Clinical trial NCT05847686
Conditions: Hematopoietic and Lymphatic System Neoplasm Metastatic Malignant Solid Neoplasm
Sponsor: University of Washington
Start date: 2023-06-27; Completion date: 2024-10-17
Enrollment: 55 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial tests the safety and side effects of psilocybin in combination with therapy for the treatment of patients with metastatic cancer and symptoms of anxiety and/or depression. Psilocybin is a substance being studied in conjunction with therapy for the treatment of anxiety and depression in patients with cancer. In this study, the psilocybin being used is derived from the mushroom psilocybe cubensis using a patented process that results in a pharmaceutical grade version of psilocybin. Psilocybin acts by activating serotonin receptors on brain cells which can change perceptions and patterns of thinking in ways that may decrease anxiety.

Detailed description:
OUTLINE:

Patients receive psilocybin orally (PO) and participate in group and individual therapy sessions on trial.

Arms: arm 1: Patients receive psilocybin PO and participate in group and individual therapy sessions on trial.
Interventions: intervention 1: Counseling intervention 2: Psilocybin intervention 3: Questionnaire Administration
Intervention descriptions: intervention 1: Participate in therapy visits intervention 2: Given PO intervention 3: Ancillary studies

Protocol documents:
ICF_000.pdf: 
 
 
Official Title: 
A phase 1/2 study of a group model of psilocybin- assisted 
therapy for cancer-related anxiety in patients with 
metastatic cancer  
 
NCT Number: 
NCT05847686 
Document Type:  
Informed Consent Form 
Date of the 
Document: 
12/27/2023  
 
 







































Prot_SAP_002.pdf: 
 
 
Official Title 
A Phase 1/2 Study of a Group Model of Psilocybin-Assisted 
Therapy for Cancer-Related Anxiety in Patients With 
Metastatic Cancer   
NCT Number 
NCT05847686 
Document Type 
Protocol and Statistical Analysis Plan 
Document Date 
1/26/2024 
 
 


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FRED HUTCHINSON CANCER CENTER
UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE
SEATTLE CHILDREN’S
Current version:  v2.2 January 16, 2024
Previous version  v2.1 November 29, 2023
Title of Protocol:
A phase 1/2 study of a group model of psilocybin-assisted therapy for cancer-related anxiety in patients 
with metastatic cancer
Investigators List:
Investigator
Professional Title
Phone Number
Anthony Back MD
Professor, University of Washington
206-619-4367
Bonnie McGregor PhD
Founder, Orion Center for Integrative Medicine
206-349-2421
Biostatistician:
Ted Gooley PhD
Professor, Fred Hutch
206-667-6533
IND Number:
165562
Investigationant:
Psilocybin PEX010, Psilo Scientific Ltd.
IND Sponsor:
Anthony Back MD
Supported by:
Psilo Scientific Ltd is providing the investigational product.
Emergency contact (24-hour) phone number:
Anthony Back 206-619-4367
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PROTOCOL SYNOPSIS 
Protocol Title
A phase 1/2 study of a group model of psilocybin-assisted therapy for cancer-
related anxiety in patients with metastatic cancer
Protocol Numbers
RG1123316 (BACK002)
IND Sponsor (if 
applicable)
Anthony Back MD
Funding Sponsor (if 
applicable)
Steven and Alexandra Cohen Foundation
Supplier of 
Investigational Product
Psilo Scientific Ltd
Trial Phase
1/2
Trial Type
Interventional
Clinical Indication
Cancer-related anxiety
Study Objectives
1. To test the safety, tolerability, and feasibility of a group model for 
psilocybin-assisted therapy for patients with stable metastatic cancer with 
clinically significant anxiety.
2. To explore the efficacy of the group model of psilocybin-assisted 
therapy on symptoms of anxiety, depression, demoralization, quality of 
life, and cancer-related post-traumatic stress. 
Study Design
Single arm
Population
Stable metastatic cancer patients
Primary Endpoints
Potentially unattended psilocybin-related distress, which is defined as the 
occurrence of participant distress that needs 1:1 facilitator attention that 
cannot be met by the 4-person facilitation team
Secondary Endpoints

Hospital Anxiety and Depression Scale, Symptoms of 
depression and anxiety using the Hospital Anxiety and 
Depression Scale (HADS) at 1 week, 8 weeks, 12 weeks, and 6 
months post psilocybin-assisted group therapy.
Exploratory Endpoints

Symptoms of depression using the Center for Epidemiologic 
Studies-Depression Scale (CES-D) at 1 week post psilocybin-
assisted group therapy  at 1 week, 4 weeks, 8 weeks, 12 
weeks, and 6 months.

Measurement of quality of life using the Functional 
Assessment of Cancer Therapy – General (FACT-G) at 1 week, 
4 weeks, 8 weeks, 12 weeks, and 6 months.

Measurement of demoralization using the Demoralization II 
(DS-II) scale at 4 weeks, 8 weeks, 12, weeks, and 6 months.

Measurement of psychosocial functioning using the 
NIH_HEALS) at 4 weeks, 8 weeks, 12 weeks, and 6 months.

Measurement of acceptance using the Peace, Equanimity, 
Acceptance in Cancer Experience (PEACE) instrument and the 
Watts Connectedness Scale at 1 week, 4 weeks, 8 weeks, 12 
weeks, and 6 months.

Measurement of retreat experience using the Mystical 
Experience Questionnaire, Communitas Scale, Challenging 
Experiences Scale, Emotional Breakthrough Scale, and the 
Psychedelic Music Questionnaire on the day of the psilocybin 
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session.
Investigational Product
Psilocybin PEX010
Dose
25 mg
Route of Administration
Oral
Regimen
Single dose + psychotherapy group and individual sessions
Treatment Groups 
This is a small group psychosocial intervention in small groups, the size of 
which will be adjusted as the trial progress according to predefined adverse 
events.
Treatment 
Schedule/Schema
Prior to psilocybin session there are 3 sessions of weekly group therapy and 
1 session of individual therapy. Day 0 = Psilocybin session. After the 
psilocybin session there are 3 sessions of weekly group therapy and 1 session 
of individual therapy. 
Efficacy Assessments
1 week, 4 weeks, 8 weeks, 12 weeks, 24 weeks
Number of Subjects
Up to 56
Estimated Duration of 
Trial
1.5 years
Duration of Participation
6 months
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Table of Contents 
1.0
INTRODUCTION TO THE PROTOCOL.......................................................................................................................................7
1.1
Introduction ..............................................................................................................................................................7
1.2
Preclinical Data..........................................................................................................................................................7
1.3
Clinical Data to Date..................................................................................................................................................8
1.4
Study Agent.............................................................................................................................................................10
1.5
Dose Rationale ........................................................................................................................................................10
1.6
Other Agents ...........................................................................................................................................................10
1.7
Risks/Benefits..........................................................................................................................................................11
2.0
OVERVIEW OF CLINICAL TRIAL .............................................................................................................................................11
2.1
Study Objectives and Endpoints..............................................................................................................................11
2.2
Study Design............................................................................................................................................................12
2.3
Estimated Accrual....................................................................................................................................................12
3.0
INCLUSION AND RECRUITMENT...........................................................................................................................................12
3.1
Eligibility of Women and Minorities........................................................................................................................12
3.2
Recruitment of Minority Groups.............................................................................................................................12
3.3
Inclusion Across the Lifespan ..................................................................................................................................12
3.4
Study Population.....................................................................................................................................................13
4.0
STUDY AGENT(S)...................................................................................................................................................................13
4.1
Primary Investigational Agent.................................................................................................................................13
5.0
SUBJECT ELIGIBLITY ..............................................................................................................................................................14
5.1
Inclusion Criteria .....................................................................................................................................................14
5.2
Exclusion Criteria.....................................................................................................................................................15
6.0
SUBJECT REGISTRATION.......................................................................................................................................................16
7.0
TREATMENT PLAN................................................................................................................................................................17
7.2
Treatment Plan Schema ..........................................................................................................................................17
7.3              Rationale………………………………………………………………………………………………………………………………………………………….. 17
7.4             Group size study considerations……………………………………………………………………………………………………………………….. 17
7.5              Group size for the first group intervention…………………………………………………………………………………………………….... 19
7.6              Rationale for facilitation team………………………………………………………………………………………………………………………….. 20
7.7              The main adverse event…………………………………………………………………………………………………………………………………..  20
7.8              Timing of adverse event recording and outcome measurements for a single group…………………………………………. 21
7.9              Efficacy analyses will be conducted after 4 groups of the same size…………………………………………………………………. 21
7.10            Examples of how the study might proceed………………………………………………………………………………………………………. 22
7.11
Administration of Investigational Agent .................................................................................................................23
7.12
Concomitant Medication and Supportive Care Guidelines.....................................................................................23
7.13
Duration of Therapy................................................................................................................................................24
7.14
Duration of Follow-Up.............................................................................................................................................25
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7.15
Dosing Delays/Dose Modifications..........................................................................................................................25
8.0
SUBJECT EVALUATION..........................................................................................................................................................25
8.1
Clinical Evaluations..................................................................................................................................................25
8.2
Screening and Baseline Evaluations........................................................................................................................25
8.3
Psilocybin session....................................................................................................................................................25
8.4
Integration visit safety checks.................................................................................................................................26
8.5
Post-Treatment Follow-up Period (specify visits based on days after psilocybin session) .....................................26
8.6
Long-Term Follow-up Period (specify duration and timing) ...................................................................................26
       8.7              Plan of Action for A Participant Exhibiting Suicidality……………………………………………………………………………………….. 26
9.0
TOXICITY MONITORING........................................................................................................................................................27
10.0
SUBJECT DISCONTINUATION OF ACTIVE TREATMENT .........................................................................................................27
11.0
CONCOMITANT MEDICATIONS ............................................................................................................................................28
12.0
ADVERSE EVENTS .................................................................................................................................................................28
12.1
Adverse Event .........................................................................................................................................................28
12.2
Serious Adverse Event.............................................................................................................................................28
12.3
Unexpected Adverse Event .....................................................................................................................................29
12.4
Monitoring and Recording Adverse Events.............................................................................................................29
12.5
Grading Adverse Event Severity..............................................................................................................................30
12.6
Attribution of an Adverse Event..............................................................................................................................30
12.7
Adverse Event Recording Period.............................................................................................................................30
12.8
Adverse Event Reporting Requirements .................................................................................................................31
13.0
CRITERIA FOR ENDPOINT EVALUATIONS..............................................................................................................................31
14.0
ASSESSMENT OF EFFICACY...................................................................................................................................................31
14.1
Efficacy and endpoint assessment ..........................................................................................................................31
14.2
Method and Timing.................................................................................................................................................32
15.0
STATISTICAL CONSIDERATIONS............................................................................................................................................32
15.1
Study Design............................................................................................................................................................32
15.2
Objectives and Hypotheses.....................................................................................................................................32
15.3
Primary/Secondary Endpoints/Hypotheses and Analytical Methods .....................................................................32
15.4
Randomization ........................................................................................................................................................33
15.5
Exploratory Analysis................................................................................................................................................33
16.0
DATA MANAGEMENT/CONFIDENTIALITY.............................................................................................................................33
17.0
DATA AND SAFETY MONITORING PLAN ...............................................................................................................................34
18.0
INVESTIGATOR OBLIGATIONS...............................................................................................................................................35
19.0
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS.....................................................................................................35
19.1
Pre-Study Documentation.......................................................................................................................................35
19.2
Study Site Training...................................................................................................................................................35
19.3
Documentation .......................................................................................................................................................35
19.4
Access to Source Data.............................................................................................................................................35
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19.5
Data Collection........................................................................................................................................................36
19.6
Protocol Interpretation and Compliance ................................................................................................................36
19.7
Study Monitoring and Data Collection....................................................................................................................36
19.8
Disclosure of Data/Publication................................................................................................................................36
19.9
Ethical Considerations.............................................................................................................................................36
19.10
Informed Consent ...................................................................................................................................................36
19.11
Institutional Review Board......................................................................................................................................37
19.12
Subject Privacy ........................................................................................................................................................37
20.0
STOPPING THE STUDY ..........................................................................................................................................................37
21.0
REFERENCES .........................................................................................................................................................................39
22.0
APPENDICES .........................................................................................................................................................................40
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1.0
INTRODUCTION TO THE PROTOCOL
1.1 Introduction
Psilocybin-assisted therapy is proving to be a potent treatment for the anxiety, distress and fear of recurrence 
experienced by people living with cancer. In randomized studies, psilocybin-assisted therapy conducted using an 
existing 2-therapist/1-patient model has shown impressive efficacy for cancer-related anxiety and existential 
distress.1-3 Larger, multisite randomized trials are being launched now. In addition, psilocybin-assisted therapy is 
being tested for a number of other indications, including depression, substance use, obsessive-compulsive 
disorder, demoralization, and—in a study Dr Back is leading—symptoms of depression and burnout in doctors 
and nurses who developed these symptoms during their frontline work in the COVID pandemic.
For patients with metastatic, incurable cancer, unrelieved anxiety and existential distress cause profound 
suffering. Of patients with metastatic cancer, 25-50% have clinically significant anxiety.4-6 These patients 
experience a sense of uncertainty, fear of future uncontrollable suffering, sense that they are burdens on the 
people caring for them, feelings of loneliness and isolation, and grief for the loss of their lives and opportunities 
missed. In longitudinal studies, existential distress and anxiety generally increases over time, and probably 
contribute to patients’ pursuit of futile medical interventions at the very end of life.7 Existing therapies are 
unsatisfactory.8 For many of these patients, their anxiety and distress impedes their ability to participate in 
psychotherapy, many decline to take antidepressant medications because of the unwanted side effect of blunting 
positive emotions, and benzodiazepines do not seem to change the course of the anxiety. 
1.2 Preclinical Data
Substantial data demonstrates the safety of psilocybin (mushroom-derived, and synthesized)
Studies in humans and nonhuman animals indicate that psilocybin has very low toxicity .9,10 
The LD50 ranged from 285mg/kg in rats and mice.11 The maximum tolerated dose of psilocybin in 
humans has not been defined or established. The best estimate of a lethal dose  for pure psilocybin in 
humans is about 19 grams. The full dose of psilocybin that will be administered in this study is 1/100 
times of the established LD50 in nonhuman animals and in humans. A Phase I trial of psilocybin 
completed in 2019 at oral doses of up to 0.6 mg/kg demonstrated no serious adverse events.12 
Psilocybin is not associated with disease or damage to any organ or system.10 More commonly, 
damage or disease to organs (as renal failure) is associated with mistakenly consuming poisonous 
mushrooms under the belief that they are psilocybin-containing mushrooms.13
Three cases of death possibly related to the direct toxic effects of Psilocybe mushrooms (the 
natural source of psilocybin) have been reported in the world literature. One fatality occurred in a 
post-cardiac transplant patient who ingested Psilocybe mushrooms.14 It is not known however 
whether psilocybin was the proximal cause of death or  whether death occurred secondary to the 
cardiac stimulant phenethylamine, which is also present in the mushrooms. In the French literature, 
another fatality linked to Psilocybe mushroom use was associated with far higher blood 
concentrations of the active metabolite of psilocybin than would be expected with the doses 
proposed in this study.15 A final fatality  from Psilocybe mushroom ingestion was mentioned in a 
1961 review but was poorly characterized, with no psilocin concentrations were reported.16
In a review of other adverse effects of psilocybin from Psilocybe mushrooms, an additional 
10 individuals were reported to have experienced accidental deaths associated with Psilocybe 
mushroom ingestion.17 In most cases, these accidental deaths resulted from falls from buildings. Given 
the documented history of use of Psilocybe mushrooms in a variety of societies and cultures, that 
there are only 3 known fatalities at best indirectly linked to the physiologic effects of mushroom 
ingestion is an argument for the general safety of this natural product. Further, a recent review of 
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the potential harm of the ingestion of Psilocybe mushrooms by the Dutch medicinal advisory board 
found that the risk of acute or chronic toxicity was low.17
To date, over 2000 participants have received psilocybin under controlled conditions in 
scientific studies with no reports of the occurrence of a significant adverse event deemed to be 
associated with drug administration. The most commonly reported adverse events from the scientific 
literature are psychological in nature and include the induction of negative emotional states and 
paranoid/delusional thinking during psilocybin sessions, as well as far less frequent reports of 
Hallucinogen Persisting Perception Disorder (HPPD).18 A review of studies conducted worldwide 
between 1999 and 2008 identified only one subject (out of 110) who experienced any persistent 
perceptual symptoms associated with HPPD and these symptoms were mild, brief, and resolved within 
three days of psilocybin exposure.19 Rates of prolonged psychiatric symptoms of any kind following 
psilocybin exposure in healthy study participants are estimated to be 0.08-0.09%. As in the phase 2 
studies, common physical adverse events associated with psilocybin administration include increased 
BP and heart rate, nausea, and headaches. In the phase 2 studies of cancer related anxiety and 
depression no cases of HPPD were identified and no participants developed any symptoms of 
paranoia or anxiety that required pharmacological intervention or anything more than reassurance from 
session facilitators.1,2 In a survey of 1993 individuals in the context of unsupervised, illicit use of 
psilocybin-containing mushrooms, 11% put self or others at risk of physical harm. Of the 
respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical 
help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring 
psychological symptoms. 3 cases appeared associated with onset of enduring psychotic symptoms 
and 3 cases with attempted suicide.20
To date, there have no reports of physical harm in patients who have received psilocybin 
under controlled conditions, and no fatalities have been associated with its use in a controlled 
clinical trial. The difference in the side-effect profile between the unknown doses of psilocybin-
containing mushrooms consumed in an uncontrolled setting and dose- controlled medically prepared 
oral psilocybin consumed in a controlled setting is thought to be in part due to the focus on the set 
and setting of the experience. The set refers to the emotional/cognitive/behavioral state/mindset and 
expectations of study participants just prior to psilocybin exposure, and the setting refers to the 
physical environment in which the exposure occurs.21
There are no confirmed reports of an overdose of synthesized or purified psilocybin meant for 
use in a clinical trial. In the United States, use of chemically synthesized psilocybin does not occur.22 
Although psilocybin in the form of mushrooms is sometimes used non-medically, medical emergencies 
due to psilocybin mushrooms are very rare (psilocybin is mentioned in only 0.1% of drug-related 
emergency department visits).23 It can be anticipated that an overdose of psilocybin might present in a 
manner similar to “serotonin syndrome”. Removal of any residual gastric drug, supportive care, and 
cautious administration of a serotonin antagonist such as risperidone are reasonable interventions; 
however, to date no cases have described similar responses with respect to psilocybin, and the doses of 
psilocybin that might provoke these physiological effects would be many times greater than even the 
highest doses used in early human studies.
1.3 Clinical Data to Date
Psilocybin-assisted therapy can relieve anxiety and existential distress by disrupting patterns of thinking that 
are ruminative, catastrophic, and persistent. The lived experience of cancer patients who have participated in 
psilocybin-assisted therapy studies using individual models reveal that patients feel more able to examine their 
fears, find meaning in their lives, and connect more deeply the people they care about.24 While scientific studies 
have yet to measure medical utilization, anecdotes describe a dramatic shift in decisions away from medical 
treatments that are invasive and isolating, such as mechanical ventilation in intensive care, and an increase in 
discussions related to advance care planning. The qualitative data, and many anecdotes published in the media, 
demonstrate that psilocybin-assisted therapy seems to allow many patients to hold a realistic appraisal of their 
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prognosis while at the same time experiencing a heightened appreciation of the parts of their lives they still enjoy 
and cherish—and these benefits have persisted in a 4 year followup study.25 While other psychotherapeutic 
approaches have been reported as valuable, their benefits take much longer to be experienced, typically weeks 
to months, and long term followup is sparse. Thus psilocybin-assisted therapy appears to have unique promise as 
a modality to treat anxiety, existential distress, and demoralization for patients with life-threatening cancer. The 
study proposed here addresses a population of patients with metastatic cancer whose need for relief from 
suffering is high. 
Established treatment models use a 2-therapist/1-patient therapy model that is extremely resource intensive, 
to a degree that will likely limit future access. For example, in two highly efficacious clinical trials, 2 therapists 
conducted 3 preparation sessions, a medication day sessions, and 3 integration sessions with a single participant. 
A single study participant required at least 30 hours of direct contact. [Assuming (3 x 90 min prep sessions) + (1 x 
7 hour medication session) + (3 x 90 min integration sessions] x 2 therapists]. This 2 therapist/1 patient model is 
likely to become a barrier to expanding access. Many therapists consider 30 hours of direct contact to be a week 
of full time work. Thus a therapist who focused exclusively on psilocybin-assisted therapy could work with up to 
48 people with cancer in a year (30 hours/week x 48 weeks). It is hard to imagine scaling up this level of resource 
intensity to provide access for the 602,000 people who died of cancer in the US 2020–if only 30% of those people 
wanted access, 12,541 therapists working full time would be required. If 8-person groups run by a facilitation 
team of 4 therapists were to be shown safe and efficacious, the number of required therapists would drop by 4-
fold, to 3,135 therapists. (To date the most established training program, at the California Institute for Integral 
Studies, has trained 559 practitioners over its 6 year history, and only a fraction of their work will be with cancer 
patients; CIIS, personal communication May 2022). 
Note that this protocol uses the term ‘facilitator’ rather than therapist, but for this protocol these terms 
both refer to the same role on the research team.
 
Limited scientific evidence is available that describes the safety and efficacy of a group model for psilocybin-
assisted therapy. There is an extensive non-clinical experience with groups using psilocybin in a community or 
ceremonial setting. However, we very few studies involving prospective data collection from a group setting are 
available to inform a group model for clinical use.26 In a University of California San Francisco (UCSF) study of 
psilocybin-assisted therapy with 18 long term HIV survivors (3 groups) showed clinically meaningful changes in 
demoralization.27 This group study used group preparation and integration sessions, but used individual 
psilocybin sessions, so does not provide data to inform a group psilocybin administration model. Another recent 
experience is from the Aquilino Cancer Center, which uses groups of 4 cancer patients who receive mostly 
individual preparation; then the group members have 4 simultaneous individual psilocybin sessions each with a 
single therapist, with a backup therapist monitoring the sessions by video (Manish Agrawal, personal 
communication, April 2022). This model is less intensive than the 2-therapist/1-patient model, but does not 
provide data about group psilocybin administration. To our knowledge, there are no published studies involving 
use of group preparation, group medication sessions, and group integration sessions that report adverse events. 
Thus, there is a gap in scientific knowledge about group models of psilocybin-assisted therapy for use in the 
United States in 2022, and this proposal describes a substantial step forward in filling that knowledge gap.
Evidence from a large body of scientific evidence from psychosocial group interventions for cancer patients 
without psychedelics suggests that the benefits of group therapy plus psilocybin could be substantial. A large 
body of empirical research has reported the beneficial effects of cancer group psychosocial interventions on 
distress, anxiety and fear of recurrence. To date, numerous randomized studies have compared different group 
interventions, with results favoring manualized group therapy sessions that result improvements in distress and 
fear of recurrence without the use of psychedelics. The state-of-the-science cancer group intervention typically 
involves groups of 8 cancer patients and 2 facilitators, and since the COVID pandemic, these interventions have 
been conducted online. Interestingly, in addition to improved psychosocial outcomes, these randomized trials also 
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demonstrate improvements in physiologic parameters: immune function, neuroendocrine function, and even 
survival.28-30
Dr McGregor (a sub-investigator on this proposal) is currently a co-investigator on a National Cancer 
Institute-funded clinical trial of a manualized group intervention for ovarian cancer survivors, has extensive 
experience designing and facilitating these group interventions, and will bring this scientific knowledge to the 
study described in this proposal. This proposal would be the first study to combine this scientific knowledge 
about cancer group interventions together with the emerging psychedelic science.
  
In summary, there exists a gap in knowledge about whether the benefits of psilocybin-assisted therapy could 
be realized in a group model, and how those groups should be structured. This study aims to fill that gap with a 
phase 1/2 psilocybin-assisted therapy intervention study in which the preparation, psilocybin, and integration 
sessions are conducted with carefully screened patients in a group setting, using a Phase 1/2 design adapted 
from cancer clinical trials that would answer foundational questions about what group size is safe, feasible, and 
efficacious. 
1.4 Study Agent
Psilocybin is a naturally occurring compound, found in a variety of mushroom species collectively called ‘magic 
mushrooms’ in lay publications. According to the most recent and comprehensive review, serotonergic 
psychedelic medications “are generally considered to be physiologically safe molecules” that chiefly 
alterconsciousness.31 Recent reviews and searches of the literature indicate thatpsilocybin – either in the form 
of mushrooms, or synthesized psilocybin -- is not associated with harm or damage to any organ or system in the 
body.18 Psilocybin can produce changes in blood pressure and heart rate, but these changes are not as strong or 
consistent as those seen after psychostimulants (amphetamines), and sometimes these changes only occur at 
one time point.31 More consistently, psilocybin can produce rapid and intense changes in mood including 
periods of anxiety or panic. Both these physiological and psychological effects are transient and do not last 
beyond the duration of drug effects.
The psilocybin that will be used in this study, PYEX psilocybin, is a partially purified fraction of the extract of 
Psilocybe cubensis mushroom fruiting bodies that is produced by Psilo Scientific Ltd. (Vancouver BC), in a patented 
process that yields a pharmaceutical grade botanical drug that meets FDA guidance for a botanical drug suitable for 
a clinical investigation. The drug product to be used is PEX010, 25 mg psilocybin capsules, and it is manufactured 
under cGMP conditions. Further CMC information is available in the accompanying Investigator’s Brochure 
describing PEX010. In a variety of studies, researchers leading clinical trials using pharmaceutical grade 
psilocybin at this dose took precautions similar to the ones we will use in this study, and observed no reactions 
requiring pharmacological intervention.2,32 This preparation of psilocybin is being used in over 25 studies in 
North America, Europe, and Australia, including a series of ongoing studies at the University of California San 
Francisco.
1.5 Dose Rationale
The dose of psilocybin to be used in this study, 25 mg, has been shown to produce equivalent results to body-
weight-based dosing in a review of experience at the Johns Hopkins Center for Consciousness Studies.33
1.6 Other Agents
There are no other pharmacologic agents used in this study. The study intervention includes psychotherapy 
sessions that are similar to established small group psychosocial interventions for cancer patients.1,34,35
1.7 Risks/Benefits
Expected benefits for participants include: reductions in symptoms of anxiety, depression, demoralization, 
existential anxiety; increases in feelings of well-being and spiritual connectedness. Possible benefits for society 
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include establishment of safe procedures for psilocybin-assisted therapy in groups, and the advancement of 
scientific knowledge in the area of psychedelic-assisted therapy.
The expected benefits outweigh the risks for study participants because: symptoms of depression, anxiety, 
demoralization, existential anxiety can lead to severe suffering for patients with metastatic cancer, and the existing 
treatment options have significant limitations. For example, about 30% of cancer patients with depressive 
symptoms respond to conventional antidepressant therapy. For patients with demoralization, antidepressants have 
no known efficacy. For patient with metastatic cancer, conventional psychotherapy has modest effects, yet 
requires a substantial investment of time and energy which can be difficult for patients with metastatic disease. 
While the evidence for psilocybin-assisted therapy is limited, existing randomized studies using an individual 
patient approach show responses that are larger in magnitude, more rapid, and more prolonged than existing 
antidepressant studies. Thus this study, which attempts to make psilocybin-assisted therapy more accessible, and is 
designed with multiple safety features, seems reasonable to propose to patients with metastatic cancer.
2.0
OVERVIEW OF CLINICAL TRIAL
This is a phase 1/2 study of psilocybin-assisted group therapy for cancer-related anxiety and distress that 
will measure safety, feasibility, and efficacy in order to establish evidence-based parameters for a group 
model of psilocybin-assisted therapy.
2.1 Study Objectives and Endpoints
2.1.1
Primary Objective. To test the safety, tolerability, and feasibility of a group model for 
psilocybin-assisted therapy for patients with stable metastatic cancer with clinically significant 
anxiety.
2.1.1.1
Primary Endpoint. The number of instances of ‘Potentially unattended psilocybin-related 
distress’, which is defined as the occurrence of participant distress during the psilocybin 
administration session on Day 0 that requires 1:1 facilitator attention that cannot be met by 
the 4-person facilitation team in small groups of different sizes that will vary over the course 
of the study; these occurrences will be identified by a study observer and validated with the 
study PI.
2.1.2
Secondary Objective. To explore the efficacy of the group model of psilocybin-assisted 
therapy on symptoms of anxiety and depression at 1 week, 4 weeks, 12 weeks, 
2.1.2.1
Secondary Endpoint. The primary measurement of anxiety and depression will be Hospital 
Anxiety and Depression Scale at 1 week, 4 weeks, 8 weeks, 12 weeks, and 24 weeks.
2.1.3
Exploratory Objective 1. To explore the efficacy of the group model of psilocybin-assisted 
therapy on symptoms of demoralization.
2.1.3.1
Exploratory Endpoint 1. Demoralization will be measured using the DS-II scale at 1 week, 4 
weeks, 8 weeks, 12 weeks, and 24 weeks.
2.1.4
Exploratory Objective 2. To explore the efficacy of the group model of psilocybin-assisted 
therapy on symptoms of quality of life.
2.1.4.1
Exploratory Endpoint 2. Quality of life will be measured using the FACT-G and Adjustment 
Disorder scales at 1 week, 4 weeks, 8 weeks, 12 weeks, and 24 weeks.
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2.1.5
Exploratory Objective 3. To explore the efficacy of the group model of psilocybin-assisted 
therapy on psychosocial functioning and connectedness.
2.1.5.1
Exploratory Endpoint 3. Cancer-related post-traumatic growth will be measured using the 
NIH-HEALS scale and the Watts Connectedness Scale at 4 weeks, 8 weeks, 12 weeks, and 24 
weeks.
2.1.6
Exploratory Objective 4. To explore the efficacy of the group model of psilocybin-assisted 
therapy on death anxiety.
2.1.6.1
Exploratory Endpoint 4. Death anxiety will be measured using the Death and Dying Distress 
Scale at 4 weeks, 12 weeks, and 24 weeks.
2.1.7
Exploratory Objective 5. To explore the quality of the group experience of the group model of 
psilocybin-assisted therapy.
2.1.7.1
Exploratory Endpoint 5. The quality of the group experience will be measured using the 
Mystical Experience Questionnaire, Emotional Breakthrough Inventory, Communitas Scale, 
and Challenging Experiences Questionnaire, and the Psychedelic Music Questionnaire on the 
day of the psilocybin session only. 
2.2 Study Design
This study is designed to define the specifications for a new model of group psilocybin-assisted therapy. 
We describe the design as a Phase 1/2 study because it combines features of Phase 1 and Phase 2 studies.  Phase 
I trials are often designed as ‘dose-finding’ studies for new drugs that focus on toxicities and adverse events as 
primary outcomes. For psilocybin the individual toxicities have already been well described by prior studies. The 
adverse outcome of interest in this study is related to episodes during the medication session when more 
participants require 1:1 attention at the same moment than can be provided by the 4-person facilitation team, 
which this study calls ‘potentially unattended psilocybin-related distress’—which is  somewhat similar to a 
‘dose-limiting toxicity’ in a typical Phase 2 drug study. In this study, the adverse event of interest, potentially 
unattended psilocybin-related distress, is ‘group-size-limiting toxicity’. (Please note that backup facilitators will be 
on hand to step in when this occurs). This adverse event is specific to the small group design used in this study. In 
addition, Phase 2 studies are often designed to measure efficacy of a therapy at different doses, and in this study 
efficacy will be measured at different group sizes by comparing these results to historical studies for cancer 
patients that provided the same number of preparation and integration therapy sessions. Thus we describe this 
study as Phase 1/2 because it will examine both adverse events and efficacy. 
2.3 Estimated Accrual
This study will accrue up to 56 participants if the small group size over the course of the study increases to 8 
participants per group. 
3.0
INCLUSION AND RECRUITMENT
3.1 Eligibility of Women and Minorities
Individuals of any sex, gender, race, or ethnicity are eligible for this study. 
3.2 Recruitment of Minority Groups
The study recruitment strategy aims to achieve representation of minority groups that reflects the demographics of 
the affected population in the catchment area. 
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3.3 Inclusion Across the Lifespan
The study design and recruitment strategy aim to achieve representation of age groups that reflect the 
demographics of the affected population. Individuals ages 18 - 85 are eligible for this study. Children (age <18) are 
excluded because insufficient data is available on prospective benefits or adverse events. Adults older than 85 are 
excluded because insufficient data is available on prospective benefits or adverse events.
3.4 Study Population
Existing studies indicate that older age is associated with decreasing anxiety for patients with metastatic cancer, 
but the the risk of depression does not vary with age. These trends however were identified in studies of older 
adults, and studies of younger adults indicate that anxiety is a notable issue, although no studies examined 
associations with age within younger adults. 
A 2021 study of Central Puget Sound demographics showed that 37% are people of color, and 63% are White non-
Hispanic/Latino. Among people of color: Asians (14%); Hispanic (10%); Black (6%); American Indian/Alaska Native 
(1%); Native Hawaiian or Other Pacific Islander (0.8%)
Projected Target Accrual
ETHNIC AND GENDER DISTRIBUTION CHART
TARGETED / PLANNED ENROLLMENT: Number of Subjects
Sex / Gender
Ethnic Category
Females
Males
Total
Hispanic or Latino
3
3
6
Not Hispanic or Latino
25
25
50
Ethnic Category Total of All Subjects*
28
28
56
Racial Categories
American Indian / Alaska Native
0
1
1
Asian
4
4
8
Native Hawaiian or Other Pacific Islander
1
0
1
Black or African American
2
2
4
White
21
21
42
More Than One Race
0
0
0
Racial Categories: Total of All Subjects*
28
28
56
4.0
STUDY AGENT(S)
4.1 Primary Investigational Agent
Psilocybin, is a 4-hydroxy-N,N-dimethyltryptamine and occurs in nature in many species of 
mushrooms, including the genera Psilocybe, Conocybe, Gymnopilus, Panaeolus, and Strophparia. Its 
chemical formula is C12H17N2O4P. Psilocybin is a potent agonist at 5-HT2A/C, and their binding potency 
to these receptors correlates with human potency as hallucinogens [7]. Psilocybin has been 
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administered to normal volunteers to measure physiological and psychological parameters at doses 
ranging from 0.045mg/kg to 0.43mg/kg [45; 51]. It has also been safely administered to patients with 
OCD at doses ranging from 0.025mg/kg to 0.3mg/kg.
Psilocybin PEX010 is a naturally occurring compound that after oral administration is metabolized to psilocin, 
which reacts antagonistically with serotonin type 2A (5-HT2A) receptors to produce the psychological and spiritual 
experiences that patients often report.  Psilocybin PEX101 is a partially purified fraction of the extract of Psilocybe 
cubensis mushroom fruiting bodies that is produced by Psilo Scientific Ltd. (Vancouver BC), in a patented process 
that yields a pharmaceutical grade botanical drug that meets FDA guidance for a botanical drug suitable for a 
clinical investigation. PEX010 will be provided to Dr. Back for this study in 25 mg psilocybin capsules that have been 
manufactured under cGMP conditions.
4.1.1
The investigational agent will be shipped directly to Dr. Back (PI) at the Harborview Investigational 
Drug Service, who is working with Dr. Back on his current psilocybin study. 
4.1.2
The investigational agent will be stored at room temperature at the Harborview Medical Center 
IDS, in a locked cabinet in the narcotics vault that has been inspected and approved for storage of 
psilocybin by the DEA and the Washington State Department of Health. 
5.0
SUBJECT ELIGIBLITY
5.1 Inclusion Criteria 
5.1.1
A diagnosis of metastatic solid tumor, or incurable hematologic malignancy that has been 
accepted by a physician in a medical record. 
5.1.2
Measurable disease is not required.
5.1.3
Previous treatment with chemotherapy: There are no minimum or maximum prior lines of 
chemotherapy.
5.1.4
18-85 years of age.
5.1.5
Required performance status, including the appropriate scale. ECOG 0-2.
5.1.6
Acceptable organ and marrow function includes: 
Hematocrit >20, Plt >20K, Liver function tests 1.5x normal, Creatinine 1.5x normal.
5.1.7
Subjects of childbearing potential must be willing to use an effective contraceptive method 
from study enrollment until at least 1 month after receiving the investigational agent(s).
5.1.8
Must be at least 4 weeks after surgery or radiotherapy at study entry, but can be receiving 
oral or iv chemotherapy if those schedules can be adjusted around the medication session 
date;
5.1.9
Motivated to participate in a group study and able in the research team’s judgment to 
participate in the small group effectively; 
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5.1.10
On pre-enrollment screening tests, they will have clinically significant anxiety or depressive 
symptoms as defined by a score of 11 or greater on the HADS-Total.
5.1.11
English speaking – able to understand the process of consent and the risk and benefits 
associated with the study, and able to give written informed consent. This is a pilot study, 
and if future larger studies are designed, consideration will be given for non-english-speaking 
subjects.
5.1.12
Must be willing to sign a medical release for the investigators to communicate directly 
with their treating clinicians (mental health professional or oncologist) and doctors to 
confirm a medication and/or medical history. 
5.1.13
Must provide at least one adult who is in contact with the participant at least once a day 
when the participant is at home who is able to verbally monitor participant-reported 
changes in the behavior and able to notify research staff of behavior changes that may 
require research staff assessment.
5.1.14
Has been off selective serotonin inhibitors for five half-lives of the drug plus 2 weeks.
5.1.15
Must avoid taking any psychiatric medications or starting a new psychiatric medication during 
the study. Should participant's doctor recommend starting a new psychiatric medication, 
participant will be required to notify the study team and the subject would withdraw from 
the study. (Use of prn benzodiazepines is allowed but high dose chronic benzodiazepine 
use must be reviewed by the PI. Use of prn gabapentoids is allowed by high dose chronic 
gabapentoid use must be reviewed by the PI.)
5.1.16
Must provide a contact (relative, spouse, close friend, or other caregiver; can be the same 
person as in 5.1.13) who is willing and able to be reached by the research team in the event 
that the participant becomes suicidal. 
5.1.17
If the potential participant is of childbearing potential, they must have a negative 
pregnancy test at baseline and prior to the medication dosing session, and must agree to 
use adequate birth control.
5.1.18
Are willing to commit to preparation sessions, medication dosing sessions, integration 
sessions, to complete evaluation instruments and commit to be contacted for all necessary 
telephone contacts.
5.2 Exclusion Criteria
5.2.1
Brain metastases that have not been treated.
5.2.2
Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 
psychiatric illness/social situations that would limit compliance with study requirements.
5.2.3
Pregnancy, breastfeeding, or expecting to conceive or father children for the duration of the 
trial through 30 days after receipt of investigational agent(s).
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5.2.4
Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion 
disorder, paranoid disorder, or schizoaffective disorder;
5.2.5
Suicidal ideation with a C-SSRS > 3;
5.2.6
Current substance abuse disorder (although prospective subjects will not be excluded for 
reasonable alcohol use that does not meet criteria for alcohol use disorder or marijuana use 
that does not meet criteria for substance use disorder);
5.2.7
Neuroleptic (including olanzapine, prochlorperazine, promethazine), and SSRI medications 
that cannot be tapered and discontinued in conjunction with the participant’s prescribing 
physician (although ondansetron can be used for nausea);
5.2.8
Unstable neurological or medical condition; history of seizure, chronic/severe headaches;
5.2.9
Any use of psychedelic drugs in high doses  (psilocybin >2 grams of dried mushrooms, LSD 
>200 micrograms) within the prior 12 months (microdosing will not require exclusion but 
participants would have to agree to discontinue microdosing 1 month before study entry);
5.2.10
Use of tramadol, due to the potential for serotonin syndrome with concomitant use of 
psilocybin.
5.2.11
Individuals who are on MOAI (monoamine oxidase inhibitors) or who have a known sensitivity 
to the drug or its metabolites. Psilocybin is contraindicated in medications that are known 
UGT (UDP-glucuronosyltransferase) enzyme modulators. The concurrent use of SSRI/SNRI 
meds 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.
5.2.12
A marked baseline prolongation of QT/QTc interval (e.g., demonstration on >1 ECG of a QTc 
interval >450 milliseconds (ms).
5.2.13
A history of additional risk factors for Torsade de Points (including but not limited to: heart 
failure, hypokalemia, family history of Long QT Syndrome) .
5.2.14
The use of concomitant medications that prolong the QT/QTc interval.
6.0
SUBJECT REGISTRATION
Subjects will be registered by the Fred Hutch/UW Study Coordinator and entered into the Clinical Trial 
Management System (CTMS, OnCore). A complete, signed study consent and HIPAA authorization are required for 
registration.
Subject IDs will be assigned by CTMS data entry. 
Signed ICFs must remain in each subject’s chart and must be available for verification by monitors or regulatory 
agencies at any time.
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7.0
TREATMENT PLAN
7.1 Overview. This study is designed to define the specifications for a new model of group psilocybin-assisted 
therapy. We describe the design as a Phase 1/2 study because it combines features of Phase 1 and Phase 2 
studies.  Phase I trials are often designed as ‘dose-finding’ studies for new drugs that focus on toxicities and 
adverse events as primary outcomes. For psilocybin the individual toxicities have already been well described by 
prior studies. The adverse outcome of interest in this study is related to episodes during the medication session 
when more participants require 1:1 attention at the same moment than can be provided by the 4-person 
facilitation team, which this study calls ‘potentially unattended psilocybin-related distress’ (note that backup 
facilitators will be on hand). This adverse event is specific to the small group design used in this study. In addition, 
Phase 2 studies are often designed to measure efficacy of a therapy at different doses, and in this study efficacy 
will be measured at different group sizes by comparing these results to historical studies for cancer patients that 
provided the same number of preparation and integration therapy sessions. Thus we describe this study as Phase 
1/2 because it will examine both adverse events and efficacy. 
7.2 Treatment Plan Schema
SCHEMA
Eligibility determination
REGISTRATION
3 Group Preparation Therapy visits
1 Individual Preparation Therapy visit
Psilocybin Session
3 Group Preparation Therapy visits
1 Individual Preparation Therapy visit
     (end of study treatments)
Outline Treatment Schedule
Day
Treatment
-14 (+/8 days)
Group Preparation First session (video)
-7 (+/8 days)
Group Preparation Second session (video)
-1 (+/- 3 days)
Group Preparation Third session (in person)
-1 (+/-3 days)
Individual Prep Visit (in person)
0
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1 (+/3 days)
Group Integration First session (in person)
1 (+/-3 days)
Individual Integ Visit (in person)
8 (+/8 days)
Group Integration Second session (video)
15 (+/8 days)
Group Integration Third session (video)
The basic group intervention structure for psilocybin-assisted therapy designed for this study
7.3 Rationale. This group intervention structure is designed to allow for historical comparison to 
studies using individual models of psilocybin-assisted therapy. Published studies using individual models 
have generally used 3 preparation sessions, a medication session, and 3 integration sessions. The group 
model used in this study will add an individual preparation session and an individual integration session 
to the 3 group preparation sessions, medication session, and 3 group integration sessions. We 
acknowledge that many patients may wish to continue integration after the study ends, which we feel is 
an important research question that merits a future study. In the individual integration sessions, the 
facilitators will discuss when integration beyond what the study provides may be useful, and participants 
will receive resources on aftercare. In addition, participants will be able to contact the study facilitators 
for supportive calls. 
7.4 Group size study considerations. An optimal group size for psilocybin-assisted therapy would have an 
acceptable incidence of adverse events attributable to the group nature of the intervention, and efficacy that is 
comparable to individual psilocybin-assisted therapy. For this study the adverse event of most interest will be 
an intense emotional experience during the psilocybin day that requires 1:1 facilitator attention. The efficacy 
measure will be the Hospital Anxiety and Depression score, already demonstrated to change in prior studies, 
which will allow historical data to be considered when assessing the potential efficacy of this group model. Since 
we are aware that demoralization is being used as a primary outcome in multicenter studies that are already 
funded, demoralization is included as another secondary outcome measure.
Our review of the group intervention literature combined with our experience with psychedelic-assisted 
interventions led us to conclude that a 6 person group with 4 study facilitators is an reasonable starting point 
for investigation. Research in cancer group psychotherapy was initiated by David Spiegel MD and Irvin Yalom MD 
at Stanford, and their work was based on extensive research in groups often done using approaches from depth 
6 participants + 4 facilitators
Preparation
Group psilocybin-assisted therapy
Summary figure
Facilitator
Team
staffing
Participant
session
Group
Prep 1
90 min
Group
Prep 2
90 min
Group
Prep 3
90 min
Medication
Session
6-7 hours
Group
Integ 1
90 min
Group
Integ 2
90 min
Group
Integ 3
90 min
Timing
Individual
Prep
50 min
1 lead
2 leads
2 leads
2 leads
2 leads +
2 associates
2 leads
2 leads
2 leads
Individual
Integration
50 min
1 lead
Integration
Med
Week -4
Week -2
Week -1
Week 0
Day 1
Week 0
Day 2-3
Week 0
Day 4-5
Week +1
Week +2
Week +3
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psychology. The state of the science now in cancer group psychotherapy that does NOT use psychedelics is a 6- to 
8-person group with 2 facilitators, which gives each participant both time to speak and be heard, with minimal 
pressure to speak, in a 75 minute session. 
Dr Back’s experience in group interventions at a legal psychedelic retreat center in the Netherlands 
(Synthesis Institute) in 2021, (conducted with group preparation, medication day, and integration), suggests that 
a group of 6 – 8 would also work well for the same reasons, but also that more than 2 facilitation team members 
would be necessary to ensure that participant safety can be addressed (e.g. participants should be accompanied 
to the bathroom), and that intense emotional experiences can be addressed with periods of 1:1 attention during 
the medication session. Dr. Back observed that a safe and efficacious experience for participants did not require 
continuous 1:1 attention for the entire medication day, and that the facilitation team was able to distribute 
attention to participant episodes where 1:1 attention was needed under direction from a lead facilitator. Dr Back 
has been working as a group facilitator with the Synthesis Institute in the Netherlands (where psilocybin is legal in 
the form of ‘truffles’) at 5 legal psilocybin retreats in 2022 and also received Synthesis Institute training in 
emergency protocols and facilitation skills. In addition, Dr Back’s group facilitation experience prior to his work 
with psychedelic-assisted therapy includes more than 20 years of group facilitation interventions in a series of 
studies funded by the National Cancer Institute.
Recent research studies from individual psychedelic medication day sessions provide useful data to 
estimate the rate of intense emotional experiences that would require 1:1 facilitator attention. For example, in 
the UCSF group psilocybin study of long term HIV survivors mentioned earlier, where group preparation and 
integration were used along with individual psilocybin sessions, there was a 44% rate of adverse events during 
the psilocybin session that were mostly time-limited episodes of fear and anxiety that were all addressed with 
facilitator verbal (e.g. coaching) and non-verbal interventions (e.g. presence, hand-holding) and did not require 
medication; the duration of these episodes was not described in the publication but none were more than 30 min 
(personal communication to Dr Back from the lead author Dr Anderson). A study at New York University (NYU) of 
psilocybin-assisted therapy for cancer patients reported a 17% rate of transient anxiety during the psilocybin 
sessions, also addressed by facilitator non-pharmacologic interventions; the duration of these episodes was not 
described but all were transient and self-limited (personal communication to Dr Back). 
For the purposes of justifying the initial 6 participant group size (with 4 study facilitators) for this study, 
the USCF and NYU data are valuable. For a hypothetical ‘worst case scenario’: if this initial group of 6 participants 
has a 50% rate of adverse events (i.e., higher than either the UCSF group study or NYU cancer study) that are 
intense emotional experiences, *and* if those adverse events happen *simultaneously*, then 3 participants 
might need 1:1 attention for some period of time. But even in this ‘worst case scenario’, if 3 participants need 1:1 
attention simultaneously, the 4-person facilitation team should be able to provide 1:1 attention to 3 participants 
easily. 
It is possible that the above ‘worst case scenario’ may not cover all needs for 1:1 attention. In this study, 
there will be backup facilitators available on-site who will have been observing the group, who will be able to 
step in to provide additional assistance at any moment if the group monitor (who is a member of the research 
team but a separate role from study facilitator) and the PI decide in the moment that additional assistance is 
warranted.
7.5 Group size for the first group intervention. In this study, the group psilocybin-assisted therapy intervention 
will start with a group of 6 screened participants and a 4-person facilitation team. This will be referred to as the 
‘6-person group level’, and a ‘series’ of up to 4 groups will be conducted at this group size. Groups will be 
conducted sequentially, so that adverse events can be tabulated and analyzed for each group before starting the 
next group. While the number of participants in each group may vary, all groups will be run by a team of 4 study 
facilitators (who will have had prior specific training in psychedelic therapy and group facilitation). Dr Back and Dr 
McGregor will perform additional study-specific training for all facilitators, which will include ethics of consent 
during a psilocybin session and acceptable modalities of touch. 
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7.6 Rationale for facilitation team. The 4-person facilitation team is a clinically practical, adaptable model that 
could set a standard for future care. This team includes two lead facilitators and two associate facilitators. 
--Lead facilitator A will (1) keep an eye on the room and allocate facilitator resources to participants who 
could benefit from attention, and (2) will guide participants with complex or intense emotional reactions to 
psilocybin. This role will be filled by the PI Dr Back for most of the groups. The lead facilitators (A and B) will be 
licensed healthcare providers with graduate-level professional training and clinical experience in psychotherapy. 
The lead facilitators (A or B) must be licensed to practice independently. Examples of acceptable professional 
credentials include clinical or counseling psychologist (PhD or PsyD), psychiatrist or other physician (MD or DO), 
Masters of Social work (MSW), licensed marriage and family therapist (LMFT), Masters Licensed Clinical 
Professional Counselor (LCPC), or licensed Psychiatric Nurse Practitioner (Psychiatric NP). 
--Lead facilitator B will have the same responsibilities with the priorities reversed. The lead facilitators 
will work together to lead the team.
--Associate facilitator C responsibilities will focus on guiding participants with emotional reactions that 
are less complex or intense. The associate facilitators must have a bachelor’s degree and at least 1 year of clinical 
experience in a licensed mental health care setting. In addition, a licensed physician be present on-site in the 
event of a physiological or psychiatric emergency.
--Associate facilitator D responsibilities will share guiding responsibilities with A, and also provide 
logistical support for trips to the bathroom, water, blankets, and ways of providing comfort.
Note that this protocol uses the term ‘facilitator’ rather than therapist, but for this protocol these terms 
both refer to the same role on the research team.
7.7 The main adverse event that we anticipate is the occurrence of participant distress that needs 1:1 
facilitator attention that cannot be met by the 4-person facilitation team, and we refer to this adverse event as 
‘potentially unattended psilocybin-related distress’. Three examples of this would be significant fear, intense 
sadness or anxiety related to ego disalusion.  These conditions would all require one to one attention for a period 
of 10 to 40 minutes.  This adverse event will be identified and recorded in real time by a group monitor who is 
separate from the 4-person facilitation team. If the group monitor identifies a participant who needs 1:1 
attention and a member of the facilitation team is unavailable to handle the participant at the level of expertise 
required, the group monitor will record that occurrence as an adverse event. The groups will be videotaped so 
that these decisions can be reviewed later to validate the monitor’s observations and decisions. In addition, the 
group monitor will check with the PI and will be empowered to bring in a backup facilitator to provide the 
participant with the attention needed, until the facilitation team can resume responsibility. 
For a 6 person group, there will be 2 backup facilitators available so for any instances of ‘potentially 
unattended psilocybin-related distress’ our research team will have the capacity to provide 1:1 participant to 
facilitator attention all participants at all times. This design affords the ability for adverse events to be identified 
and recorded, while also ensuring that all group participants receive the attention they need even as group sizes 
are changed through the course of the study. We anticipate that ‘potentially unattended psilocybin-related 
distress’ will be most likely to occur during the 2-4 hours of peak psilocybin effect. 
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7.8 Timing of adverse event recording and outcome measurements for a single group
 
Other adverse events could challenge the capacity of the 4-person facilitation team to manage the safety of all 
group members adequately. For example, if more than 4 participants became seriously nauseated at the same 
time, at a level requiring assessment and intervention, a backup facilitator might be indicated.
Adverse events will be reviewed by the research team after each group. As the first series of 6-person groups 
are conducted, adverse events will be tabulated and reviewed after each medication day. These adverse events 
will be reviewed by the research team to determine if the next group should proceed at the same group size, or if 
the group size should be decreased. As a rough benchmark, we shall consider an observed adverse event rate of 
10% or more as potentially too high to allow increase in group size or continued enrollment to the current group 
size.  
7.9 Efficacy analyses will be conducted after 4 groups of the same size. The efficacy of the group psilocybin-
assisted therapy intervention will be conducted after 4 groups have been conducted at one group size. The 
primary outcome for this analysis will be the HADS Total score, which in other studies has been shown to be 
responsive to psilocybin-assisted therapy in people with cancer. The primary outcome analysis from 4 groups will 
be informally compared to existing studies of psilocybin-assisted therapy in patients with cancer, in order to 
assess whether the efficacy of the group psilocybin-assisted therapy appears to be comparable to the results 
shown by prior published studies. The objective of this trial is not to statistically compare to historical numbers, 
but rather to see if the HADS values currently are roughly similar to the prior studies.1-3
Towards this end, we hope to see changes (pre- vs. post-psilocybin) in the HADS-Total score on the order 
of 1.0 standard-deviation (sd) unit. An observed effect size of 1.0 sd units or more would be largely considered to 
be at least comparable to previous studies and, depending on analysis of safety, could lead to an increase in the 
group size to see if both safety and potential efficacy can be maintained.  This assessment will consider the 
totality of the data, not just simple the mean change in HADS and the proportion of adverse events. Other 
measures will be taken into account as will the demographics of the patient population and proximity to 
anticancer treatment.
In addition, we have included demoralization as a secondary outcome as we are aware that it is being 
used as a primary outcome in a multisite randomized study that will include cancer patients that is planned but 
are not yet recruiting participants.(Anderson, personal communication Dec 2022) 
The judgment of our investigator team (that includes experience in psychedelic therapy, cancer group 
psychosocial interventions, and cancer clinical trial statistical analysis) is that the combination of statistical 
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analyses and expert judgment will result in reasonable decisions (in conjunction with a Trial Decision-Making 
Committee) to determine as the study progresses whether the group size should increase or decrease according 
to a set of Guiding Principles described below. Three examples of these decisions are described below.
7.10 Examples of how the study might proceed
Example 1 explanation. The study begins with 6 person groups, and 4 groups are conducted. No adverse events 
are recorded. The efficacy analysis indicates the decrease in anxiety is comparable to that seen in individual 
psilocybin-assisted therapy. The “Trial Decision-Making Committee” (explained further below) then decides that 
the group size should be increased to 7 person groups. After three 7-person groups, 2 instances of ‘potentially 
unattended psilocybin-related distress’ is recorded. Because the observed adverse event rate has reached 10%, 
the research team decides to terminate the study. The study recommendation would be for 6 participants with 
the 4-person facilitation team.
Example 1 graphic of how the study might proceed:
Two additional examples of how the study might proceed:
Example 2. The study begins with 6-person groups, and four groups are conducted. In the first four 
groups, 1 adverse event of a ‘potentially unattended psilocybin-related distress’ is recorded. The efficacy analysis 
of the primary outcome from these 4 groups (= 24 participants) suggests that efficacy is comparable. The Trial 
Decision-Making Committee makes a judgment that a group size of 8 is feasible to test. After 4 groups of 8 
persons, 1 adverse event is recorded, and the efficacy analysis is comparable. The study recommendation would 
be that 8 person groups with a 4 person facilitation team is adequate *if* a backup facilitator is available.
Example 3. The study begins with 6-person groups, and each of the first 3 groups records 1 instance of a 
‘potentially unattended psilocybin-related distress’. The Trial Decision-Making Committee determines that the 
study continue with 5-person groups. Four 5-person groups are conducted, with zero instances of ‘potentially 
unattended psilocybin-related distress. The efficacy analysis from the 5-person groups indicates the decrease in 
anxiety is comparable to that seen in individual psilocybin-assisted therapy. The study recommendation would be 
for 5-person groups with a 4-person facilitation team.
Trial decision-making committee
The Trial Decision-Making Committee is a specific feature of this proposal that will make decisions about 
how the trial should proceed with regards to group size changes over time. This committee is like a Data and 
Safety Monitoring Committee in that it will review adverse events data for each group, review statistical analyses 
of potential efficacy for each series of 4 groups, and will review individual adverse events with the investigators. 
6
6
6
6
7
7
7
0 
0 
0 
0 
1 
0 
1 
#Participants 
per group 
Study 
Timeline 
Adverse 
events
Efficacy 
Analysis 
After 4 
6 person 
Groups: 
Acceptable
Decision to 
Increase 
Group Size 
Because 
Adverse 
Event Rate 
= 0%
Decision to 
Terminate 
7 person series 
because 
Adverse Event 
Reached 10%
Conclusion: 
Optimal 
Group Size = 6 
6 participants + 4 facilitators
Preparation x 3   Med      Integrate x 3
Research 
Team 
Milestones
Group 
intervention 
structure 
Month 1.         2.                       3                         4.                        5                        6 
7                        8
Adverse 
Event 
Analysis & 
Review 
after each 
Group
Backup 
Facilitator 
Called I n
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However, this committee is different from a Data Safety Monitoring Committee in that it will be composed of the 
study investigators and external experts (with expertise in legal group psilocybin experiences in the Netherlands, 
bioethics, psycho-oncology, and psychotherapy), and they will discuss changes proposed by the investigators to 
group size and vote on investigator proposals. The Trial Decision-Making Committee will have 5 members, 
including Dr Back, Dr McGregor, two study facilitators, two external experts (chosen for their expertise in group 
intervention clinical trials and psychedelic therapy) and one cancer patient who has experienced psychedelic 
therapy in a clinical trial. The PI will review trial progress and updates the committee after each group. If there 
are no adverse events, the committee may not meet until an efficacy analysis from a series of 4 groups at the 
same size is available. If there are adverse events, the committee will meet to discuss the adverse event, the 
outcome, and PI’s proposal about how to proceed. Changes in group size of 1 or 2 participants will be allowed.
These examples define the following Guiding Principles that the Trial Decision-Making Committee will use in 
making decisions about group size as the study progresses:
Guiding Principle 1: Adverse group events that are directly related to exceeding the capacity of the 4-
person facilitation team ensure participant safety and are critical for study determination of a safe and 
efficacious group size. 
Adverse group events will be recorded and documented, but the study team will be able to respond to 
‘potentially unassisted psilocybin-related distress’ within a short time (<15 min) so as to mitigate the impact on 
an individual study participant. As a rough benchmark, we shall consider an observed AE rate of 10% or more to 
be excessive.
Guiding Principle 2: Measured efficacy of the group-size-specific-outcomes is another important factor 
for reaching a study determination of optimal group size. 
Optimal group size would have efficacy at least comparable to individual psilocybin-assisted therapy, or 
at least define the tradeoff in efficacy vs group size. Based on prior work, we consider benchmark for “at least 
comparable” to be a change in HADS-Total score from pre-psilocybin to post-psilocybin to be 1.0 sd units or 
more.  
Guiding Principle 3: Assessment of adverse events should take into account participant-specific features 
and group-specific features. 
A participant-specific feature might lead to refinement of screening criteria for participants rather than 
terminating conduct of another group at the same size. A group-specific feature might mean that 2 adverse 
events in a single group are given different weight than 1 adverse event in two successive groups. 
7.11 Administration of Investigational Agent
The investigational agent in this study, Psilocybin PEX010, will be administered once, on Day 0, orally, with water.
7.12 Concomitant Medication and Supportive Care Guidelines
Adverse event management during the psilocybin session. Reviews of the published 
literature on synthesized and botanical psilocybin indicate that the physiological and psychological 
effects are transient. The patient will be monitored at all times by trained research and/or medical 
staff. The study facilitator team will remain in attendance during the entire session. On the 
medication day, participants will be reminded that they have agreed to remain supervised by the 
study facilitators until the acute effects of psilocybin have subsided, and all participants will be 
accompanied by a facilitator to dinner after the medication session, and then to their individual 
rooms for bedtime. There will be a study staff person available through the night for any concerns 
that a participant might raise after the medication session. 
Most study procedures can and will be immediately stopped if participants request or if they 
are exhibiting significant distress. However during the psilocybin session, once participants have taken 
the psilocybin, the psychological effects cannot be immediately terminated and must be managed until 
the psilocybin effect has worn off. The medication day session with psilocybin will be performed in a 
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non-hospital setting that minimizes distraction and interruption, with a team of specially trained study 
facilitators and backup facilitators, and the participant will be monitored by specially trained 
facilitators who will have the skills to provide reassurance and a safe environment for the duration 
of the session.
If during the medication session, a participant does experience extreme distress, the PI may 
prescribe a designated ‘rescue’ medication in the event of symptoms that require it during or after the 
medication dosing session. Rescue medications may be a benzodiazepine, zolpidem, or other 
anxiolytic or sedative according to the physician's clinical judgment.
Following the Investigator’s Brochure, although there have been no reports of their use in well-
reported clinical trials with oral psilocybin, medications will be available for the treatment of causal 
symptomatic hypertension, agitation, or severe psychosis. 
If any participant develops an adverse reaction to the psilocybin as reported by them or as 
assessed by a member of the research team, we will ensure that the participant receives appropriate 
medical or psychiatric care. The level and exact type of care will depend on whether the adverse event 
occurs during the medication session where study facilitators will be in attendance or after the 
medication session when the participant is at home. Finally, the participant may be withdrawn from the 
study if his/her withdrawal is in the best interests of either the participant or of the research (e.g., due to 
a medical condition making the procedures unsafe or any condition making interpretation of the results 
difficult).
Overnight monitoring for safety if an adverse event is occurring: The PI and study facilitators 
will closely monitor the participant's medical status during all study interventions.  The staff take 
whatever medical steps are safely possible to reduce the need for an additional holding period after 
the medication session is over. For the participants who opt to participate in this study at a rustic 
retreat center, staying overnight at the retreat center will be required, and a night call clinician will 
be available in-person throughout the first night after the medication session for participant 
concerns. For participants to opt to participate in this study at the urban day-retreat center, who 
return home at the end of each day, a night call clinician will be available by phone through the first 
night after the medication session. No published psilocybin study done since 2015 has reported the 
need for overnight hospital admission after a medication session involving psilocybin and while an 
overnight hospitalization will be available in this study, and the PI has not heard of any anecdotal 
cases of overnight observation being required in a clinical trial setting.
Emotional Responses and Discomfort During the Psilocybin Medication Session, or During 
Preparation or Integration Sessions: The study facilitators will be specially trained to work with cancer 
patients and also in working with group psilocybin experiences. The facilitator manual outlines first- and 
second-line interventions for emotional responses or any psychological reactions that may be 
experienced. In studies since 2000 conducted at academic research centers, no participants required 
‘rescue’ medication for psychological reactions during the medication session or in preparation or 
integration sessions—emotional distress did occur, but was successfully managed with non-
pharmacologic  psychotherapeutic interventions. 
Inappropriate Interactions with Study Facilitators. At all times during in-person preparation, 
medication day, and integration sessions, a therapist will not be alone and unmonitored with a 
participant during the psilocybin session at any time.
7.13 Duration of Therapy
Participants in this study will receive one psilocybin session, along with associated therapy 
sessions. The entire duration of this psilocybin-assisted therapy from Prep 1 through Integration 3 is 
approximately 6 weeks.
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7.14 Duration of Follow-Up
Participants will receive questionnaires to complete at 1 week, 4 weeks, 8 weeks, 12 weeks, and 
24 weeks after their psilocybin session. 
7.15 Dosing Delays/Dose Modifications
Dosing delays are not applicable. If a subject develops a complication that requires them to 
withdraw from the study during the 6 weeks of therapy, we will need to re-enroll them in a new small 
group and they will start again from Prep 1. 
Dose modifications will be not be done. The dose of psilocybin is fixed for all body weights at 25 
mg, and this fixed dose has been shown to produce equivalent results in a large historical comparison to 
body weight dosing at the Johns Hopkins Center for Consciousness Studies. 
8.0
SUBJECT EVALUATION
8.1 Clinical Evaluations
Clinical evaluations take place according to the Study Calendar (Appendix A). 
8.2 Screening and Baseline Evaluations
Screening/Baseline Visits will occur within 2 months of the first zoom call. Procedures to be performed during the 
Screening/Baseline Visit are as follows:

Physical Examination

Neurological Exam

Blood pressure

Performance Status (specify appropriate performance scale)

Labs (which may be done at outside labs within 2 months of the screening visit)
o
Hematology: CBC, differential, platelets
o
Serum Chemistries: including calcium, magnesium, SGOT, SGPT, alkaline phosphatase, LDH, total 
bilirubin, BUN, creatinine, electrolytes, and glucose

Baseline questionnaires
8.3 Psilocybin session

Blood pressure at start of session and 1 hour after administration. If the 1 hour BP is elevated above 140/90 
mm Hg, the BP will be repeated hourly until it returns to baseline

Labs to be done at start of session 
o
Urine pregnancy test for participants of childbearing potential

At the end of the medication dosing session:
o
Participants will complete paper or computer-based questionnaires designed to assess acute 
subjective experiences associated with the medication dosing session within 24 hours of completing 
the session.
o
Study facilitators will assess the participant’s mood and suicidality with the C-SSRS if indicated. 
o
Participants will remain under observation by the facilitation and research team until the 
facilitation team judges that their perception, cognition, functioning, and judgment are 
adequate for them to go to bed safely.
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8.4 Integration visit safety checks

Facilitators will be alert to participant symptoms of anxiety or depression on integration visit safety checks 
and will reach out after the group session to any participant who may need additional support and 
assessment. An announcement will be made at the beginning of every session inviting any participant to 
send an individual chat message to the facilitator or to text the study coordinator if any concerns related to 
suicidality are arising. The study coordinator will then perform an C-SSRS assessment and contact the PI for 
further assessment.
8.5 Post-Treatment Follow-up Period (specify visits based on days after psilocybin session)
Subjects will have visits 14 days after EOT, 28 days after EOT, and 90 days after EOT.  Assessments to be 
performed at these visits are as follows:
--Integration sessions are as follows:
Group Integration 1 is in-person, on Day 3 of the retreat
Individual Integration 1 is in-person, on Day 3 of the retreat
Group Integration 2 is about a week after leaving the retreat, is virtual, using a secure video platform
Group Integration 3 is a week after the prior session, is virtual, using a secure video platform
--Any participant who appears to display any warning signs of a worsening mood (more withdrawn, more hopeless, 
more helpless in any session will be contacted immediately after a session for an assessment including C-SSRS 
suicidality assessment. That C-SSRS would be done on a private phone or video call.
--Online questionnaires will be completed after the psilocybin session at:
2 weeks
4 weeks
8 weeks
12 weeks
24 weeks
Once these visits and assessments have been completed, the subject will be considered as having completed 
participation in the clinical trial.  If a subject enrolls in another study or requires additional cancer treatment, the 
visit or assessment dates may be adjusted to accommodate the subject’s schedule.  
If a subject is unable/unwilling to return for any scheduled visits after the end of trial (EOT), the subject will be 
considered as having completed study requirements at the EOT.
8.6 Long-Term Follow-up Period (specify duration and timing)
Subjects will be contacted by site staff by telephone, email, or mail at 6 months after the psilocybin session to 
complete scheduled study questionnaires.
8.7 Plan of Action for A Participant Exhibiting Suicidality
For suicidality exhibited on a video call (preparation session or integration session):
--the study PI (a physician with training in assessing suicidality) or co-investigator (a PhD psychologist also trained 
to assess suicidality) will immediately call the participant individually, and will conduct a narrative assessment of 
suicidal wish, method, intent, and plan according to the FDA guidelines on assessing suicidality in clinical trials 
involving an IND. The assessment will also include administration of the C-SSRS, the instrument approved by the 
FDA for assessing suicidality in IND clinical trials.
--for a participant with active suicidal ideation (which may include method, or intent, or plan), the study PI will 
immediately consult the Attending Psychiatrist in the Harborview Emergency Room, who is available 24 hours/day 
to discuss the case.
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--based on the Attending Psychiatrist’s recommendations, the study PI may ask the participant to come to the 
Harborview Emergency Room immediately. If the participant lives a long distance from Harborview Medical Center, 
the study PI will contact the participant’s medical provider (which the PI secures during the consent process) to find 
an appropriate local referral. 
For suicidality exhibited at the retreat:
--the study PI (a physician with training in assessing suicidality) or co-investigator (a PhD psychologist also trained 
to assess suicidality) will immediately assess the participant individually in person, and will conduct a narrative 
assessment of suicidal wish, method, intent, and plan according to the FDA guidelines on assessing suicidality in 
clinical trials involving an IND (attached). The assessment will also include administration of the C-SSRS, the 
instrument approved by the FDA for assessing suicidality in IND clinical trials.
--for a participant with active suicidal ideation (which may include method, or intent, or plan), the study PI will 
immediately consult the Attending Psychiatrist in the Harborview Emergency Room, who is available 24 hours/day 
to discuss the case. 
--If the Attending Psychiatrist recommends that the patient be seen in an Emergency Room, the study PI will 
discuss whether the best plan would be for the participant to be transported to the Harborview Emergency Room 
(a 2 hour drive) or to be seen locally at Mason General Hospital (a 15 min drive) which does not have a psychiatrist 
on call.
9.0
TOXICITY MONITORING
Both acute and chronic toxicities are recorded. Monitoring for acute toxicity takes place during and immediately 
following IP administration for a period of 8 hours at the study site. Subjects are observed for the development of 
an immediate localized allergic reaction or anaphylactic reaction or emotional reaction during this time. 
A rare reported complication of psilocybin use is Hallucinogen Persisting Perceptual Disorder (HPPD), which 
results in visual perceptual distortions that are generally mild (this is sometimes described as the visual equivalent 
of tinnitus). This has not been reported in a recent clinical trial but this condition has been reported in anecdotes 
in the lay literature. Because this is a rare condition and there is no clear treatment, subjects will be warned about 
this in the consent process, reminded after the psilocybin session, and assessments will be individualized to the 
subject’s symptoms. 
There are no known unacceptable toxicity treatments. However, it should be noted that during the psilocybin 
session that emotional distress or fear or even paranoia is best treated first with facilitator attention and calming, 
with medical treatments like benzodiazepines or antipsychotics used as a last resort. In recent clinical trials with 
investigators at New York University and Johns Hopkins, these ‘rescue’ medications have never been used 
(personal communications, A. Back).
10.0
SUBJECT DISCONTINUATION OF ACTIVE TREATMENT
Subjects may be removed from this study at any time at their discretion *except* during the psilocybin session. 
Subjects may also be removed from this protocol if they develop any untoward side effects from the study 
medications. In addition, there are stopping rules in place for lack of efficacy and excessive toxicity as detailed in 
the statistical section.
If a subject withdraws consent to participate in the study or aspects of the study, attempts should be made to 
obtain permission to record survival data up to the protocol-described end of the subject follow-up period. Survival 
data are important to the integrity of the final study analysis. Documentation in the medical record should state 
that the subject is withdrawing from the study and what, if any, selected data the subject will permit the investigator 
to obtain.
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During the psilocybin session, the subject will be able to withdraw from the study once the study facilitators and PI 
have assessed the subject and determined that they are safe for discharge from the session. 
Follow for subjects who withdraw will be dependent on their willingness to be in contact with the PI, but the PI will 
offer informal followup at the subject’s convenience in order to detect and report adverse outcomes.
Subjects who withdraw will likely not be replaced unless they withdraw before the psilocybin session at a time when 
a new subject could be recruited to join the small group prior to the first Preparation session. 
An explanation for discontinuing treatment is recorded for each subject discontinuing treatment on the 
appropriate CRF/eCRF. The Sponsor, or its designee, must be notified immediately if a subject discontinues 
treatment. All subjects, irrespective of treatment status, will continue to be followed for survival. Treatment in 
this study must be discontinued for any of the following reasons:

if the Sponsor decides to stop the study;

at Investigator’s discretion;

at the subject’s request;

if the subject enrolls in a trial of another investigational agent;

Grade 4 or life-threatening toxicity (See Section 12, Adverse Events) attributable to study agent;

toxicity reactions of Grade 3 or higher, according to the grading in Appendix XX - NAME Grading Scale as 
identified in Section 10

pregnancy;

any mental health emergent or urgent condition.
11.0
CONCOMITANT MEDICATIONS

Subjects may take small amounts of topical or inhaled corticosteroids, as well as corticosteroids used as 
replacement therapy for adrenal steroids, e.g., <0.75 mg of dexamethasone, or equivalent.

Subjects may take doses of nonprescription strength NSAIDS, acetaminophen (paracetamol), ibuprofen or 
acetylsalicylic acid (aspirin) for non-chronic headache, muscle pain, trauma, or prophylaxis as long the 
dosing regimens comply with the recommended dose in the product labeling.

Subjects may receive antihistamine therapy for colds or allergies at non-prescription doses, but subjects 
should not take these medications within 5 days before or after IP administration.

Subjects may take vitamin supplements within a dose range not associated with toxicity.

Other treatments and medications that may affect immune function, that have known or suspected anti-
tumor activity, or that could interfere with the imaging assessment of disease progression are not allowed 
for subjects prior to crossover. A list that gives examples of such therapies is included in the study manual.

The use of other investigational agents is not permitted.

Active immunotherapy is not allowed for any subject.
12.0
ADVERSE EVENTS
12.1 Adverse Event 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a 
medicinal product; the event does not necessarily have a causal relationship with study drug administration or 
usage. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not considered related to the medicinal (investigational) product.
 
12.2 Serious Adverse Event 
An AE is classified as a serious adverse event (SAE) if it meets one of the following criteria:
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Fatal
The AE resulted in death.
Life threatening
The AE placed the subject at immediate risk of death. This classification does 
not apply to an adverse event that hypothetically might cause death if it 
were more severe. 
Hospitalization
The AE required or prolonged inpatient hospitalization. Hospitalizations for 
elective medical or surgical procedures or treatments planned before 
enrollment in the treatment plan or routine check-ups are not SAEs by this 
criterion. Admission to a palliative unit or hospice care facility is not 
considered to be a hospitalization. 
Disabling/incapacitating 
The AE resulted in a substantial and persistent disruption of the subject’s 
ability to carry out normal life functions. 
Congenital anomaly or birth 
defect
An adverse outcome in a child or fetus of a subject exposed to the molecule 
or treatment plan regimen before conception or during pregnancy. 
Medically significant
The AE did not meet any of the above criteria, but could have jeopardized 
the subject and might have required medical or surgical intervention to 
prevent one of the outcomes listed above. 
12.3 Unexpected Adverse Event
An unexpected adverse event is defined as an event that has a nature or severity, or frequency that is not 
consistent with the applicable investigator brochure.  “Unexpected,” as used in this definition, refers to an adverse 
drug experience that has not been previously observed and reported rather than an experience that has not been 
anticipated based on the pharmacological properties of the study drug.
12.4 Monitoring and Recording Adverse Events
All AEs will be assessed by the investigator or qualified designee and recorded in the CRFs. The investigator should 
attempt to establish a diagnosis of the event on the basis of signs, symptoms and/or other clinical information. In 
such cases, the diagnosis should be documented as the adverse event and/or serious adverse event and not 
described as the individual signs or symptoms. The following information should be recorded:

Description of the adverse event using concise medical terminology

Description as to whether or not the adverse event is serious, noting all criteria that apply 

The start date (date of adverse event onset)

The stop date (date of adverse event resolution)

The severity (grade) of the adverse event 

A description of the potential relatedness of the adverse event to study drug, a study procedure, or other 
causality 

The action taken due to the adverse event

The outcome of the adverse event
Subjects who terminate early or who experience a non-serious AE considered to be possibly or definitely related to 
the investigational study agent will be contacted at the time intervals specified in the study for questionnaire 
assessments with an email asking them how they are doing. If the AE has persisted or has created complications, 
the PI will request a phone call to hear a more detailed report of the AE, including the information in the above list. 
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12.5 Grading Adverse Event Severity
All AEs will be graded in severity but this study will not use the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5.0 because that grading scale is designed for anticancer agents. For this study we will use 
the following grading system that was approved by the FDA:
--Mild adverse event (does not affect patient activity)
--Moderate adverse event (mild disruption in usual activity)
--Severe (major disruption in usual activity)
12.6 Attribution of an Adverse Event
Association or relatedness to the study agent will be assessed by the investigator as follows:
Definite
(must have all 4)

Has a reasonable temporal relationship to the intervention

Could not have readily been produced by the participant’s clinical state or have 
been due to environmental or other interventions

Follows a known pattern of response to intervention

Disappears or decreases with reduction in dose or cessation of intervention and 
recurs with re-exposure
Probable
(must have 3)

Has a reasonable temporal relationship to the intervention

Could not have readily been produced by the participant’s clinical state or have 
been due to environmental or other interventions

Follows a known pattern of response to intervention

Disappears or decreases with reduction in dose or cessation of intervention
Possible
(must have 2)

Has a reasonable temporal relationship to the intervention

Could not have readily been produced by the participant’s clinical state

Could not readily have been due to environmental or other interventions

Follows a known pattern of response to intervention
Unlikely
(must have 2)

Does not have a temporal relationship to the intervention

Could readily have been produced by the participant’s clinical state

Could have been due to environmental or other interventions

Does not follow a known pattern of response to intervention

Does not reappear or worsen with reintroduction of intervention
For general AE assessment, an AE is considered related if it is assessed as definitely, probably, or possibly related; 
unrelated if it is assessed as unlikely related or unrelated. 
12.7 Adverse Event Recording Period
AEs will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to a 
study-related intervention in this study, through the date of the last questionnaire at 24 weeks.  AEs with an onset 
date prior to the first exposure to a study intervention will not be recorded, except in the case of clinically 
significant worsening of the AE during the specified AE monitoring time frame. 
12.8 Adverse Event Reporting Requirements 
12.8.1 Reporting to the IRB
The investigator or designee must report events to the IRB of record in accordance with the policies of the 
IRB for expedited reporting and continuing review.
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12.8.2 Reporting to the Coordinating Center [and/or Lead Investigator]
There are no external clinical sites. Thus the PI will be collecting all reports of AEs directly and an additional 
procedure is not required.
12.8.3 Reporting to FDA
The sponsor-investigator assumes responsibility for IND safety reporting to the FDA and participating 
investigators, in accordance with regulations under 21 CFR 312.32.
The sponsor-investigator will assess each reported event for seriousness, expectedness, and the 
relationship to the investigational product.
For determination of IND safety reporting, AE attribution will be assessed according to the suspected 
adverse reaction definition in 21 CFR 312.32, as an AE for which there is a reasonable possibility that the 
drug caused the adverse event, where “reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the AE.  Suspected adverse reactions that are serious and unexpected 
will be reported to the FDA as an IND safety report.
SAEs that do not meet IND Safety Report criteria will be reported to the FDA as part of annual reporting 
responsibilities described under 21 CFR 312.33.
12.8.4  Reporting to Psilo Scientific Ltd
Psilo Scientific Ltd is providing the investigational product for use in the study.  All SAEs occurring during 
the AE reporting period must be reported to Psilo Scientific within 5 days of study team awareness by the 
study PI.
13.0
CRITERIA FOR ENDPOINT EVALUATIONS
All the endpoint evaluations in this study are self-reported questionnaires addressing mental health symptoms, 
quality of life, and other symptoms. All the evaluation questionnaires are scientifically validated, are listed in the the 
Schedule of Evaluations (Appendix A) and are included in the IRO application. 
14.0
ASSESSMENT OF EFFICACY
14.1 Efficacy and endpoint assessment
Note that the primary endpoint in this study is an adverse event, and efficacy is the secondary endpoint. 
Primary Endpoint: Potentially unattended psilocybin-related distress, which is defined as the occurrence 
of participant distress that needs 1:1 facilitator attention that cannot be met by the 4-person facilitation team.
The secondary endpoint is the measurement of symptoms of depression and anxiety using the 
Hospital and Anxiety Depression Scale-Anxiety score (HADS) at 28 days (4 weeks) after the psilocybin session.
 
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14.2 Method and Timing
Primary endpoint: Will be assessed by a study monitor, who will in attendance at the psilocybin session, 
and will note potentially unattended psilocybin-related distress, alert the PI or one of the lead facilitators 
immediately. When either the PI or lead facilitator confirms the study monitor’s determination that a potentially 
unattended psilocybin-related distress event has occurred, the backup facilitator will be immediately brought in. 
This endpoint could occur at any time during the 6-8 hour psilocybin session but is most likely between hours 2-4, 
when the psilocybin is having its peak effect.
Secondary and exploratory endpoint: Questionnaires that will be completed online according to the study 
schedule in Appendix A.
15.0
STATISTICAL CONSIDERATIONS
15.1 Study Design 
This study was designed in close consultaton with Ted Gooley PhD, biostatistician, to adapt an approach used for 
Phase 2 dose-finding studies to this Phase 1/2 group-size-finding study.
15.2 Objectives and Hypotheses
Primary Objective: To test the safety, tolerability, and feasibility of a group model for psilocybin-
assisted therapy for patients with stable metastatic cancer with clinically significant anxiety.
Hypothesis:. The number of participants per group in a small group model of psilocybin-assisted therapy 
administered by a 4-person facilitation team that demonstrates safety will be between 6 and 8 participants with 
stable metastatic cancer.
Secondary Objective: To explore the efficacy of the group model of psilocybin-assisted therapy on 
symptoms of anxiety, depression, demoralization, quality of life, and cancer-related post-traumatic stress. 
Hypothesis: The small group model of psilocybin-assisted therapy with demonstrated safety will also 
demonstrate efficacy, defined as improvement in the Hospital Anxiety and Depression Scale—Total score (HADS-
Total) that is comparable to historical data from studies using an individual model of psilocybin-assisted therapy.
15.3 Primary/Secondary Endpoints/Hypotheses and Analytical Methods
Primary outcome analyses. Descriptive statistics will be used to analyze ‘potentially unattended psilocybin-
related distress’, and will be tabulated after each group intervention (which will happen approximately every 
month). The Trial Decision-Making Committee will review adverse event reports after each group, and will make 
a recommendation about how the trial should proceed (e.g., proceed at same group size; proceed at smaller size; 
or if 4 groups at the same size have been conducted, proceed to efficacy analysis). Thus we will change the 
facilitator:patient ratio based on the observed number of ‘potentially unattended psilocybin-related distress’ 
events. (See examples in Section 7.10) In the same way that a 10% incidence of certain non-life-threatening drug-
related toxicities are considered clinically acceptable in routine practice for anticancer agents, a 5-10% incidence 
of psilocybin-related distress in a group setting that requires calling in an extra facilitator may in the future be 
considered clinically acceptable if group psilocybin-assisted therapy is demonstrated to have that level of safety 
in this study.  
Efficacy analyses of measures of anxiety and other symptoms. A pre-post analytic strategy will be used for a 
series of 4 groups, with the primary measure (HADS) compared at Day -14 (where the medication day = Day 0) 
and Day 28. We expect that we will see in improvement in the mean HADS value (day 28 vs. day -14), where 
“improvement” is meant as a mean change in HADS of less than zero.  There is no comparison group in this trial, 
and for each group size, we’ll be estimating the “effect size” of change in HADS, where effect size is defined as 
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the mean change divided by the standard deviation of change. To calculate standard deviation, we shall ignore 
the potential “group” effect and consider all individuals within an intervention group as independent from each 
other as well as independent from individuals from other intervention groups. While we are hoping to see 
changes in HADS that are at least comparable to previous studies and this assessment will be descriptive, we will 
formally test the null hypothesis that the mean change in HADS is statistically different from the fixed value of 0. 
With 24 subjects (4 6-person groups) and assuming independence between subjects, this study will have 90% 
power to observe a statistically significantly (at the one-sided significance level of 0.05) reduced change from the 
fixed value of 0 if the true distribution of change in HADS is 0.6 standard-deviation units from 0.  
The Trial Decision-Making Committee will review efficacy analyses after each series of 4 groups at the 
same size, and will make a recommendation about how the trial should proceed (e.g., proceed at larger group 
size if efficacy comparable to historical data; proceed at smaller group size, if efficacy is not comparable; or 
conclude trial).
15.4 Randomization
All subjects in this study will be receiving psilocybin. A future study could compare group psilocybin-assisted 
therapy to individual psilocybin-assisted therapy with random assignment to each study arm.
15.5 Exploratory Analysis 
Descriptive statistics will be used for the exploratory outcomes in order to allow for comparison to historical 
controls, as a secondary analysis of efficacy. A qualitative interview after Visit 8 and before Visit 9  will provide 
subject perspectives on the group experience, what might be improved in future studies, and the value of 
interacting with other group members during the therapy sessions and at the retreat. 
16.0
DATA MANAGEMENT/CONFIDENTIALITY
16.1 Data Type 
A. Types and amount of scientific data expected to be generated in the project: 
This study will provide data from scientifically valid questionnaires and a qualitative interview completed by study 
subjects who provide ratings and descriptions of their symptoms, and experience with psilocybin-assisted group 
therapy. In addition, this study will collect data on blood pressure, subject distress, and subject adverse events 
during the psilocybin session.
The questionnaires include questions about mental health symptoms (including depressive symptoms, anxiety, 
demoralization, post-traumatic growth), suicidality, and future plans (advance care planning). A complete list of the 
questionnaires is in Appendix A.  
B. Scientific data that will be preserved and shared, and the rationale for doing so: 
The raw questionnaire data, interview data, and blood pressure, distress and adverse event data, and data for 
administrative linkages will be stored within a secure computing environment. All direct respondent identifiers 
(e.g., names and addresses) will be removed and maintained in a secure file for future contact purposes. 
If this scientific data is shared in the future (no plans exist at this time, subject identifiers will not be shared. 
C. Metadata, other relevant data, and associated documentation: 
Documentation to be made publicly available to the research community will include a list of the questionnaires 
(which are publicly available), study procedures, qualitative codebook, and research procedures (such as 
components of the screening evaluation), as well as study-level meta-data.
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16.2  Related Tools, Software and/or Code: 
Scientific data will be processed and analyzed with SAS, SPSS, and Excel, as well as Dedoose for qualitative data. 
16.3 Standards
To facilitate data use, the study will use standard processing and documentation protocols adopted by the Inter-
university Consortium for Political and Social Research (ICPSR) for data formats and dictionaries as well as for 
variable names, descriptions, and labels. 
Demographic, economic, and relationship questions will be based on NCI standards. 
16.4 Data Preservation, Access, and Associated Timelines 
A. Repository where scientific data and metadata will be archived: 
Data and metadata will be archived on secure UW research servers. Access is restricted to authorized study staff. 
B. Who will receive what records, where, and when.
Only authorized study staff will have access to identifier files, study databases, and CRFs. CRFs that are completed 
by hand during psilocybin sessions will be stored in a locked cabinet in the PI’s office, and will be transferred to 
electronic data files stored on secure UW servers designed for research data. 
C. Protections for privacy, rights, and confidentiality of human research participants: 
Subjects’ identifying information is only accessed by approved staff as part of the project duties within a secure 
computing environment. All questionnaire data will be identified only by a study code during collection and 
analysis. 
The privacy, rights, and confidentiality of human subject participants in this study will be protected through the 
suppression of all direct respondent identifiers, the careful classification of any potentially identifying data as 
restricted access, and we have applied for a Certificate of Confidentiality.
16.5 Oversight of Data Management and Sharing: 
Monitoring of and compliance with this Data Management and Sharing Plan will be the responsibility of the 
project’s Principal Investigator. The plan will be implemented and managed by professional staff working under the 
direction of the PI.
17.0
DATA AND SAFETY MONITORING PLAN
Institutional support of trial monitoring will be in accordance with the Fred Hutch/UW/SC Cancer Consortium 
Institutional Data and Safety Monitoring Plan (DSMP).  Under the provisions of this plan, Fred Hutch Clinical 
Research Support (CRS) coordinates data and compliance monitoring conducted by consultants, contract research 
organizations, or Fred Hutch employees unaffiliated with the conduct of the study.  Independent monitoring visits 
occur at specified intervals determined by the assessed risk level of the study and the findings of previous visits per 
the institutional DSMP. 
In addition, protocols are reviewed at least annually and as needed by the Consortium Data and Safety Monitoring 
Committee (DSMC), Fred Hutch Scientific Review Committee (SRC) and the Fred Hutch Institutional Review Board 
(IRB).  The review committees evaluate accrual, adverse events, stopping rules, and adherence to the applicable 
data and safety monitoring plan for studies actively enrolling or treating subjects.  The IRB reviews the study 
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progress and safety information to assess continued acceptability of the risk-benefit ratio for human 
subjects.  Approval of committees as applicable is necessary to continue the study.
The trial will comply with the standard guidelines set forth by these committees and other institutional, state, and 
federal guidelines.
18.0
INVESTIGATOR OBLIGATIONS
The PI is responsible for the conduct of the clinical trial at the site and oversight of the treatment of all study 
subjects. The PI must assure that all study site personnel, including sub-Investigators and other study staff 
members, adhere to the study protocol and to all applicable regulations and guidelines regarding clinical trials both 
during and after study completion.
The PI must ensure that all subjects are informed of the nature of the program, its possible hazards, and their right 
to withdraw at any time, and each subject signs a form indicating their consent to participate prior to undergoing 
any study-related procedures. 
19.0
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS
19.1 Pre-Study Documentation
The following documentation required by the FDA must be received by the IND Sponsor, or its designee, prior to 
initiation of the trial: FDA Form 1572; curricula vitae of the PI and all Sub-Investigators; signed Protocol Agreement; 
copy of the correspondence from the IRB indicating approval of the protocol and Informed Consent Forms, signed 
by the IRB chairperson or designee; an IRB membership list containing the names and occupations of the IRB 
members; copy of the Informed Consent Forms that were reviewed and approved by the IRB.
19.2 Study Site Training
Before initiation of the study, the IND Sponsor or its designated representatives will review and discuss the 
following items with the Investigator and clinic staff: the protocol, study procedures, record keeping and 
administrative requirements, drug accountability, AE reporting, Good Clinical Practice guidelines, CRF/eCRF 
completion guidelines, monitoring requirements, and the ability of the site to satisfactorily complete the protocol. 
Additional documents with instructions for study compliance and CRF/eCRF completion will be provided.
19.3 Documentation
The documentation of clinical data must be stored by the IND Sponsor according to legal requirements. The PI and 
study staff are responsible for maintaining a comprehensive and centralized filing system containing all study-
related documentation. These files must be suitable for inspection by the IND Sponsor (if applicable), the FDA, 
and/or other applicable regulatory agencies at any time, and should consist of the following elements: subject files 
(complete medical records, laboratory data, supporting source documentation, and the Informed Consent); study 
files (the protocol with all amendments, copies of all pre-study documentation, and all correspondence between 
the FDA (as needed), IRB, site, and IND Sponsor (if applicable)); and drug accountability files, containing a complete 
account of the receipt and disposition of the study drug.
19.4 Access to Source Data
The PI will permit the Cancer Consortium representatives or, if applicable, IND Sponsor's representatives, to 
monitor the study as frequently as deemed necessary to determine that protocol adherence and data recording are 
satisfactory. The CRF/eCRF and related source documents will be reviewed in detail at each site visit. Only original 
source documents are acceptable for review. This review includes inspection of data acquired as a requirement for 
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participation in this study and other medical records as required to confirm information contained in the CRF/eCRF, 
such as past history, secondary diagnoses, and concomitant medications. Other study records, such as 
correspondence with the IND Sponsor, IRB, and other committees, as well as  screening and drug accountability 
logs will also be inspected. All source data and study records must also be available for inspection by 
representatives of the FDA or other regulatory agencies.
19.5 Data Collection
Electronic case report forms must be completed and submitted for each subject enrolled in the study. Any changes 
or corrections made to the CRF/eCRF must be subsequently reviewed and signed by the PI. All data fields in the 
CRF/eCRF must be completed to avoid queries.
19.6 Protocol Interpretation and Compliance
The procedures defined in the protocol are carefully reviewed by the PI and his/her staff prior to the time of study 
initiation to ensure accurate representation and implementation. Protocol amendments, if any, are reviewed and 
implemented promptly following IRB approval and FDA authorization to proceed (if applicable). The IND Sponsor is 
responsible for submitting protocol amendments to the FDA as described in 21 CFR § 312.30 (Protocol 
Amendments) and other regulatory agencies according to national, state, or local requirements. 
For this study, the IND Sponsor-Investigator, or its designee, is always available to answer protocol- or subject-
related questions.
19.7 Study Monitoring and Data Collection
The IND sponsor-investigator will monitor adherence to the protocol, applicable FDA regulations and/or other 
regulatory agencies national, state, or local requirements, and the maintenance of adequate and accurate clinical 
records. Electronic case report forms are reviewed to ensure that key safety and efficacy data are collected and 
recorded as specified by the protocol. The IND Sponsor or its designee is permitted to access source documentation 
as needed to appropriately monitor the trial.
19.8 Disclosure of Data/Publication
Individual subject medical information obtained as a result of this study is considered confidential and disclosure to 
third parties other than those noted below is prohibited. Such medical information may be given to the subject’s 
personal physician or to other appropriate medical personnel responsible for the subject’s welfare. Data generated 
as a result of this study are to be available for inspection on request by the FDA or other regulatory agencies, and 
by the IRB.
19.9 Ethical Considerations
The Investigator agrees to conduct this study in accordance with applicable United States FDA clinical trial 
regulations and guidelines, applicable United States FDA clinical trial regulations and guidelines, the ICH E6 (R2) 
GCP guidelines, the European Union Directive 2001/20/EC for clinical trials conducted in the European Union, the 
IRB and local legal requirements and with the Declaration of Helsinki (1989). The Investigator will conduct all 
aspects of this study in accordance with all national, state, and local laws of the applicable regulatory agencies.
19.10
Informed Consent
The PI assumes the responsibility of obtaining written Informed Consent for each subject or the subject’s legally 
authorized representative before any study-specific procedures are performed.
Subjects meeting the criteria set forth in the protocol will be offered the opportunity to participate in the study. To 
avoid introduction of bias, the Investigator must exercise no selectivity with regard to offering eligible subjects the 
opportunity to participate in the study. Subjects or parents/legal guardians of all candidate subjects will receive a 
comprehensive explanation of the proposed treatment, including the nature of the therapy, alternative therapies 
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available, any known previously experienced adverse reactions, the investigational status of the study drug, and 
other factors that are part of obtaining a proper Informed Consent. Subjects will be given the opportunity to ask 
questions concerning the study, and adequate time to consider their decision to or not to participate.
Informed Consent will be documented by the use of a written Consent Form that includes all the elements required 
by FDA regulations and ICH guidelines. The IND Sponsor or designee will review the informed consent prior to 
submission to the IRB. The form is to be signed and dated by the subject or subject's legally authorized 
representative and by the person who administers the consent process. A copy of the signed form will be given to 
the person who signed it, the original signed Consent Form will be filed with the subject’s medical records, and 
copy maintained with the subject’s study records. The date and time of time of the Informed Consent must be 
recorded in the source documents.
If an amendment to the protocol changes the subject participation schedule in scope or activity, or increases the 
potential risk to the subject, the Informed Consent Form must be amended. Any amended Informed Consent must 
be reviewed by the IND Sponsor or designee (if applicable) and approved by the IRB prior to use. The revised 
Informed Consent Form must be used to obtain re-consent from any subjects currently enrolled in the study if the 
subject is affected by the amendment, and must be used to document consent from any new subjects enrolled 
after the approval date of the amendment.
19.11
Institutional Review Board
The PI will assure that an appropriately constituted IRB that complies with the requirements of 21 CFR Section 56 or 
written assurance of compliance with ICH E6(R2) guidelines will be responsible for the initial and continuing review 
and approval of the clinical study. Before initiation of the study, the PI or designee will forward copies of the 
protocol and Consent Form to be used for the study to the IRB for its review and approval. 
The PI or designee will also assure that all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others will be reported promptly to the IRB, and that no changes will be made to the 
protocol without prior IND Sponsor (if applicable) and IRB approval, except where necessary to eliminate apparent 
immediate hazards to human subjects.
If the study is under an IND, copies of relevant study-related correspondence between the Investigator and the IRB 
may be provided to the IND Sponsor, or its designee, by the Investigator. The PI or designee must promptly notify 
the IRB of any SAE occurring at the site or of any safety reports received from the IND Sponsor or designee 
according to the requirements of the IRB of record.  The Investigator or designee will be responsible for submitting 
periodic progress reports to the IRB at intervals appropriate to the degree of subject risk involved in the study, but 
not less than once per year and at the completion or termination of the study.
19.12
Subject Privacy
The IND Sponsor and the Investigator affirm and uphold the principle of the subject's right to privacy. The IND 
Sponsor, its designees, and the Investigator shall comply with applicable national and local privacy laws.
To verify compliance with this protocol, the IND Sponsor or  designee will require that the Investigator permit the 
IND Sponsor or designee’s monitor to review the subject's original medical records. Should access to such medical 
records require a waiver or authorization separate from the statement of Informed Consent, the Investigator will 
obtain such permission in writing from the subject before the subject is entered into the study.
20.0
STOPPING THE STUDY
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The Sponsor-Investigator may decide to stop the study at any point, for any reason. The following reasons will lead 
to premature termination of the trial:

New convincing information leading to unfavorable risk-benefit assessment of the investigational agent, 
including occurrence of significant toxicity associated with the investigational agent.

Sponsor-investigator’s decision that continuation of the trial is unjustifiable for medical or ethical reasons.
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21.0
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Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX. Acute psychological and physiological effects of 
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22.0
APPENDICES
Appendix A:
Study Calendar
Appendix B:
ECOG Performance Status Scale
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Appendix A Study Schedule
*Note that the C-SSRS, a clinician-administered instrument that is required at the screening visit. Visit 3 (the day before the psilocybin session), and Visit 5 (the 
day after the psilocybin session. At other visit, the C-SSRS will be done at the discretion of the facilitators and will require an individual call (it will not be 
administered during a group visit).
**The time window for completing the V4 questionnaires is 24 hours.
***The qualitative interview will be done during a time window starting after V8 up to V9. 
Schedule for Activities For A Participant
Purpose
Screen visit Group
Prep #1
Group
Prep #2
Group
Prep #3
Medi-
cation
Integra-
tion #1
Integra-
tion #2
Integra-
tion #3
Follow
-up
Study day
-15+
-14
-7
-1
0
1
8
15
28
Visit number
V0
V1
V2
V3
V4
V5
V6
V7
V8
Research activity
Demographics
X
Eligibility Determination
X
Medical exam
X
Informed consent
X
Caregiver contact info
X
Labs, ECG, urine tox review
X
Pregnancy screen (if applicable)
X
X
PI review of inclusion/exclusion
X
Psychiatric evaluation
X
Education re expectations
X
X
Preparation Session (group)
X
X
X
Preparation Session (individual)
X
Medication (psilocybin)
X
Medication dosing monitoring
X
Integration psychotherapy
X
X
X
Adverse event reporting
X
X
X
X
X
X
X
X
Research activity
Measures
Hosp Anxiety Depr Scale (HADS)
X
X
X
X
FACT-G
X
X
X
CES-D
X
X
X
Adjustment Disorder Questionnaire
X
X
X
Watts Connectedness Scale
X
X
X
Peace Acceptance (PEACE)
X
X
X
NIH-HEALS
X
X
X
Demoralization II (DS-II)
X
X
X
Death and Dying Distress Scale
X
X
X
Suicidality (C-SSRS)*
X
X
X
X
X
X
X
Mystical Experience Questionnaire**
X
Emotional Breakthrough
X
Challenging Experiences Q**
X
Communitas Scale**
X
Psychedelic Music Questionnaire**
X
Qualitative interview***
X
Adverse events
X
X
X
X
X
X
X
X
X
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Follow up measures for participants randomized to psilocybin
Purpose
Follow
up
Follow
up
Follow
up
Study Day
56
(8 wk)
84
(12 wk)
168
(24 wk)
  Visit number
V9
V10
V11
Research activity
  Measures
  Hosp Anxiety Depr Scale (HADS)
X
X
X
  FACT-G
X
X
X
  CES-D
X
X
X
Adjustment Disorder Questionnaire
X
X
X
Watts Connectedness Scale
X
X
X
Peace Acceptance (PEACE)
X
X
X
NIH-HEALS
X
X
X
Demoralization II (DS-II)
X
X
X
Death and Dying Distress Scale
X
X
X
Adverse events
X
X
X
Please note that these “Visits” are not actually in-person or virtual visits but are questionnaire followups only, but we 
are calling them “Visits” for the purpose of data tracking and analysis. 
*Note that the C-SSRS will not be done at Visits 9, 10, and 11 because those Visits do not involve clinician contact.
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Appendix B ECOG Performance Scale
GRADE
SCALE
0
Fully active, able to carry out all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light housework, office work
2
Ambulatory and capable of all self-care but unable to carry out work activities. Up and about more than 
50% of waking hours. 
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
5
Dead
Fred Hutch IRB
Approved 
1/26/2024