Visual Surround Suppression and Perceptual Expectation Under Psilocybin
Phase: PHASE1
Conditions: Perception Disturbance, Visual Suppression, Psychedelic Experiences
Sponsor: University of Minnesota

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ANCILLARY REVIEWS 
 
Which ancillary reviews do I need and when do I need them? 
Refer to HRP-309 for more information about these ancillary reviews. 
Select yes or 
no 
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If yes… 
Impact on 
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Include Gillette resources, 
staff or locations 
Gillette Scientific review and Gillette 
Research Administration approval is 
required.  Contact: 
research@gillettechildrens.com   
Required 
prior to IRB 
submission 
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Involve Epic, or Fairview 
patients, staff, locations, or 
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The Fairview ancillary review will be 
assigned to your study by IRB staff 
Contact: ancillaryreview@Fairview.org 
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must be 
received 
prior to IRB 
committee
/ 
designated 
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Consider 
seeking 
approval 
prior to IRB 
submission
. 
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devices, biologics, tobacco, or 
dietary supplements or data 
subject to FDA inspection? 
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See: 
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e  
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Complete the AURPC Human Use 
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Contact: barmstro@umn.edu  
Approval 
from these 
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s must be 
received 

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Resonance Research (CMRR) 
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Protocol Title 
VISUAL SURROUND SUPPRESSION AND PERCEPTUAL 
EXPECTATION UNDER PSILOCYBIN 
Principal 
Investigator/Faculty 
Advisor 
Name: Jessica L. Nielson, PhD 
Department: Psychiatry & Behavioral Sciences 
Telephone Number: (612) 624-9469 
Email Address: jnielson@umn.edu 
Student Investigator 
Name: Link Swanson 
Current Academic Status (Student, Fellow, Resident): Student 
  
Department: Cognitive science 
Telephone Number:  612-625-8736 
Institutional Email Address: link@umn.edu 
Scientific Assessment 
HRPP facilitated scientific assessment 
IND/IDE # (if 
applicable) 
IND146989 
IND/IDE Holder 
Jessica L. Nielson, PhD 
Investigational Drug 
Services # (if 
applicable) 
5591 
Version 
Number/Date: 
Version 10: May 18, 2023 
 
PROTOCOL COVER PAGE 
 
 
 
 

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REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
1 
8/28/2020 
Changed UBACC to the use of the 
MacCAT-CR 
No 
2 
10/02/2020 
Adding language about video 
recording all study visits, adding 
inclusion criteria for wearing face 
masks/coverings at all times during 
study visits, description of mixed in-
person and Zoom study visits, adding 
survey screening, and adding e-
consenting. 
Yes 
3 
12/09/2020 
Adding information about required 
COVID testing prior to in-person visits, 
and adjusting visit schedules for 
enrolled participants that test positive 
for COVID prior to a visit to allow for 
quarantine and reschedule. Also 
applies to study staff who will also be 
asked to get tested prior to in-person 
visits, and adjusting scheduling of 
visits if quarantine is needed. 
Yes 
4 
07/20/2021 
Adding heart rate and respiratory rate 
data collection during MRI scans 
No 
5 
10/29/2021 
Adding a debriefing session for visits 
3a and 5a over zoom (or in person) 
following each dosing session, adding 
a follow up EEG and psychophysics 
measurement during visit 6, updates 
to how MRI and EEG data will be 
stored and analyzed, updates to 
blood draws, and additional devices 
noted that will be used for data 
access and analysis, and updates to 
I/E criteria. 
Yes 
6 
01/14/2022 
Adding additional time for 
preparatory sessions totaling 8 hours; 
Yes 

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adding 4 additional measures for 
verbal and visual learning and 
memory, the adverse childhood 
experiences questionnaire, and the 
emotional breakthrough inventory; 
adding an adapted set of questions to 
the Matrix reasoning section of the 
WASI to assess divergent thinking; 
adjusting total hours in the study to 
reflect this, and adjusting the 
compensation to reflect the extra 
hours; updating the mask mandate 
for in person dosing visits; creating 
more structure around staff COVID 
testing requirements for in-person 
visits; adding that staff and 
participants be up-to-date on COVID 
vaccines, per CDC guidelines; updated 
language for CMRR MRI usage as 
updated by the facility. 
7 
11/29/2022 
Adding an administration of the 
subjective experience questionnaires 
at the end of the day on each dosing 
day; Collecting psychophysics and EEG 
starting at 2 hours into the dosing 
session, without taking a break 
between psychophysics and EEG; 
Extending the time frame for visits 1 
and 2 to have some overlap; 
Participant facing materials for 
preparation/rapport building; 
extending the washout time between 
dosing sessions from 2 weeks to 1 
month to account for carry-over 
effects; Add ECG recording for 
participants to exclude anyone with a 
QTc greater than 450 msec, based on 
the FDA Guidance of Clinical 
Evaluation of QT/QTc Interval 
Prolongation and Proarrhythmic 
Potential for Non-Antiarrhythmic 
Drugs, collected at baseline, and at 
the end of the day on each dosing 
session (visits 2 and 4). 
 
Yes 

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8 
01/06/2023 
Reverting to a 2-week washout 
between dosing sessions due to 
funders not approving this change. 
Clarification on hours for preparatory 
sessions for visits 2 and 4. 
Yes 
9 
05/18/2023 
Updating ICF to include language 
about potential repeated MRI 
risks/side effects. Also removing BMI 
as an exclusion criterion, removing 
language about COVID safety as the 
guidelines continue to evolve to 
reflect that we will adopt the current 
institutional guidelines to prevent the 
spread of COVID-19, and updating our 
phone screen to include more 
information to help determine 
ineligibility around mental health 
symptoms and substance abuse to 
help with enrollment failures. 
Yes 
 
 
 

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Table of Contents 
 
1.0 
Objectives 
11 
3.0 
Study Endpoints/Events/Outcomes 
15 
4.0 
Study Intervention(s)/Investigational Agent(s) 
15 
5.0 
Procedures Involved 
18 
6.0 
Data and Specimen Banking 
35 
7.0 
Sharing of Results with Participants 
36 
8.0 
Study Population 
36 
10.0 
Local Number of Participants 
41 
11.0 
Local Recruitment Methods 
41 
12.0 
Withdrawal of Participants 
42 
14.0 
Potential Benefits to Participants 
48 
15.0 
Statistical Considerations 
48 
16.0 
Health Information and Privacy Compliance 
49 
17.0 
Confidentiality 
53 
18.0 
Provisions to Monitor the Data to Ensure the Safety of Participants 
53 
19.0 
Provisions to Protect the Privacy Interests of Participants 
54 
20.0 
Compensation for Research-Related Injury 
55 
21.0 
Consent Process 
55 
22.0 
Setting 
56 
23.0 
Multi-Site Research: N/A 
57 
24.0 
Coordinating Center Research: N/A 
57 
25.0 
Resources Available 
57 
26.0 
References 
58 
 
 

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ABBREVIATIONS/DEFINITIONS 
 
5D-ASC = 5 dimensional altered states of consciousness 
5-HT = 5 hydroxytryptamine (AKA serotonin) 
5HT1A = 5HT 1A receptor 
5HT2A = 5HT 2A receptor 
ACE = Adverse Childhood Experiences 
AE = Adverse event 
ARC = Ambulatory Research Center 
BDNF = Brain Derived Neurotrophic Factor 
BMI = Body mass index 
BVMT = Brief Visual Memory Test 
CMRR = Center for Magnetic Resonance Research 
COVID = COVID-19, Coronavirus Disease 2019 
CRF = Case report form 
CRP = C-reactive Protein 
CRU = Clinical research unit 
C-SSRS = Columbia Suicide Severity Rating Scale 
DEA = Drug Enforcement Agency 
DSM = Diagnostic and Statistical Manual  
EBI = Emotional Breakthrough Inventory 
EDI = Ego dissolution inventory 
EEG = Electroencephalogram  
ECG/EKG = Electrocardiogram 
ELISA = Enzyme-Linked Immunosorbent Assay 
FDA = Food and Drug Administration 
fMRI = Functional Magnetic Resonance Imaging 
GFAP = Glial Fibrillary Acidic Protein  
GPCR = G-protein coupled receptor 
HPPD = Hallucinogen persisting perception disorder  
HVLT = Hopkins Verbal Learning Test 

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IDS = Investigational Drug Services 
I/E = Inclusion/Exclusion criteria 
IL-1β = Interleukin 1 beta 
IL-6 = Interleukin 6 
IL-10 = Interleukin 10 
IFN-γ = Interferon gamma 
LGN = Lateral geniculate nucleus 
MAOI = Monoamine oxidase inhibitor 
MacCAT-CR = Macarthur Competence Assessment Tool For Clinical Research 
MEG = Magnetoencephalography 
MINI-7 = Mini international neuropsychiatric interview, English version 7.0.2 for DSM-5  
MMN = Mismatch negativity 
MSI = Minnesota Supercomputing Institute 
PANAS = Positive and negative affect schedule 
PI = Principal Investigator 
QTc = QT corrected for heart rate (QTc) interval reflects ventricular repolarization 
RMEQ-30 = Revised mystical experiences questionnaire 
rsfMRI = Resting state functional magnetic resonance imaging 
s100β = S100 calcium-binding protein beta 
SAE = Serious adverse event 
SNRI = Selective norepinephrine reuptake inhibitor 
SSRI = Selective serotonin reuptake inhibitor 
TGFβ-1 = Transforming growth factor beta 1 
TNFα = Tumor necrosis factor alpha 
TNF-R1 = Tumor necrosis factor receptor 1 
TNF-R2 = Tumor necrosis factor receptor 2 
UCHL-1 = Ubiquitin C-Terminal Hydrolase L1 
UMN = University of Minnesota 
vERP = Visual event related potentials 
WASI-II = Wechsler Abbreviated Scale for Intelligence-II 

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1.0 
Objectives 
 
Purpose: The proposed study will address the critical need for more precise characterizations of 
the acute visual effects of the drug psilocybin by measuring the impact of acute psilocybin 
intoxication on a perceptual task known as visual surround suppression, compared to an active 
placebo control. The data collected in the proposed experiment will make important 
contributions to knowledge of how psilocybin impacts contextual processing in the brain. 
Moreover, this will in turn inform the neurobiology of visual surround suppression in general, 
providing the first investigation of links between surround suppression and serotonergic 
pathways in humans. Furthermore, the impact of psilocybin on surround suppression will 
complement recent discoveries of differences in surround suppression present in certain clinical 
populations. Taken together, these points suggest that our relatively simple and 
straightforward study could have significant payoff in its contribution to knowledge, not only of 
the effects of psilocybin but also of key brain processes underpinning human vision and context 
processing more broadly.  
1.1 Specific Aims:  
 
Aim 1a will test the acute impact of psilocybin on the strength of the psychophysical 
surround suppression effect. Healthy volunteers will complete a visual task at baseline (pre-
drug administration) and again after either an oral dose (25mg) of psilocybin or Niacin (100mg) 
placebo control (baseline, 2 hours post-drug administration, 2 week followup). The 
psychophysical measurements are made via forced-choice binary (yes/no) responses to 
questions about participants’ perceptions of visual stimuli. The data collected from this Aim will 
provide a psychophysical characterization of the impact of psilocybin on visual surround 
suppression.  
 
 
Aim 1b will test the acute impact of psilocybin on the strength of known surround 
suppression-related vERPs measured with EEG. Neural data will be collected as participants 
complete the visual tasks in Aim 1a (baseline, 2 hours post-drug administration, 2 week 
followup). The data collected will provide a neurophysiological characterization of the effect of 
psilocybin on the target vERPs commonly associated with visual surround suppression.  
 
2.0 
Background 
Significance of Research Question/Purpose:  
Psilocybin, the perception-altering drug found in ‘magic mushrooms’, has recently gained 
accelerated scientific interest. Psilocybin reliably produces acute alterations in visual 
perception. However, the acute effects of psilocybin on the processing of visual information is 
largely unknown. This gap in current knowledge, combined with the rapidly increasing interest 
in psilocybin, has created a critical research need with three prongs. First, while the therapeutic 
mechanisms of psilocybin remain unknown, recent theories converge around the hypothesis 
that psilocybin changes how the brain applies contextual information to incoming stimuli 

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(Carhart-Harris, 2019; Swanson, 2018). Importantly, the visual surround suppression paradigm, 
widely used to study contextual processing in visual perception, has not been studied in 
humans under psilocybin. Furthermore, the role of the serotonergic system has not been 
previously investigated in the field of surround suppression.  
To address this need, we will administer psilocybin to healthy volunteers and ask them 
to complete visual tasks. The visual tasks will use the surround suppression paradigm (Schallmo 
and Murray, 2016) to measure the degree to which surrounding stimuli can influence the 
perception of a target stimuli. The influence of surrounding stimuli is measured using two 
distinct methodologies: (1) a psychophysical (behavioral) measurement, and (2) a 
neurophysiological (EEG) measurement. EEG data will be analyzed for well-known event-related 
potentials (vERPs) commonly associated with visual surround suppression (Schallmo and 
Murray, 2016). Our hypothesis is that the psychophysical data will show weakened surround 
suppression effects under psilocybin and that the associated vERPs measured with EEG will also 
be attenuated. The feasibility of our design is supported by numerous previous studies in which 
various perceptual tasks have been administered to participants under psilocybin. Our team is 
well-qualified to execute the proposed experiment as it is composed of experts in visual 
perception with demonstrated expertise in surround suppression paradigms; experts on 
psychedelic drugs; previous experience with EEG measurements and data analysis; and licensed 
clinical psychiatrists. Our proposed experiment will make significant contributions to existing 
knowledge of the effects of psilocybin and to our understanding of the neurobiological 
mechanisms of visual surround suppression and contextual processing in the brain.  
Psilocybin, like other serotonin 2A receptor (5-HT2AR) agonist psychedelic drugs, 
produces psychoactive effects that impact information processing across many modalities in 
the brain, including perception, emotion, cognition, and sense of self (Barrett et al., 2018; 
Muthukumaraswamy et al., 2013; Schartner et al., 2017; Studerus et al., 2011; Swanson, 2018). 
Recently, psilocybin has received increased attention due to preliminary evidence of its efficacy 
as a treatment for certain mental health disorders (Bogenschutz and Ross, 2018; Carhart-Harris 
and Goodwin, 2017). However, due to the lack of basic neuroscience on psychedelic drug 
effects, “large gaps in our knowledge” remain, including a “lack of understanding of the 
mechanism of action of psychedelic drugs” (Lieberman and Shalev, 2016, 1198–99). 
 
We feel that investigating the visual effects of psilocybin is feasible with a high-yield 
scientific payoff that would directly address this knowledge gap. Why focus on the visual effects 
of psilocybin? The visual system is a (relatively) well-understood brain function compared with 
higher cognitive functions. Thus, if we can capture precise data on psilocybin’s impact on visual 
processes, we can leverage existing knowledge of the visual system to better understand the 
mechanisms of psilocybin’s effects. An additional but no less valuable payoff runs in the reverse 
direction, where a better understanding of the visual effects of psilocybin can advance our 
neuroscientific understanding of visual processes in the brain more generally (Carter et al., 
2005a; Swanson, 2018).  
 
Prior investigations into the visual effects of psilocybin have measured acute changes in 
motion processing (Carter et al., 2004), object completion (Kometer et al., 2011), and binocular 

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rivalry (Carter et al., 2005b, 2007). However, no previous study has attempted to measure 
visual context processing under psilocybin. This is a significant research gap, given the fact that 
a number of recent theories hypothesize that psilocybin disrupts context-driven expectation 
across the brain (Carhart-Harris and Friston, 2019; Swanson, 2018). The surround suppression 
paradigm enjoys widespread support as a technique for measuring context effects in human 
visual processes (Schallmo et al., 2018a, 2019; Schallmo and Murray, 2016). However, the 
neurochemical underpinnings of surround suppression remain unclear. Surround suppression 
has been investigated using pharmacological interventions, including drugs that activate 
GABAergic, cholinergic, dopaminergic, and noradrenergic pathways (Kosovicheva et al., 2012; 
Read et al., 2015; Schallmo et al., 2018a). Importantly, surround suppression has not been 
studied in human subjects using serotonergic activation, however it has recently been studied 
in mice (Michaiel et al., 2019). Thus, knowledge of psilocybin’s effect on surround suppression 
will make significant contributions to questions that are of great interest to scientists working 
to discover the mechanisms of psychedelic drugs as well as those working to discover the 
neurochemistry of surround suppression. An investigation measuring surround suppression in 
humans under psilocybin is therefore of the utmost importance. 
 
Our research question is “What is the impact of acute psilocybin intoxication on visual 
surround suppression in healthy human subjects?” The significance of our research question in 
the context of existing literature is explained in further detail in section 2.3 below. 
 
2.1 Preliminary Data: 
We have not collected preliminary data.  
 
2.2 Existing Literature:  
Surround suppression, a perceptual phenomenon which has been reliably measured in 
numerous human and animal studies, occurs when the response to a target stimulus becomes 
attenuated (suppressed) when that stimulus is embedded (surrounded) in the context of 
neighboring stimuli (Angelucci and Bressloff, 2006; Cavanaugh et al., 2002; Nurminen and 
Angelucci, 2014; Schallmo et al., 2018a, 2018b; Schallmo and Murray, 2016; Webb et al., 2005). 
This effect can be measured psychophysically, where a participant is asked to choose a binary 
(yes/no) answer to questions about their perception of the stimuli. In addition, surround 
suppression impacts neural responses to stimuli and this neural impact can be measured using 
neuroimaging techniques, including EEG, MEG, or fMRI. In summary, previous studies have 
shown that human visual processing is highly context-dependent, and surround suppression 
offers an experimental paradigm capable of measuring context effects using both 
psychophysical and neuroimaging techniques. 
Importantly, the surround suppression paradigm has been leveraged to discover distinct 
perceptual abnormalities in clinical populations, including schizophrenia (Schallmo et al., 2015; 
Tadin et al., 2006; Tibber et al., 2013), bipolar disorder (Schallmo et al., 2015), major depressive 

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disorder (Golomb et al., 2009; Norton et al., 2016), autism spectrum disorder (Foss-Feig et al., 
2013; Rosenberg et al., 2015; Sysoeva et al., 2017), epilepsy (Yazdani et al., 2017), Alzheimer’s 
disease (Zhuang et al., 2016), and migraine (Battista et al., 2010). Our research question is 
directly relevant to this literature, as it will help to illuminate the relationship (if any) between 
psilocybin’s perceptual effects and the perceptual abnormalities found in various clinical 
phenomena. Furthermore, our research may provide insights into the neurochemical 
underpinnings governing the differences in surround suppression found in clinical populations.  
The neurochemical mechanisms of surround suppression remain unclear. A variety of 
reports have investigated the GABA system in human studies (Cook et al., 2016; Read et al., 
2015; Song et al., 2017; van Loon et al., 2012; Yoon et al., 2010) and animal models (Adesnik et 
al., 2012; Haider et al., 2010; Ma et al., 2010; Nienborg et al., 2013; Ozeki et al., 2004, 2009; 
Sato et al., 2016; Shushruth et al., 2012). However, recent work has cast doubt on the 
hypothesis that surround suppression is directly mediated by GABA (Read et al., 2015; Schallmo 
et al., 2018a). Pharmacological agents are often used to investigate the role of neurochemicals 
in a given brain function. A small number of human studies have measured the impact of 
pharmacological agents on surround suppression. Previous investigations have targeted 
GABAergic pathways using the drugs ethanol (Read et al., 2015) and lorazepam (Schallmo et al., 
2018a); cholinergic pathways using the drugs donepezil (Gratton et al., 2017; Kosovicheva et al., 
2012) and caffeine (Nguyen et al., 2018); dopaminergic pathways using the drug bromocriptine 
(Gratton et al., 2017); and noradrenergic pathways using the drug guanfacine (Gratton et al., 
2017).  
Importantly, drugs that target serotonergic pathways have not been tested for their 
impact on human surround suppression. However, one recent animal study used the 
serotonergic psychedelic drug DOI to robustly induce weakened surround suppression 
measured in mouse V1 (Michaiel et al., 2019). Based on their findings, the authors argue that 
the serotonin 2A (5HT-2A) receptor “may be important for adjusting the influence of context in 
visual cortical processing” (Michaiel et al., 2019, 3481; emphasis added). Thus, the state of the 
current literature strongly warrants the use of serotonergic pharmacological agents paired with 
surround suppression tasks to probe for links between the serotonin system and visual context 
processing in the brain. 
Psilocybin is a serotonin 2A receptor agonist psychedelic drug that can dose-
dependently induce acute changes in perception, including alterations of object boundaries 
(Kometer and Vollenweider, 2016), illusions of perceived size or shape of objects (Carter et al., 
2004; Isbell, 1959), alterations in motion perception (Carter et al., 2004), changes in the 
subjective meaning of percepts (Carbonaro et al., 2018; Muthukumaraswamy et al., 2013), and 
hallucinations (Carbonaro et al., 2018; Kometer and Vollenweider, 2016). Psilocybin was found 
to slow the switch rate and rhythm of the visual binocular rivalry phenomenon (Carter et al., 
2005b, 2007). Psilocybin has been shown to acutely impair higher (global) levels of visual 
motion processing (Carter et al., 2004) and modal visual object completion (Kometer et al., 
2011). However, low-level (local) motion processing (Carter et al., 2004), low-level line 

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orientation processing (Barrett et al., 2018), and early (preattentive) mismatch negativity 
(MMN) processing are not impacted by psilocybin (Bravermanová et al., 2018; Umbricht et al., 
2003).  
EEG (and MEG) studies consistently show reductions in oscillatory power across a broad 
frequency range under psilocybin (Kometer et al., 2011, 2013, 2015; Muthukumaraswamy et 
al., 2013; Schartner et al., 2017; Tyls et al., 2016). Reductions in the power of alpha-band 
oscillations, localized mainly to parietal and occipital cortex, have been correlated with intensity 
of subjective visual effects (Kometer et al., 2013; Muthukumaraswamy et al., 2013; Schartner et 
al., 2017). Reductions in alpha power localized to anterior and posterior cingulate cortices and 
the parahippocampal regions have been correlated with ego-dissolution effects and mystical-
type experiences (Kometer et al., 2015; Muthukumaraswamy et al., 2013). Although oscillatory 
power decreases, overall whole-brain signal diversity actually increases and the increase in 
signal diversity correlates with the intensity of subjective effects (Schartner et al., 2017).  
In conclusion, our research question is of great interest to scientists from a diversity of 
fields, including perceptual neuroscience, neuropsychopharmacology, and clinical 
psychopathology. Given that psilocybin can reliably produce robust psychophysical and 
neurophysiological changes, we expect that our surround suppression measurements will be 
significant. Based on the above considerations of existing literature, we strongly feel that our 
research has the potential to close existing knowledge gaps and address multiple critical 
research needs. 
 
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome:  
We will obtain a psychophysical (behavioral) measurement of the impact of acute psilocybin 
intoxication on visual surround suppression in healthy human volunteers. Baseline data will be 
collected as participants complete the perceptual tasks pre-drug administration. Participants 
will repeat the tasks again 2 hours after an oral dose of psilocybin, and at 2 week followup. 
 
3.2 Secondary Endpoint(s)/Event(s)/Outcome(s):  
We will obtain a neurophysiological (EEG) measurement of the impact of acute psilocybin 
intoxication on the vERPs commonly associated with visual surround suppression. Prior to the 
start of the dosing session, we will collect baseline EEG data for each participant. After the 
dosing session has begun, EEG data will be recorded again during both task completion time 
points (2 hours after an oral dose of psilocybin or placebo control), as well as at 2 week 
followup, as described in the Primary Endpoint above. 
 
4.0 
Study Intervention(s)/Investigational Agent(s) 

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4.1 Description:  
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a naturally-occurring 
tryptamine compound found in an estimated 144 different species of mushrooms worldwide 
(Guzmán, 2005; Guzmán et al., 1998). Humans have intentionally consumed psilocybin-
containing fungi for ritual and medicinal purposes for more than 3,000 years in Mesoamerican 
cultures (Carod-Artal, 2015) and possibly also in prehistoric European cultures (Akers et al., 
2011; Schultes et al., 2006; Wasson and Wasson, 1957). Today, psilocybin-containing 
mushrooms remain one of the most widely-used hallucinogens worldwide (Johnson et al., 
2018b). When administered orally, psilocybin undergoes rapid first-pass dephosphorylation into 
the drug psilocin (4-Hydroxy-N,N-dimethyltryptamine) (Brown et al., 2017; Horita and Weber, 
1961). Psilocin activates a number of G protein-coupled receptors (GPCRs) several of which 
likely contribute to its overall profile of subjective effects (Ray, 2010). However, the subjective 
psychoactive effects of psilocybin critically depend on the drug’s ability to activate the 5-HT2A 
(Glennon et al., 1984; Kometer et al., 2013) and 5HT1A (Pokorny et al., 2016) receptors.  
In controlled settings, psilocybin has a robustly established physical and psychological 
safety profile (Brown et al., 2017; Hasler et al., 2004; Johnson et al., 2008; Johnson and 
Griffiths, 2017). Psilocybin has been generally well-tolerated by subjects in experimental studies 
(Dos Santos et al., 2018), both in clinical populations (Carhart-Harris et al., 2017a, 2018; 
Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016) and in healthy volunteers (Barrett et 
al., 2018; Bravermanová et al., 2018; Carhart-Harris et al., 2012, 2013; Carter et al., 2005b; 
Gouzoulis-Mayfrank et al., 2002; Griffiths et al., 2011; Grimm et al., 2018; Hasler et al., 1997; 
Kometer et al., 2015; Kraehenmann et al., 2015; Muthukumaraswamy et al., 2013; Nicholas et 
al., 2018; Quednow et al., 2012; Schartner et al., 2017; Turton et al., 2014; Umbricht et al., 
2003; Vollenweider et al., 2007; Wittmann et al., 2007). The most common acute physiological 
effects include a moderate increase in pulse and blood pressure (Gouzoulis-Mayfrank et al., 
1999; Griffiths et al., 2006; Johnson et al., 2008) and delayed, transient, dose-dependent 
headaches (Johnson et al., 2012).  
Risk of adverse psychological reactions collectively known as “bad trips” involve acute 
states of distress characterized by fear, panic, anxiety, disturbing feelings, and troubling 
thoughts (Johnson et al., 2008). These reactions can be minimized and mitigated in a controlled 
experimental session using a variety of well-established techniques that include careful 
screening of subjects, training of study personnel, holding the dosing session in a secure and 
comfortable physical environment, careful preparation of participants, and following 
established pre-session, session, and post-session protocols (Johnson et al., 2008).  
Long-range risks, while very unlikely, include the possibility of triggering substance 
abuse, prolonged psychotic episodes, and lasting perceptual abnormalities (Johnson et al., 
2008). Psilocybin has an extremely low abuse potential (Johnson et al., 2018a), does not induce 
cravings or withdrawal (Johnson et al., 2018a), and does not activate dopaminergic reward 
circuits critical to substance use disorders (Nichols, 2004). Psilocybin is thus generally regarded 
as safe to introduce to drug-naive subjects without risk of initiating abuse or habitual use 
(Johnson et al., 2008, 2018a). Lasting perceptual abnormalities can occur, especially in naive 

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users, although their occurrence is rare and in most cases are very brief, not regarded as 
detrimental, and sometimes even regarded as pleasurable (Johnson et al., 2008). Hallucinogen 
persisting perception disorder (HPPD), a condition in which the acute perceptual effects of the 
drug persist for prolonged periods after the peak effects have subsided, is extremely rare, 
mostly associated with LSD use in combination with cannabis, and has not been reported as 
having occurred in participants in any modern studies with psychedelic drugs (Martinotti et al., 
2018). Nonetheless, careful follow-up on perceptual abnormalities is recommended (Johnson et 
al., 2008). 
The relative safety of psilocybin extends beyond controlled clinical settings, as 
epidemiological data on illicit and ritual use shows that adverse reactions leading to 
hospitalization are relatively rare (Johnson et al., 2018b; Leonard et al., 2018). Since there is 
little to no risk of physical overdose (Brown et al., 2017; Johnson et al., 2008), most 
hospitalizations resulting from illicit use in the general population are due to emotional distress 
and unstable mental states (Leonard et al., 2018) and subside within 48 hours (Johnson et al., 
2018b; Tylš et al., 2014).  
In summary, psilocybin has a proven track record of safety when administered in 
controlled experimental settings that follow established protocols (Brown et al., 2017; Dos 
Santos et al., 2018; Hasler et al., 2004; Johnson et al., 2008; Johnson and Griffiths, 2017). 
Although not completely without risks, psilocybin does not impose unusual danger compared 
with other standard experimental treatments and interventions. 
 
4.2 Drug/Device Handling:  
Psilocybin is a tryptamine derivative presenting as a white crystalline solid with a 
melting point of 220-228°C. It is stable over extended periods in dark storage at controlled 
room temperature. Psilocybin is soluble in 20 parts boiling water or 120 parts boiling methanol. 
For use in clinical studies, psilocybin is provided as 25 mg capsules (white opaque, Capsugel 
Vcaps Plus HPMC size 2). Psilocybin will be obtained from Usona Institute in Madison, WI and 
stored in the Investigational Drug Service (IDS) Pharmacy at UMN. UMN IDS will handle all 
psilocybin allocation and storage, and will provide the compound as needed for each testing 
session. We will create a system which will allow the IDS staff to enter variables necessary for 
our minimization randomization procedure as described which will allow the IDS staff to 
determine the participant’s group to ensure the double blind. All participants, family members, 
and the entire research team will be blinded to testing group and order.   
The active placebo niacin, also known as vitamin B3, is provided as 100 mg capsules 
(white opaque, Capsugel Vcaps Plus HPMC size 2). Niacin is United States Pharmacopeia (USP)-
grade and also provided by Usona in the same capsules to maintain the blind. 
Within the week of the dosing/testing session at the CRU, one of the MD psychiatrists 
will formally request the study drug using the IDS calendar system. One person from the study 
team that will be running the testing session, plus one member of the CRU clinical staff, will 

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walk over to IDS together to receive the study drug and bring it to the participant. Any unused 
product will be immediately returned to IDS. 
 
 
4.3 
Biosafety: N/A 
4.4 
Stem Cells: N/A 
4.5 
Fetal Tissue: N/A 
 
5.0 
Procedures Involved 
5.1 Study Design:  
The study involves a randomized, double blind, placebo controlled, crossover design 
with two different groups pairing the psychoactive drug psilocybin, or the active placebo Niacin, 
with a combination of perceptual tasks.  
Randomization and Double-Blind: Participants who meet criteria for entry into the study 
(based on the telephone screen and the clinical interview) and consent to participate will be 
randomized to psilocybin first (group A) or niacin first (group B), using an adaptive minimization 
randomization method. The purpose of the procedure is to ensure that the 2 groups are similar 
with respect to age and gender. Specifically, the minimization procedure will balance age 
groups (45 years or below/above 45 years) and gender. Following the evaluation, the study 
coordinator will share numerical values for these variables along with the subject ID number 
through a secure system (Box Secure Storage) with the study statistician who will use 
participant information to assign a blinded randomization group (A or B) using the minimization 
procedure. 
The study statistician will then pass the blinded group assignment to IDS. Before the first 
participant is randomized, IDS will randomly assign “psilocybin first” “niacin first” to the letters 
A, and B; this assignment (of group to treatment letter) will not be communicated to anyone 
outside of IDS until the study is complete and the study team is ready to break the blind. 
Randomization will occur after Visit 1 (Day 0), when it is confirmed all eligibility criteria are met 
and before Visit 2, with a maximum 30-day window between them. 
Participants will have one training/baseline session, followed by 2 experimental sessions 
in randomized order for each of the drug conditions (psilocybin or niacin placebo). We will test 
subjects under the influence of 25mg of psilocybin (condition 1) or 100mg of active placebo 
control (niacin or, condition 2). 
We will test two groups for each of these conditions. Group A will be given psilocybin 
first, and active placebo Niacin second (N=20) and tested on surround suppression and EEG 
recording starting at 2 hours after ingestion of the experimental compound. Group B will be 
given niacin on their first dosing day and psilocybin on their second dosing day (N=20) and 
tested on surround suppression and EEG recording starting at 2 hours after ingestion of the 
experimental compound.  

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Furthermore, this study will be conducted in two phases. A pilot phase (n=6) will be 
completed before full study. For this phase, we will enroll an initial 6 subjects to work through 
the feasibility of implementing the study design, and to determine if any modifications need to 
be made for the full study design. We will start off slow and only enroll a single participant for 
the first 1-2 participants to test out the full protocol and closely monitor any potential problems 
that may arise that would need to be modified or removed from the design. See section 5.3 for 
more information on this pilot phase. Once this phase is complete, we will commence with the 
full study. See Figure 1.    
 
 
Figure 1. Timeline of study design for the A) pilot phase to test the feasibility of the protocol 
prior to initiating the B) full study design in our cohort. 
 
5.2 Study Procedures:  
Additional Procedures for COVID Screening. Participants and study personnel (e.g. staff, 
students, volunteers, or anyone with direct participant contact) will adhere to institutional 
guidelines around COVID-19 risk and safety and adjust our precautions accordingly as they 
evolve. These guidelines will be communicated to the participants at the time they are in effect, 
and implemented accordingly. 
 
Initial Survey and Phone Screening. Interested candidates will be contacted through a survey in 
REDCap to gather preliminary eligibility criteria and contact information (see Appendix A), and 

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interested participants that meet our basic inclusion criteria will be contacted via phone or 
Zoom to determine if they meet additional criteria for scheduling an in-person interview to 
determine final eligibility and enrollment. Phone screens will be conducted by the study 
coordinator and will adhere to an approved phone script (see Appendix B). All study visits and 
assessments performed remotely over the phone or Zoom will have both audio and video 
recordings (when applicable) of each visit.  
 
VISIT 1: 
In-person consent/interview screening. Participants that pass the survey and telephone 
screens will be invited to the ARC to be consented and interviewed by the research coordinator, 
to be consented and tested. Participants will be screened on the assessments outlined below to 
determine final eligibility for enrollment into the study. Participants will receive a physical exam 
to assess overall health, urine for pregnancy testing, as well as blood draws to screen for blood-
based biomarkers of major health problems and for baseline cytokine levels, a diagnostic 
interview with the MINI-7 to assess presence or history of mental illness and substance abuse, 
and a review of their personal and family medical history, and measure weight and vitals. Blood 
draws for health screening at baseline will be collected in green top tubes containing lithium 
heparin as an anticoagulant, and 2.5mL of blood will be collected and analyzed at the UMMC 
West Bank Children’s Hospital lab. Blood draws for cytokine testing will be collected in red top 
serum separator tubes that contain a clot activator but no anticoagulants, preservatives, or 
separator material, and we’ll collect 6mL of whole blood per participant. Participants will be 
screened for uncontrolled hypertension with two separate measurements of blood pressure 
using a blood pressure cuff during their visit. They will be brought in for a second visit (visit 1b) 
within 1 week of visit 1a to obtain two additional blood pressure measurements to assess 
whether they have uncontrolled hypertension, which will be determined if their average blood 
pressure across the 2 days and 4 measurements is greater than 140/90mmHg. We will also 
collected ECG data to test whether they have a QTc greater than 450 msec, based on the FDA 
Guidance of Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for 
Non-Antiarrhythmic Drugs. Those that do have a QTc greater than 450 msec will be excluded 
from the study. 
Candidates who do not meet all of the inclusion and/or one or more of the exclusion criteria 
will not be enrolled into the study.  
 
Clinical Assessment. Assessment interviews will be conducted by trained research team 
members, directly after the consent process.  
Assessment of General Psychopathology and Demographic Information (Zoom option). To 
describe our sample and to determine criteria for ineligibility, we will screen for the presence of 
Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) (American 
Psychiatric Association, 2013a) psychiatric diagnoses (American Psychiatric Association, 2013b) 
using the MINI-7 (Sheehan et al., 1998).  We will also administer the Adverse Childhood 

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Experience (ACE) questionnaire, which is a 10-item assessment of childhood abuse that predicts 
health concerns in adults (Feliti et al., 1998). Clinicians formulate the diagnosis combining all 
clinical information. Following the clinical evaluation, the study team will review all clinical 
information and determine final eligibility to decide whether the participant will move forward 
to randomization. 
Neurocognitive assessments.  
• The Wechsler Abbreviated Scale for Intelligence-II will be used to estimate intellectual 
functioning (in person). An add-on will be used during the Matrix Reasoning subtest to 
test for divergent thinking, a form of creative thinking and cognitive flexibility used in 
other psychedelic research studies (Kiraga et al., 2021). In addition to the standard 
response about which answer is correct, participants will be asked to provide alternative 
answers they think also might be correct. 
• The 5D-ASC  (Zoom option) is a 94-item questionnaire that measures altered states of 
consciousness, and consists of 5 dimensions/subscales (Dittrich, 1998), including 
“Oceanic Boundlessness” (27 items), “Anxious Ego Dissolution” (21 items), “Visionary 
Restructuralization” (18 items) “Auditory Alterations” (15 items) and “Reduction of 
Vigilance” (12 items). This validated scale has been used in multiple research studies 
aiming to understand the subject experience of psychedelic drugs (Carhart-Harris et al., 
2016; Hasler et al., 2004; Hysek and Liechti, 2012; Liechti et al., 2017; Schmid et al., 
2014; Vollenweider et al., 2007; Vollenweider and Kometer, 2010).  
• The RMEQ-30 (Zoom option) is a 30-item measure that consists of 4 orthogonal 
dimensions that represent different aspects of a mystical experience, including mystical 
experiences, positive mood, transcendence of space and time, and ineffability (Barrett 
et al., 2015; Maclean et al., 2012). Previous work has linked certain domains of the 
mystical experience with positive outcomes (Garcia-Romeu et al., 2014; Griffiths et al., 
2018; MacLean et al., 2011).  
• The PANAS (Zoom option) is a self-report of positive and negative affect and has been 
used in both clinical and nonclinical populations to measure mood affect (Crawford and 
Henry, 2004; Watson et al., 1988).  
• The 5-factor personality inventory (NEO-FFI) (Costa and McCrae, 2008) (Zoom option) 
will be administered at baseline testing, as well as at the final follow up session. 
Previous research with psilocybin in healthy volunteers has shown that mystical 
experiences occasioned by psilocybin in the appropriate set and setting leads to 
increases in the openness domain of the NEO-FFI (MacLean et al., 2011), and that those 
who score higher on the neuroticism domain may be more prone to difficult 
experiences on psilocybin (Barrett et al., 2017) and may require more attention during 
parts of the dosing session.  
• We will also administer the Ego-Dissolution Inventory (EDI) to participants (Zoom 
option), which is a validated assessment of both ego dissolution (ED) and ego-inflation 
(EI) applied in previous psilocybin research (Nour et al., 2016). Ego dissolution has been 

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correlated to improved mental health outcomes associated with psilocybin-occasioned 
experiences. 
• BVMT-R™, which has been used to measure changes in cognitive function linked to 
neuroplasticity in schizophrenia patients undergoing targeted cognitive training (Fisher 
et al., 2009; https://www.parinc.com/Products/Pkey/30). BVMT-R measures 
visuospatial memory where participants are shown a stimulus page and asked to draw 
as many of the figures as possible in their correct location on their own page, and then 
retested 25 minutes later for memory recall, followed by a recognition trial where they 
are asked which of the figures were included in the original stimulus. 
• HVLT-R™ has also been used to measure changes in cognitive function linked to 
neuroplasticity in schizophrenia patients undergoing targeted cognitive training (Fisher 
et al., 2009; https://www.parinc.com/Products/Pkey/130). HVLT-R is a word-list learning 
and memory test. 
• EBI has been developed and used in psilocybin clinical trials to measure emotional 
breakthrough, which has been linked to longer term changes in psychology function 
(Roseman et al., 2019). 
Neuroimaging Procedures. All brain imaging will be completed at the CMRR on a 3T whole 
body Siemens MAGNETOM scanner (Siemens Medical Solutions, Erlangen, Germany) using a 
standard Nova coil. We will take a series of scans during a single session to collect structural 
and functional fMRI data. Data will be collected from participants during baseline assessment 
and within 24 hours following each dosing day, and again at 3-4 days and 7 days after each 
dosing session for a total of 7 scans per participant. After an initial structural scan, we will 
collect resting state fMRI to test changes in BOLD signal in brain networks known to be 
impacted by psilocybin and other 5HT2A receptor mediated psychedelics, including the default 
mode network (Carhart-Harris et al., 2014). Heart rate and respiratory rate data will also be 
collected during the scan to account for artifacts that may confound results during resting state 
scan. We will then perform a series of task-based scans using the same visual tasks tested 
during the EEG dosing session (SEE Psychophysics section under Visits 2 and 4). We will then 
perform a diffusion-weighted MRI (dMRI) scan to look for changes in structural connections in 
white matter, which has been shown previously in animal models with serotonergic 
psychedelics (Ly et al., 2018). Data will be processed using standard software packages (e.g., the 
FMRIB Software Library (FSL - FslWiki)), which is an open-source software library that contains 
tools for statistical analysis and image processing for MRI brain imaging data).  
The same study procedures, except consent, demographics and medical history will be 
performed at Visits 3, 5, 6 and 7. Pregnancy test will be collected on Visit 1, 2, 3, 4, and 5. EEG 
and psychophysics will be collected on visits 2, 4, and 6, and fMRI will be collected on Visits 1, 3, 
and 5. Regarding blood draws, two separate tubes of blood will be collected at Visits 1, 3, and 5 
for serum chemistry and cytokine assays. 
 
VISITS 2 and 4 

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Dosing Session. Dosing sessions will involve 8 hours of preparatory visits (2a-d) before the day 
of the first dosing session, and one hour before the second dosing session (4a), which will occur 
either in person in the dosing room in CRU or over Zoom if preferred, and will be recorded for 
both audio and video. During these 4 preparatory visits, which will last approximately 2 hours 
each prior to the first dosing session, and 1 hour prior to the second dosing, for a total of 9 
hours, participants will meet with at least one of their dosing session monitors that will be 
sitting with them, and discuss what to expect during the dosing session, and what food 
preferences they have for two meals they will be offered during their time in the CRU. This visit 
also serves to help build rapport and common understanding between the two monitors and 
the participants prior to the dosing session, to review the participants personal history and 
anything that might come up during the dosing sessions (see visual aid that will be used for this 
in Appendix H), as well as an opportunity to educate the participants more on the procedures 
that will occur during the day, and the purpose of the study and the characteristics of the study 
drug. Participants will be asked to get at least 6-8 hours of sleep, and get dropped off in the 
morning by a trusted familiar individual. Once checked and settled into the room, participants 
will be allowed the option to remove their mask during the day, if that feels more comfortable 
for them. Prior to the administration of psilocybin or placebo, the participants will be given a 
brief physical exam, including a pregnancy test, breathalyzer for alcohol content, and measuring 
weight and vital signs. Participants will then be asked to answer a few questions on a checklist 
about their substance use since being enrolled in the study to assess whether they have 
engaged in activities that would make them ineligible and withdrawn from the study (see 
Appendix C). If they pass, we will proceed to the dosing session after a team member from the 
CRU and one of the study team members will walk over to IDS to receive the study compound, 
and escort it back to the testing room. The dosing sessions will be recorded using video 
equipment in the room for the duration of the visit. 
Participants will undergo baseline testing for outcome measures and preparatory 
interviews with the co-facilitators of the dosing sessions. On each of the testing day sessions 
(approximately 8 hours each), a hospital room in the CRU will be set up to create the optimal 
setting for a psychedelic experience, per the guidance and recommendations of other 
researchers performing work with these compounds in controlled clinical settings (Johnson et 
al., 2008). The room will not have windows, and will be equipped with a private bathroom in 
the room for when participants need to excrete urine, feces or vomit. The hospital bed will be 
set up with blankets and pillows to keep participants comfortable. We will place decorations 
around the room with neutral art/photographs of nature, and will have the participants bring 
some personal item with them that they find helpful for their own well-being (this may vary, 
but could include a stuffed animal, a sacred item or other totem that they use to help in their 
past experiences in altered states of consciousness). 
Participants will receive a 25mg/70kg dose of psilocybin, or 100mg dose of the niacin 
placebo, in a private, quiet space and encouraged to focus their attention inward for the 
majority of the experience, using eye shades and headphones with instrumental music. 
Participants will be lying on a comfortable surface. At least two monitors will be present for the 
duration of the participants stay in the research unit to monitor them. One of those monitors 

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will have either an RN (Clinical Research Unit staff) or MD degree, with experience managing 
behavioral emergencies, including de-escalation, calming and preventing elopement. The other 
monitors that do not have an RN or MD have extensive field experience providing support for 
psychedelic crisis situations at festivals and other events where people take recreational 
psychedelics and come to the facility designated for people seeking out psychological support 
during a psychedelic-induced crisis. Other monitors that will serve as the second person will be 
trained accordingly. We will call these monitors “sitters” and they will be positioned near the 
participant during the portion of the session where they are laying down with eye shades and 
listening to music. Sitters will be trained in fundamental guidelines for helping people navigate 
a psychedelic experience, adapted from models of harm reduction services offered at festivals 
for people having a difficult experience. Examples include instances where the participant 
arises from their headphones and eyeshades, and the sitters will engage with the participant 
using a supportive and non-directive approach, maintaining an empathic presence, while 
encouraging them to maintain their focus inward in between testing sessions for the duration 
of the experience. At least one sitter will be present at all times to be able to respond to verbal 
and non-verbal behavior with communication or supportive touch. Supportive touch will be 
discussed during the consent and enrollment process. We will ask the participants what their 
comfort level is for supportive touch, while ensuring that extensive touch, such as hugging or 
cuddling will not be allowed, even if requested. We will simply, if they consent before the 
dosing session, provide a hand on the back, arm, or hold their hand during challenging or 
stressful parts of the experience. We will ask for their permission anytime a supportive touch 
seems warranted, and will only touch if they have agreed beforehand during the consent 
process, and with a verbal confirmation during the dosing experience. The consent and extent 
of supportive touch will be assessed and agreed upon with the participant during enrollment, 
and confirmed on the day of testing. We will ensure that we have an MD physician present in a 
nearby room in the CRU for the duration of each dosing session to monitor safety and 
guide/provide interventions should medical situations arise that require the physicians care. 
 
Schedule for checking vital signs. In order to monitor participant safety during the dosing 
sessions, we will monitor their heart rate and blood pressure throughout the session. Heart rate 
will be measured with a pulse oximeter and blood pressure will be measured with a pressure 
cuff. We will measure vital signs 15 minutes before dosing, and then again at 15, 30, 45, 60, 90, 
120 minutes and three, four, six and eight hours after dosing, with an allowable time deviation 
of +/- 5 minutes to account for any delays during the day for checking vitals. In the event of a 
hypertensive emergency where blood pressure rises above 180/120mmHg (systolic/diastolic), 
and they are experiencing other associated symptoms of potential organ damage, including 
chest pain, shortness of breath, back pain, numbness/weakness or difficulty speaking, then we 
will stop the session and call a code 21, per our crisis communication plan (see appendix D). In 
the unexpected event that we do have a participant with a hypertensive emergency (Johnson et 
al 2008), we will immediately administer sublingual clonidine while we wait for emergency 
personnel to arrive. Our physicians do not feel administering an IV injection would be wise, as 
in the altered state of consciousness, this may exacerbate their symptoms, as would having an 

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IV catheter placed for the duration of the dosing session. The emergency room is in the building 
adjacent to the Clinical Research Unit, accessible via underground tunnels, and calling a code 21 
will alert emergency personnel to come to our dosing room to treat the participant and transfer 
them to the emergency department. 
Participants experience will be interrupted in order to conduct the EEG and behavioral 
testing during the peak of the experience (starting 2 hours after ingestion of study drug). EEG 
will be administered by trained study staff using a dry-electrode wireless headset paired to a 
computer and monitor that will be used to administer the surround suppression task.  
EEG. We will use an EEG paradigm to measure responses to the presentation of simple visual 
stimuli (e.g., black and white stripes) presented on a computer. Subjects will be asked to 
respond to the appearance of the visual stimuli via button press (Figure 2). We will record EEG 
signals from multiple scalp sites (electrodes) using a 21-channel dry electrode EEG system. 
Subjects will be asked to keep their eyes focused on the screen during the task, and to remain 
as still as possible to ensure higher data quality. Subjects will be monitored by study staff (in the 
testing room) during the experiment. EEG data using a dry electrode system will be collected in 
the CRU testing room during baseline and on dosing session days for consistency of 
environment/setting. EEG sessions will be conducted by study staff that are trained to collect 
EEG data. 
Psychophysics behavioral task. We will use visual behavioral tasks to assess perceptual 
functioning and learning in human subjects. Subjects will see a series of simple images (e.g., 
gray stripes) presented on a computer screen and will be asked to make basic judgments about 
their appearance (e.g., report which of the two images appears stronger). Subjects will make 
responses by pressing buttons on a response device (e.g., keyboard). Subjects will be asked to 
keep their head position stable on a chin rest and to focus their eyes at the center of the screen 
during the task. Behavioral data will be collected in subject testing space located in the CRU. 
Subjective experience questionaires at end of dosing session. Once the subjective effects of 
the study drug have subsided, prior to being discharged from the CRU, we will administer 
subjective experience questionnaires (5D-ASC, RMEQ-30, EDI, EBI) related to how their 
experience was during the day on the study drug. 
 
Assessment of participant before discharge from dosing session. Prior to being released to a 
trusted family member or friend at the end of the session, we will assess the participant to 
make sure they are safe to leave. We will do a physical and mental health assessment, including 
measuring vital signs, ECG, mental health status and responses to questions about thought 
processes, such as suicidal ideation with the CSSRS or other concerning symptoms (see 
appendix E).  If the participant is displaying symptoms that need to be continually monitored, 
we will discuss with the clinical staff whether to admit them for follow-up care. Additional 
follow-up care that is needed will be billed to the participants health insurance.  
 

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Figure 2. Schematic of surround suppression task (Schallmo and Murray, 2016)  
 
Safety. Participants will be instructed to immediately inform the study team if any serious 
concerns arise with their health during the study. The team will assess all adverse effects, 
including frequency, severity and relationship to study drug. For participants that experience 
adverse psychological effects, including, but not limited to suicidal ideation, likely or 
probably related to study drug, the participant will be instructed to speak with a mental 
health professional to assess their status, either by Drs. Kathryn Cullen or Ranji 
Varghese (clinical Co-Investigators). Participants will be given a list of phone numbers 
to call in the event that they are experiencing distress, such as suicidal ideation, 
including the study investigator at the telephone number listed on the first page of the 
consent forms, and instructed that if they feel they are crisis, that they can call 911 
and/or a Nationwide Suicide Hotline that is answered 24 hours a day with a skilled, 
trained counselor. One example is the National Suicide Prevention Lifeline at 1-800-
273-TALK (8255). 
Participants will be pre-prescribed antipsychotics and antianxiety medications in case the 
participants or the study staff want to stop the psilocybin experience with these 
pharmacological interventions.  These costs will be paid for by the study funding. Some 
antipsychotics, like Risperidone, are able to bind to 5HT2A to block the activation of this 
receptor in the presence of psilocybin, whereas anti-anxiety medications, such as 
benzodiazepines, will help calm down the participants should they become agitated or too 

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anxious during the testing session. See Appendix D for more information on the crisis 
commination plan. 
At the end of each experimental session (8 hours post-drug administration), participants will be 
released into the care of a trusted friend or family member to drive them home. (Prior to 
dosing on the day of each experimental session, participants will be required to confirm that 
they have arranged for reliable transportation).  
 
Visits 3 and 5 
Digital Journal. Throughout the study, participants will also be asked to keep a digital journal 
that will be submitted after each dosing session (Visit 3 and Visit 5), and at the end of the study 
(Visit 7) to document their qualitative and subjective experience for content analysis. Within 1 
week after their dosing session, participants will be asked to write for 30-60 minutes to 
describe the content of their experience, and any reflections or interpretations they derived 
from the experience to help determine the subjective information of their drug experience. 
These will be collected in a REDCap form (see Appendix F) and sent out to participants via email 
or text after completion of the dosing session, and a follow-up email or text towards the end of 
the week if they have not completed the form. 
 
Debriefing session. One day following each dosing session (Visits 3a and 5a), study staff will 
meet with the participant for about 60 minutes (either in person at CMRR prior to MRI, or 
remotely over Zoom) to discuss the dosing session the previous day, and debrief on anything 
they want to discuss or process with the study staff. 
 
Blood Draws. All blood draws will be performed by the clinical staff onsite, and blood samples 
will be stored at the Cytokine Reference Lab on campus for cytokine assays, and serum 
chemistry will be processed by Fairview. Samples will be collected at baseline (Visit 1) and again 
at Visit 3 (a,b,c) and Visit 5 (a,b,c). 
 
MRI. See CMRR section below (5.5). 
 
 
All neuropsychiatric, baseline and follow up testing will be conducted in the ARC (or Zoom, if 
appropriate), and all fMRI sessions will be collected at CMRR. All dosing sessions and EEG data 
collection will be performed in the CRU. The study coordinator will greet each participant upon 
arrival, and escort them to the different locations for data collection and testing. 
 

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Participants will be monitored at each visit for adverse events  (Zoom option), including 
for suicidal thoughts, and given at least 2 weeks between dosing/testing sessions for drug 
washout. After completion of final dosing sessions, participants will undergo follow up 
assessments at 2 weeks (Visit 6) and 2 months after the final dosing session for study closeout 
(Visit 7). 

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Schedule of Events 
 
 
Enrollment and 
Baseline Testing 
Visit 1* 
Dosing 
Session 
Study Visit 2^ 
(Condition 1) 
Study 
Visit 3# 
(Follow up 
and 
Washout) 
Dosing 
Session Study 
Visit 4^ 
(Condition 2) 
Study Visit 
5#  
(Follow up 
and 
Washout) 
Study Visit 
6  
(Follow up) 
Study 
Visit 7 
(follow up 
and close 
out) 
COVID+ and other 
time deviations for 
Visit Window 
Adjustment 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
Time Point 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Week 6 
Week 12 
Informed consent 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Psilocybin or Placebo 
 
X 
 
X 
 
 
 
Concomitant 
medication review 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
(including height and 
weight) 
X 
X 
X 
X 
X 
X 
X 

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Enrollment and 
Baseline Testing 
Visit 1* 
 
Dosing 
Session 
Study Visit 2^ 
(Condition 1) 
 
Study 
Visit 3 
(Follow up 
and 
Washout) 
 
Dosing 
Session Study 
Visit 4^ 
(Condition 2) 
 
Study Visit 
5 (Follow 
up and 
Washout) 
 
Study Visit 
6 (Follow 
up) 
 
Study 
Visit 7 
(follow up 
and close 
out) 
COVID+ Visit Window 
Adjustment 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
Vital signs (including 
heart rate and blood 
pressure) 
X 
X# 
X 
X# 
X 
X 
X 
ECG 
X 
X 
 
X 
 
 
 
Serum Chemistry and 
cytokine testing a 
X 
 
X 
 
X 
 
 
Pregnancy test b 
X 
X 
X 
X 
X 
 
 
Alcohol intoxication 
screenc 
 
X 
 
X 
 
 
 
Adverse event review 
and evaluation 
X 
X 
X 
X 
X 
X 
X 
Neurophysiology/EEG 
X 
X 
 
X 
 
X 
 
MRI 
X 
 
X 
 
X 
 
 

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Enrollment and 
Baseline Testing 
Visit 1* 
Dosing 
Session 
Study Visit 2^ 
(Condition 1) 
Study 
Visit 3 
(Follow up 
and 
Washout) 
Dosing 
Session Study 
Visit 4^ 
(Condition 2) 
Study Visit 
5 (Follow 
up and 
Washout) 
Study Visit 
6 (Follow 
up) 
Study 
Visit 7 
(follow up 
and close 
out) 
COVID+ Visit Window 
Adjustment 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
MINI-7 
X 
 
 
 
 
 
X 
WASI-II Intelligence 
Assessmentd 
X 
 
X 
 
X 
X 
X 
5-D Altered States of 
Consciousness Rating 
Scale (5D-ASC) 
 
X 
X 
X 
X 
X 
X 
X 
Digital Journal 
 
 
X 
 
X 
 
X 
Revised Mystical 
Experiences 
Questionnaire 
(RMEQ-30) 
X 
X 
X 
X 
X 
X 
X 
Ego Dissolution 
Inventory (EDI) 
X 
X 
X 
X 
X 
X 
X 

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Enrollment and 
Baseline Testing 
Visit 1* 
Dosing 
Session 
Study Visit 2^ 
(Condition 1) 
Study 
Visit 3 
(Follow up 
and 
Washout) 
Dosing 
Session Study 
Visit 4^ 
(Condition 2) 
Study Visit 
5 (Follow 
up and 
Washout) 
Study Visit 
6 (Follow 
up) 
Study 
Visit 7 
(follow up 
and close 
out) 
COVID+ Visit Window 
Adjustment 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
+/- 7-14 
days$ 
Positive and Negative 
Affect Schedule' 
(PANAS) 
X 
 
X 
 
X 
X 
X 
NEO-FFI Personality 
Questionnaire 
X 
 
 
 
 
 
X 
ACE 
X 
 
 
 
 
 
 
BVMT-R 
X 
 
X 
 
X 
X 
X 
HVLT-R 
X 
 
X 
 
X 
X 
X 
EBI 
X 
X 
X 
X 
X 
X 
X 
COLUMBIA-SUICIDE 
SEVERITY RATING 
SCALE (CSSRS) 
X 
X 
X 
X 
X 
X 
X 

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Enrollment and 
Baseline Testing 
Visit 1* 
Dosing 
Session 
Study Visit 2^ 
(Condition 1) 
Study 
Visit 3 
(Follow up 
and 
Washout) 
Dosing 
Session Study 
Visit 4^ 
(Condition 2) 
Study Visit 
5 (Follow 
up and 
Washout) 
Study Visit 
6 (Follow 
up) 
Study 
Visit 7 
(follow up 
and close 
out) 
Debrief/Integration@ 
 
 
X 
 
X 
 
 
Complete Case 
Report Forms (CRFs) 
X 
X 
X 
X 
X 
X 
X 
a: Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, LDH, phosphorus, 
potassium, total protein, AST, ALT, sodium. For cytokine testing: Blood draws will be collected and stored for analysis by the 
cytokine reference library, and will include ELISA analyses for total BDNF, CRP, TGFβ-1, and GFAP; High Sensitivity Luminex Panel 
for TNFα, IL-1β, IL-6, IL-10, IFN-γ; and a 4 plex Luminex Panel for TNF-R1, TNF-R2, s100β, UCHL-1. 
b: Urine pregnancy test (people of childbearing potential). 
c: Breathalyzer on dosing session days for presence of alcohol 
d: An additional modification will be added to the matrix reasoning subtest to assess divergent/creative thinking. 
* Visit 1 will be conducted over 2 separate days to obtain 4 independent blood pressure measurements to test for uncontrolled 
hypertension, determined as an average blood pressure greater than 140/90mmHg. 
# Blood pressure monitoring during dosing sessions will be performed with a blood pressure cuff and will be taken 15 minutes 
before dosing, and then again at 15, 30, 45, 60, 90, 120 minutes and three, four, six and eight hours after dosing to monitor 
potential hypertensive emergencies, allowing for +/- 5 minutes to account for any delays. 
^ Visits 2 will be conducted over 5 separate days, where participants will spend 8 hours total doing preparatory sessions with their 

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session monitors before the dosing session (4 x 2 hour sessions) to prepare them for the dosing session and help develop and 
maintain rapport between the participant and the session monitors. Only one hour of preparation before the second dosing 
session on visit 4 will be needed to check-in with participants on any new developments or concerns. 
# Visits 3 and 5 each will be conducted over 3 separate days to conduct a follow up assessment, as well as to get repeated 
measures for fMRI data and blood draws in the days immediately following the dosing sessions (visits 2 and 4, respectively). 
$ Based on evolving guidance adjustments for quarantine times from the Centers for Disease Control and Prevention (CDC). This 
will not compromise the integrity or quality of the data, and to account for scheduling logistics that may require overlap between 
visit 1 and visit 2 for baseline testing and the preparatory sessions. 
https://www.cdc.gov/media/releases/2021/s1227-isolation-quarantine-guidance.html 
@ Participants will meet with the study staff the day after each dosing session and have a 60-minute debrief to discuss and process 
their experience with the dosing session with the study stuff. This will be done prior to initiating any follow up questionnaires, 
blood draws or MRI scans for visits 3 and 5.  
 

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5.3 Study Duration:  
It will take approximately 12 weeks for a single participant to be enrolled and complete 
the study. For the pilot phase of the study, we will enroll an initial 6 subjects to work through 
the feasibility of implementing the study design, and to determine if any modifications need to 
be made for the full study design. For the pilot phase, we will start off slow and only enroll a 
single participant for the first 1-2 participants to test out the full protocol and closely monitor 
any potential problems that may arise that would need to be modified or removed from the 
design. We will assess the results from participant #1 after the 1-week follow up after the 
second dosing session, and then we will begin enrolling the second participant. After these first 
2 subjects have completed the full protocol (about 17 weeks from start date), the team will get 
together and discuss the results and any issues that arose that may need to be considered and 
modified for additional participants. If the protocol implementation for the first 2 subjects goes 
well without needing to modify anything, we will then stagger enrollment and anticipate 
completing the pilot phase in the first year of the study. For the full study design with N=40 
participants, we will run 2 participants per week, and stagger the enrollment of each additional 
participant after the previous participant has completed the follow up after the first dosing 
session, and anticipate the implementation of the full study design across all participants to 
take approximately 3.5 years, or 5 years total for the pilot and full study design. 
 
5.4 Use of radiation: N/A 
5.5 Use of Center for Magnetic Resonance Research: The research team will utilize the 
CMRR Center’s screening tools and adhere to the screening SOP during enrollment 
of all research participants in this protocol.  The CMRR Center’s screening tools 
and SOP are IRB approved under the CMRR Center Grant (HSC# 1406M51205) and 
information regarding screening procedures is publicly available on the CMRR 
website (CMRR Policies / Procedures).    
 
6.0 
Data and Specimen Banking 
6.1 Storage and Access:  
Data will be collected using a combination of paper and electronic measures. All paper 
measures will be entered and stored in an online database (REDCap), and source documents for 
all data collected will be scanned to PDF and stored in UMN Box. Online measures will be linked 
to the database for direct data upload. Staff and students will be granted access on an 
individual basis with individual username and password. Electronic measures will be transferred 
and stored to this same online database. All stored data will be de-identified. And data 
containing PHI will be stored in the HIPAA-compliant UMN Box location and will only be 
accessed by approved study personnel that have permission to access participant PHI. 
Additional de-identified EEG and fMRI data will be stored in OpenNeuro for possible data 

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sharing with the scientific community and deposition of data into repositories that are required 
for publishing findings in the scientific literature. Additionally, the supplier of the psilocybin 
compound, Usona Institute, requires access to de-identified safety data from the study. 
Because we are not sharing any identifiable information with Usona or OpenNeuro, neither a 
DUA or BAA is required. We have a signed agreement with Usona for the transfer of the 
compound in exchange for de-identified safety data.  
Specimen blood samples will be processed for analysis and then stored by the Cytokine 
Reference Lab service. These samples will be stored at -80C for at least 5 years to allow for 
follow-up tests that may be required, such as if new tests become available, or if manuscript 
reviewers request additional analyses. 
 
6.2 Data: 
The following measures will be collected and stored for future analysis: Demographic 
information including sex, age, race, ethnicity, MINI-7, medical history, vital signs and ECG, 
blood test and physical exam results, neuroimaging, EEG and surround suppression task data, 
5D-ASC, PANAS, RMEQ-30, NEO-FFI, EDI, CCSRS, WASI-II, cytokine assay and serum chemistry 
results and digital journal data, as well as all audio and video recordings. 
 
6.3 Release/Sharing:  
For data releases, request for sharing will be made to the PI, Jessica Nielson or the student 
investigator, Link Swanson, and/or co-investigators Michael-Paul Schallmo, Kathryn Cullen or 
Ranji Varghese and granted on an individual basis. 
 
7.0 
Sharing of Results with Participants 
7.1 Participants that complete MRI scans will be offered a copy of their scan on disc. A 
written report detailing information gathered at the clinical assessment (MINI-7), 
including psychiatric diagnosis, will be shared with participants provider(s) of 
choice upon receiving signed release of records from the participant. Additional 
specific measures gathered will be shared with participants providers upon signed 
request. General findings after data analysis will be shared with all participants in 
the form of a mailed letter.  
7.2 Sharing of genetic testing: N/A 
7.2.1 Disclosure of results: N/A 
7.2.2 If returning results to participants: N/A 
7.2.3 Future analysis of genotypes: N/A 
8.0 
Study Population 

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8.1 Inclusion Criteria:  
● Gender: Any 
● Age: 25-65 
● Demographic group: Any 
● Have given written informed consent 
● Have at least a high-school level of education or equivalent (e.g. GED), and be able to 
read and write in English 
● General health status: Participants should be in good physical and psychiatric health. 
● Experience taking psilocybin (at the PI’s discretion).  
● Participants must also have a person that can reliably transport them to and from the 
CRU for dosing session days.  
● Geographic location: Minnesota counties that are approximately within 1 hour driving 
distance to Twin Cities, including not limited to Hennepin, Ramsey, Washington, Anoka, 
Wright, Carver, Scott, Dakota, Sherburn  
● Agrees to adhere to current COVID-19 safety precautions implemented at 
MHealth/Fairview 
● Agrees to refrain from using recreational drugs while enrolled in the study, including, but 
not limited to, hallucinogens, ketamine, and marijuana. 
 
8.2 Exclusion Criteria:  
● Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other 
psychotic disorders (except due to another medical condition), or Bipolar I or II Disorder, 
personality disorder, major depressive disorder, posttraumatic stress disorder, panic 
disorder, obsessive compulsive disorder, dysthymic disorder. 
● Current or past history within the last 5 years of meeting DSM-5 criteria for a moderate 
or severe alcohol or drug use disorder (excluding caffeine, nicotine, and hallucinogens) 
● Those with a first or second-degree relative with a current or past history of meeting 
DSM-5 criteria for schizophrenia or other psychotic disorders or bipolar I or II disorder, 
because they might have an underlying genetic susceptibility for psychosis. 
● Presence of symptoms of the following DSM-5 disorders within the past 6 months (as 
assessed by the MINI-7): 
o Major depressive Episode  
o Suicidality 
o Manic and Hypomanic Episodes  
o Panic disorder  
o Agoraphobia  
o Social Anxiety Disorder  
o Obsessive-Compulsive Disorder  
o Posttraumatic Stress Disorder  
o Alcohol Use Disorder  
o Substance Use Disorder (Non-Alcoholic)  
o Psychotic Disorders and Mood Disorders with Psychotic Features  

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o Anorexia Nervosa  
o Bulimia Nervosa 
o Binge Eating Disorder 
o Generalized Anxiety Disorder  
o Antisocial Personality Disorder  
o Mood Disorders:  
o Major Depressive Disorder (MDD)   
o MDD with Psychotic Features  
o Bipolar I 
o Bipolar II 
o Other Specified Bipolar and Related Disorder 
● Presence of abuse or dependence of drugs measured by the MINI-7 in the past 12 
months: 
o Lithium, Sodium Valproate (Depakote), Lamotrigine (Lamictal) – Manic/Bipolar 
disorders 
o Stimulants: amphetamines, "speed", crystal meth, “crank”, Dexedrine, Ritalin, 
diet pills. 
o Cocaine: snorting, IV, freebase, crack, "speedball". 
o Opiates: heroin, morphine, Dilaudid, opium, Demerol, methadone, Darvon, 
codeine, Percodan, Vicodin, OxyContin.  
o Dissociative Drugs: PCP (Phencyclidine ,"Angel Dust", "Peace Pill", “Hog”), or 
ketamine (“Special K”). 
o Inhalants: "glue", ethyl chloride, “rush”, nitrous oxide ("laughing gas"), amyl or 
butyl nitrate ("poppers"). 
o Cannabis: marijuana, hashish ("hash"), THC, "pot", "grass", "weed", "reefer". 
o Sedatives, Hypnotics or Anxiolytics: Quaalude, Seconal ("reds"), Valium, 
Xanax, Librium, Ativan, Dalmane, Halcion, barbiturates, Miltown, GHB, 
Roofinol, “Roofies”. 
o Miscellaneous: steroids, nonprescription sleep or diet pills. Cough Medicine? 
● History of medication or substance induced psychosis. 
● Medically significant condition considered unsuitable for the current study (e.g. 
diabetes, epilepsy, severe cardiovascular disease, etc) 
● History of suicide attempts or mania 
● Positive pregnancy test or currently breast-feeding 
● Currently taking on a regular (e.g., daily) basis any prescription medications, with the 
exception of birth control or other hormone therapy 
● A strong bias either for or against psychedelic substances, or if their responses about 
psychedelic use indicate that they abuse them from frequent use (more than once per 
month, with the exception of microdosing). 
● MRI EXCLUSION: we will also exclude anyone with head trauma, claustrophobia 
incompatible with scanning, cardiac pacemaker, implanted cardiac defibrillator, 
aneurysm brain clip, inner ear implant, prior history as a metal worker and/or certain 
metallic objects in the body that cannot be approved for MR scanning by the CMRR 
safety committee, history of clinically significant vertigo, seizure disorder, middle ear 

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disorder, or double vision, or tattoos that were done less than 4 weeks from the first 
scheduled MRI. 
● Significant movement disorders including tardive dyskinesia that could disrupt EEG 
recordings will also be excluded. 
● Uncontrolled hypertension, with an average blood pressure reading across 4 
measurements over 2 separate days greater than 140/90mmHg. 
● ECG with a QTc greater than 450 msec, based on the FDA Guidance of Clinical 
Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-
Antiarrhythmic Drugs. 
● Unwilling to adhere to current COVID-19 safety precautions. 
 
8.3 Screening: 
Initial screening and consent: We will send out an initial REDCap survey via email to 
interested participants that contact the study team expressing interest in the study, followed by 
telephone or zoom interviews with potentially eligible participants using an IRB-approved script 
and screening form to determine eligibility. We will schedule potentially eligible participants for 
an in-person meeting to fully explain study procedures and risks. If they are interested in 
participating, we will then obtain signed consent from the participant. 
Clinical assessment: Assessment interviews with participants will be conducted by the 
clinical research coordinator, directly after the consent process. A consensus meeting at the 
end of the interviews will incorporate information from interviews and all rating scales.  
Assessment of General Psychopathology and Demographic Information. To describe our 
sample and to determine criteria for ineligibility, we will screen for the presence of DSM-
5  psychiatric diagnoses (American Psychiatric Association, 2013b), including, but not limited to, 
schizophrenia, bipolar disorders, personality disorders, depression, post-traumatic stress 
disorder, obsessive compulsive disorder, substance abuse disorder, etc. We will use the 
COLUMBIA-SUICIDE SEVERITY RATING SCALE to assess past and current suicidal ideation 
(Posner et al., 2011).  
 
9.0 
Vulnerable Populations 
9.1 
Vulnerable Populations:  
Population / Group 
Identify whether any of the following 
populations will be targeted, included 
(not necessarily targeted) or excluded 
from participation in the study.  
Children 
Excluded from Participation 
Pregnant women/fetuses/neonates 
Excluded from Participation 

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Prisoners 
Excluded from Participation 
Adults lacking capacity to consent 
and/or adults with diminished capacity 
to consent, including, but not limited 
to, those with acute medical conditions, 
psychiatric disorders, neurologic 
disorders, developmental disorders, 
and behavioral disorders 
Excluded from Participation 
Non-English speakers 
Excluded from Participation 
Those unable to read (illiterate) 
Excluded from Participation 
Employees of the researcher 
Excluded from Participation 
Students of the researcher 
Excluded from Participation 
Undervalued or disenfranchised social 
group 
Excluded from Participation 
Active members of the military (service 
members), DoD personnel (including 
civilian employees) 
Excluded from Participation 
Individual or group that is approached 
for participation in research during a 
stressful situation such as emergency 
room setting, childbirth (labor), etc. 
Excluded from Participation 
Individual or group that is 
disadvantaged in the distribution of 
social goods and services such as 
income, housing, or healthcare. 
Included/Allowed to Participate 
Individual or group with a serious 
health condition for which there are no 
satisfactory standard treatments. 
Excluded from Participation 
Individual or group with a fear of 
negative consequences for not 
participating in the research (e.g. 
institutionalization, deportation, 
disclosure of stigmatizing behavior). 
Excluded from Participation 
Any other circumstance/dynamic that 
could increase vulnerability to coercion 
or exploitation that might influence 
Excluded from Participation 

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consent to research or decision to 
continue in research. 
 
Additional Safeguards: Disadvantaged groups will be Included/Allowed to Participate as part of 
this research but information will not be collected as to the participants status.  
Therefore, this research does not add any additional risk to this group. Participant 
confidentiality will be protected. Participants will have the freedom to decline 
participation and the right to withdraw at any time without penalty. Participant 
confidentiality will be protected. Participants will have the freedom to decline 
participation and the right to withdraw at any time without penalty.  
 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented:  
Local Number of Participants to be Consented:  46 participants are needed for data analysis and 
we anticipate needing to consent 75 participants to meet that goal. 
 
11.0 Local Recruitment Methods 
11.1 Recruitment Process:  
● We will post advertisements in the community via flyers and local newspapers. 
● We will advertise through the internet, social media (Facebook, Twitter, Meetup, etc.) 
and community outlets about our study. We will engage a HIPAA compliant and IRB-
approved system connected with a REDCap screening form. 
● We will maintain a social media presence to promote the study and enhance visibility to 
the community. 
● We will make regular presentations about the research to community organizations 
including neighborhood groups and the Psychedelic Society of Minneapolis member 
base. 
 
11.2 Identification of Potential Participants:  
● For physical flyers in the community, potential participants will self-identify based on 
limited information present. They will contact research staff via phone and/or email. 
● For internet and social media advertisements, potential participants will self-identify 
based on limited information present. They will contact research staff via phone and/or 
email or REDCap form. 

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● Social media presence will direct traffic to IRB-approved website with contact 
information for the research team listed and a link to the REDCap screening survey (see 
Appendix A). 
● At community presentations potential participants will not be identified by research 
staff. Potential participants will have the opportunity to self-identify and request more 
information about research participation.  
 
11.3 Recruitment Materials:  
● Internet advertisement (for public display, potential participant self-identify) 
● REDCap survey (basic eligibility criteria to determine who to follow up with over 
phone/zoom) 
● Phone script (study summary to potential participants during phone screen) 
● Phone screen (telephone screening form for potential participant eligibility) 
 
11.4 Payment:  
Participants will be compensated directly using the Greenphire ClinCard. Each task 
completed will have attached a specific compensation amount. Once the task is completed 
research staff will load the amount attached to that task on to the participants Greenphire 
ClinCard. Participant compensation will provide participants $30/hour for their time on 
psilocybin or control dosing days (two 8-10 hour sessions, $600), and $20/hour for other 
assessments and study visits (Baseline testing, preparatory sessions, 7 MRIs, 4 follow up visits = 
47 hours, $940). Total possible compensation per participant = $1540. All participants will 
complete a W-9.  
 
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances:  
Participants will be withdrawn from the research study if any of the following occur while 
enrolled: 1) participant meets any exclusionary criteria; 2) participant becomes suicidal with 
intent and plan; 3) participant engages in other harmful behavior towards themselves or others 
that requires urgent/emergency medical care; 4) participant experiences intolerable adverse 
effects from the psilocybin or niacin, including allergic reaction; 5) participant fails to adhere to 
protocol requirements; and/or 6) participant withdraws consent. Decision to withdraw based 
on these criteria will be determined at the PI’s discretion. 
 
12.2 Withdrawal Procedures:  

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If a participant withdraws or is withdrawn from the research study, no more data will be 
collected on them. Previous data collected will be stored and analyzed as planned, unless 
exclusionary criteria is met. If the participant is withdrawn they will be notified by phone or in-
person and any scheduled appointments for the research study will be cancelled.   
12.3 
Termination Procedures:  
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party. If the study is 
prematurely terminated or suspended, the PI will promptly inform the IRB and will provide the 
reason(s) for the termination or suspension. The study team will notify the participants of the 
study termination.  
Circumstances that may warrant termination or suspension include, but are not limited to: 
● Determination of unexpected, significant, or unacceptable risk to participants 
● Insufficient compliance to protocol requirements 
● Data that are not sufficiently complete and/or evaluable 
The study may resume once concerns about risks, protocol compliance, and/or data quality 
procedures are addressed and satisfy the IRB. Data collected for the study prior to the study 
termination will be handled in the following manner: 
● If the study is terminated due to safety reasons, the data related to adverse events will 
be evaluated.  
● If the study is terminated for any other reason, the regulatory and/or institutional 
document/data retention policies will apply.   
 
13.0 Risks to Participants 
13.1 Foreseeable Risks:  
Immediate risks  
In controlled settings, psilocybin has a robustly established physical and psychological 
safety profile (Brown et al., 2017; Hasler et al., 2004; Johnson et al., 2008; Johnson and 
Griffiths, 2017). Psilocybin has been generally well-tolerated by subjects in experimental studies 
(Dos Santos et al., 2018), both in psychiatric patients (Carhart-Harris et al., 2017a, 2018; 
Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016) and in healthy volunteers (Barrett et 
al., 2018; Bravermanová et al., 2018; Carhart-Harris et al., 2012, 2013; Carter et al., 2005b; 
Gouzoulis-Mayfrank et al., 2002; Griffiths et al., 2011; Grimm et al., 2018; Hasler et al., 1997; 
Kometer et al., 2015; Kraehenmann et al., 2015; Muthukumaraswamy et al., 2013; Nicholas et 
al., 2018; Quednow et al., 2012; Schartner et al., 2017; Turton et al., 2014; Umbricht et al., 
2003; Vollenweider et al., 2007; Wittmann et al., 2007). The most common acute physiological 
effects include a moderate increase in pulse and blood pressure (Gouzoulis-Mayfrank et al., 
1999; Griffiths et al., 2006; Johnson et al., 2008) and delayed, transient, dose-dependent 
headaches (Johnson et al., 2012).  

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Risk of adverse psychological reactions collectively known as “bad trips” involve acute 
states of distress characterized by fear, panic, anxiety, disturbing feelings, and troubling 
thoughts (Johnson et al., 2008). Acute adverse psychological reactions can be minimized and 
mitigated in a controlled experimental session using a variety of well-established techniques 
that include careful screening of subjects, training of study personnel, holding the dosing 
session in a secure and comfortable physical environment, careful preparation of participants, 
and following established pre-session, session, and post-session protocols (Johnson et al., 
2008). Should such states arise, and the participant is unable to work through this reaction and 
resolve on its own, we will have the nurse on site to assess any major physical complications 
that may arise, and if needed, pre-prescribed anti-anxiety or anti-psychotics will be 
administered after consultation about the case with the psychiatrist/clinician on call for the 
testing sessions. See Appendix D for a description of our crisis communication plan, should such 
a situation arise. 
Long-range risks  
Long-range risks, while very unlikely, include the possibility of triggering substance 
abuse, prolonged psychotic episodes, and lasting perceptual abnormalities (Johnson et al., 
2008). Psilocybin has an extremely low abuse potential (Johnson et al., 2018a), does not induce 
cravings or withdrawal (Johnson et al., 2018a), and does not activate dopaminergic reward 
circuits critical to substance use disorders (Nichols, 2004). Psilocybin is thus generally regarded 
as safe to introduce to drug-naive subjects without risk of initiating abuse or habitual use 
(Johnson et al., 2008, 2018a). Lasting perceptual abnormalities can occur, especially in naive 
users, although their occurrence is rare and in most cases are very brief, not regarded as 
detrimental, and sometimes even regarded as pleasurable (Johnson et al., 2008). Hallucinogen 
persisting perception disorder (HPPD), a condition in which the acute perceptual effects of the 
drug persist for prolonged periods after the peak effects have subsided, is extremely rare, 
mostly associated with LSD use in combination with cannabis, and has not been reported as 
having occurred in participants in any modern studies with psychedelic drugs (Martinotti et al., 
2018). Nonetheless, careful follow-up on perceptual abnormalities is recommended (Johnson et 
al., 2008). Prolonged psychotic reactions to psilocybin in clinical settings is extremely rare and 
has not occurred in participants in studies. 
The relative safety of psilocybin extends beyond controlled clinical settings, as 
epidemiological data on illicit and ritual use shows that adverse reactions leading to 
hospitalization are relatively rare (Johnson et al., 2018b; Leonard et al., 2018). Since there is 
little to no risk of physical overdose (Brown et al., 2017; Johnson et al., 2008), most 
hospitalizations resulting from illicit use in the general population are due to emotional distress 
and unstable mental states (Leonard et al., 2018) and subside within 48 hours (Johnson et al., 
2018b; Tylš et al., 2014).  
In summary, psilocybin has a proven track record of safety when administered in 
controlled experimental settings that follow established protocols (Brown et al., 2017; Dos 
Santos et al., 2018; Hasler et al., 2004; Johnson et al., 2008; Johnson and Griffiths, 2017). 

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Although not completely without risks, psilocybin does not impose unusual danger compared 
with other standard experimental treatments and interventions.  
Niacin can elevate heart rate and cause the skin to become flushed, and some digestive 
complications at high doses, however we will not be giving participants a high enough dose to 
induce serious forms of these complications, but participants may experience them to some 
degree. 
Risks of a Blood Draw: Events associated with venipunctures include discomfort, slight 
bruising, bruising, bleeding, lightheadedness, fainting, infection at the venipuncture site, 
nausea, anxiety and swelling at the venipuncture site. Blood draws will occur in a lab or clinical 
research unit and done by qualified medical professionals trained in phlebotomy. 
EEG: Use of the electrodes during the electrophysiology session requires that subjects 
wear an electrode cap, which some people find uncomfortable. We will measure the subject’s 
brain waves while they are at rest and when the subject is performing a number of tasks. Some 
minor skin irritation is possible in reaction to the electrode cap application; however, reddening 
of the skin from the pressure of the electrodes typically resolves within 24 hours. Subjects will 
be notified that scalp discomfort from the use of EEG equipment typically resolves within 24 
hours. Study staff will provide support for the participants should they appear to become 
fatigued or frustrated during EEG. Subjects have the liberty of discontinuing this procedure at 
any point. 
MRI Scanning: The MRI scanning device will be a 3.0 Tesla MRI scanner. This device has 
been evaluated by the FDA as having non-significant risk for persons more than one month of 
age and data already reviewed by the UMN IRB indicate that the 3.0 Tesla magnetic field does 
not pose a significant risk to human volunteers. All participants will be screened according to 
CMRR policies to minimize risks to participants. These are the specific risks related to MRI 
scanning: 
1)    Exposure to high magnetic field: The primary known hazard associated with exposure to a 
static high magnetic field is that the magnet exerts a strong force on ferromagnetic objects. 
Metallic objects that are entered the magnetic field can accelerate into the magnet potentially 
causing damage to the magnet or persons in the magnet room. In addition, implanted metallic 
objects can be displaced. MRI may not be appropriate in the presence of the following 
conditions: cardiac pacemaker; metal fragments in eye, skin, body; mechanical heart valve 
replacement; brain clips; venous umbrella; being a sheet-metal worker or welder; aneurysm 
surgery; intracranial bypass; renal, aortic clips; middle ear, eye, joint, or penile implants; joint 
replacements; hearing aid; neurostimulator; insulin pump; intra-uterine device (IUD); 
shunts/stents anywhere in the body; metal mesh/coil implants; metal plate/pin/screws/wires 
anywhere in the body, any other metal implants; permanent eyeliner or permanent artificial 
eyebrows. All participants will be thoroughly screened first over the phone before enrollment, 
then using the CMRR Safety Screening Form at the day of MR scanning. Participants that do not 
pass screening will not enter the CMRR where magnetic fields exist. 

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2)    Radiofrequency (RF): Radiofrequency pulses impart small amounts of energy into the 
participant. No ionizing radiation is used with MRI. Because the pulse sequences to be used fall 
within FDA guidelines and will not be operated outside of safe limits, we do not expect any 
hazard associated with power deposition. To prevent inadvertent application of significant 
energies which may result in heating, the scanning systems include monitoring with both a 
hardware and a software monitor. Participants will be instructed to report any heating 
sensation immediately, and that the scan could be stopped at any time if this occurs. 
3)    Peripheral nerve stimulation: Peripheral nerve stimulation from rapidly switching magnetic 
fields (dB/dt) during the scanning procedure may occur. As a result, the participant may 
experience muscle twitching or tingling sensations lasting seconds to minutes. This is 
considered to occur seldomly. Participants are instructed that if twitches do occur, they should 
immediately inform the operator. This would be a short-lived side effect and reversible. 
4)    Acoustic noise: MR imaging creates acoustic noise because of pulsing currents through the 
gradient coils within the magnetic field. A repetitive tapping sound occurs as a result. Ear plugs 
are provided to the participant to prevent hearing damage and provide comfort 
5)    Claustrophobia: Some people undergoing this procedure become anxious and afraid when 
in closed spaces. Participants will be instructed that they can stop procedure at any time. The 
MRI technologist will be in communication with the participant during the scan and ask them 
how they are doing. In addition, participants will be given a squeeze ball to communicate an 
urgent need or concern. Participants are screened for claustrophobia before enrollment. 
6)    Anatomical abnormalities revealed: There is a possibility that the MRI scan would reveal 
unknown and unlooked for abnormalities such as a cyst, vascular abnormality or a tumor. The 
scan results will be routinely sent to a radiologist for review. If an abnormality is uncovered, the 
participants are informed of the results of the radiology review and are encouraged to follow 
up with their physician. We would provide participants physicians with a copy of the imaging 
data that we collect upon request. 
7)    Dizziness and nausea: Dizziness and nausea are rare though may occur if the participants 
head moves around while they are inside the magnet. If this occurs, this would be acute and 
reversible, and should resolve within a few minutes without intervention. 
Clinical Assessment: Some of the question’s participants will be asked may make them feel 
uncomfortable or upset. These pertain to psychiatric and medical history, behavioral and 
psychiatric symptomatology, and personal illegal drug use. Participants are informed that they 
do not have to answer any question that makes them feel uncomfortable. Coordinators 
interviewing the participants will remind them of this, as well as use empathy to gauge their 
discomfort. Staff will be sufficiently trained to handle these situations.  
Privacy/Confidentiality Risks: Participation in research may involve a loss of privacy due 
to the nature of the questions that are asked during assessment visits and/or data collected. 
However, records will be handled as confidentially as possible. All participants will be assigned a 
unique study identifier that will be used to label all of their records only be accessible to specific 
study staff listed in the Delegation of Authority log. This link will connect the participant’s 

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identifying information, such as name, etc., to their assigned ID number. No identifying 
information will be used in any report or publications that may result from this study. All study 
records will be kept in a secure database. Paper records will be kept in locked cabinets in locked 
rooms. 
Severity and relationship of adverse events: The Principal Investigator will be responsible for 
determining whether an adverse event (AE) is expected or unexpected.  An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with 
the risk information previously described for the study intervention.  
The following guidelines will be used to describe severity.  
 
• Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
• Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
The degree of certainty about causality will be graded using the categories below.  
 
• Related – The AE is known to occur with the study intervention, there is a reasonable 
possibility that the study intervention caused the AE, or there is a temporal relationship 
between the study intervention and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study 
intervention and event onset, or an alternate etiology has been established. 
 
13.2 Reproduction Risks:  
There are no known risks of MRI imaging to someone who is pregnant or an unborn 
fetus, however we will not scan someone who is pregnant. Participants will be screened for 
pregnancy over the phone before enrollment and a pregnancy test will be administered at the 
CMRR before scanning to ensure the participant is not pregnant. 
There are no known risks of psilocybin to someone who is pregnant, however niacin is 
not recommended, so we will be screening participants who are pregnant and performing 
pregnancy tests before administering any intervention. 
 

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13.3 Risks to Others: There are no risks to individuals who do not participate. 
 
14.0 Potential Benefits to Participants 
14.1 Potential Benefits: 
Benefits have been reported anecdotally and therapeutically in many published scientific 
research studies using psilocybin. Participants from previous research in healthy controls report 
having mystical experiences induced by taking psilocybin which were some of the most 
significantly meaningful experiences of their lives. This resulted in a sense of well-being that 
lasted long after the experience (Griffiths et al., 2006, 2011, 2018; MacLean et al., 2011). 
However, this benefit is not guaranteed. 
 
15.0 Statistical Considerations 
15.1 Data Analysis Plan:  
For this pilot study, EEG and fMRI data will be analyzed using standard software and toolboxes. 
EEG data will be processed to eliminate artifacts (e.g., eye movements). EEG signal amplitudes 
will be analyzed statistically to compare across subject groups and experimental conditions, as 
with the behavioral data. fMRI data will be analyzed using standard software (e.g. FMRIB 
Software Library, others) according to standard protocols used previously in psychedelic 
neuroimaging research (Atasoy et al., 2017; Carhart-Harris et al., 2017b; Deco et al., 2018; 
Roseman et al., 2018) and human connectome project pipelines used at CMRR. Data will either 
be analyzed on CMRR secure servers, or on the Minnesota Supercomputing Institute (MSI) 
servers. Other measures of RMEQ-30, WASI-II, 5D-ASC, EDI, EBI, PANAS, NEO-FFI, 
HVLT-R, BVMT-R, CSSRS, cytokines, vital signs and diagnostic tests will be analyzed in 
statistical software programs (e.g. R, SPSS, etc) for significant differences between groups, and 
assessed for statistically significant relationships with EEG, fMRI and the psychophysics tasks. 
The team investigators and coordinator will be blinded to condition, however an independent 
study statistician that will not have any interaction with study participants will perform all 
blinded data analysis, with unblinded secondary analyses performed by Dr. Nielson, Dr. 
Swanson and the study coordinator. 
 
15.2 Power Analysis: 
Previous work with surround suppression tasks by Co-Investigator (Schallmo et al., 2019) 
determined the appropriate number of participants with the smallest effect sizes and 
corresponding standard deviations found that 16 subjects would provide an a priori power of 
92% for detecting a significant difference in surround suppression between experimental 
conditions. Assuming that some drop out may occur, we decided to have 20 participants per 
drug group (age, sex and baseline clinical variables balanced). 
 

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15.3 Statistical Analysis: 
We will test hypotheses about differences between baseline EEG signal and 
psychophysics tasks performed under both psilocybin and the active placebo control during the 
surround suppression task. We will test changes in primary and secondary endpoints between 
baseline and each of the drug conditions using univariate repeated measures ANOVA, as well as 
a mixed-effects regression model (random intercept by participant) controlling for additional 
co-variates such as treatment order, age, sex, and other relevant predictors at baseline that are 
significantly different between groups. If diagnostic tests reveal poor adherence to model 
assumptions, equivalent non-parametric tests will be used instead. We will also test changes in 
resting state fMRI networks from baseline, and 1-day, 3-days and 7-days after exposure to the 
experimental compound and placebo control. Will use independent component analysis (ICA) 
to identify functionally meaningful resting state networks using the FMRIB Software Library 
(FSL). Significance will be tested at p<.05. 
  
15.4 Data Integrity:  
Data collection is the responsibility of the clinical trial staff under the supervision of the 
site PI. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. All information and data collected from and about participants 
during the research study will be de-identified and kept in the participants folder in a locked 
cabinet in a locked room accessible only by research staff. Identifiable forms such as screening 
forms containing DOB and consent forms will be kept separate from participant data.  All 
research staff and volunteers are required to complete data safety and security and HIPAA 
training according to University of Minnesota policy. All data electronically stored and 
transferred will be de-identified and any identifiable pieces of information stored electronically 
will be kept secure accessible by only research staff and will be encrypted if transferred or using 
secure portal such as Box.  
 
16.0 Health Information and Privacy Compliance 
 
16.1 
Select which of the following is applicable to your research: 
☐ My research does not require access to individual health information.   
 
☒ I am requesting that all research participants sign a HIPCO approved HIPAA 
Disclosure Authorization to participate in the research (either the standalone 
form or the combined consent and HIPAA Authorization). 
☐ I am requesting the IRB to approve a Waiver or an alteration of research 
participant authorization to participate in the research. 
Appropriate Use for Research:  

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We will only be accessing and retaining records from research participants who have consented 
to be in the study. We will carefully match the participants information with their appropriate 
records, and only IRB-approved study staff will have access to these records. If at any time the 
participant decides to withdraw their consent from the study, all copies of their records will be 
destroyed in a HIPAA-compliant shredder. 
 
 
16.2 
Identify the source of Private Health Information you will be using for your 
research (Check all that apply)   
☐ I will use the Informatics Consulting Services (ICS) available through CTSI (also 
referred to as the University's Information Exchange (IE) or data shelter) to 
pull records for me 
☒ I will collect information directly from research participants. 
☐ I will use University services to access and retrieve records from the Bone 
Marrow Transplant (BMPT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) database. 
☐ I will pull records directly from EPIC. 
☐ Other.  Describe:  
 
 
16.3 
Explain how you will ensure that only records of patients who have agreed to 
have their information used for research will be reviewed. N/A 
☐ I will retrieve record directly from axiUm / MiPACS 
☐ I will receive data from the Center for Medicare/Medicaid Services  
☐ I will receive a limited data set from another institution  
16.4 
Approximate number of records required for review: N/A 
 
16.5 
Please describe how you will communicate with research participants during the 
course of this research.  Check all applicable boxes 
☐ This research involves record review only. There will be no communication 
with research participants. 
☐ Communication with research participants will take place in the course of 
treatment, through MyChart, or other similar forms of communication used 
with patients receiving treatment.  

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☒ Communication with research participants will take place outside of 
treatment settings. If this box is selected, please describe the type of 
communication and how it will be received by participants.  
- 
 We will communicate with participants via telephone (using a study-
specific phone number) for pre-screening, appointment scheduling, 
appointment reminders, etc. We will also communicate through text 
message or unsecure email if the participant agrees in writing by signing 
the GUIDELINES AND CONSENT FOR TEXT MESSAGE CORRESPONDENCE 
FOR RESEARCH PARTICIPANTS and/or GUIDELINES AND CONSENT FOR 
UNSECURED EMAIL CORRESPONDENCE FOR RESEARCH PARTICIPANTS. 
16.6 
Access to participants 
 The research team will be permitted to access sources of private information 
because all participants will be required to sign a HIPAA waiver at the time of 
informed consent. 
16.7 Location(s) of storage, sharing and analysis of research data, including any links to 
research data (check all that apply).   
☐ In the data shelter of the Information Exchange (IE)  
 ☐ Store 
☐ Analyze 
☐ Share 
☐ In the Bone Marrow Transplant (BMT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) Database  
 ☐ Store 
☐ Analyze 
☐ Share 
☒ In REDCap (recap.ahc.umn.edu)  
 ☒ Store 
☐ Analyze 
☐ Share 
☐ In Qualtrics (qualtrics.umn.edu) 
 ☐ Store 
☐ Analyze 
☐ Share 
☒ In OnCore (oncore.umn.edu)  
 ☒ Store 
☐ Analyze 
☐ Share 
☒ In the University’s Box Secure Storage (box.umn.edu) 
 ☒ Store 
☐ Analyze 
☐ Share 
☐ In an AHC-IS supported server. Provide folder path, location of server and IT 
Support Contact: 
The path should be in the form of “\\vp.ahc.umn.edu\vp\Research\Study0004” 
HIPCO requires this information to verify the data are in a properly encrypted 
server. 

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 ☐ Store 
☐ Analyze 
☐ Share 
☒ In an AHC-IS supported desktop or laptop. Provide UMN device numbers of all 
devices where such information will be stored, location(s) of device(s) and IT 
Support Contact: 
AHC-IS supported laptop, device # 20170890, # 20192519, and # 20191654; and 
AHC-IS supported desktops, device # 20201941 and # 20201942. 
 ☒ Store 
☒ Analyze 
☐ Share 
☒ Other. Blood samples that are collected from participants at the CRU will be 
labeled with a de-identified subject code and date, and aliquoted by the study 
staff and stored by the Cytokine Reference Lab (CRL). Samples will be logged using 
a de-identified label/code for study participants to keep track of their location 
within the storage boxes housed in the CRL freezer. De-identified samples will be 
analyzed by the cytokine laboratory. Only approved study staff will have access to 
identifying information for these samples. Additional data processing and analysis 
for MRI and EEG data will be done on either the CMRR server, or on the MSI server 
due to the size and complexity of the data. Additionally, de-identified processed 
EEG and fMRI data will also be shared in OpenNEURO (openneuro.org). Audio and 
video recording from Zoom sessions will be stored on the AHC-IS supported laptop 
temporarily after each study visit, and then transferred to the UMN Box secure 
storage for the study. Audio and video recordings from video camera collected 
during in-person dosing sessions will be transferred to the AHC-IS supported 
laptop temporarily after each session and then transferred to the UMN Box secure 
storage for the study. A secure, encrypted, AHC-IS supported external hard drive 
will be used for temporary storage and analysis of video data, due to large file 
sizes of the videos. Only approved study personnel will have access to the UMN 
Box folder for this study, and audio/video data will be used to monitor adherence 
to lab protocols and for education and training purposes for study personnel. 
 
16.8 Consultants. Vendors. Third Parties. None 
 
16.9 Links to identifiable data: Identifying information about research participants will 
be contained in a password-protected spreadsheet that is stored on AHC-IS 
approved devices by the approved study team members, as well as backed up in 
UMN Box. Only approved study staff will have access to identifying information 
and will only be permitted to access this on approved devices and on UMN Box. 
 
16.10 Sharing of Data with Research Team Members. Data will only be shared with 
research team members through UMN Box. De-identified EEG and fMRI data will 
also be deposited into OpenNEURO (openneuro.org). 

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16.11 Storage and Disposal of Paper Documents: Any paper documents will be scanned 
to PDF and stored in the HIPAA compliant UMN Box. Paper records containing 
any PHI will be shredded in a HIPAA approved paper shredder/disposal 
container. 
 
17.0 Confidentiality 
17.1 Data Security:  
All information and data collected from and about participants during the research study will be 
de-identified and kept in the participants folder in a locked cabinet in a locked room accessible 
only by approved research staff. Identifiable forms such as screening forms containing DOB and 
consent forms will be kept separate from participant data. All research staff and volunteers are 
required to complete data safety and security and HIPAA training according to University of 
Minnesota policy. All data electronically stored and transferred will be de-identified and any 
identifiable pieces of information stored electronically will be kept secure accessible by only 
research staff and will be encrypted if transferred or using secure portal such as Box or 
REDCap. We will be applying for a Certificate of Confidentiality (CoC) through the FDA once we 
have IRB approval. 
 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
18.1 Data Integrity Monitoring.  
Data integrity monitoring will be conducted at outset, every 6 months, and upon study closing 
by the Clinical and Translational Science Institute monitor assigned to the Department of 
Psychiatry and Behavioral Sciences. The monitor will review an on-site regulatory binder as well 
as participant folders to ensure compliance to the protocol, SOP and other regulatory 
requirements. The monitor will review consent forms, completion of source documents and 
case report forms, and appropriate documentation for protocol deviations, personnel changes, 
staff training, and adverse events, etc. The monitor will have access to and review all necessary 
documents at a set appointment time. Monitoring reports will indicate enrollment numbers, 
select changes since the last monitoring visit and any unresolved queries. The research staff will 
be expected to resolve all queries, and notify monitor of these resolved queries, within 10 days 
of receiving the monitoring report.  
 
18.2 Data Safety Monitoring.  
A Data Safety Monitoring Board will be appointed for this research study. The DSMB will 
initially meet prior to enrolling the first participant, and then again after we have completed the 

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first three participants during the pilot phase to assess any SAE/AE or other issues. We will 
determine together whether we can move forward with the full study design or if modifications 
need to be made. For the full study design, the team will meet regularly after each additional 10 
participants are enrolled and complete the study protocol throughout the duration of the 
study. Research staff will prepare a report for the DSMB at least 1 week prior to each scheduled 
meeting. This report will include a protocol synopsis, study personnel, brief statement of 
purpose, projected timetable and schedule, study summary including a summary of protocol 
changes, enrollment/participant status, protocol deviations, and adverse event tables 
(incidence, severity, listing of serious adverse events, adverse events, and deaths) and anything 
else pertinent to the study, participant safety or DSMB oversight. Safety information will be 
collected on Case Report Forms, adverse event and protocol deviation logs, and on memos 
(memo-to-file) requiring additional explanation and PI signature.  
The DSMB, along with FDA and UMN IRB, would determine the need to immediately 
suspend research based on any individual SAE/AE as well as collective AE/SAE parameters. The 
DSMB, in addition to the FDA and UMN IRB, will be notified of any SAE immediately. The DSMB 
will be notified in each annual report of the following: AE log (frequency, severity, corrective 
treatment, duration, relation to study drug, and serious or not serious of each event by 
participant ID), AE incidence and severity by body system, and listing SAE/deaths. 
See Appendix (G) for the DSMB members and charter. 
 
19.0 Provisions to Protect the Privacy Interests of Participants 
19.1 Protecting Privacy:  
At initial screening, potential participants will be screened for a privacy interest request to 
gauge ability to accommodate such request and still compete the study. If the potential 
participant passes initial screening and indicates interest, they will be informed that if they have 
specific privacy request throughout the course of the study, to let study staff know and we will 
accommodate such request within the limits of the protocol and if unable to meet request staff 
will inform participant. If the participant indicates a specific “privacy interest” request research 
staff will discuss the feasibility of such request with participant and jointly decide feasibility of 
participation. If the request appears feasible within the activities of the study, such request will 
be met by research staff. In addition, upon review of the activities of the research study at the 
consent process, the participant will be asked if they would care to place limits on whom they 
interact with or whom they provide personal information within the confines of the research 
study. If the participant indicates they do not wish to place limits on their “privacy interest”, no 
further action will be taken. At the start of each subsequent research study visit, while engaging 
with the participant on their continued willingness to participate, the participant will be asked 
again about any changes they would like to make to their “privacy interest” request.  
 
19.2 Access to Participants:  

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The research team will not access any medical records or other sources of private information 
outside of information without the participants written consent.  
 
20.0 Compensation for Research-Related Injury 
20.1 Compensation for Research-Related Injury:  
In the event that research-related activities result in an injury, treatment will be provided to the 
participant (e.g., first aid, emergency treatment, and follow-up care as needed). Care for such 
injuries will be billed in the ordinary manner to the participant or the participant’s insurance 
company.  
 
20.2 Contract Language: N/A 
21.0 Consent Process 
21.1 Consent Process (when consent will be obtained):  
Potential participants will participate in the consent process at the very first scheduled visit, the 
Enrollment/Baseline Study Visit 1, before any study procedures are conducted or remotely via 
Zoom using REDCap e-consent. They will receive copies of the combined consent and HIPAA 
form via email or USPS mail at least 24 hours before this appointment. The initial consent 
process will take place with research staff in a previously reserved room within the Ambulatory 
Research Center (ARC) at the University of Minnesota Department of Psychiatry (F212) Fairview 
Riverside West Building. During the initial consent visit staff will review the consent forms 
highlighting the most salient points such as study title, purpose, procedures, risks, benefits, 
alternatives, confidentiality, research related injury, voluntariness, and any additional 
signing/initial blocks such as permission to re-contact in the future and share data outside of 
this research study. Talk back method will be used during the consent visit to ensure potential 
participants are understanding these points. In addition, an approved version of the The 
MacArthur Competence Assessment Tool for Clinical Research 
 (MacCAT-CR) specific to this study will be used with all participants during the consent process. 
Potential participants that are not able to complete the MacCAT-CR or score less than 2 points 
on each question will not be consented and enrolled into the study. If a potential participant 
scores 0 or 1 on any question the information pertinent to that question will be reviewed and 
discussed with the participant. If the potential participant is then able to answer the question in 
full and research staff determines the potential participant fully understands the material, they 
will be scored the 2 points and then consented and enrolled (assuring all answers are scored 2 
points). In addition to University and department mandatory consent training for appropriate 
research staff, all new staff will be trained in consent for this research study including observing 
the consent process, mock consent and observed for consent process. Throughout the course 
of the research study, participants will be gauged of their comprehension of scheduled 
procedures as well as comfort and willingness to complete these procedures by staff at each 

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visit/procedure. Consent will be documented in writing by signature on the Consent Form and 
completed MacCAT-CR form. Research staff obtaining consent will also sign each of these 
applicable forms.  
Additionally during the consent process, participants will be instructed on criteria that would 
disqualify them during the course of the study, including 1) participant meeting any 
exclusionary criteria during the course of the study; 2) participant becomes suicidal with intent 
and plan; 3) participant engages in other harmful behavior towards themselves or others that 
requires urgent/emergency medical care; 4) participant experiences intolerable adverse effects 
from the psilocybin or niacin, including allergic reaction; 5) participant fails to adhere to 
protocol requirements; and/or 6) participant withdraws consent. Decision to withdraw based 
on these criteria will be determined at the PI’s discretion. 
 
21.2 Waiver or Alteration of Consent Process (when consent will not be obtained): N/A 
21.3 Waiver of Written/Signed Documentation of Consent (when written/signed 
consent will not be obtained):  A waiver of written/signed consent will be needed 
for the REDCap survey and phone screen. 
21.4 Non-English Speaking Participants:  
This study will not be enrolling non-English speaking participants.  
 
21.5 Cognitively Impaired Adults, or adults with fluctuating or diminished capacity to 
consent: N/A 
21.6 Adults Unable to Consent: 
● 
Permission: N/A 
● 
Assent: N/A 
● 
Dissent: N/A 
 
22.0 Setting 
22.1 Research Sites:  
Sites for Recruitment: 
● Community bulletin boards: IRB-approved Flyers will be posted on community boards 
such as in coffee shops, cafes and community centers, and around the Twin Cities 
campus, where permission is granted.  
● Internet advertisement: Similar advertisements will be posted through internet forums 
where IRB approved.  
● Community groups: We will engage community groups, including the Psychedelic 
Society of Minneapolis, which has over 780 members on Meetup, and over 2500 

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followers across social media platforms who have experience taking psychedelics in 
their past (and growing). 
 
Sites for Research Procedures 
● Ambulatory Research Center, UMN Department of Psychiatry: Consent process, clinical 
and baseline assessments will take place in rooms within the ARC, and blood draws at 
Fairview laboratory in the same building. 
● Clinical Research Unit, Phillips-Wangensteen Building: Dosing sessions and EEG 
recordings 
● Center for Magnetic Resonance Research (CMRR): The CMRR will be used for 3T MR 
scanning at baseline, and at repeated time points after dosing sessions. 
● The study coordinator will greet and escort the participants between sites when 
necessary. 
 
22.2 International Research: N/A 
23.0 Multi-Site Research: N/A 
24.0 Coordinating Center Research: N/A 
25.0 Resources Available 
25.1 Resources Available:  
● Recruitment feasibility: Research coordinator and study staff will work on recruitment.  
● Student investigator will be monitored and accompanied by the study PI/mentor during 
all study procedures. 
● Workload feasibility: Research coordinator will work on this study at 100% time. In 
addition, the student investigator and study staff will be assisting the work. CMRR data 
acquisition and infusions/blood draws will enlist paid staff of Fairview/M Health to 
perform these procedures.  
● Facility resources: The facilities listed above are adequate for these procedures.  
● Medical resources available to participants 
● Training oversight 
o Delegation of Authority log will show which personnel are delegated to which 
study procedures.  
o Protocol training log will show all personnel up-to-date on current protocol 
versions. 

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o Psychological assessment training will be conducted by Department training 
programs for the MINI-7, and Kathyrn Cullen or Ranji Varghese will consult on 
results. 
● Phlebotomy will be conducted by trained Fairview/M Health staff. 
 
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