest in participation. Interested patients will be scheduled to meet 
with the study psychiatrist and given the opportunity to review the inform consent form either on 
paper (ICF) or electronically (eICF). Additionally, for reference the following link to the Heffter 
Research Institute website will be given to potential participants: https://www.heffter.org/future-
research. This website provides information about psilocybin-assisted therapy research in 
patients with cancer and features video accounts from previous participants in similar studies.
Visit V0: full screening + enrollment (patient’s home or remote)
Patients who signed the inform consent form (ICF) or the electronic ICF (eICF) will have a first 
visit (V0) with the study psychiatrist and the investigator, taking place either at their home or 
remotely, to confirm their eligibility, and complete screening assessments including: the 
Demoralization Scale-II (DS-II); the Columbia-Suicide Severity Rating Scale (C-SSRS); the 
Confusion Assessment Method (CAM) and medical and psychiatric history. Physical 
examination and vital signs will be obtained from the clinical team and/or patient chart and 
reviewed by the study psychiatrist and the investigator. The lead physician will review last 
available bloodwork and exclude patients who have elevated AST and ALT five times above the 
normal laboratory limit. The lead physician as part of the medical evaluation will observe for 
clinical signs of liver disease, including confusion, asterixis or jaundice. Patients with these 
symptoms suggestive of liver failure will be excluded from the study. Only patients who meet all 
eligibility criteria will be enrolled in the study. Caregivers of enrolled patients will be offered to 
consent for the caregiver survey (CarGOQoL), the HADS, and the post-intervention qualitative 
interview. The study staff will follow the registering processes described in Section 4.0. 
The duration of V0 will be 30-60 min. 
5.1.2
Treatment regimen
Visit V1: baseline assessment + preparation session #1 (patient’s home or remote)
V1 includes baseline assessment and a first preparation session with the study therapists (see 
section below for details about the therapy dyads). 
Baseline assessment consists in patient-reported questionnaires that patients will complete on 
paper either on their own prior to V1 or with the help of a study staff member. Baseline 
assessment includes the following measurements (see details in section 5.1.5): the Functional 
Assessment of Chronic Illness therapy – Palliative Care  (FACIT-Pal); the PROMIS pain 
interference scale (if pain presented); the Hospital Anxiety and Depression Scale (HADS A and 
D); the PROMIS social isolation scale; the Life Attitude Profile – revised, Death acceptance 
subscale (LAP-R, DA); the FACIT-spirituality; the Schedule of Attitudes Toward Hastened 
Death (SAHD). Consenting caregivers will complete the CarGOQoL and HADS at V1. In 
addition, the study psychiatrist will complete the C-SSRS and the CAM. 
Following baseline assessments, the lead therapist (LT) and the co-therapist (CT) will conduct  
the first preparation session. The main objectives of the preparation sessions are to educate 

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patients and families on psilocybin-assisted therapy, to build rapport between them and the study 
therapists, and to identify intentions for the psilocybin session as well as personal themes and 
struggles that might impact the psilocybin experience.
V1 and V2 will be conducted within about a week to a month prior to the psilocybin session. 
The duration of V1 will be up to 90 min (30 min assessment + 60 min preparation). 
Visit V2: preparatory session #2 (patient’s home or remote)
The second preparatory session (V2) will take place at home or remotely. Patients and therapists 
will conduct V2 assessments as indicated on the schedule of assessment (see 5.1.6) and continue 
to set expectations for treatment, discuss set and setting and build the therapeutic alliance. 
The duration of V2 will be up to 75 min (15 min assessment + 60 min preparation). 
Visit V3: psilocybin session (hospice facility) – day 0
The psilocybin session will take place in an individual room at the Care Dimensions Hospice 
House and will last 8 h (30 min assessment + 7h30 hour psychotherapeutic support). 
Participants will arrive at 8 am and complete the following assessments at V3, prior to receiving 
the medication: DS-II and HADS A and D. In addition, the lead therapist will complete the C-
SSRS and the CAM. 
The participant will take the study drug capsule (psilocybin 25 mg) under the therapy team 
supervision as soon as possible – typically between 9 and 9:30 am. No dose modifications will 
be necessary.
Blood pressure and heart rate will be measured at the following time-points after psilocybin 
administration: 30, 60, 120, 180, 240, 300, and 360 min.
During the psilocybin session, facilitators’ role will be to monitor, assist and support patients 
while they are experiencing the effect of the medicine. The monitoring will focus on vital signs 
and distress level. The assistance and support, whether it’s physical or emotional will follow 
patients’ needs in a non-directive way. At the onset of the study agent effect, therapists will 
invite participants to lie down on the bed, put on eyeshades and put on headphones that will play 
a pre-selected play-list throughout the session. Therapists will encourage participants to focus 
inward and stay open to and present with whatever their inner experience is. 
Psilocybin effect on perception and consciousness lasts 4 to 6 hours in most individuals. When 
the participant appears to have returned to his/her baseline psychological and physiological state, 
and he or she expresses a readiness to begin the discharge process, they will complete the 
Mystical Experience Questionnaire (MEQ-30) and the Challenging Experience Questionnaire 
(CEQ), and the Lead Therapist and co-investigator will determine if participant is safe and ready 
to be discharged home. Patients who are unable to be discharged home for medical or psychiatric 

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reasons will have the possibility to stay overnight at the hospice house for medical supervision. If 
for any reason the patient cannot stay at the hospice house and their situation requires medical 
supervision, arrangements would be made by the study team to admit them to a hospital.  
Visit V4: Integration session #1 (patient’s home or remote) – Day 1 (up to day 3)
The integration session 1 will occur the day after the psilocybin session (allowable window 3 
days) and start with medical and psychological assessment as indicated on the schedule of 
assessments. 
The objective of the integration sessions is to help patients consolidate insights gained from the 
psilocybin experience. Patient will have the opportunity to discuss their experience with the goal 
of maximizing the therapeutic benefit. 
The duration of V4 will be 75 min (15 min assessment + 60 min preparation). 
Visit V5: Integration session #2 (patient’s home or remote) – Day 7 (up to day 14)
The integration session 2 will occur within 14 days after the psilocybin session. After V5, patient 
clinical follow-up will be continued as part of usual care by the hospice team. 
The duration of V5 will be 75 min (15 min assessment + 60 min preparation). 
Summary of treatment regimen
Regimen Description
Agent
Premedications; 
Precautions
Dose
Route
Schedule
Psilocybin
None
25 mg 
PO in under 5 
mins
Visit 3
Psychotherapy
Focus
Length
Therapists 
Schedule
Preparation 1
60 min
Visits 1
Preparation 2
Psychoeducation, 
intention setting 
and relaxation 
technics
60 min
Visits 2
Psilocybin 
session
Inner-directed 
psychotherapeutic 
support
7h30 
Visits 3
Integration 1
60 min
Visits 4
Integration 2
Debriefing, 
journaling and 
goals setting
60 min
Lead therapist 
and co-therapist
Visits 5
Unscheduled Visits

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Additional visits or phone calls may be scheduled to perform procedures other than those listed 
above. This may be done for patient’s safety and will be based on the judgment of the study staff.
5.1.3
Therapists dyads 
Therapy teams will be composed of a Lead Therapist and a Co-Therapist. The dyads will be 
present at all therapy sessions, namely V1, V2, V3, V4 and V5. 
The LT will be an actively licensed, Master’s-level or doctoral-level MD/PhD/PsyD-level 
psychotherapist. The CT will hold a minimum of a bachelor’s degree and be trained in mental 
health or spiritual care. Preference will be given to those with experience working in the hospice 
field and/or prior experience working in clinical research trials, especially with psilocybin. 
5.1.4
Post-intervention assessments 
Visits V6a,b…: Post-intervention outcome measures
Post-intervention period will consist of outcome measures at V4, V5, V6a and subsequent 
monthly visits (see detailed outcomes in section 5.1). We will conduct these visits at home or 
remotely depending on the patient and family situation. We anticipate that given their terminal 
condition, participants might not be able to complete post-intervention measures or may only be 
able to complete part of them. To reduce administrative burden, we will not report those missing 
questionnaires as protocol violations. 
Qualitative assessment
All sessions between the therapists and the participant during the intervention period will be 
audio and video recorded for fidelity rating, qualitative analysis and education purposes. 
In addition, after the intervention, we will conduct audio-recorded semi-structured interviews 
with patients and caregivers to qualitatively assess feasibility and outcomes. Patient interviews 
will be conducted as soon as possible after the first or second integration session (V4 or V5) in 
order to optimize acceptability data collection in a context – hospice - defined by the potential 
for rapid clinical deterioration. Caregivers’ post-dosing interviews will be conducted within the 
same timeframe but may be conducted later if needed. 
Semi-structured interviews with a selected sample of hospice staff providers involved in enrolled 
participants’ care will also be conducted. The main objective of these interviews is to explore 
hospice staff’s perspectives on the feasibility and acceptability of the PATH study intervention. 
We will recruit a convenient sample of 5-7 clinicians who were actively involved in the care of 
study participants and represent a diversity of perspectives and roles (e.g. physicians, nurses, 
social workers, chaplains and team leaders). Recruitment of hospice staff will happen at 3 
different times over the study enrollment period, each time after 4 or 5 patients have completed 
the study intervention. The recruitment email will include information needed for informed 
verbal consent. We request a waiver of documented informed consent for hospice staff.

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Participating hospice staff will receive $50 gift cards to acknowledge their time and 
contribution. 
 
The interviews with hospice staff will be conducted in-person or remotely (over the phone or a 
DFCI Zoom account), last about 40 min and be audio-recorded. Audio recording will start only 
after participant’s information and verbal consent, according to the interview script attached. 
Recording will be transcribed verbatim using a HIPAA compliant service. All recordings and 
transcripts will be stored in secure, restricted-access locations. Recordings and transcripts will be 
tied to a unique study ID number, and the only documents linking the study ID to identifiable 
information are in restricted access files stored securely in restricted access folders. Potential 
patient’s health information will be de-identified, and all audio recordings will be destroyed 
when analyses are complete. 
5.1.5
Instruments measuring study outcomes:
Demographic questionnaire (V0)
Variables of interest will be obtained via self-report and include: age, ethnicity, race, marital 
status, education, and occupational status. 
Medical Record Review (V0, V5, V6a,b…) 
A member of the study team will record clinical data, including diagnosis, disease stage, and 
treatments. Comorbidities or current medical history will also be extracted from medical records.
Demoralization Scale-II (Baseline [V1], V5, V6a,b…)
The DS-II measures of the experience of disheartenment and helplessness and is well validated 
in terminally ill patients.43 It’s a 3-point response, self-report scale comprising 16 items and 2 
subscales (meaning and purpose, and distress and coping ability). The presence of baseline 
moderate-to-severe demoralization, as measure by a DS-II score ≥ 8, is necessary for inclusion in 
this study. For V5 assessment, we will ask subjects how they felt over the past week instead of 
over the past two weeks as originally framed in the instrument. 
Estimated time for administration: 3 minutes
Hospital Anxiety and Depression Scale (Baseline [V1], V5, V6a,b…)
HADS was developed for use in medically ill patients and validated in palliative care 
populations.44,45 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. Participating subject’s caregivers also will 
complete the HADS at V1, V5 and V6a,b…
Estimated time for administration: 5 minutes
Functional Assessment of Chronic Illness Therapy - Palliative Care 14 (Baseline [V1], V5, 
V6a,b…)
FACIT-Pal 14 measures quality of life in palliative care patients. It has good internal consistency 
and there is evidence of construct validity.46 FACIT-Pal 14 consists in 14 items, and subjects rate 
how they felt during the previous week on a 5-point Likert scale.

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Estimated time for administration: 3 minutes
PROMIS Pain Interference Scale – 8 items (Baseline [V1], V5, V6a,b…)
The PROMIS is a National Institutes of Health (NIH) Roadmap initiative that aims at providing 
precise, reliable, valid, and standardized questionnaires measuring patient-reported outcomes 
across the domains of physical, mental, and social health.51 
The PIS measures the self-reported consequences of pain on relevant aspects of a person’s life 
and may include the extent to which pain hinders engagement with social, cognitive, emotional, 
physical, and recreational activities.52 We will use 8 validated items pertaining to social and 
emotional consequences of pain during the previous week, that subjects will rate on a 5-point 
Likert scale. The PIS will only be collected from a patient if the patient indicates pain at a given 
assessment period.
Estimated time for administration: 2 minutes
Life Attitude Profile – revised, Death acceptance subscale (Baseline [V1],V6a)
LAP-R Death Acceptance is a validated, self-rated 9-item, 7-point Likert scale assessing 
acceptance and anxiety about death.53 
Estimated time for administration: 2 minutes
Social Isolation Scale-6a (Baseline [V1], V5, V6a,b…)
The PROMIS SIS-6a assesses perceptions of being avoided, excluded, detached, disconnected 
from, or unknown by, others. We will use the short form of the instrument consisting in a 6-item, 
5-point Likert scale.54
Estimated time for administration: 2 minutes
Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (Baseline [V1], 
V5, V6a,b…)
The FACIT-sp-12 scale is a measure of spiritual well-being validated for use in cancer and 
widely used in palliative care research.47,48 The FACIT-sp-12 has subscales that measure faith, 
meaning and peace, which are broadly consistent with conceptual models of spiritual well-
being.55
Estimated time for administration: 2 minutes
Mystical Experience Questionnaire (V3 [end of session] or V4)
The MEQ-3056 is a self-report questionnaire that evaluates discrete mystical experiences induced 
by serotoninergic psychedelics and is sensitive to detecting psilocybin-induced mystical 
experiences.7 In addition to a MEQ total score, the questionnaire generates four empirically 
derived factors: mystical; positive mood; transcendence of time and space; and ineffability.
Estimated time for administration: 10 minutes
Challenging Experience Questionnaire (V3 [end of session] or V4)
The CEQ is a validated instrument with 26 items rated on a 5-item Likert scale, characterizing 
psychologically difficult aspects of experiences occasioned by psilocybin, according to seven 
factors: grief, fear, death, insanity, isolation, physical distress, and paranoia.57
Estimated time for administration: 5 minutes

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Schedule of Attitudes toward Hastened Death (Baseline [V1], V6a)
The SAHD is a reliable and valid measure of desire for death among terminally ill patients. It 
includes 20 items that subjects rate as true or false.58,59
Estimated time for administration: 5 minutes
Columbia-Suicide Severity Rating Scale (Baseline V0, [V1], V2, V3, V4, V5)
The C-SSRS will be used to assess suicide potential or tendency as a study entry criterion and 
monitored throughout the study. 
The C-SSRS is a semi-structured interview designed to assess the severity and intensity of 
suicidal ideation, suicidal behavior, and non-suicidal self-injurious behavior over a specified 
time period.60 The measurement of suicidal ideation is based on five “yes” or “no” questions 
with accompanying descriptions arranged in order of increasing severity. If the patient answers 
“yes” to either questions 1 or 2, the intensity of ideation is assessed in five additional questions 
related to frequency, duration, controllability, deterrents, and reasons for the most severe suicidal 
ideation. Suicidal behavior is assessed by asking questions categorizing behaviors into actual, 
aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. 
If any item(s) on the C-SSRS are answered “yes”, the primary investigator or physician 
investigator must review the patient’s responses in order to (a) at screening and Baseline 
determine the patient’s study eligibility and potential need for referral to a mental health 
professional, and (b) during the study evaluate the patient’s need for appropriate medical 
management such as a referral to a mental health professional. 
A significant suicide risk is defined by suicidal ideation with intend and a plan as endorsed on 
item 5 on the C-SSRS within the past month at V0 or since previous visit later during the study. 
This must be reported as an AE or SAE as appropriate and followed up accordingly. 
Additionally, if a patient responds “yes” to any of the suicidal ideation questions 1 through 3, the 
investigator should apply clinical judgment to determine the need for reporting this as an AE or 
SAE and the need for any appropriate referral. 
The C-SSRS will be collected at every visit.
Estimated time for administration: 3 minutes
Confusion Assessment Method (Baseline V0, [V1], V2, V3, V4, V5)
The CAM will be used to assess delirium as a study entry criterion and monitored throughout the 
study. 
The CAM instrument is a clinician-rated diagnosis tool assessing the presence, severity, and 
fluctuation of 9 delirium features: acute onset, inattention, disorganized thinking, altered level of 
consciousness, disorientation, memory impairment, perceptual disturbances, psychomotor 
agitation or retardation, and altered sleep-wake cycle. The CAM diagnostic algorithm is based on 
four cardinal features of delirium: 1) acute onset and fluctuating course, 2) inattention, 3) 
disorganized thinking, and 4) altered level of consciousness. A diagnosis of delirium according 
to the CAM requires the presence of features 1, 2, and either 3 or 4. The CAM demonstrated 
sensitivities from 94–100%, specificities from 90–95%, positive predictive accuracy of 91– 94%, 
negative predictive accuracy of 90–100%, interrater reliability ranging from .81–1.00; and 
convergent agreement with other mental status tests including the Mini-Mental State 
Examination (MMSE).61,62
The CAM will be collected at every visit.

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Estimated time for administration: 5 minutes
Reactions to Research Participation Questionnaire Revised (V5)
The RRPQR assess patient’s experience and acceptability related to participation in clinical 
research according to 5 factors: participation, personal benefit, emotional reactions, perceived 
drawbacks and global evaluation. It is a validated, 23-item and 5-poinit Likert scale.63
Estimated time for administration: 5 minutes
CareGiver Oncology Quality of Life questionnaire (Baseline [V1], V5, V6a,b…)
The CarGOQoL is a well-designed and well-validated 29-item, multidimensional,
self-administered questionnaire assessing QoL of cancer caregivers.
Estimated time for administration: 10 minutes
Semi-structured Interview guides – patient (after V5) and caregiver (after V5) 
The semi-structured interview guides – patient and caregivers will explore acceptability and 
subjective experiences from the patient’s and the caregiver’s perspective, respectively. They will 
explore the acceptability of the intervention through seven component constructs: affective 
attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness 
and self-efficacy (see theoretical framework of acceptability in section 12.1). To explore 
patient’s experience, we will focus on expectations before the treatment, subjective experience 
during the psilocybin effect and effects post-treatment.
Estimated time for administration: 30-60 minutes
Semi-structured Interview guides – hospice staff (convenient sample after each 5 patients 
completing study intervention)
The semi-structured interview guide – hospice staff explores the study intervention’s feasibility 
and acceptability from the hospice staff’s perspective. 
Estimated time for administration: 40 minutes
5.1.6
Recorded Content
All therapy sessions will be recorded for research and training purposes. Audio/video recording 
means may include Digital A/V recording devices and Zoom local recording for in-person and 
remote visits, respectively. The recordings are necessary for developing the experimental 
treatment and assessing adherence to the Treatment Manual. Any requests for use of video 
outside of research and training requests will result in participants (or their health care proxy if 
the participant is no longer able to consent) receiving information on the request. They will have 
control over any presentation of this material beyond viewing by researchers or regulatory 
agencies. 
The sponsor-investigator uses encrypted, secure technology to transfer and store recordings (e.g. 
DFCI’s secured DropBox), but there is always a risk of a security breach. The sponsor-
investigator is committed to taking preventative measures to avoid such an event. Only 
investigators/delegated study members will have access to this data. Recorded content will be 
erased from the recording device’s memory disk once transferred. No recording will be stored on 
the cloud. In the case of a security breach, the participant and/or their families will be notified, 

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and all efforts will be made to minimize the dissemination of recorded content. Recorded 
contents will be destroyed by the Sponsor-Investigator after sufficient storage.  
5.2.
Pre-Treatment Criteria
5.2.1. Cycle 1, Day 1

Vital signs in the normal range

Palliative Prognosis Score  50 %

No significant suicide risk

No delirium

No contra-indicated medication
5.2.2. Subsequent Cycles 
None
5.3.
Agent Administration
Administration – A capsule of psilocybin is administered orally with a full glass of water. 
Capsules should not be opened or chewed.
Dosing – This is a single dose study. Capsules contain 25 mg of pharmaceutical grade 
psilocybin, corresponding to the recommended dose in previous studies of healthy volunteers64,65 
and cancer patients8,9,27. 
Observation period – The participant will have adequate counselling and preparation ahead of 
dosing, and after ingesting the dose will be attended by two therapists, for the subsequent 8 
hours. The setting will minimize distraction and interruption, and the patient will be attended  
following the dose by the therapists trained in providing reassurance and a safe environment until 
the effects of the single dose have dissipated. Upon discharge from the study setting, the patient 
will be delivered to the care of a responsible individual who can observe the patient for the 
remainder of 24 hours after the dose was administered.
Protocol specific procedures –Blood pressure and heart rate will be measured at the following 
time-points after psilocybin administration (V3): 30, 60, 120, 180, 240, 300, and 360 min (10 
minutes). Although there have been no reports of their use in well reported clinical trials with 
oral psilocybin, medications should be available for the treatment of causal symptomatic 
hypertension, agitation, or severe  psychosis. Typically, these  supplies are two dosage units  of  
labetalol, nitroglycerin, lorazepam and/or diazepam, and risperidone or similar orally-
disintegrating antipsychotic.
Oral Agents – Participants will be advised to avoid consuming high fat meals for one hour before 
and after study drug consumption. Examples of foods to avoid include those high in butter, 
cream, oil, cheese, whole milk, mayonnaise, salad dressing, jam, syrup, honey, nuts, as well as 

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soft drinks, juices, sweets or desserts, pastas, breads, crackers, chips and meats. No other 
protocol specific procedures are necessary.
Caregiver Precautions – Study participants should not drive or operate heavy machinery for 24 
hours post study drug consumption. 
5.4.
General Concomitant Medication and Supportive Care Guidelines
Psilocybin is contraindicated in participants who are on monoamine oxidase inhibitors or who 
have a known sensitivity to the drug or its metabolites. It is contraindicated in medications that 
are known uridine diphosphate glucuronosyltransferase enzyme modulators. It is contraindicated 
in patients with schizophrenia or bipolar disease, or in those with first degree relatives with these 
disorders. The concurrent use of selective serotonin reuptake inhibitor/serotonin-norepinephrine 
reuptake inhibitors (SSRI/SNRI) medications is assumed to be contraindicated due to the 
potential to increase the risk of serotonin syndrome and/or to attenuate the binding of psilocin to 
the HT2A receptor.
Prior to enrollment participants will be screened per the clinical protocol for contraindicated 
psychologic conditions or interacting medications by a licensed physician on the study team.
Because there is a potential for interaction of psilocybin with other concomitantly administered 
drugs through the cytochrome P450 system, the study team will review the concurrent use of all 
other drugs, over-the-counter medications, or alternative therapies at every visit.  The PI should 
be alerted if the participant is taking any agent known to affect or with the potential to affect 
selected CYP450 isoenzymes. Appendix C presents guidelines for identifying 
medications/substances that could potentially interact with the study agent(s).
5.5.
Criteria for Taking a Participant Off Protocol Therapy
The planned duration of therapy is a 2 to 4 weeks, including 2 preparation sessions, 1 dosing 
session with a single intake of the study agent and 2 integration  sessions. Treatment will be 
halted in the setting of:
Inability to ingest study medication on the dosing day (V3)
Intercurrent illness that prevents administration of treatment
Unacceptable adverse event(s)

Participant demonstrates an inability or unwillingness to comply with the oral 
medication regimen, the psychotherapy support regimen and/or documentation 
requirements
Participant decides to withdraw from the protocol therapy

General or specific changes in the participant's condition render the participant 

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unacceptable for treatment in the judgment of the treating investigator
Participants will be removed from the protocol therapy when any of these criteria apply.  The 
reason for removal from protocol therapy, and the date the participant was removed, must be 
documented in the case report form (CRF). Alternative care options will be discussed with the 
participant.
When a participant is removed from protocol therapy and/or is off of the study, the participant’s 
status must be updated in OnCore in accordance with REGIST-OP-1.
5.6.
Duration of Follow Up
Participants will be followed for 6 months (24 weeks) after removal from protocol therapy or 
until death, whichever occurs first.  Participants removed from protocol therapy for unacceptable 
adverse event(s) will be followed until resolution or stabilization of the adverse event.
5.7.
Criteria for Taking a Participant Off Study
Participants will be removed from study when any of the following criteria apply:

Lost to follow-up

Withdrawal of consent for data submission

Death

Investigators discretion
The reason for taking a participant off study, and the date the participant was removed, must be 
documented in the case report form (CRF). In addition, the study team will ensure the 
participant’s status is updated in OnCore in accordance with REGIST-OP-1.
6. DOSING DELAYS/DOSE MODIFICATIONS
There will be no modifications to the dose of psilocybin given to study participants. 
Modifications of the number, length, content and day of preparation and integration sessions will 
be allowed after the first few patients, as finding the most feasible, safe and effective dose of 
psychotherapeutic support and refining the treatment manual are major objectives of this study. 
Decisions to modify the psychotherapeutic protocol will be made by the PI and the study 
psychiatrist. Changes and reasons for changes will be documented.  
7. ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
following list of reported and/or potential AEs (Section 7.1) and the characteristics of an 
observed AE (Section 7.2) will determine whether the event requires expedited reporting in 
addition to routine reporting. Because this study is being completed in patients with terminal 
illness, medical events or deaths due to the primary diagnosis (e.g. cancer) are expected. 

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The research team will not require expedited reporting to the DF/HCC IRB for primary 
diagnosis-related medical events or deaths (see section 7.4.4 below).
The principal investigator will be responsible for monitoring and reporting all adverse events to 
the DFCI IRB for this study, but in the event that the principal investigator is unavailable, the co-
investigators will assume this responsibility. The role of the responsible person is to 1) identify 
the concern, 2) develop the appropriate response to the concern with the use of consultants if 
necessary and 3) ensure proper reporting of concerns to the IRB. 
All potential adverse events will be reported to the PI. The PI in consultation with Co-
investigators will classify events according to level of severity. Details will be recorded on an 
adverse case report form as well as logged on a secure spreadsheet for reporting to the IRB. 
The adverse event case report form will include a description of all undesirable experiences, 
required interventions, and an assessment of the subject after the event if possible.  An estimate 
of the extent of injury, and prevention strategies will be reported. The principal investigator will 
classify the relationship of the study protocol to the event as follows:

Unrelated: The event is clearly related to factors such as the subject’s clinical state, not with 
the study protocol.

Unlikely: The event was most likely related to factors such as the subject’s clinical state, 
not with the study protocol.

Possible: The event follows a reasonable temporal sequence associated with participating in 
the study and/or is consistent with events related to responding to queries about stress/drug 
craving but is possibly related to factors such as the subject’s clinical state.

Probable: The event follows a reasonable temporal sequence associated with participating 
in the study and/or is consistent with events related to dosing of psilocybin in the study and 
cannot be reasonably explained by factors such as the subject’s clinical state. 

Definite: The adverse event is clearly related to the investigational agent/procedure – i.e. an 
event that follows a reasonable temporal sequence from administration of the study 
intervention, follows a known or expected response pattern to the suspected intervention, 
that is confirmed by improvement on stopping and reappearance of the event on repeated 
exposure and that could not be reasonably explained by the known characteristics of the 
subject’s clinical state.
The severity of an adverse event in both groups is defined as a qualitative assessment of the 
degree or intensity of an adverse event as determined by the principal investigator following 
CTCAE Version 5.0 severity ratings:

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). 

Grade 3 Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL. 

Grade 4 Life-threatening consequences; urgent intervention indicated. 

Grade 5 Death related to AE. 
A Semi-colon indicates ‘or’ within the description of the grade. A single dash (-) indicates a 

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Grade is not available. Not all Grades are appropriate for all AEs. Therefore, some AEs are 
listed with fewer than five options for Grade selection.
7.1.
Adverse Events and Potential Risks 
Previous studies in healthy volunteers and cancer participants (advanced and non-advanced 
cancer) have shown oral psilocybin to be well-tolerated in a controlled setting. No drug-related 
serious adverse events were reported. Overall, the most commonly reported adverse events 
associated with psilocybin administration are psychological  in  nature  and  include  transient 
anxiety,  negative  emotional  states  and  paranoid/delusional  thinking  during  psilocybin  
sessions.35,66,67 Such transient episodes of fear or anxiety respond well to reassurance and have 
not required pharmacological intervention. In previous clinical experience, acute psychological 
events were resolved by the end of the dosing day. Rates  of  prolonged  psychiatric  symptoms  
of  any  kind  following  psilocybin  exposure  in  healthy  study  participants  are  estimated  to  
be  0.08-0.09%.  
Cardiovascular  changes  including  increased  BP  and  heart  rate,  mild and transient nausea,  
and mild and transient headaches are also reported with psilocybin administration. 
These events are therefore examined further in this section in the population of patients with 
cancer who participated in recent psilocybin trials.
The Harbor-UCLA Study was a randomized, double-blind, placebo-controlled crossover design 
study (NCT00302744) to evaluate the efficacy of psilocybin in 12 adults (11 females) with 
advanced-stage cancer (various types) and reactive anxiety.68 The dosing sessions were spaced 
several weeks apart, and participants would receive either oral psilocybin (0.2 mg/kg) or oral 
placebo (niacin, 250 mg) in  a  randomized  order.  Assessments  included  monitoring  for  
temperature,  heart  rate  and  blood  pressure, and dosing sessions concluded with self-reported 
participant outcomes. The duration of follow-up was six months following the second dosing 
session. 
No serious adverse events were reported during the study, and no adverse psychological effects 
arose from treatment. Adverse events were collected during study administration and  solicited  
during  monthly  follow-up  phone  calls.  No  untoward  cardiovascular  sequelae  was  
observed, though treatment with psilocybin produced transient increases in blood pressure (BP) 
and heart rate as compared to placebo. In response to psilocybin, mean maximum systolic BP 
increased from 117 ± 4.3 mm Hg to 138.9 ± 6.4 mm Hg, mean maximal diastolic BP increased 
69.6 ± 2.7 mm Hg to 75.9 ± 3.4 mm Hg, and mean maximal heart rate increased from 70.4 ± 4.3 
beats per minute to 81.5 ± (5.8) beats per minute. No additional information on adverse event 
reporting was available.
The John Hopkins Study was a randomized, double-blind, crossover study (NCT00465595) to 
investigate the effects of  psilocybin  dose  (low  vs  high  dose)  on  a  variety  of  outcome  
measures  relevant  to  anxiety  or  depressive  disorders  exacerbated  by  cancer  diagnosis.8 
Participants  were  initially randomized to either the low dose oral psilocybin (0.014 mg/kg or 
0.042 mg/kg), meant to act as placebo, or high dose oral psilocybin (0.31 mg/kg or 0.43 mg/kg), 
followed by crossover approximately  five  weeks  later.  The  low  dose  was  permanently  

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adjusted  to  0.014  mg/kg  due  to concern that a 0.042 mg/kg dose might not serve effectively as 
an inactive placebo, and the high dose was similarly adjusted from 0.43 mg/kg to 0.31 mg/kg 
after two of the first three participants to receive the 0.43 mg/kg dose were discontinued from the 
study. Monitoring for adverse events occurred  during  dosing  days  up  to  six  hours  post-dose,  
and  participant  reported  outcomes  were  solicited for up to six months following the second 
dose. 
No serious adverse events were attributed to psilocybin. The most frequent adverse events 
occurring during psilocybin dosing sessions (both low dose and high dose) are shown in Table 
7.1-1.  With the exception of headache, all adverse events had resolved fully by the end of the 
sessions. The most  frequent adverse events were transient moderate increases in systolic and/or 
diastolic blood pressure  (DBP)  after  psilocybin,  psychological  discomfort,  anxiety,  and  
physical  discomfort.  Episodes of elevated systolic blood pressure (>160 mm Hg) occurred in 18 
of 53 (34%) high dose sessions, as compared to 17% (N = 9) of the low dose “placebo” sessions. 
Episodes of elevated diastolic blood pressure (>100 mm Hg) occurred in 7 of 53 (13%) high dose 
sessions, and 1 of 52 (2%)  of  the  low  dose  sessions.  One  participant experienced  a  transient 
peak  blood pressure (214/114 mm Hg) during  the  high  dose  session  that  met  severity  
criteria,  but  not  the  duration  (15 minutes) criteria for pharmacologic intervention, and 
therefore no intervention was delivered. 
Psychological discomfort was reported in 17 of 53 (32%) of high dose sessions and 6 of 52 
(12%) low dose sessions. Anxiety was reported in 14 of 53 (20%) of high dose sessions, and 8 of 
52 (15%) low dose sessions. Episodes of physical discomfort (any type) occurred in 21% of high 
dose sessions and 8% of low dose sessions. 
One instance of mild headache was reported during a high dose session. Toward the end of this 
study, the study team became interested in documenting the occurrence of delayed headache 
after psilocybin sessions. Of the 11 (of 53) participants queried, two (18%) reported moderate 
headache following their high dose sessions.
Table 7.1-1: Adverse events reported during dosing sessions
Spontaneously reported adverse events that occurred following psilocybin sessions that were 
judged to be possibly related to drug administration were rare, with four occurring following the 
low dose session  and  one  occurring  following  the  high  dose  session  (Table 7.1-2).  The  
reported  adverse  events judged to be possibly related to drug administration following lower-
dose sessions included instances of a feeling of fullness in the chest (n=1), anxiety (n=1), 
insomnia (n=1) and decreased appetite (n=1). One instance of leg pain occurred following a 

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higher-dose session. There were no cases of hallucinogen persisting perception disorder (HPPD) 
or prolonged psychosis.
Table 7.1-2: Adverse events reported after the psilocybin dosing session
The New York University Study was  a  randomized,  double-blind,  placebo-controlled  
crossover  study  (NCT00957359) to investigate the efficacy of a single psilocybin dosing 
session versus placebo (in conjunction with psychotherapy) to treat clinically significant anxiety 
or depression in adults who received a cancer diagnosis.9,28  Participants  were  initially  assigned  
to  receive  oral  psilocybin  (0.3mg/kg)  or  placebo  (niacin,  250  mg),  administered  during  an  
8-hour  treatment  session.  Crossover  to  the  other  arm  occurred  seven  weeks  after  the  first  
administration.  Adverse  events  were monitored throughout the trial, including during and after 
dosing sessions. Primary outcomes of potential improvement of participant anxiety and 
depression were measured through 26 weeks after the second dosing session.
The most common adverse events that occurred during the psilocybin dosing sessions (before 
and after crossover, N = 28) included elevated systolic (>160 mm Hg) and diastolic BP (>100 
mm Hg), headache and migraine, anxiety, and  nausea.  None  of  the  elevated  BP  episodes  
required  pharmacological intervention. One participant died as a result of cancer disease 
progression. Four subjects were withdrawn from the study due to disease progression and passed 
away shortly after withdrawal from the study. These serious adverse events were not attributed to 
psilocybin. Adverse  events  that  occurred  outside  the  dosing  sections  were  collected,  and  
causality  from  psilocybin was assessed (Table 7.1-3). Three of 11 events (27%) were 
determined to be possibly related to psilocybin administration.
Table 7.1-3: Adverse events not occurring during the psilocybin dosing sessions

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The University of California San Francisco study was single-arm, open-label, pilot study of 
psilocybin-assisted group therapy (NCT02950467). Participants were Gay-identified older long-
term AIDS survivor (OLTAS) men ≥ 50 years old, recruited from the community, who suffer 
from moderate-to-severede moralization (DemoralizationScale-II≥8). They receive 8-10 open-
label group therapy sessions over 8 weeks and one open label psilocybin individual  session (0.3 
mg/kg or 0.36 mg/kg po). Safety was evaluated with multiple measures. Every study visit 
included an adverse events assessment interview and the Columbia Suicidality Severity Rating 
Scale (C-SSRS) interval interview. Adverse events assessments during the medication visit 
included spontaneous participant self-report, events observed by clinicians, and symptoms
derived from the Challenging Experiences Questionnaire57 administered the next day. During 
psilocybin sessions, blood pressure and heart rate were assessed at regular intervals of
30 min for the first two hours, and then 60 min thereafter. At end-of-treatment, participant 
perceptions of benefits and harms from the intervention were assessed by a 7-point Likert scale 
(1= none at all; 7=extremely). The Schedule of Attitudes towards Hastened Death (SAHD) was 
administered at baseline, end-of-treatment and 3-month follow-up. The Montreal Cognitive 
Assessment (MoCA) was performed at enrollment and end-of-treatment. Because they were
added after Cohort 1 completed the study, only Cohorts 2 and 3 completed the Alcohol Use 
Disorder Identification Test (AUDIT) and Drug Use Disorders Identification Test (DUDIT) at 
baseline and at the 3-month follow-up with a ‘last 3 month’ recall period. 
Overall, zero serious adverse reactions and two unexpected adverse reactions to psilocybin were 
detected, and seven participants experienced self-limited, severe expected adverse reactions. 
Serious adverse events and adverse events are detailed in the following table. 
Table 7.1-4: Adverse events during the UCSF study

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7.2.
Adverse Events list for psilocybin 
Based on the studies presented in the previous section, the following adverse events might be 
expected after subjects are given the study agent.  
7.2.1. Psychological adverse events

Anxiety  

Negative  emotional  states  

Paranoid/delusional  thinking  
7.2.2. Physical adverse events

Increased  blood pressure  

Increased heart  rate  

Nausea 

Headaches 

Fatigue 

Insomnia

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7.3.
Adverse Event Characteristics

CTCAE term (AE description) and grade:  The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting.  All appropriate treatment areas should have access 
to a copy of the CTCAE version  5.0.  A copy of the CTCAE version  5.0 can be 
downloaded from the CTEP web site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.

For expedited reporting purposes only:  
-
AEs for the study agent that are listed above should be reported only if the adverse 
event varies in nature, intensity or frequency from the expected toxicity information 
which is provided.
-
Other AEs for the protocol that do not require expedited reporting are outlined in the 
next section (Expedited Adverse Event Reporting) under the sub-heading of Protocol-
Specific Expedited Adverse Event Reporting Exclusions.

Attribution of the AE:
-
Definite – The AE is clearly related to the study treatment.
-
Probable – The AE is likely related to the study treatment.
-
Possible – The AE may be related to the study treatment.
-
Unlikely – The AE is doubtfully related to the study treatment.
-
Unrelated – The AE is clearly NOT related to the study treatment.
7.4.
Adverse Event Reporting 
7.4.1. In the event of an unanticipated problem or life-threatening complications treating 
investigators must immediately notify the Principal Investigator.
7.4.2. Investigators must report to the Principal Investigator any adverse event (AE) that occurs 
after initial dose, during treatment, or within 30 days of last treatment on the local 
institutional SAE form (eCRF). 
7.4.3. DF/HCC Adverse Event Reporting Guidelines
Site investigators will report AEs to the sponsor per DF/HCC requirements, and the 
Dana-Farber Cancer Institute IRB per IRB policies. The table below indicates which 
events must be reported to the DF/HCC Sponsor Investigator, Dr. Beaussant.
DF/HCC Reportable Adverse Events(AEs) to sponsor-investigator
Attribution
Gr. 2 & 3 AE
Expected
Gr. 2 & 3 AE 
Unexpected
Gr. 4 AE Expected
Gr. 4 AE
Unexpected
Gr. 5 AE 
Expected or 
Unexpected
Unrelated
Unlikely
5 calendar days
5 calendar days
5 calendar days
5 calendar days*
24 hours*

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Possible
Probable
Definite
5 calendar days
5 calendar days
5 calendar days
5 calendar days*
24 hours*
* For participants enrolled and actively participating in the study or for AEs occurring within 30 days of the last 
intervention, events must be reported within 1 business day of learning of the event.
7.4.4. Protocol-Specific Adverse Event Reporting Exclusions
For this protocol only, the AEs/grades listed below do not require expedited reporting to 
the DFCI IRB.  However, they still must be reported through the routine reporting 
mechanism (i.e. case report form).
CTCAE SOC
Adverse 
Event
Grade
Prolongation of 
Hospice stay
Attribution
Comments
Nausea
1,2
Gastrointesti
nal disorders
Vomiting
1
Ataxia
1,2,3
Cognitive 
disturbanc
e
1,2,3
Depressed 
level of 
consciousn
ess
1,2,3
Dizziness
1,2,3
Headache
1,2
Lethargy
1,2
Nervous 
system 
disorders
Tremor
1,2,3
Agitation
1,2,3
Anxiety 
1,2,3,4
Confusion
1,2,3
Delirium
1,2,3
Delusions
1,2,3
Depression
1,2,3
Euphoria
1,2,3
Hallucinati
ons
1,2,3
Psychiatric 
disorders
Insomnia
1,2,3
Up to Day 1
Related
The primary effects 
of the psilocybin are 
psychological and can 
bring about a very 
broad range of 
changes in perception 
and mood during the 
hours the drug is 
active. At times, 
subjects may 
experience anxiety, 
panic, or paranoia. 
The majority of 
reactions from 
psilocybin change 
rapidly, are easily 
managed with proper 
guidance and resolve 
by the end of the 
dosing session (7-10 
hours). In many 
patients, they may be 
associated with the 
therapeutic effect of 
psilocybin-assisted 
therapy.
Therefore, such 
expected effects do 
not require expedited 

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Psychosis
1,2,3
Restlessnes
s
1,2,3
reporting to the 
Principal Investigator 
or the DFCI IRB as 
long as they follow 
the natural arch of the 
psilocybin effect.
Other AE or SAEs related 
to underlying terminal 
condition
1,2,3,4
,5
GIP
Unrelated
The context of this 
study – hospice – is 
defined by the 
potential for rapid 
clinical deterioration 
in enrolled patients. 
Should such 
deterioration occur 
and appear clearly 
related to the 
underlying terminal 
condition in the 
judgement of the 
investigators, they do 
not require expedited 
reporting to the 
Principal Investigator 
or the DFCI IRB
7.5.
Reporting to the Food and Drug Administration (FDA)
The Sponsor will be responsible for all communications with the FDA. The Sponsor will report 
to the FDA, regardless of the site of occurrence, any serious adverse event that meets the FDA’s 
criteria for expedited reporting following the reporting requirements and timelines set by the 
FDA.
7.6.
Reporting to Local Risk Management
Participating investigators will report to their local Risk Management office any participant 
safety reports, sentinel events or unanticipated problems that require reporting per institutional 
policy. 
7.7.
Routine Adverse Event Reporting
All Adverse Events must be reported in routine study data submissions to the Principal 
Investigator on the toxicity case report forms.  AEs reported through expedited processes 
(e.g., reported to the IRB, FDA, etc.) must also be reported in routine study data 
submissions.

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7.8.
Reporting to drug manufacturer
The sponsor will promptly report all adverse events related to the Investigational Drug to Usona 
as agreed per the contract and set forth below.
Format of Transfer
Data should be transferred in one of the following formats if possible:

CDISC ODM XML file (preferred)

Comma Separated Value file 
If the study’s data collection procedures do not enable export in one of these formats, the 
Investigator agrees to work with Usona to identify a mutually agreeable format in which required 
data can be transferred to Usona. 
Data Requirements
Category
Timing
Minimum data to be reported
Dosing 
Information 
End of Study
Dates and times of doses
Treatment received 
Dose received
Adverse Events 
(AEs)
End of Study 
AE Name
Discovery (spontaneous or solicited)
Start date
End date or ongoing
Severity
Relationship to study drug
Action taken
Resolution
Seriousness
Concomitant 
Medications
End of Study
Medication
Dose
Dose frequency
Start date
End date
Indication
Serious Adverse 
Events (SAEs)
Immediate 
(within 5 days of 
knowledge)
Full case report enabling completion of MedWatch 
Form 3500. Transmit to: usonasae@ 
usonainstitute.org; tel. +1 608-210-6005
Pregnancy
Immediate 
(within 5 days of 
knowledge) & 
follow-up through 
30-days post-
delivery or first 
well-child visit
Initial report
Gravidity
Parity
Estimated delivery date
Prenatal care (including initiation relevant to 
gestation)
Pregnancy complications and dates

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Medications used during pregnancy
Follow-up report: Delivery
Gravidity
Parity
Estimated delivery date
Pregnancy outcome
Date of delivery
Duration of labor
Type of delivery
Postpartum complications
Infant birth weight
Apgar scores (1 min, 5 min)
NICU admission
Complications of newborn during hospitalization
Date of hospital discharge or death
Birth defects noted at birth
Follow-up report: Well Child Visit
Summary of diagnostic tests
Complications
Updates on past findings/anomalies
A serious adverse event (SAE) is an adverse drug or biologic or device experience occurring 
during any study phase (i.e., screening, admission, treatment, or follow-up), and at any dose of 
the study drug, comparator or placebo, that results in one or more of the following criteria:

Results in death

Is life-threatening* 

Requires in-patient hospitalization (i.e., admission) or prolongation of existing 
hospitalization

Results in persistent or significant disability** or incapacity

Is a congenital abnormality or birth defect (in an offspring)

Is an important medical event that may not result in death, be life-threatening, or require 
or prolong hospitalization may be considered an SAE when, based upon appropriate 
medical judgment, the event may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the outcomes listed above.  Examples of important 
medical events include events requiring intensive treatment in an emergency department, 
or convulsions that do not require in-patient hospitalization, or the development of drug 
dependency or drug abuse.
* Life-threatening SAE: Any AE that places the subject, in the view of the investigator, at 
immediate risk of death from the reaction as it occurred; it does not include a reaction that, had it 
occurred in a more severe form, might have caused death.

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** Definition of disability: A substantial disruption of a person’s ability to conduct normal life 
functions. 
8. PHARMACEUTICAL INFORMATION OF PSILOCYBIN
A list of the adverse events and potential risks associated with the investigational agent 
administered in this study can be found in Sections 7.1 and 7.2.
8.1.
Psilocybin background
Psilocybin 3-[2-(dimethylamino) ethyl]-1H-indol-4-yl] dihydrogen phosphate is a natural 
product produced  by  numerous  species  of  Psilocybe mushrooms. The  phosphate  group  is  
enzymatically  cleaved in the body to produce psilocin, an agonist at a variety of serotonin 
receptors, the most important of which, for its behavioral effects, is the 5-HT2A receptor.1,2 
Psilocybin was first isolated from Psilocybe mushrooms in 1957, followed by de novo synthesis 
in 1958. It was marketed worldwide in  the  1960s  as  Indocybin™ for  experimental  and  
psychotherapeutic  purposes.  Although  it  was  well  tolerated  and  demonstrated  potentially  
useful  effects,  it  was  classified  as  a  controlled  substance in the U.S., placed in Schedule I in 
1970, and effectively removed from clinical use or scientific  study.  Psilocybin,  and  similar  
drugs  such  as  lysergic  acid  diethylamide  (LSD)  and  mescaline,  fall  into  a  
pharmacological  class  that  we  refer  to  in  this  application  as  “classic  psychedelics” to 
differentiate them from other psychoactive substances (ex. 3,4-methylenedioxy-
methamphetamine;  MDMA)  that  have  different  psychological/behavioral  effects  and  
different adverse effect profiles and risk/benefit ratios than psilocybin.  
Several  lines  of  evidence  suggested  that  serotonergic  hallucinogens,  such  as  psilocybin,  
have  clinical potential for inducing therapeutically-beneficial behavior change in a variety of 
psychiatric conditions and in individuals with psychological distress associated with a serious 
medical illness. 
8.2.
Importance of a Supportive Set and Setting Protocol
Due  to  the  psychoactive  nature  of  psilocybin,  the  safety  of  participants  in  clinical  trials  
can  be  enhanced by testing psilocybin within a “set and setting” protocol (Lyons & Carhart-
Harris, 2018).69 By addressing the set (the emotional/cognitive/behavioral state/mindset and 
expectations of study participants just prior to psilocybin exposure) and setting (the physical 
environment in which the exposure occurs) of the experience, the risk of the subject reporting an 
event which was distressing or  injuring  themselves  can  be  reduced.  This  approach  generally  
incorporates  three  components:  1) preparation, 2) drug session, and 3) post session meetings to 
integrate the classic hallucinogen experience. 
In the first phase, participants undergo pre-exposure preparation sessions designed to build 
rapport with the facilitators who would be present during the drug exposure session and to 
identify personal themes and struggles that might be especially likely to impact the session 
experience. In the second phase, the drug session itself is conducted by two facilitators who are 
present throughout the session. Sessions are typically conducted in a room designed to be quiet, 

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comfortable,  and  aesthetically  pleasing,  and  participants  are  encouraged  to  wear  eyeshades  
and  listen to a program of music through headphones during the drug exposure to aid them in 
focusing their attention inward. In the third phase, participants are engaged in a series of drug-
free interview meetings of variable frequency, sometimes over a period of several weeks, to 
discuss their session experience thoroughly with the goal of maximizing its therapeutic benefit.
 
8.3.
Description
Psilocybin is a tryptamine derivative. Its chemical name is [3-[2-(dimethylamino)ethyl]-1H-
indol-4- yl] dihydrogen phosphate. The molecular structure is the following: 
Figure 8.1-1: Molecular structure of psilocybin
Following  oral  administration  (0.224  mg/kg)  of  psilocybin,  average  blood  concentration  of  
the  active metabolite psilocin was calculated to be 8.2 ± 2.8 ng/mL after 105 ± 37 minutes, 
yielding an  estimated  dose-normalized  bioavailability  of  psilocybin to  be  52.7  ±  20% (N  = 
3).  Psilocin typically appears in plasma within 15 minutes after oral administration. Psilocin 
half-life following oral administration of psilocybin was found to be approximately 3 ± 1.1 hours 
and is detectable for up to  24  hours  after  administration.3,4  The  levels  of  psilocin  peaked  at  
approximately  80  minutes,  but  the  peak  psilocin  concentration  was  more  gradually  
attained  in  some  subjects  than  in  others,  suggesting  metabolism rates can vary between 
individuals.3 
Psilocin is metabolized to 4-hydroxyindole-3-acetic acid by deamination and demethylation via 
liver enzymes  such  as  monoamine  oxidase,  and  aldehyde  dehydrogenase (Figure  8.1-2).4  
Psilocin is also extensively glucuronidated by the UDP- glucuronosyltransferase  (UGT)  family  
of  enzymes,  with  the  highest  glucuronidation  activity  demonstrated by UGT1A10.70 The 
amount of psilocin glucuronide-excreted renally has been shown to exceed that of psilocin over a 
24-hr time period, and analysis of psilocin in urine over 24 hours after a single dose has shown 
that less than 4% of the overall clearance of psilocin occurs through renal excretion.71The 
pharmacokinetics  of  psilocybin (as  psilocin) are  linear over the dose range of 0.3–0.6 
mg/kg.3,71  
Figure 8.1-2: Metabolism of psilocybin

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8.4.
Form
For  use  in  Usona  sponsored  clinical  studies,  psilocybin  is  provided  as  25  mg  capsules  
(size  2,  hydroxypropyl methyl cellulose (HPMC), white)
8.5.
Storage and Stability
Psilocybin  capsules  are  packaged  individually  into  high-density  polyethylene  bottles (30 
cc). Bottles must be maintained at room temperature. 
Psilocybin presents as a white crystalline solid with a melting point of 220-228°C.  It  is  stable  
over  extended  periods  in  dark  storage  at  controlled  room  temperature.  Psilocybin is soluble 
in 20 parts boiling water or 120 parts boiling methanol. 
8.6.
Compatibility
Not applicable
8.7.
Handling
Psilocybin is a controlled substance listed in Schedule I. Capsules of psilocybin will be 
maintained in a locked, substantially constructed cabinet in a secured location, in accordance 
with Drug Enforcement Agency (DEA) regulations. In accordance with these requirements, the

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Schedule I license holder, and pre-defined authorized individuals trained by the license I holder, 
will be responsible for storing, dispensing, and administering the psilocybin. 
8.8.
Availability
Psilocybin will be provided by Usona Institute at no cost and the study sponsor (Yvan Beaussant, 
MD, MSc) will order the drug once all regulatory requirements are approved. The study will 
cover the shipping costs. 
8.9.
Preparation
Not applicable
8.10.
Administration
Capsules will be administered orally, with water, per the associated clinical protocol. Capsules 
should not be opened or chewed. 
In case a patient vomit after the drug is administered, assuming the pill was swallowed and 
entered the stomach (not just gagging on the capsule and spiting an intact capsule back out) – we 
will not administer another capsule because in theory they might have ingested some portion of 
the Investigational Product. We will record whether the capsule is present in the emesis and 
make note of that in patient’s records. This then would be an exception in dosing practices and 
likely will be an outlier.
8.11.
Ordering
Psilocybin is not commercially available. It will be obtained through Usona Institute, a  non-
profit  medical  research  organization  founded  in  2014.  Usona  Institute  conducts  and  
supports  biochemical  and  clinical  research  to  further  the  understanding  of  the  therapeutic  
effects  of  psilocybin  and  other  consciousness-expanding  medicines. Usona  has  developed 
psilocybin for oral administration (25 mg, single-dose) in conjunction with a supportive set and 
setting protocol for major depressive disorder (MDD). Additional information about Usona can 
be found at www.usonainstitute.org and in the Investigator Brochure.
The study drug will be shipped to and logged at Care Dimensions facility (Lincoln house). 
Authorized individuals will dispense the study drug after the order is transmitted from the study 
psychiatrist with name, date of birth and medical record number of the study participant. 
Dispensed drug will be obtained by the study team who will sign a log kept in the same cabinet 
the study drug is stored to ensure that all study drug is accounted for. 
8.12.
Accountability
The investigator, or a responsible party designated by the investigator, will maintain a careful 
record of the inventory and disposition of the study drug in a drug accountability record form 
along with any DEA required forms

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8.13.
Destruction and Return
Expired or unused supplies of psilocybin will be returned to Usona or destroyed according to 
controlled substance disposal and institutional guidelines. Return or destruction will be 
documented on the drug accountability record form and any DEA-required forms.
9. CONCOMITANT MEDICATIONS AND TAPERING INSTRUCTIONS
If the participant is being treated with psychiatric drugs at the time they are recruited into the 
study, they will discuss medication tapering with the study psychiatrist and the hospice 
physician. If needed, the drugs will then be tapered in an appropriate fashion to avoid withdrawal 
effects. They will be discontinued long enough before the first Experimental 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). 
The therapists will request information about any changes in medication just prior to all 
intervention sessions. The study psychiatrist will be responsible for reviewing and confirming all 
medications collected during the study. 
All medications, over the counter (OTC) and prescription will be collected from screening 
through V5. Throughout the protocol all medications used to treat AEs will be collected and all 
changes including discontinuations or additions to psychiatric medications will be collected. 
Medications will be recorded on the concomitant medications CRF.
In general, any MAOi will require a washout of at least 14 days or five half-lives of the 
medication or active metabolite (whichever is greater) plus one week for symptom stabilization. 
The Medication Tapering Table includes phenelzine, an example MAOi, (half-life of 11.6 hours) 
with a minimum of 14-day washout as requested. However, this table is not exhaustive. The 
washout time for any drug not listed on the table will be at least 5 times the half-life of the drug 
or active metabolite, plus 1 week for symptom stabilization.
Participants must be willing to refrain from taking any contra-indicated psychiatric medications 
during the active portion of the study. 
As we expect individuals on hospice to be receiving medications to control symptoms such as 
pain, nausea and anxiety, all efforts will be made to not disrupt a patient’s medication regimen 
unless the medication is contraindicated or carries a risk of interfering with psilocybin. 
Medications, such as opioids, may be given to patients during the trial to control pain, with 
efforts being made to not administer medications during the peak effect of psilocybin. 

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The PI may prescribe a designated rescue medication in the event of symptoms that require it 
during or after the Experimental Session (e.g. insomnia or severe anxiety that does not respond 
to other non-pharmacologic management outlined in the treatment manual). Rescue medications 
may be a benzodiazepine, zolpidem, or other anxiolytic or sedative according to the physician's 
clinical judgment. SSRIs, SNRIs, and MAOIs should not be used as rescue medications.
10. RISKS AND MITIGATION STRATEGY IN RESPONSE TO THE SARS-COV2 
PANDEMIC
Care Dimensions has taken the following steps to ensure the safe delivery of care: 

Additional mandatory staff education on infection prevention procedures, the COVID-19 
virus, and Care Dimensions precautions and procedures, so all staff have the latest 
information.
 

Employees and volunteers are required to stay home when feeling sick. They must be 
fever free for 24 hours before returning to work.
 

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
Employees and volunteers are being strongly discouraged from travelling internationally. 
Those returning from a CDC Level 3-defined country or certain US communities with 
widespread ongoing disease and travel restrictions may not return to work or see patients 
until 14 days after their return.
 

Employees and volunteers who have had prolonged close contact to someone with 
confirmed or presumed diagnosis with COVID-19 or who has traveled to the countries or 
communities listed above, must report this to their manager to assess whether they need 
to self-quarantine for 14 days.
 

Employees are not permitted to attend any conferences and have been instructed to avoid 
large public gatherings.
 

Patient visits in most facilities have been reduced to nurses, social workers, chaplains, 
and hospice aides to comply with DPH guidelines.
 

Working with each hospital and nursing facility to comply with their individual 
regulations and screening of our staff.
 

Visitors to the hospice houses (in particular the Care Dimensions Hospice House in 
Lincoln where V3 of this study occurs) have been restricted to immediate family 
members (as defined by the patient) only, with a maximum of 2 visitors at at time and 6 
per patient, per day. Visitors are screened upon entrance for temperature, symptoms and 
potential COVID-19 exposure to assess need for further precautions, and must wear a 
mask at all times while in the hospice house. Common areas of the houses are closed and 
visitors must stay in patient rooms. 
 

Cleaning services at our offices and hospice houses include enhanced disinfection of all 
high-touch surfaces such as doorknobs, handles, counters and railings and common 
equipment.
 

All in-person support groups, trainings and meetings with non-staff members at our 
facilities have been suspended. Some support groups have started to meet online.
 

Routine work-related meetings are being held virtually with video and teleconferencing 
and staff are prohibited from working at more than one Care Dimensions location.
 

Care Dimensions equips clinical staff with a supply of hand sanitizer, anti-bacterial wipes 
and personal protective equipment (PPE) such as masks, gowns and goggles. 
 

Care Dimensions has a comprehensive Emergency Operations Plan, which has been 
activated and will be amended as this crisis response progresses.
In order to mitigate the risk of SARS-CoV-2 virus transmission during the study, the Principal 
Investigator, Study Team Members, and Study Subjects will adhere to Care Dimensions  

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guidelines. All study activities that don’t necessitate in-person interaction with patients, families 
and/or staff, or within the study team, will be conducted remotely. 

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11. STUDY CALENDAR
 

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12. DATA REPORTING / REGULATORY REQUIREMENTS
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 7.0 
(Adverse Events: List and Reporting Requirements).
12.1.
Data Reporting
12.1.1. Method
The DF/HCC Office of Data Quality (ODQ) will collect, manage, and perform quality checks on 
the data for this study.
12.1.2. Responsibility for Data Submission
Responsibility for Data Submission: Investigative sites are responsible for submitting data and/or 
data forms to the Office of Data Quality (ODQ) in accordance with DF/HCC policies.
12.2.
Data Safety Monitoring
The DF/HCC Data and Safety Monitoring Committee (DSMC) will review and monitor toxicity 
and accrual data from this study. The committee is composed of medical oncologists, research 
nurses, pharmacists and biostatisticians with direct experience in cancer clinical research.  
Information that raises any questions about participant safety will be addressed with the Sponsor-
Investigator and study team.
The DSMC generally reviews each protocol up to four times a year with the frequency 
determined by the outcome of previous reviews. Information to be provided to the committee 
may include: up-to-date participant accrual; current dose level information; DLT information; all 
grade 2 or higher unexpected adverse events that have been reported across all sites; summary of 
all deaths occurring within 30 days of intervention for Phase I or II protocols; for gene therapy 
protocols, summary of all deaths while being treated and during active follow-up; any response 
information; audit results, and a summary provided by the study team. Other information (e.g. 
scans, laboratory values) will be provided upon request.
13. STATISTICAL CONSIDERATIONS
13.1.
Primary outcome variables
This study is an open label, single center, concurrent mixed-methods phase 2 trial. The primary 
objective is to pilot test a novel protocol of psilocybin-assisted therapy in patients receiving 
hospice care. Primary outcomes will relate to the following features of feasibility: 
•
Enrollment: number screened per month; number enrolled per month; average time delay 
from screening to enrollment

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•
Retention: number of sessions completed; retention rates for study measures; reasons for 
dropouts
•
Completion of assessment: proportion of planned assessments that are completed; duration 
of assessment visits; reasons for dropouts
•
Acceptability: acceptability ratings; qualitative assessments; reasons for dropouts
Benchmark for feasibility: treatment and week 1 assessments will be successfully completed in 
at least 60% of recruited subjects.
Benchmark for acceptability:  80% of subjects who completed Week 1 assessment will 
evaluate favorably (agree or strongly agree) acceptability on the global evaluation factors of the 
RRPQ (See section 5.1)
To guide our evaluation of acceptability in the proposed project, we will use seven component 
constructs as defined in the following figure: affective attitude, burden, ethicality, intervention 
coherence, opportunity costs, perceived effectiveness and self-efficacy.72
13.2.
Secondary outcome variables
13.2.1. Safety outcomes: 
•
Changes in vital signs: During psilocybin session, monitoring of heart rate, blood pressure, 
respiratory frequency and oxygen saturation. 
•
Adverse events (AEs) and serious adverse events (SAEs): Longitudinal follow-up and 
analysis of the relationship with psilocybin-assisted psychotherapy (see section 7).
•
Suicidal risk: suicidal ideations or plans will be assessed via the C-SSRS at each visit (see 
section 5.1)
•
Delirium: signs of delirium will be assessed through the CAM (see section 5.1) 
13.2.2. Efficacy outcomes 
•
Global quality of life: FACIT-Pal 14
•
Physical domain: PIS 

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•
Psychological domain: HADS A and D; LAP-R; CEQ 
•
Social domain: SIS
•
Spiritual domain: FACIT-sp; DS- II; SAHD; MEQ-30
•
Caregiver quality of life and psychological distress: CarGOQoL; HADS A and D
13.3.
Sample size and statistical plan 
13.3.1. Sample size justification
Patients with a PPS score of 50% and above have a median survival of 43 days or greater.73 We 
anticipate that we will need to treat at least 10 patients for feasibility data to be relevant. To 
account for patients who are unable to complete the intervention because of clinical decline, we 
plan to recruit 15 patients. 
Assuming that treatment and week 1 assessment will be completed on 10-15 patients, the 90% 
exact binomial confidence intervals for the feasibility rate will be between (30.3%-85.0%) – for 
10 patients - and (36.0%-81.0%) – for 15 patients.
Assuming that between 6 (out of 10) and 9 (out of 15) patients will be able to assess the 
acceptability, the 90% exact binomial confidence intervals for the acceptability rate will be 
between (41.8% - 99.1%) – for 10 treated patients, out of which 60% deem the procedure 
“feasible” -  and (57.1% - 99.4%) – for 15 treated patients, out of which 60% deem the procedure 
“feasible”.
We will use the treatment effect size calculated for this study to inform the sample size of the 
upcoming corresponding confirmatory trial.
Accrual targets are as follow: 
Accrual Targets
Sex/Gender
Ethnic Category
Females
Males
Total
Hispanic or Latino
2
+
1
=
3
Not Hispanic or Latino
6
+
6
=
12
Ethnic Category: Total of all subjects
8 (A1)
+
7 (B1)
=
15 (C1)
Racial Category
American Indian or Alaskan Native
0
+
0
=
0
Asian
1
+
1
=
2
Black or African American
2
+
1
=
2
Native Hawaiian or other Pacific 
Islander
0
+
0
=
0
White
5
+
5
=
10

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Racial Category: Total of all subjects
8 (A2)
+
7 (B2)
=
15 (C2)
(A1 = A2)
(B1 = B2)
(C1 = C2)
13.3.2. Safety analysis 
The Safety Population will consist of all enrolled participants who receive study treatment. This 
population will be used for all summaries of participant accountability, demographic and baseline 
data, and safety information, including AE incidence. 
The Full Analysis Set (FAS) will consist of all participants who receive the dose of psilocybin and 
will be used for all summaries of efficacy. 
The Per Protocol (PP) population will consist of all participants in the FAS who do not have a major 
protocol deviation which is defined as a deviation which may significantly affect efficacy for that 
participant. Major protocol deviations will be reviewed and determined prior to database lock.
13.3.3. Efficacy analysis 
Since this is a single treatment open-label study, no statistical testing will be performed. We will use 
descriptive statistics and thematic coding to analyze quantitative and qualitative data 
respectively, and joint display for the integration of the two. 
Qualitative analysis will deploy thematically coding of interview transcripts using content 
analysis, an inductive and deductive approach. At least two investigators with experience in 
qualitative analysis will independently code the first four interviews. They will compare their 
coding, refine common theme, identify new themes, and iteratively refine the codebook. 
Discrepancies will be resolved through discussion with other investigators until consensus is 
reached. We will use Dedoose qualitative analysis software to support content analysis.
The FAS and PP populations will be used for each secondary efficacy endpoint (change in respective 
scores from baseline (V1) to Week 1 (V5), Week 3 (V6a) and subsequent monthly visits until death 
or Week 24), if the two sets are not identical. For each of the secondary endpoints, measuring change 
from Baseline, a repeated measures analysis will be performed. Comparisons with baseline will be 
performed at the 0.05 testing level. Secondary endpoints that are dichotomous variables (for 
example, proportion of participants who are responders, remitters and sustained remitters) will be 
summarized as frequencies. Scores for all efficacy endpoints will be summarized over time using 
descriptive statistics for all visits during the observation period.
14. PUBLICATION PLAN
The results will be made public within 24 months of reaching the end of the study. The end of 
the study is the time point at which the last data items are to be reported, or after the outcome 
data are sufficiently mature for analysis, as defined in the section on Sample Size, Accrual Rate 
and Study Duration. If a report is planned to be published in a peer-reviewed journal, then that 
initial release may be an abstract that meets the requirements of the International Committee of 

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Medical Journal Editors. A full report of the outcomes should be made public no later than three 
(3) years after the end of the study. 

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70. Manevski N, Kurkela M, Höglund C, et al. Glucuronidation of psilocin and 4-hydroxyindole 
by the human UDP-glucuronosyltransferases. Drug Metab. Dispos. 2010;38(3):386–395. 
71. Hasler F, Bourquin D, Brenneisen R, Vollenweider FX. Renal excretion profiles of psilocin 
following oral administration of psilocybin: a controlled study in man. Journal of 
Pharmaceutical and Biomedical Analysis. 2002;30(2):331–339. 
72. Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview 
of reviews and development of a theoretical framework. BMC Health Services Research. 
2017;17(1):88. 
73. Harrold J, Rickerson E, Carroll JT, et al. Is the palliative performance scale a useful predictor 
of mortality in a heterogeneous hospice population? J Palliat Med. 2005;8(3):503–509. 

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APPENDIX A
STUDY MEASUREMENT SCALES 
A1 – Patient demographic data
1.
How old are you? _________ years old
2.
What is your current gender identity?
Male
Female
Transgender Male/Trans Man/ Female-to-Male
Transgender Female/Trans Woman/Male-to-Female
Genderqueer, neither exclusively male nor female
Other (please specify): _____________
3.
Which of the following most closely describes your race?
White
African American or Black
Hispanic or Latino
Asian or Asian American
Native American or Alaska Native
More than one race
Other (please specify): __________
Prefer not to answer
4.
Which of the following most closely describes your current relationship status?
Single, never married
Living with someone as if married/long-term partner
Married
Divorced/Separated
Widowed/Loss of a long-term partner
Other (please specify): ________
5.
What is your highest level of education?
11th grade or less
High school graduate or GED
2 years of college/associate degree/technical school
College graduate (BS or BA)
Masters degree
Doctorate/Medical degree/Law degree

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A2 – Family caregiver demographic data 
1.
How old are you? _________ years old
2.
What is your current gender identity?
Male
Female
Transgender Male/Trans Man/ Female-to-Male
Transgender Female/Trans Woman/Male-to-Female
Genderqueer, neither exclusively male nor female
Other (please specify): _____________
3.
Which of the following most closely describes your race?
White
African American or Black
Hispanic or Latino
Asian or Asian American
Native American or Alaska Native
More than one race
Other (please specify): __________
Prefer not to answer
4.
Which of the following most closely describes your current relationship status?
Single, never married
Living with someone as if married/long-term partner
Married
Divorced/Separated
Widowed/Loss of a long-term partner
Other (please specify): ________
5.
What is your highest level of education?
11th grade or less
High school graduate or GED
2 years of college/associate degree/technical school
College graduate (BS or BA)

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Masters degree
Doctorate/Medical degree/Law degree
6.
Which of the following were you doing last week with regards to your current job?
Working full-time
Working part-time
Not currently working but going to school
Retired
On layoff or unemployed
Not currently working for health reasons
Not currently working to take care of house, family, or the care recipient
Other (please specify): __________________________
7.
How long have you been the caregiver of your loved one?
_____years (mark “0” if less than a year)
_____ months
8.
What is your relationship to the care recipient (patient)?
I am a spouse or partner of care recipient
I am a child of care recipient
I am a sibling of care recipient
I am a parent of care recipient
I am a friend of care recipient
Other relationship (please specify) _________________
9.
In an average week, how many hours do you provide care or assistance to the care recipient?
Up to 8 hours per week
9-19 hours
20-39
40 or more
Don’t know/not sure
 

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A3 – Palliative Performance Scale

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A4 – Demoralization Scale – II (DS-II)
DS-II
For each statement below, please indicate how much (or how strongly) you have felt
this way over the last two weeks by circling the corresponding number.
1. There is little value in what I can offer others.
0
1
2
2. My life seems to be pointless.
0
1
2
3. My role in life has been lost.
0
1
2
4. I no longer feel emotionally in control.
0
1
2
5. No one can help me.
0
1
2
6. I feel that I cannot help myself.
0
1
2
7. I feel hopeless.
0
1
2
8. I feel irritable.
0
1
2
9. I do not cope well with life.
0
1
2
10. I have a lot of regret about my life.
0
1
2
11. I tend to feel hurt easily.
0
1
2
12. I feel distressed about what is happening to me.
0
1
2
13. I am not a worthwhile person.
0
1
2
14. I would rather not be alive.
0
1
2
15. I feel quite isolated or alone.
0
1
2
16. I feel trapped by what is happening to me.
0
1
2
Never
Sometimes
Often

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A5 – Hospital Anxiety and Depression Scale 

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A6 – Functional Assessment of Chronic Illness Therapy - Palliative Care 14 
Below is a list of statements that other people with your illness have said are important. Please circle 
or mark one number per line to indicate your response as it applies to the past 7 days.
Not at
all
A little 
bit
Some-
what
Quite
a bit
Very 
much
GP1
I have a lack of energy ................................ .........................
0
1
2
3
4
GP2
I have nausea................................ ................................ .......
0
1
2
3
4
GP4
I have pain ................................ ................................ ...........
0
1
2
3
4
GE6
I worry that my condition will get worse.............................
0
1
2
3
4
GF3
I am able to enjoy life................................ ...........................
0
1
2
3
4
GF5
I am sleeping well ................................ ................................
0
1
2
3
4
GF7
I am content with the quality of my life right now..............
0
1
2
3
4
GS2
I get emotional support from my family ..............................
0
1
2
3
4
Sp21
I feel hopeful ................................ ................................ .......
0
1
2
3
4
GE1
I feel sad ................................ ................................ ..............
0
1
2
3
4
Pal4
I feel like a burden to my family................................ .........
0
1
2
3
4
Pal5
I am constipated ................................ ................................ ..
0
1
2
3
4
Pal14
I am able to openly discuss my concerns with the people 
closest to me................................ ................................ ........
0
1
2
3
4
B1
I have been short of breath ................................ ..................
0
1
2
3
4

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A8 – PROMIS Pain Interference Scale 

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A9 – Life Attitude Profile – revised, Death acceptance subscale 
Life attitude profile revised (LAP-R) – Death Anxiety
SA
Strongly 
Agree
A
Agree
MA
Moderately 
Agree
U 
Undecided
MD
Moderately 
Disagree
D
Disagree
SD
Strongly 
Disagree
1.
I think I am generally much less concerned about 
death than those around me.  
SA A MA U MD D SD
2.
Death makes little difference to me one way or 
another.
SA A MA U MD D SD
3.
Even though death awaits me, I am not concerned 
about it.
SA A MA U MD D SD
4.
I would neither fear death nor welcome it.
SA A MA U MD D SD
5.
Since death is a natural aspect of life, there is no 
sense worrying about it.
SA A MA U MD D SD
6.
Some people are very frightened of death but I am 
not.
SA A MA U MD D SD
7.
The thought of death seldom enters my mind.
SA A MA U MD D SD
8.
I accept death as another life experience.
SA A MA U MD D SD

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A10 – Social Isolation Scale-6a 

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A11 – Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 
Please circle or mark one number per line to indicate your response as it applies to the past 7
days.
ADDITIONAL CONCERNS
Not at
all
A little
bit
Some-
what
Quite
a bit
Very
much
Sp1
I feel peaceful......................................................................
0
1
2
3
4
Sp2
I have a reason for living.....................................................
0
1
2
3
4
Sp3
My life has been productive................................................
0
1
2
3
4
Sp4
I have trouble feeling peace of mind...................................
0
1
2
3
4
Sp5
I feel a sense of purpose in my life .....................................
0
1
2
3
4
Sp6
I am able to reach down deep into myself for comfort .......
0
1
2
3
4
Sp7
I feel a sense of harmony within myself .............................
0
1
2
3
4
Sp8
My life lacks meaning and purpose.....................................
0
1
2
3
4
Sp9
I find comfort in my faith or spiritual beliefs......................
0
1
2
3
4
Sp10
I find strength in my faith or spiritual beliefs .....................
0
1
2
3
4
Sp11
My illness has strengthened my faith or spiritual beliefs....
0
1
2
3
4
Sp12
I know that whatever happens with my illness, things
will be okay.........................................................................
0
1
2
3
4

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A12 – Mystical Experience Questionnaire 
instructions: looking back on the entirety of your psychedelic session, please rate the degree
to which at any time during that session you experienced the following phenomena. Answer each
question according to your feelings, thoughts, and experiences at the time of the psychedelic
session. In making each of your ratings, use the following scale: 0 none/not at all; 1 so slight
cannot decide; 2 slight; 3 moderate; 4 strong (equivalent in degree to any other strong
experience); 5 extreme (more than any other time in my life and stronger than 4). Feel free to
use ‘half-point in-between scores’ if these are applicable.
0
1
2
3
4
5
1
Loss of your usual sense of time. (T)
2
Experience of amazement. (P)
3
Sense that the experience cannot be described adequately in words. (I)
4
Gain of insightful knowledge experienced at an intuitive level
5
Feeling that you experienced eternity or infinity.
6
Experience of oneness or unity with the objects
and/or persons perceived in your surroundings.
7
Loss of your usual sense of space. (T)
8
Feelings of tenderness and gentleness. (P)
9
Certainty of encounter with ultimate reality (in the sense of being able to
‘know’ and ‘see’ what is really real at some point during your experience).
10
Feeling that you could not do justice to
your experience by describing it in words. (I)
11
Loss of your usual sense of where you were. (T)
12
Feelings of peace and tranquillity. (P)
13
Sense of being ‘outside of’ time, beyond past and future. (T)
14
Freedom from the limitations of your personal self and feeling of
unity or bond with what was felt to be greater than your personal self.
15
Sense of being at a spiritual height.
16
Experience of pure being and pure awareness
(beyond the world of sense impressions).
17
Experience of ecstasy. (P)
18
Experience of the insight that “all is One”.
19
Being in a realm with no space boundaries. (T)
20
Experience of oneness in relation to an “inner world” within.
21
Sense of reverence.
22
Experience of timelessness. (T)
23
You are convinced now, as you look back on your experience, that in it you
encountered ultimate reality (that you ‘knew’ and ‘saw’ what was really real).
24
Feeling that you experienced something profoundly sacred and holy.
25
Awareness of the life or living presence in all things.
26
Experience of the fusion of your personal self into a larger whole.
27
Sense of awe or awesomeness. (P)
28
Experience of unity with ultimate reality.
29
Feeling that it would be difficult to communicate your own
experience to others who have not had similar experiences. (I)
30
Feelings of joy. (P)
scores/%’s: transcendence (T) =
/30 =
%; positive mood (P) =
/30 =
%
ineffability (I) =
/15 =
%; mystical =
/75 =
%; total score =
/150 =
%.

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A13 – Challenging Experience Questionnaire 

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A14 – Schedule of Attitudes toward Hastened Death

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A15 – Columbia-Suicide Severity Rating Scale 
Screen Version
SUICIDE IDEATION DEFINITIONS AND PROMPTS
Past
month
Ask questions that are bolded and underlined.
YES
NO
Ask Questions 1 and 2
1) Wish to be Dead:
Person endorses thoughts about a wish to be dead or not alive anymore, or wish to fall asleep
and not wake up.
Have you wished you were dead or wished you could go to sleep and not wake up?
2) Suicidal Thoughts:
General non-specific thoughts of wanting to end one’s life/commit suicide, “I’ve thought about
killing myself” without general thoughts of ways to kill oneself/associated methods, intent, or
plan.
Have you actually had any thoughts of killing yourself?
If YES to 2, ask questions 3, 4, 5, and 6. If NO to 2, go directly to question 6.
3) Suicidal Thoughts with Method (without Specific Plan or Intent to Act):
Person endorses thoughts of suicide and has thought of a least one method during the
assessment period. This is different than a specific plan with time, place or method details
worked out. “I thought about taking an overdose but I never made a specific plan as to when
where or how I would actually do it….and I would never go through with it.”
Have you been thinking about how you might kill yourself?
4) Suicidal Intent (without Specific Plan):
Active suicidal thoughts of killing oneself and patient reports having some intent to act on such
thoughts, as opposed to “I have the thoughts but I definitely will not do anything about them.”
Have you had these thoughts and had some intention of acting on them?
5) Suicide Intent with Specific Plan:
Thoughts of killing oneself with details of plan fully or partially worked out and person has
some intent to carry it out.
Have you started to work out or worked out the details of how to kill yourself? Do
you intend to carry out this plan?
6) Suicide Behavior Question:
Have you ever done anything, started to do anything, or prepared to do anything to
end your life?
Examples: Collected pills, obtained a gun, gave away valuables, wrote a will or suicide note,
took out pills but didn’t swallow any, held a gun but changed your mind or it was grabbed from
your hand, went to the roof but didn’t jump; or actually took pills, tried to shoot yourself, cut
yourself, tried to hang yourself, etc.
If YES, ask: How long ago did you do any of these?
Over a year ago?
Between three months and a year ago?
Within the last three months?

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A16 – Confusion Assessment Method 
Acute Onset 
1.
Is there evidence of an acute change in mental status from the patient’s baseline? 
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Inattention
(The questions listed under this topic are repeated for each topic where applicable.) 
2A. 
Did the patient have difficulty focusing attention (for example, being easily distractible or having difficulty
keeping track of what was being said)? 
  Not present at any time during interview
  Present at some time during interview, but in mild form
  Present at some time during interview, in marked form 
  Uncertain
2B. 
(If present or abnormal) Did this behavior fluctuate during the interview (that is, tend to come and go or
increase and decrease in severity)?
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
2C. 
(If present or abnormal) Please describe this behavior. 
Disorganized Thinking 
3. 
Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear 
or illogical flow of ideas, or unpredictable, switching from subject to subject?
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Altered Level of Consciousness 
4. 
Overall, how would you rate this patient’s level of consciousness?
  Alert (normal) 
  Vigilant (hyperalert, overly sensitive to environmental stimuli, startled very easily) 
  Lethargic (drowsy, easily aroused) 
Stupor (difficult to arouse) 
  Coma (unarousable) 
  Uncertain
Disorientation 
5. 
Was the patient disoriented at any time during the interview, such as thinking that he or she was somewhere 
other than the hospital, using the wrong bed, or misjudging the time of day? 
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Memory Impairment 
6. 
Did the patient demonstrate any memory problems during the interview, such as inability to remember 
events in the hospital or difficulty remembering instructions? 
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Perceptual Disturbances
7. 
Did the patient have any evidence of perceptual disturbances, such as hallucinations, illusions, or
misinterpretations (for example, thinking something was moving when it was not)? 
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Psychomotor Agitation 
8A. 
At any time during the interview, did the patient have an unusually increased level of motor activity, such as
restlessness, picking at bedclothes, tapping fingers, or making frequent, sudden changes in position?
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Psychomotor Retardation 
8B. 
At any time during the interview, did the patient have an unusually decreased level of motor activity, such as 
sluggishness, staring into space, staying in one position for a long time, or moving very slowly?
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Altered Sleep-Wake Cycle 
9. 
Did the patient have evidence of disturbance of the sleep-wake cycle, such as excessive daytime sleepiness 
with insomnia at night?
 YES
 NO
 UNCERTAIN
 NOT APPLICABLE
Scoring:
For a diagnosis of delirium by CAM, the patient must display: 
1. 
Presence of acute onset and fluctuating discourse
AND 
2. 
Inattention 
AND EITHER 
3. 
Disorganized thinking 
OR 
4. 
Altered level of consciousness 

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A17 – Reactions to Research Participation Questionnaire Revised 
This questionnaire asks for your opinions about what it was like for you to participate in
this study. Your responses will be used to help us understand more about what it is like to 
be a research participant.
I.
From the list below, please rank the top three reasons why you decided to participate 
(1= most important 2= second most important 3= third most important).
____
I was curious
____
To help others
____
To help myself
____
I don’t know
____   Thought it might
improve my access to
health care 
____
Felt I had to
____
For the money
____
I didn’t want to
say no
      ____    Other (Please explain _______________________ 
II. The following questions deal with your reactions to participating in this study. Please 
circle the number that best describes your response.
Strongly
disagree 
(No) 
Disagree 
Neutral 
(Maybe) 
Agree 
Strongly agree 
(Yes) 
1. I gained something positive 
from participating.
1 
2 
3 
4 
5 
2. Knowing what I know now, I
would participate in this
study if given the
opportunity. 
1 
2 
3 
4 
5 
3. The research raised
emotional issues for me that I 
had not expected.
1 
2 
3 
4 
5 
4.
I gained insight about my 
experiences through research
participation.
1 
2 
3 
4 
5 
5. The research made me think 
about things I didn’t want to
think about.
1 
2 
3 
4 
5 
6. I found the questions too
personal. 
1 
2 
3 
4 
5 
7. I found participating in this
study personally meaningful.
1 
2 
3 
4 
5 
8. I believe this study’s results
will be useful to others.
1 
2 
3 
4 
5 
9. I trust that my replies will be 
kept private.
1 
2 
3 
4 
5 

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Strongly
disagree 
(No) 
Disagree 
Neutral 
(Maybe) 
Agree 
Strongly agree 
(Yes) 
10. I experienced intense
emotions during the research
session and/or parts of the 
study. 
1 
2 
3 
4 
5 
11. I think this research is for a 
good cause.
1 
2 
3 
4 
5 
12. I was treated with respect
and dignity. 
1 
2 
3 
4 
5 
13. I found participating
beneficial to me.
1 
2 
3 
4 
5 
14. I was glad to be asked to
participate.
1 
2 
3 
4 
5 
15. I like the idea that I 
contributed to science.
1 
2 
3 
4 
5 
16. I was emotional during the
research session.
1 
2 
3 
4 
5 
17. I felt I could stop
participating at any time
1 
2 
3 
4 
5 
18. I found participating boring. 
1 
2 
3 
4 
5 
19. The study procedures took
too long.
1 
2 
3 
4 
5 
20. Participating in this study
was inconvenient for me.
1 
2 
3 
4 
5 
21. Participation was a choice I
freely made. 
1 
2 
3 
4 
5 
22. Had I known in advance
what participating would be
like I still would have agreed
to participate.
1 
2 
3 
4 
5 
23. I understood the consent
form. 
1 
2 
3 
4 
5 

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A18 – CareGiver Oncology Quality of Life questionnaire 
Answer each question by checking the case that comes closest to what you thought or felt during the last four weeks.
Someof thequestionsconcern your privatelife. Thesequestionsarenecessary to evaluateevery aspect of your quality of
life. However, if you do not know how to respond to aquestion or if a question does not concern you, skip to the next
question.
During the last four weeks, in connection with the person
you help, have you …
Never
Not at all
Rarely
A little
Sometimes
Moderately
Often
A lot
Always
Enormously
1
Been worried, anxious?
2
Been sad, depressed?
3
Been emotionally tired, worn out?
4
Been stressed?
5
Felt a lack of freedom?
6
Been bothered by the feeling of being confined?
7
Been bothered by the fact that your life was
entirely devoted to the care recipient? 
8
Been embarrassed to be the only person to
provide assistance?
9
Been satisfied with information given by health
care providers (doctors, nurses…)?
10
Been reassured by the health care providers 
(doctors, nurses…)?
Review copy
Do not use without permission

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Quality of Life Questionnaire : CarGOQoL
CarGOQoL 1.2 English (USA) – CareGiver Oncology Quality of Life
Page 4/4
During the last four weeks, in connection with the person
you help, have you …
Never
Not at all
Rarely
A little
Sometimes
Moderately
Often
A lot
Always
Enormously
22
Felt you made a difference for the person you 
are helping?
23
Felt useful?
24
Could rest, relax?
25
Could take care of yourself, pay attention to
your own health?
26
Been assisted, supported, understood by your
family?
27
Been assisted, supported, understood by your
friends?
28
Had difficulties in your intimate, emotional life?
29
Had a satisfying love and sexual life?
Thank you for your participation
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Quality of Life Questionnaire : CarGOQoL
CarGOQoL 1.2 English (USA) – CareGiver Oncology Quality of Life
Page 3/4
During the last four weeks, in connection with the person
you help, have you …
Never
Not at all
Rarely
A little
Sometimes
Moderately
Often
A lot
Always
Enormously
11
Felt that your role as caregiver was recognized 
by health care providers (doctors, nurses…)?
12
Had financial difficulties (lodging,
transportation…)?
13
Had other difficulties (lodging, transportation…)?
14
Encountered difficulties in the administrative
process (health insurance paperwork and other
paperwork related to the cancer illness? 
15
Experienced feelings of guilt?
16
Been bothered by a feeling of helplessness
against disease?
17
Felt a feeling of injustice, anger, or rebellion?
18
Had sleeping difficulties?
19
Had problems with your appetite?
20
Been physically tired, worn out?
21
Had the impression that your health was fragile?
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