Clinical trial NCT03248167
Conditions: Alcohol Use Disorder Post Traumatic Stress Disorder
Keywords: Cannabidiol
Sponsor: NYU Langone Health
Start date: 2019-09-16; Completion date: 2022-04-20
Enrollment: 95 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This project aims to determine whether cannabidiol (CBD), a compound derived from the cannabis plant, is effective in treating alcohol use disorder (AUD) in individuals with comorbid posttraumatic stress disorder (PTSD). Investigators will test the hypothesis that oral cannabidiol (CBD) will reduce alcohol drinking in individuals with AUD comorbid with PTSD. To test this hypothesis, 48 otherwise healthy adult participants with moderate or severe AUD and PTSD will be randomized to treatment with either CBD (600 mg daily) or placebo, for a period of 6 weeks, such that both participants and study staff are blind to treatment condition. Participants (each treated for 6 weeks) will be continuously recruited over a study period of 14 months until 48 have completed. Baseline and weekly data will be collected on alcohol usage and PTSD symptoms, and investigators will assess whether CBD treatment leads to a greater improvement in these measures relative to placebo, and whether reduction in alcohol drinking is temporally linked to improvement in PTSD symptoms. Subjects will also participate in a task designed to quantify the psychological and physiological links between negative emotion produced by re-experiencing PTSD trauma, and alcohol craving. The task will be administered following 4 weeks of treatment. Treatment-associated reduction in alcohol craving elicited by trauma-associated negative emotion between CBD and placebo groups will be compared. This study will be the first to test whether CBD is effective in treating alcohol addiction and in treating PTSD in humans, and the first to examine the interaction between these treatment effects. Results will serve as proof of concept and provide guidance for a future larger clinical trial. Because CBD is a safe, readily available drug, such a trial would have an immense potential to prevent death, medical illness, and psychological suffering associated with AUD and PTSD. Further, because the brain circuits via which CBD acts to produce hypothesized effects are relatively well-understood, results may substantially advance understanding of the neurobiological basis of alcohol addiction.

Detailed description:
In this project, investigators aim to test the hypothesis that CBD will reduce alcohol drinking in individuals with AUD comorbid with PTSD. CBD is currently a medical research focus because it shows promise for treating anxiety and other brain disorders, but does not produce a 'high' like other parts of cannabis, has not been shown to be addictive, and is safe, with few or no side effects. AUD, which is one of the most common and most debilitating psychiatric conditions, is often associated with other comorbid psychiatric disorders - in particular, PTSD: depending on the population studied, 30-60% of individuals with AUD also have PTSD, with high comorbidity rates in military veterans. Evidence from animal models and clinical studies suggests that the negative emotion caused by PTSD symptoms intensifies craving for alcohol during alcohol withdrawal, perpetuating the addictive cycle; further, evidence shows that the brain circuits underlying negative emotion and addiction are linked in a forebrain area called the extended amygdala, which provides a neuropharmacological target to simultaneously treat both negative emotion and alcohol addiction in individuals with AUD and PTSD. CBD is known to inhibit brain activity in the extended amygdala, leading to reduced anxiety in both animal models and humans. CBD also reduces addictive alcohol seeking in animal models.

Arms: arm 1: 6 weeks, such that both participants and study staff are blind to treatment condition. arm 2: 6 weeks, such that both participants and study staff are blind to treatment condition.
Interventions: intervention 1: Cannabidiol intervention 2: Placebos
Intervention descriptions: intervention 1: 600 mg daily intervention 2: This project aims to determine whether cannabidiol (CBD) is effective in treating alcohol use disorder (AUD) comorbid posttraumatic stress disorder (PTSD). To address this aim, investigators will conduct a clinical trial in which CBD will be administered to 48 individuals with AUD comorbid with PTSD, and assess alcohol intake and PTSD symptoms. The aim is to test the hypothesis that CBD will reduce alcohol drinking in individuals with AUD comorbid with PTSD. To test this hypothesis, 48 otherwise healthy adult participants with moderate or severe AUD and PTSD will be randomized to treatment with either CBD (600 mg daily) or placebo, for a period of 6 weeks, such that both participants and study staff are blind to treatment condition.

Protocol documents:
Prot_SAP_001.pdf: 
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A PHASE I/II RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF CANNABIDIOL 
AS A TREATMENT FOR ALCOHOL USE DISORDER COMORBID WITH POSTTRAUMATIC STRESS 
DISORDER 
 
Principal Investigator: 
Charles Marmar, MD 
NYU School of Medicine, Department of Psychiatry 
One Park Ave 
Charles.marmar@nyumc.org 
646-754-4855 
NYULMC Study Number: 
S17-00949 
Funding Sponsor: 
National Institute on Alcohol Abuse and Alcoholism (NIAAA/NIH) 
IND/IDE Number:  
140108 
Regulatory Sponsor: 
Charles Marmar, MD 
NYU School of Medicine, Department of Psychiatry 
One Park Ave. 
Charles.marmar@nyumc.org 
646-754-4855 
Michael Bogenschutz, M.D. 
Professor of Psychiatry, NYU School of Medicine 
Bellevue Hospital Center 
462 First Avenue 
A Building, 8th Floor, Rm. A832 
New York, NY 10016 
Phone No: (646) 501-4026 
Email: Michael.Bogenschutz@nyumc.org 
Study Product: 
Cannabidiol 
Study Product Provider: 
Tilray 
ClinicalTrials.gov Number 
NCT03248167 
 
 


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Initial version:  July 19, 2018  
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Amended: July 25, 2018  
                                    
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Amended: Nov 20, 2018  
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Amended: August 21, 2019  
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Amended:  September 16, 2019 
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Amended: October 18, 2019 
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Amended: December 9, 2019 
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Amended: December 26, 2019 
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Amended: January 8, 2020 
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Amended: February 11, 2020 
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Amended: March 2, 2020 
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Amended: May 18, 2020 
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Amended: August 5, 2020 
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Amended: August 28, 2020 
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Amended: October 2, 2020 
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Amended: December 3, 2020 
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Amended: December 24, 2020 
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Amended: May 14, 2021 
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Amended: June 23, 2021 
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Amended: October 6, 2021 
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Amended: October 26, 2021 
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Study number: S17-00949 
Page 3 
Version: 4.3 
 
 
Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of Human 
Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable US 
government research regulations, and institutional research policies and procedures. The International 
Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred to as 
“ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with FDA and DHHS regulations. The 
Principal Investigator will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from the sponsor and documented approval from the Institutional Review Board (IRB), except where 
necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of 
this study have completed Human Subjects Protection Training. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center. Do not disclose or use except as authorized in 
writing by the study sponsor 
Interventional Template Version: 03/20/2018 
 
 
 


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Contents 
 
1  
Key Roles ....................................................................................................................................................10 
2  
Introduction, Background Information and Scientific Rationale ..........................................................10 
2.1  
Background Information and Relevant Literature ...............................................................................10 
2.2  
Name and Description of the Investigational Agent ............................................................................11 
2.3  
Rationale .............................................................................................................................................13 
2.4  
Potential Risks & Benefits ...................................................................................................................14 
3   
Objectives and Purpose ............................................................................................................................14 
3.1  
Primary Objective ................................................................................................................................14 
3.2  
Secondary Objectives .........................................................................................................................14 
4  
Study Design and Endpoints ....................................................................................................................15 
4.1  
Description of Study Design................................................................................................................15 
4.2  
Study Endpoints ..................................................................................................................................15 
5  
Study Enrollment and Withdrawal ...........................................................................................................17 
5.1  
Inclusion Criteria .................................................................................................................................17 
5.2  
Exclusion Criteria ................................................................................................................................17 
5.3  
Vulnerable populations .......................................................................................................................18 
5.4  
Strategies for Recruitment and Retention...........................................................................................18 
5.5  
Duration of Study Participation ...........................................................................................................20 
5.6  
Total Number of Participants and Sites ..............................................................................................20 
5.7  
Participant Withdrawal or Termination ................................................................................................20 
5.8  
Premature Termination or Suspension of Study .................................................................................21 
6  
Study Agent (Study drug, device, biologic, vaccine etc.) and/or Procedural Intervention ...............21 
6.1 
Study Agent(s) and Control Description .............................................................................................21 
6.1.1 
Acquisition ...........................................................................................................................................21 
6.1.2 
Formulation, Appearance, Packaging and Labeling ...........................................................................21 
6.1.3 
Product Storage and Stability .............................................................................................................22 
6.1.4 
Preparation ..........................................................................................................................................22 
6.1.5 
Dosing and Administration ..................................................................................................................22 
6.1.6 
Route of Administration .......................................................................................................................22 
6.1.7 
Starting Dose and Dose Escalation Schedule ....................................................................................22 
6.1.8 
Dose Adjustments/Modifications/Delays.............................................................................................22 
6.1.9 
Duration of Therapy ............................................................................................................................22 
6.2 
Study Agent Accountability Procedures..............................................................................................22 
6.3 
Study Behavioral or Social Intervention(s)..........................................................................................23 
7 
Study Procedures and Schedule .............................................................................................................24 
7.1 
Study Procedures/Evaluations ............................................................................................................24 
7.2 
Laboratory and Voice-markers Procedures/Evaluations ....................................................................26 
7.3 
Study Schedule ...................................................................................................................................27 
7.4 
Concomitant Medications, Treatments, and Procedures....................................................................34 
7.5 
Prohibited Medications, Treatments, and Procedures........................................................................34 
8 
Definitions of Key Terms ..........................................................................................................................34 
9 
Specification of Safety Variables .............................................................................................................35 
10 
General Guidelines ....................................................................................................................................35 
10.1 
Solicitation of AEs ...............................................................................................................................35 
10.2 
Preplanned Hospitalization or Procedure ...........................................................................................35 
10.3 
Reports of Cancer ...............................................................................................................................35 
10.4 
Specific guidelines for assessing laboratory values as adverse events .............................................35 
11 
Assessment of Adverse Events ...............................................................................................................35 
11.1 
Expectedness ......................................................................................................................................36 
11.2 
Severity ...............................................................................................................................................36 
11.3 
Relatedness ........................................................................................................................................36 
12 
Monitoring Adverse Events ......................................................................................................................36 


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Known Potential Toxicities of Study Drug ..............................................................................................37 
14 
Other Significant Adverse Events............................................................................................................37 
15 
Reporting Procedures ...............................................................................................................................37 
15.1 
AE Reporting .......................................................................................................................................37 
15.2 
SAE Reporting ....................................................................................................................................38 
15.3 
UP Reporting .......................................................................................................................................39 
15.4 
Pregnancy Reporting ..........................................................................................................................40 
16 
Reporting of Investigational Medicinal Product Quality Complaints ...................................................40 
16.1 
Defect or Possible Defect in the IP .....................................................................................................40 
16.2 
Temperature Deviations ......................................................................................................................40 
17 
Study Halting Rules ...................................................................................................................................40 
18 
Safety Oversight ........................................................................................................................................40 
19 
Clinical Monitoring ....................................................................................................................................41 
20 
Statistical Considerations.........................................................................................................................41 
21 
Source Documents and Access to Source Data/Documents ...............................................................45 
22 
Quality Assurance and Quality Control...................................................................................................45 
23 
Ethics/Protection of Human Subjects .....................................................................................................46 
23.1 
Ethical Standard ..................................................................................................................................46 
23.2 
Institutional Review Board ..................................................................................................................46 
23.3 
Informed Consent Process .................................................................................................................46 
23.3.1 Consent/Assent and Other Informational Documents Provided to Participants .................................46 
23.3.2 Consent Procedures and Documentation ...........................................................................................46 
23.4 
Participant and Data Confidentiality ....................................................................................................47 
23.5 
Future Use of Stored Data ..................................................................................................................48 
24 
Data Handling and Record Keeping ........................................................................................................49 
24.1 
Data Collection and Management Responsibilities ............................................................................49 
24.2 
Study Records Retention ....................................................................................................................49 
24.3 
Protocol Deviations .............................................................................................................................49 
24.4 
Publication and Data Sharing Policy ...................................................................................................50 
25 
Study Finances ..........................................................................................................................................50 
25.1 
Funding Source ...................................................................................................................................50 
25.2 
Costs to the Participant .......................................................................................................................51 
25.3 
Participant Reimbursements or Payments .........................................................................................51 
26 
Conflict of Interest Policy .........................................................................................................................51 
27 
References..................................................................................................................................................52 
 


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List of Abbreviations 
 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CSOC 
Clinical Study Oversight Committee 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
FFR 
Federal Financial Report 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
MOP 
Manual of Procedures 
n 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
US 
United States 
CBD 
Cannabidiol 
THC 
Tetrahydrocannabinol 
AUD 
Alcohol Use Disorder 
PTSD 
Post-Traumatic Stress Disorder 


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Protocol Summary 
 
Title 
A Phase I/II Randomized, Double-Blind, Placebo-Controlled Trial of 
Cannabidiol for Alcohol Use Disorder comorbid with Post Traumatic Stress 
Disorder 
Brief Summary 
The proposed study is a double-blind, randomized proof-of-concept study 
designed to assess feasibility and contrast effects of CBD treatment to those of 
placebo on safety, drinking-related outcomes and PTSD related outcomes in 
patients with AUD+PTSD. We will evaluate the safety of an extended daily CBD 
treatment regimen in an AUD+PTSD population, measure resulting CBD, THC, 
and anandamide levels, and generate preliminary data on the impact of CBD on 
alcohol use, PTSD symptoms, and neuropsychological and neurophysiological 
domains implicated in AUD and PTSD. 150 participants will be enrolled to 
randomize 48 eligible participants who fully meet study criteria in a 5:3 ratio to 
receive either 600mg CBD/day (PO) or placebo respectively for 6 weeks (N=30 
participants on CBD and N=18 participants on placebo). Clinical interviews or 
portions of the interview will be audio taped to ensure quality control. De-
identified audio recordings of participants who consent to participate in the 
voice-markers analysis will be encrypted and sent via secure sites for analysis 
to a HIPAA compliant specialized labs. 
 
Phase 
Clinical study phase I/II 
Objectives 
To assess the safety and feasibility of administering CBD in an AUD+PTSD 
population; to generate preliminary data on the effect of CBD in reducing self- 
reported measures of alcohol use and PTSD symptoms and the impact of CBD 
upon neurophysiological and neuropsychological domains relevant to 
AUD+PTSD; to assess plasma for CBD, THC and anandamide levels. 
Methodology 
Double-blind, placebo-controlled 
Endpoint 
Primary endpoints: Adverse events and scores on psychomotor and cognitive 
tasks, number of drinks per day and PCL-5 total score. Secondary endpoints: 
circulating concentrations of CBD, THC and anandamide. 
Study Duration 
2 years 
Participant Duration 
9 weeks 
Duration of IP 
administration 
6 weeks 
Population 
n=48 (randomized) 18–70 year-old males and females with moderate to 
severe AUD, as well as a DSM diagnosis of either PTSD or subthreshold 
PTSD in the New York area. 
Study Sites 
New York University Grossman School of Medicine 
Number of participants 
150 participants expected to be enrolled, 48 participants expected to be 
randomized 
Description of Study 
Agent/Procedure 
Cannabidiol PO 600mg/day 
Reference Therapy 
Placebo with medication management 
Key Procedures 
Blood draws 


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Statistical Analysis 
The primary outcome measure for AUD, the number of drinks per day, is the change 
from baseline to treatment end (week 6, T8), as analyzed with a Mixed Model 
Repeated Measures (MMRM) with within and between group comparisons. The 
primary outcome measure for PTSD, PCL-5 total score, and secondary outcomes 
for traumatic stress induced craving from the human laboratory task, and AUD and 
PTSD related domains will be analyzed in the same manner. 
 
For secondary outcomes of 
plasma levels within- and between-group comparisons 
of plasma CBD levels will be assessed at baseline (pre-CBD levels), following 
45 minutes (T1- 45min post-CBD levels), 1 day (T2- 45min post-CBD levels), 1 
week (T3- 45min post-CBD and pre-CBD levels), 2 weeks (T4- 45min post-CBD 
and pre-CBD levels), 4 weeks (T6- 45min post-CBD and pre-CBD levels),6 weeks 
(T8- 45min post-CBD and pre-CBD levels), and 7 weeks (T9- pre-CBD levels) 
after the first CBD vs. 
placebo dose. Effects
 of dose will be assessed and the 
interaction between group and time-points will be evaluated. 


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Schematic of Study Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1 Key Roles 
Charles Marmar, MD, Principal Investigator 
NYU School of Medicine, Department of Psychiatry 
One Park Ave. 8th Floor 
(646) 754-4855 
Charles.marmar@nyumc.org 
 
Esther Blessing, MD, PhD, Co-Investigator 
NYU School of Medicine, Department of Psychiatry 
One Park Ave. 8th Floor 
(646) 754-4808 
Esther.Blessing@nyumc.org 
 
Michael Bogenschutz, M.D, Co-Investigator. 
Bellevue Hospital Center 
462 First Avenue 
A Building, 8th Floor, Rm. A832 
New York, NY 10016 
(646) 501-4026 
Michael.Bogenschutz@nyumc.org 
 
Gene Laska Ph.D, Co-Investigator. 
New York University Langone School of Medicine 
One Park Avenue. 8th Floor 
New York, NY 10016 
(646) 754-4828 
Eugene.Laska@nyumc.org 
 
John Rotrosen, MD, Co-Investigator 
New York University School of Medicine 
Department of Psychiatry 
One Park Ave, 8th Fl 
(646) 754-4763 
John.Rotrosen@nyumc.org 
 
2 Introduction, Background Information and Scientific Rationale 
 
2.1 Background Information and Relevant Literature 
 
Need for improved treatments for AUD comorbid with PTSD 
Alcohol use disorder (AUD) is one of the most common and debilitating psychiatric disorders. It has a lifetime 
prevalence of ~29.1% in the United States, and is a major cause of medical and social disability, preventable 
death and economic burden ($249 billion in 2010) [1, 2]. Several medications are available for treating AUD, 
however associated effect sizes treatment compliance rates remain low [3] [4, 5]. A major barrier to improving 
medical treatment of AUD is the high level of heterogeneity between individuals with this disorder: AUD 
comprises multiple clinical subtypes with distinct patterns of alcohol misuse and distinct psychological and 
neurobiological disturbances. This means that a given medication may only work for certain subtypes of AUD 
patients, leading to overall lower treatment effectiveness in the absence of more targeted approaches. Differing 
co-existing psychiatric disorders (present in a high proportion of individuals with AUD) make an important 
contribution to this heterogeneity in [6-8]. The National institute of Alcohol use disorder (NIAAA) has therefore 
emphasized ongoing drug development should address this heterogeneity by targeting potential treatments to 
specific AUD subpopulations including psychiatric comorbidities, particularly those that are common, that 
involve severe AUD, and have low treatment response [6-8]. 
Based on these criteria, the NIAAA recently mandated research to target medications to AUD comorbid with 
post-traumatic stress disorder (PTSD) [6-8]. PTSD is a condition that may develop following a traumatic event: 
it involves intrusive thoughts about the traumatic event, avoidance of event relevant stimuli, negative changes 


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in mood and cognition, heightened vigilance and physiological arousal. PTSD is present in 30–60% of 
individuals diagnosed with AUD and conversely 20–70% of individuals diagnosed with PTSD meet criteria for 
AUD, with higher rates in military veterans; there this comorbidity (AUD+PTSD) represents a significant 
proportion of all AUD [9-14]. Subthreshold PTSD criteria requires that at least six symptoms of PTSD are present, but 
do not meet full threshold criteria due to failure to meet criterion specifiers. Previous research has shown that subthreshold 
PTSD is a clinically relevant concept. For instance, it has been found that psychiatric outpatients with subthreshold PTSD 
had social and occupation morbidity levels comparable to those with fully-threshold PTSD [104]. Other research has also 
found high rates of psychiatric comorbidity and psychosocial impairment in a sizable epidemiologic study [105]. Similar 
outcomes have been shown in samples of veterans [103]. When examining the leading subthreshold definitions utilized 
by clinicians the Six-symptom definition was found to trend toward significance and perform the best of all four definitions 
tested [102]. In addition, AUD+PTSD/subthreshold PTSD is associated with more severe AUD, higher mortality 
and impairment and poorer response to treatment. Findings also suggest that this comorbidity involves a vicious 
cycle in which each disorder exacerbates and impedes treatment of the other [10, 12, 15-22]; therefore, 
coordinated treatment of both disorders should be more efficacious than treating each disorder in isolation. 
Various medications have been tested for AUD or efficacy in randomized clinical trials involving 
AUD+PTSD/subthreshold PTSD patients. However, no Phase III trials have been reported [23]. 
 
Stress induced craving and extended amygdala activation as a target for treating AUD+PTSD 
Perhaps the most promising medication target for treating AUD+PTSD/subthreshold PTSD is the addiction 
domain of stress-induced alcohol craving, with the neurobiological substrate of increased activity in the 
extended amygdala. Clinical studies find that AUD+PTSD/subthreshold PTSD patients use alcohol as a 
coping mechanism to reduce stress associated with PTSD/subthreshold PTSD [10, 12, 15-22, 24-26]. Animal 
models show stress and alcohol craving are linked by common neurobiological circuits, namely the extended 
amygdala, and that pharmacological inhibition of stress or ethanol-withdrawal associated activity in this area 
simultaneously reduces both anxiety and ethanol-seeking behaviors [27-29]. Receptor actions implicated in 
this inhibitory effect include cannabindoid 1 (CB1) receptor stimulation and 5-HT1a receptor activation [27-29]. 
Clinical and human experimental studies support the idea that increased stress and amygdala activation 
increases alcohol craving and use. In AUD patients who report alcohol use to mitigate negative emotions, 
higher amygdala reactivity predicts future problem drinking [30]. In PTSD/subthreshold PTSD patients, PTSD 
symptoms predict alcohol craving and use [16, 31]; further, a hyper-reactive amygdala response to threat, and 
heightened sympathetic physiological arousal including skin conductance and heart rate, reliably distinguishes 
PTSD/subthreshold PTSD from controls and predicts PTSD symptoms [2, 32-34]. The well-validated human 
laboratory paradigm of guided trauma imagery-elicited alcohol craving shows that trauma re-experiencing 
elicits negative emotion, physiological arousal, and alcohol craving [35-39]. 
 
Potential for CBD to treat AUD+PTSD/subthreshold PTSD by targeting stress induced extended 
amygdala activation Cannabidiol (CBD), a pharmacologically broad spectrum anxiolytic and non-
psychotomimetic phytocannabinoid contained in cannabis, is a promising drug candidate for reducing negative 
emotion-induced alcohol craving. In animal models, CBD produces anxiolytic, anti-compulsive, anti-fear-
conditioning and pro-fear-extinction effects, by acting at serotonin 1A (5-HT1a) and CB1 receptors within 
extended amygdala areas (the central nucleus [40], bed nucleus of the stria terminalis [41-43] and nucleus 
accumbens shell [44]), and within functionally connected brain regions including the periaqueductal grey [45], 
prelimbic and infralimbic regions of the medial prefrontal cortex [46], and hippocampus [47], reviewed in [48]. 
CBD indirectly increases endocannabinoid agonism at the CB1 receptor [49], an action that reduces extended 
amygdala output and alcohol seeking [50]. CBD also potently reduced ethanol seeking in animal models of 
relapse during 7-days of treatment, and drug seeking remained fully attenuated up to 5 months following 
treatment termination [51]. In human experimental studies, CBD at doses between 300–800 mg rapidly (within 
2 hours) reduces subjective anxiety in both healthy and social anxiety disorder subjects, and reduces threat 
related amygdala activity and sympathetic arousal measured by skin conductance [52], reviewed in [48]. 
Importantly, skin conductance and amygdala activation were reduced by CBD in a closely correlated manner 
[53], suggesting threat related sympathetic arousal may serve as a proxy for amygdala activation [52]. These 
findings suggest that CBD will reduce extended amygdala activity and negative emotion associated with PTSD 
symptoms, and thereby, reduce alcohol craving and use. Further findings suggest that human laboratory 
measures of the subject and physiological effects of traumatic stress upon emotional state and alcohol 
craving may serve as a useful measure of drug target engagement. 
 
a. 
Name and Description of the Investigational Agent 


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Cannabidiol (CBD) is a phytocannabinoid constituent of cannabis that lacks the psychotomimetic and rewarding 
effects of tetrahydrocannabinol (THC) [54], and has an excellent safety profile in the human experimental 
studies and clinical trials reported thus far [43, 55]. CBD is a schedule 1 drug, a class that includes compounds 
with high potential for abuse and no medical value. Contrary to this scheduling, CBD does not appear to possess 
a high abuse potential. Nonetheless, this formulation has not been FDA-approved for medical use. Therefore, 
this study will be performed under an Investigational New Drug Application (140108). 
 
CBD has a broad spectrum of pharmacological effects. As distinct from THC, CBD is a very low-affinity 
cannabinoid 1 (CB1) receptor ligand; nevertheless CBD appears to achieve an agonist effect at this receptor, 
potentially by inhibiting fatty acid amide hydroxylase (FAAH), which is the enzyme responsible for hydrolysis 
the endocannabinoid anandamide, which acts as CB1 agonist [49]. In addition to its impact on the 
endocannabinoid system, CBD also acts as an agonist at the serotonin 1A (5-HT1A) receptor [42, 56]; 
produces allosteric modulation of ligand-binding kinetics at μ and δ opioid receptors [57]; increases 
intracellular calcium through activation of transient receptor potential vanilloid type 1 (TRPV1) cation 
channels [58]; enhances adenosinergic neurotransmission via inhibition of the adenosine transporter [59]; 
CBD also regulates, directly or indirectly, the peroxisome proliferator-activated receptor-γ, the orphan G- 
protein-coupled receptor 55, the equilibrative nucleoside transporter, additional TRP channels, glycine 
receptors and GABA receptors [11, 12, 19, 21]. CBD may also have non-receptor based enzymatic and other 
effects. Only some of these actions (CB1 and 5-HT1A actions) have been related to animal model effects of CBD 
anxiolytic or anti-addictive effects [48]. 
 
2.2.1 Preclinical Data 
As discussed, extensive evidence in animal models shows that CBD reduces anxiety behaviors, compulsive 
behaviors, panic response and physiological stress responses by inhibiting extended amygdala activation 
and promoting response in the hippocampus and medial prefrontal cortex [48]. This suggests the potential 
to reduce stress-induced craving. Several other effects of CBD may also act improve PTSD symptoms and 
combat alcohol addiction. Cannabidiol modifies consolidation and reconsolidation, suggesting the ability to 
modify traumatic memories [48, 60]; CBD produces several pro-cognitive effects: including protecting against 
ethanol induced neurotoxicity [61], promoting hippocampal neurogenesis [47],  and attenuating cognitive 
impairment in several animal models of neurodegenerative disease [62] [63]. 
 
Animal model studies also show that CBD reduces addictive behaviors: CBD reduces cue-induced heroin 
seeking, potentiates extinction of cocaine- and amphetamine-induced conditioned place preference [64], 
and normalizes heroin-seeking-induced changes in glutamatergic GluR1-containing amino-hydroxy- methyl-
isoxazolepropionic (AMPA) receptors and CB1 receptor expression in the nucleus accumbens [65] induced 
by alcohol intoxication in a delay discounting task 6-15 days after the cessation of   treatment. 
 
2.2.2 Clinical Data to Date 
Clinical trials in PTSD or anxiety: No clinical trials of CBD for PTSD/subthreshold PTSD have been reported, 
nor for any anxiety related outcome – although some trials in anxiety may be currently in progress. In human 
experimental studies, CBD at doses between 300–800 mg rapidly (within 2 hours) reduces subjective anxiety 
in both healthy and social anxiety disorder subjects, and CBD reduces threat-related amygdala activity and 
sympathetic arousal measured by skin conductance [66] [43, 48, 52]. 
 
Clinical trials in AUD: No extended clinical trials of CBD’s effects in alcohol use disorder or any addictive 
disorder have yet been reported. However, there are limited studies of CBD’s acute effects on addiction- related 
behaviors. The only study to assess the impact of CBD on alcohol-related behaviors found no impact of 200mg 
of CBD on symptoms of intoxication in healthy volunteers [67]. CBD was also reported to reduce cigarette 
smoking in dependent humans [68], and a single case study reported that daily CBD prevented marijuana 
withdrawal symptoms [69]. 
 
Other clinical data: A considerable and rapidly growing number of human experimental studies and clinical trials 
of CBD’s effects in other neuropsychiatric disorders (other than PTSD/subthreshold PTSD or AUD) have been 
conducted. Findings in general show CBD to have multiple therapeutic effects, including anxiolytic, anti-
addictive, anticonvulsive, antipsychotic and analgesic [70], combined with an excellent safety profile and lack 
of adverse effects [43, 55]. GW pharmaceuticals is developing CBD (Epidiolex®) as a medication for the 
treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, and recently completed 
successful Phase 3 trials in 2016 [71, 72], and a successful Phase 2 trial in schizophrenia  [73]. 
 
2.2.3 
Dose Rationale (If applicable) 


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The proposed dose of 600 mg (~8 mg/kg) daily is within the range of doses (300–800 mg) shown to be anxiolytic 
in humans, is expected to be safe and tolerable in humans and to yield steady state levels within a safe and 
therapeutic range. 
 
Anxiolytic target dose. As discussed above, human experimental studies showed that acute oral CBD in the 
300–800 mg range was anxiolytic in humans, suggesting daily dosing should have similar therapeutic effects. 
Potentially cautioning against much higher doses, preclinical studies suggest attrition of anxiolytic effects may 
occur at the highest doses [48] although no such data yet support this in humans. 
 
Safety: CBD was found to be safe and well tolerated in all Phase I and Phase IIa clinical trials (>10) reported 
thus far, which included daily doses up to 1000 mg PO and treatment durations up to 6 weeks, whereas doses 
up to 1500 mg daily have been reported safe in case studies, reviewed in [43, 74]. We considered dose titration, 
but elected not to because acute doses of up to 1500 mg, and repeated daily doses of up to 1000 mg were 
previously safe and well tolerated [43, 74]. Regarding interactions with alcohol, a double-blind, randomized 
placebo controlled acute dosing trial showed that 200 mg PO CBD did not increase the psychomotor effects of 
alcohol (1gm/kg) or blood alcohol levels [67]. Relevant to the AUD population, CBD showed no risk for abuse 
liability in humans [75]. 
 
Potential for dose accumulation: Regarding repeated dosing pharmacokinetics, two studies in adults that 
assessed plasma levels over repeated dosing showed no progressive accumulation of CBD levels, including a 
6-week trial of oral CBD at 700 mg daily [67, 76]. Preliminary data with transdermal CBD up to 30mg/kg/day in 
rodents shows no serum accumulation over 7 days of treatment (Weiss, unpublished data). Therefore, under 
the proposed dosing regimen we expect to achieve steady-state serum levels of CBD within a week. 
 
2.3 Rationale 
There is an urgent need for medications that are effective in treating AUD+PTSD/subthreshold PTSD 
comorbidity, and which are targeted to specific addiction domains and their neurobiological substrates. Pre-
clinical and human experimental findings suggest the phytocannabinoid CBD is a promising candidate 
medication for reducing stress induced craving by inhibiting extended amygdala output, in addition to potential 
anti-addictive, traumatic and addictive memory modifying and pro-cognitive effects, thereby providing an 
integrated treatment for both AUD and PTSD/subthreshold PTSD. This promise is augmented by CBD’s proven 
safety record, lack of intoxicating effects and low potential for abuse. Clinical trials of CBD in other disorders 
together with human experimental studies provide a strong basis for determining a suitable therapeutic dose 
for AUD+PTSD/subthreshold PTSD. There are few or no clinical trials reported of CBD for AUD, 
PTSD/subthreshold PTSD, or more generally for stress and addiction disorders, creating a mandate for the 
current trial. 
The proposed study is a double-blind, randomized proof-of-concept study designed to assess feasibility and 
contrast effects of CBD treatment to those of placebo on safety, drinking-related outcomes and 
PTSD/subthreshold PTSD related outcomes in patients with AUD+PTSD/subthreshold PTSD. We will evaluate 
the safety of an extended daily CBD treatment regimen in an AUD+PTSD/subthreshold PTSD population and 
measure resulting CBD, THC, and anandamide levels. We will also generate preliminary data on the impact of 
CBD on alcohol use, PTSD symptoms, a human laboratory traumatic stress induced craving task, 
neuropsychological and neurophysiological domains implicated in AUD and PTSD/subthreshold PTSD, and 
cognitive ability. Cannabidiol levels will be obtained from CBD-treated participants to estimate the plasma levels 
corresponding with putative therapeutic effects and to determine whether dose accumulation occurs. THC 
levels will be obtained from CBD-treated participants to determine whether CBD metabolites are converted 
into THC, as has been suggested in the literature [77]. Anandamide levels will be obtained from all participants 
to test whether CBD elevates plasma anandamide, and to provide preliminary data for relating anandamide 
levels to putative therapeutic effects. Following screening and baseline assessments, 48 participants will be 
randomized in a 5:3 ratio to receive either 600mg CBD/day (PO) or placebo respectively for 6 weeks (N=30 
participants on CBD and N=18 participants on placebo). Safety measures (adverse events, cognitive and 
motoric function), drinking related outcomes and PTSD symptoms will be assessed weekly throughout the 
study. Human laboratory tasks, neuropsychological domains implicated in AUD and PTSD/subthreshold PTSD 
and cognition will be assessed at baseline and at the end of treatment. Measurement of circulating levels of 
Delta-9 THC, 11-Hydroxy Delta-9 THC and Delta-9 Carboxy THC will be obtained from CBD-treated 
participants only at baseline, 45 minutes, 1 day, 1 week, 2 weeks, 4 weeks, 6 weeks, and 7 weeks after treatment 
with the first dose of CBD vs. placebo. Anandamide levels will be obtained from both CBD- and placebo-treated 
participants at the aforementioned timepoints. 
 


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2.4 Potential Risks & Benefits 
 
2.3.1 
Known Potential Risks 
The available evidence suggests that CBD is safe and well-tolerated in human participants. Numerous studies, 
including several blinded, placebo-controlled trials, have revealed few adverse effects of CBD orally in doses 
ranging from 10 mg to 1500 mg per day; there have been no reported effects on blood pressure, heart rate, or 
respiratory rate, no negative mood effects, and no psychomotor slowing. Commonly reported treatment-
emergent adverse events in Phase 3 trials of CBD for Lennox-Gastaut or Dravet  Syndrome included diarrhea, 
somnolence, pyrexia, decreased appetite, vomiting, fatigue, lethargy, convulsion, and elevated liver enzymes. 
All participants in these trials were on concomitant anti-seizure medications. CBD is not noticeably 
psychoactive. 
 
2.3.2 
Incidental Findings 
In some cases, the safety blood draw results may indicate an abnormality with (or without) a clinical 
significance. Every blood draw performed in this study will be saved and handled under the standard PHI 
confidentiality restrictions and regulations employed for patients’ information. The results are always reviewed 
by a licensed nurse practitioner or an MD, who may then detect an abnormality. If clinically useful information 
is uncovered, either the Principal Investigator or another clinician on the study will speak to the participant in 
person or on the telephone regarding the new information. A copy of the original report will also be provided 
to the participant who will then be advised to consult with their treating physician. 
 
2.3.3 
Known Potential Benefits 
Participants may or may not experience clinical benefit from this study. Pre-existing clinical data suggest a 
possibility that the study drug could produce anxiolytic and anti-addictive effects. Aspects of study participation 
likely to be beneficial include free medical and psychiatric evaluations, and the attention and support of 
participating in a clinical trial.  
 
3  Objectives and Purpose 
 
3.1 Primary Objective 
The primary objective is to obtain a preliminary assessment of the safety, tolerability, efficacy, and effect size 
of CBD in reducing self-reported measures of alcohol use and PTSD symptoms in the AUD+PTSD/subthreshold 
PTSD population. 
We predict that treatment with 600mg CBD daily will be well tolerated with no greater psychomotor or other 
motor side effects compared to treatment with placebo. We predict that CBD will be associated with a greater 
reduction in drinks per day and PTSD symptoms (total PCL-5 score) compared to placebo. 
 
3.2 Secondary Objectives 
Secondary objectives of this study are as follows. 
1) To assess the effect of CBD upon plasma CBD and THC levels when administered to patients with 
AUD+PTSD/subthreshold PTSD. We predict that within-group plasma CBD levels will stabilize within one 
week, i.e. 45 minutes post-CBD dosing levels obtained after 1 week of treatment will not differ from those 
obtained after 4 weeks of treatment. 
2) To contrast the effects of CBD to those of placebo on psychological and cognitive domains relevant to AUD 
and PTSD/subthreshold PTSD. Relative to placebo, we predict that CBD will improve self-report measures 
of craving, anxiety, mood, and self-efficacy, and improve cognitive function. We will also specifically target 
the domain of traumatic stress induced craving using a human laboratory task. We predict that relative to 
placebo, CBD will lead to a greater attenuation in subjective traumatic stress and alcohol cue-induced 
craving and accompanying physiological stress response. 
3) To assess the effect of CBD on plasma anandamide levels. We will contrast levels of plasma anandamide 
between samples taken at baseline and after CBD treatment, and between samples taken at predicted pre- 
and 45 minutes post-dosing CBD levels. We predict that relative to placebo, CBD will lead to an increase 
in plasma anandamide between these time points. 
4) To assess the temporal relationship between the onset in reduction of PTSD symptoms and the onset in 
reduction of AUD symptoms. We predict that a reduction in PTSD symptoms will precede a reduction in 


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AUD symptoms. 
Exploratory Aim 1:  To examine voicemarkers as a function of a patient’s AUD and PTSD status and to 
develop assessment models that use lexical and prosodic features to classify a patient’s AUD and PTSD 
status. 
 
4 Study Design and Endpoints 
 
4.1 Description of Study Design 
 
The proposed study is a phase I/II, single-center, double-blind, randomized proof-of-concept study designed to 
assess safety and feasibility in the AUD+PTSD/subthreshold PTSD population and contrast effects of CBD 
treatment to those of placebo on drinking-related outcomes and PTSD symptoms. We will evaluate the safety 
of an extended daily CBD treatment regimen in an AUD+PTSD/subthreshold PTSD population, measure 
resulting  plasma and CBD and THC levels, generate preliminary data on the impact of CBD on alcohol 
consumption and PTSD symptoms, assess the effect of CBD on a human laboratory measure of traumatic-
stress induced craving and neuropsychological measures  relevant  to  AUD  and  PTSD/subthreshold PTSD,  
and  assess  the  effect  of  CBD  dosing  no plasma anandamide levels. 
 
150 participants are expected to be enrolled in the study prior to screening and randomization. Following 
screening and baseline assessments, 48 participants who fully meet study criteria are expected to be 
randomized in a 5:3 ratio to receive either 600mg CBD/day (PO) or placebo respectively for 6 weeks (N=30 
participants on CBD and N=18 participants on placebo). This dose was selected to optimize anxiolytic affects 
to target stress induced alcohol craving. Assessments of drinking and PTSD related outcomes will be completed 
at baseline and weekly over 6 weeks of treatment, with an assessment one week following the end of treatment. 
The human laboratory task and assessments of cognitive function will be completed at baseline and at the end 
of 6 weeks of treatment. Measurement of circulating levels of CBD, THC, and THC metabolites (Delta-9 THC, 
11-Hydroxy Delta-9 THC and Delta-9 Carboxy THC) will be obtained from CBD-treated participants at baseline, 
45 minutes, 1 day, 1 week, 2 weeks, 4 weeks, 6 weeks, and 7 weeks after treatment with the first dose of CBD 
vs. placebo. Anandamide levels will be obtained from both CBD- and placebo-treated participants at the 
aforementioned time-points.  
 
Outcomes will include drinking outcomes; PTSD symptoms; responses to personalized trauma and alcohol 
scripts designed to elicit stress- and cue-induced craving and anxiety; cognitive function; circulating levels of 
CBD, THC and anandamide and safety measures (adverse events, cognitive and motoric function), and 
psychological domains relevant to AUD+PTSD/subthreshold PTSD including self- reported craving, depression, 
and anxiety across 6 weeks of treatment and one week following the end of treatment. 
 
Voice-markers: High-fidelity audio recordings from in-person or remote sessions of clinical interviews will be 
collected at screening. The audio recordings will be encrypted and transferred via secure transfer methods to 
a HIPAA compliant specialized entity for quality control and voice-makers analyses. If the participant gives their 
consent, the collected audio recordings will be used to examine voice-markers as a function of a patient’s AUD 
and PTSD status and to develop assessment models that use lexical and prosodic features to classify a 
patient’s AUD and PTSD status. All the recordings will be de-identified and labeled with a unique study code 
number for each participant in the study. Study personnel of the HIPAA compliant specialized entity receiving 
voice-marker data will not have access to link participants’ study code to any identifying information collected 
throughout the study. These personnel will not be able to re-identify study participants associated with the 
respective data using the unique identifiers. If the recorded audio data has any identifying information 
embedded in the recordings, that information will be removed by study staff, who will review each audio file 
and delete any PHI before the file is sent to the specialized lab. Once the files are received, the specialized lab 
will double check the data for any PHI and if found, this will be removed prior to the data being used. 
 
4.2 Study Endpoints 
 
4.2.1 Primary Study Endpoints 
The primary study endpoint for alcohol use will be number of drinks per day assessed by the Time Line Follow 
Back methodology [78]. The primary study endpoint for PTSD symptoms will be the PCL-5 total score.   Safety 
will be assessed by collection of adverse events at all visits after treatment is initiated in addition to LFTs 
collected at screening, as well as weeks 2, 6, and 7 to assess the liver function during and after treatment 


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with study medication. 
4.2.2 Secondary Study Endpoints Secondary Alcohol use endpoints 
Secondary efficacy endpoints are the percent carbohydrate-deficient transferrin (CDT); the percentage of heavy 
drinking days (four or more drinks for women or five or more drinks for men per drinking day) averaged for each 
treatment week; weekly average severity of alcohol craving assessed by the Penn Alcohol Craving scale 
[79]; weekly percentage of very heavy drinking days (8+/10+ drinks per day for women and men 
respectively); weekly percentage of days abstinent; weekly percentage of subjects with no heavy drinking days, 
and weekly percentage of subjects that are ‘present and clean’, i.e. present to provide breath alcohol levels 
(BAC) and have a BAC of zero [80]. 
 
AUD-related measures 
The Penn Alcohol Craving Scale (PACS) [79] will be used to assess craving. This scale has 5 Likert-scaled 
items with excellent internal consistency and evidence of predictive, construct, and discriminant validity. Self- 
efficacy will be assessed using the Alcohol Abstinence Self-Efficacy Scale (AASE) [81], a self-report 
questionnaire which has been used widely in the alcohol treatment research, both as a predictor of outcome 
and as a patient-treatment matching variable [82]. Craving, self-efficacy, and alcohol use will be assessed 
before treatment (baseline), week 1, week 4, week 6, and at one week following the completion of treatment. 
Mood and Anxiety will be measured with the Beck Anxiety Inventory (BAI) [99] and Beck Depression Inventory-
II (BDI-II) [100] scales at baseline, treatment weeks 1, 4 and 6, and at one week following treatment completion. 
 
Risk of suicidality will be assessed by a licensed study provider using the Columbia-Suicide Severity Rating 
Scale (C-SSRS) [98] as part of each study visit.  
 
PTSD-related measures 
The PCL-5 will be administered at baseline, weeks 2, 4, 6 and 7. In addition to the PCL-5 score (primary PTSD 
endpoint), childhood trauma (child abuse and neglect) will be assessed at baseline using the self-report 
Childhood Trauma Questionnaire (CTQ) (28 item). 
 
Traumatic stress and cue response task 
The Cue and Stress Response Task will be performed at the 4- week time-point using methodology developed 
in Rajita Sinha’s lab, similar to those in used in past studies with alcohol dependent patients [84]. Dr. Sinha will 
provide consultation on the implementation of these methods. Briefly, imagery scripts will be developed at 
baseline. Traumatic stress imagery scripts will be based on a recent highly stressful traumatic situation the 
participant has experienced unrelated to alcohol use. Alcohol cue scripts will be derived from a recent event 
that included alcohol-related stimuli and led to alcohol use. Neutral or relaxing scripts will also be developed. 
All scripts will be developed by obtaining specific details of stimulus and response, including contextual details, 
cognitive and verbal content, affective experience, and bodily sensations. These details form the basis of a 5-
minute imagery script, which will be developed for each of the three conditions. Imagery sessions will be 
structured with a 5-minute pre-imagery period, a 5-minute imagery period, and a 5-minute recovery period. 
Pulse, skin conductance, heart rate variability, and blood pressure will be monitored during each imagery 
session with an ADInstruments PowerLab 4/30 Galvanic Skin Response device and a Contec Patient Monitor. 
In Human laboratory studies with CBD, skin conductance and amygdala activation were reduced by CBD in a 
closely correlated manner [52], suggesting threat-related sympathetic arousal may serve as a proxy for 
amygdala activation [53]. 
 
Participants will complete Likert scale ratings of vividness, craving, anxiety, and the 30-item Differential Emotion 
Scale [84] following each of the three periods. After each condition, a progressive relaxation procedure will be 
implemented to facilitate return to baseline of vital signs, craving and anxiety, an approximate period of 10 
minutes, as shown in previous research from the Sinha lab [84]. The entire imagery protocol will take 120 
minutes. The order of the sessions will be randomized and counterbalanced among participants. The task will 
be completed at T6 (the end of 4 weeks of treatment with 600mg daily). At this point, we expect steady-state 
plasma CBD levels to have been reached.  
 
Plasma CBD, THC and anandamide levels 
Measurement of circulating levels of CBD, THC, Delta-9 THC, 11-Hydroxy Delta-9 THC and Delta-9 Carboxy 
THC will be obtained from CBD-treated participants at baseline (pre-CBD levels), following 45 minutes (T1- 


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45min post-CBD levels), 1 day (T2- 45min post-CBD levels), 1 week (T3- 45min post-CBD and pre-CBD levels), 
2 weeks (T4- 45min post-CBD and pre-CBD levels), 4 weeks (T6- 45min post-CBD and pre-CBD levels),6 
weeks (T8- 45min post-CBD and pre-CBD levels), and 7 weeks (T9- pre-CBD levels) after the first CBD vs. 
placebo dose. Anandamide levels will be obtained from both CBD- and placebo-treated participants at the 
aforementioned timepoints. All three levels (CBD, THC and anandamide) will be determined via High 
Performance Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) by the Nathan Kline Institute. 
 
Psychomotor and subjective effects of CBD 
Basic motoric and cognitive function will be evaluated throughout treatment with several established field 
sobriety tests, including a walk-and-turn task, one-leg stand, Romberg’s test, finger-finger test, and counting 
backwards [85]. The Addiction Resource Center Inventory (ARCI), 49-item version [86], will be used as a 
measure of the intoxicating effects and abuse potential of CBD. Breath Alcohol Concentration (BAC) will also 
be measured to ensure participants are not under the influence of alcohol during administration of these tasks. 
 
Cognitive Function 
Several established neuropsychiatric and cognitive tasks will be administered to evaluate the impact of CBD 
vs. placebo treatment on cognitive domains potentially affected by CBD and/or THC. The Rey Auditory Verbal 
Learning Task (RAVLT) will be used to assess episodic memory [87], the Mental Rotation Task (MRT) will 
evaluate visuospatial ability [88, 89], a Time Reproduction Task (TRT) will measure encoding and retrieval of 
time intervals [67] and several WM Span tasks (OSpan, RSpan, SymSpan, RotSpan) will measure working 
memory capacity [90, 91]. Cognitive function will be measured at day 1 (T2) and at the end of treatment (T8). 
 
3 Study Enrollment and Withdrawal 
 
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Males and females age 18-70 
2. DSM-5 diagnosis of moderate or severe AUD 
3. DSM-5 diagnosis of PTSD with Clinician Administered PTSD Scale (CAPS-5) OR subPTSD diagnosis 
(meeting criterion A, F, G, H and at least 6 symptoms across any criteria B-E) with Clinician Administered PTSD 
Scale (CAPS-5) 
4. Able to provide voluntary informed consent 
5. At least 4 heavy drinking days (4 or more drinks per day for a woman, 5 or more drinks per day for a 
man) in the 30 days prior to screen 
6. If of childbearing potential (male or female), are willing to use approved form of contraception from screening 
for duration of the trial 
7. Able to provide at least two locators 
8. Endorse desire to cut down or stop drinking 
9. Agrees to abstain from all other cannabinoid use for the duration of the study 
10. Confirms they are reliably domiciled 
 
5.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Current alcohol withdrawal (CIWA-Ar score >7) 
2. Exclusionary medical conditions (e.g. current severe alcohol withdrawal requiring medical hospitalization, 
significantly impaired liver function) 
3. DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder I 
4. High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or 
the informed consent process, based on investigator’s clinical evaluation (e.g., evidence of serious personality 
disorder, antisocial behavior, serious current stressors, lack of meaningful social support) 
5. Exposure to trauma in the last 30 days, including police duty or military service 
6. Current significant suicidality (assessed using the C-SSRS), any significant suicidal behavior in the past 12 
months, or any history of serious suicide attempts requiring hospitalization, or current significant homicidality 
7. History of Severe Traumatic Brain Injury (TBI; as indicated by Loss of Consciousness > 24 hours) 
8. DSM-5 diagnosis of current mild cannabis use disorder and/or moderate or severe substance use disorder 
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9. Significant laboratory abnormalities, including significantly impaired liver function, serious abnormalities of 
complete blood count or metabolic panel 
10. Active legal problems likely to result in incarceration within 12 weeks of treatment initiation 
11. Pregnancy or lactation 
12. Current use of exclusionary medications, including cannabinoids; treatments for addictions including alcohol; 
moderate to strong inhibitors of CYP3A4 or CYP2C19; medications metabolized primarily by CYP3A5 or 
CYP3A7; and medications with a narrow therapeutic index which are substrates of CYP3A4, UGT1A9, UGT2B7, 
CYP2C8, CYP2C9, CYP2C19, CYP1A2, or CYP2B6. 
13. Current treatment for AUD (with exceptions of: AA/12-step treatment and/or psychosocial treatment initiated 
more than 2 months prior to the screening visit) 
14. Current treatment for methadone or opioid abuse 
15. Psychotherapy for PTSD or other psychiatric condition, if initiated within 2 months of screening 
16. Inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency 
Department stays 
17. A positive urine drug screen for opioids at screen, baseline, or any later visits. If a participant has a positive 
drug screen for THC or cocaine at screen, baseline or a later visit- their enrollment will be subject to the clinical 
judgement of the Principal Investigator. Please refer to the Medical and Psychiatric Safety SOP for further details. 
 
5.3 Vulnerable populations 
This study will not enroll any vulnerable populations. As per the exclusion criteria, all enrolled participants will 
have the capacity to consent. Capacity will be determined by MD or PhD qualified research staff as per the 
legally specified criteria for determination of decision making capacity, assessed by verbal responses from the 
participant. 
 
5.4 Strategies for Recruitment and Retention 
 
Subjects will be approximately 48 women and men, age 18-70, with moderate to severe AUD and PTSD or 
subthreshold PTSD, recruited from the public through local media advertisements. Participants will be recruited 
between approximately November 2018 and August 2021.  
 
48 men and women with moderate to severe AUD and comorbid PTSD or subthreshold PTSD will be recruited 
from the community and from local clinical programs. We will initiate contact with subjects through multimodal 
outreach including contacts with treating clinicians in medical and psychiatric clinics at the Cohen Veteran Center 
(600 recruited annually) and Military Family Clinic at NYUMC (500 enrolled annually); Manhattan VA, Bronx, 
Manhattan and Brooklyn VA PTSD clinics and other VA medical centers within the greater New York City area 
(over 1300 with PTSD and comorbid AUD); Women’s Mental Health Consortium of NY, Derner Institute at 
Adelphi University; addiction services sites, including the detox unit and Chemical Dependency Outpatient 
Program at Bellevue (11,400 visits annually, combined), Psychiatry Outpatient Clinic and Primary Care Clinic at 
Bellevue hospital, addiction services at the Manhattan and Brooklyn VA, and at the Federally Qualified Health 
Center (FQHC), an outpatient psychiatry clinic at NYU Lutheran Medical Center (115,000 visits annually). 
Additionally, patients will be recruited at the Nathan Kline Institute/Rockland Psychiatric Center and Gouverneur 
Health. Fliers and brochures will be distributed by clinicians to potentially interested participants.  
 
Clinicians will be asked to only refer individuals who they believe are appropriate for the study, can safely delay 
treatment for 24 hours and who are capable of deciding to participate. At the time of referral, clinicians will 
provide study staff with names, contact information, and relevant clinical information for interested patients, who 
will sign an authorization form allowing the clinic to release their relevant information to study staff. Once referrals 
are given, the study team will access EPIC to determine the participant’s initial eligibility. Dr. Marmar and the 
study coordinators will maintain relationships with clinicians at these institutions in order to generate referrals. 
Additionally, the study team will use NYU’s DataCore service to gather information from EPIC for current NYU 
patients who may be eligible. Participants can be referred to the study by their physician, the clinic, or through 
DataCore reports. To gather the information from EPIC, DataCore will request a report. Data gathered will be 
used to identify subjects that did not opt out of being contacted for research, and who fit eligibility criteria for this 
study. The data gathered will include inclusionary and exclusionary criteria, including the following information: 
 
Inclusion Criteria: 
-18-70 years old 
WITH diagnosis of PTSD (Post Traumatic Stress Disorder) OR Acute Stress Disorder OR Adjustment Disorder 
AND Alcoholism OR Alcohol Use Disorder OR Alcohol Abuse WITHOUT a diagnosis of Schizophrenia OR 


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Bipolar I.  
 
DataCore will request this information from EPIC monthly. Once a patient has been deemed potentially eligible 
for the study, and is also noted in EPIC as having consented to be contacted for research, approved staff will 
e-mail potential participants’ treating physicians following scheduling the patient for their assessment visit. 
Approved staff will contact potential participants identified through EPIC by either email, MyChart, or by phone. 
Due to sharing the same recruitment resources, the phone consent and screen will be identical to those used 
in Dr. Charles Marmar’s study, s18-01405. Any recruitment information sent by email will use Send Safe email 
(or will be done through MyChart). Once contact is made, approved recruitment language will be used to 
communicate the reason for contact and potential participants will be asked if they are interested in participating 
in this specific study. If the potential participants agree, the study team will provide with information regarding 
the next steps for participation. If a participant requests information regarding opting out of further recruitment 
for all research, they will be directed to contact our team. 
 
Active recruitment will also take place through social media sources, including Facebook, Twitter, Instagram, 
Reddit, Craigslist, clinical trial pre-screening services like StudyKik, Patient Wise, BuildClinical, and TrialFacts, 
online research recruitment sites such as ResearchMatch, VolunteerMatch ClinicalConnection, Antidote, and 
TrialSpark, online forums, local newspapers and other print media (i.e. Bushwick Daily, Queens Chronicle, New 
York Post, Schneps Media etc.), online periodicals such as Time Out Magazine, Military Times and Schneps 
media, radio advertisements within New York City, online targeted advertisement services from companies such 
as the Washington Post, email newsletters such as Division of Veteran Services, through academic email 
listservs (including Child and Adolescent Mental Health Studies [CAMS] listserv),  at social service agencies, 
community mental health clinics, community organizations, local professional organizations, residential 
treatment facilities, consenting support and recovery centers, regional employee assistance programs, religious 
organizations, cultural centers, social clubs, local shops, and local universities. Fliers and brochures will be 
distributed by clinicians to potentially interested participants. Additionally, the study team will use NYU’s 
DataCore service to gather information from EPIC for current NYU patients who may be eligible. 
 
TrialFacts: TrialFacts is a referral service that targets advertisements to individuals who may be eligible for the 
study. Participants are provided with detailed information about the study and then complete a brief IRB-
approved questionnaire. Participants who complete the questionnaire have consented to collection of their 
responses to the questionnaire, including their contact information, as well as TrialFacts’ sharing their information 
with the study team. Trialfacts provides the study team with the respondents’ questionnaire responses and 
contact information (name, phone number, email, state, zip code, gender, and DOB) if they meet minimum 
eligibility requirements via a restricted access spreadsheet. If not eligible, TrialFacts releases the questionnaire 
responses but not the respondents’ contact information. The study team may request ineligible respondents’ 
contact information from TrialFacts to double-check on responses on an as needed basis.  
 
Eligible, participants are invited to book an appointment for the phone screen using the TrialFacts online platform. 
If they do not book an appointment, the study team reaches out to the participant to schedule.  If the participant 
chooses to book online, they are sent a calendar invitation and a confirmation email.With an online booking, 
TrialFacts sends the participant email reminders 24 hours and 1 hour before their phone screen appointment, 
and text message reminders 1 hour and 10 minutes before the phone screen appointment. 
 
After the study team completes the phone screen, the restricted access spreadsheet is updated with participant’s 
enrollment status and/or reason for exclusion in order to help TrialFacts better target audiences. The study team 
only indicates whether the participants was enrolled or not enrolled and which of the exclusion criteria were met. 
The reasons for exclusion on the spreadsheet are limited to: not enough drinking days; current life stressors; 
exclusionary medication; exclusionary medical condition; exclusionary psychiatric disorder; exclusionary 
treatment; drug use; no PTSD; age; scheduling; new treatment; unwilling to use contraceptives; recent trauma; 
behavioral concerns; and legal issues. No identifiers or health information are added to the spreadsheet.  
 
Potential participants can either call the study line directly to speak with research staff or they can follow the 
link to a study screening questionnaire located at the bottom of the flyers and ads. The link re-directs to a 
secure, RedCap survey. Potential participants will indicate that they consent to complete the survey 
electronically before completing the questionnaire. Staff will contact respondents who meet minimum eligibility 
criteria via phone, email, and/or text message. Respondents will indicate their preferred method of contact on 
the RedCap survey.   
 
BuildClinical: BuildClinical is an advertising and referral service that targets advertisements to individuals 


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who may be eligible for the study. Study advertisements will be developed, IRB approved, and then 
optimally deployed across web platforms to target and engage the study population via the BuildClinical 
patient advertising network. Individuals who click on a BuildClinical ad will be redirected to a brief IRB 
approved REDCap questionnaire. BuildClinical provides the study team with the respondents’ questionnaire 
responses and contact information (name, phone number, email, and state) if they meet minimum eligibility 
requirements via a HIPAA compliant internet portal. The internet portal is a one-way transfer of information 
from BuildClinical to the study team. The study team will not share any additional information with 
BuildClinical. All BuildClinical ads will be submitted to the IRB for approval prior to use.  
 
All potential participants will be asked to complete a brief pre-screening interview either in person or by 
telephone, using an IRB approved, and scripted pre-screening form describing the basic facts of the study and 
inquiring about inclusion and exclusion criteria. (See request for waiver of authorization and waiver of 
documentation of consent). Study staff conducting the screening may ask follow-up questions or use the 
Timeline Followback tool to clarify responses and assess eligibility. An abridged version of the LEC (Life Events 
Checklist) will be completed during the pre-screening interview. Participants who pass the pre-screening 
interview (i.e., those who appear likely to qualify for the study and remain interested in participating) will be 
scheduled for a screening visit.  
 
Individuals that do not pass the pre-screening or decline to enroll in the study will be asked whether they would 
like their information retained so they can be contacted for future research purposes. Participants may also opt-
in to being re-contacted for the current study if their PTSD and/or AUD symptoms are near the inclusion 
threshold. If they decline, all information collected will be de-identified and all PHI information will be destroyed 
at the end of the study. The study team will have no linking information for those who fail the pre-screen or 
decline participation. If they assent to re-contact, PHI data collected on the initial screening form will be retained 
only for and shared with NYU-affiliated researchers strictly for the purpose of re-contacting for future research 
opportunities.  
 
Participants in Dr. Marmar’s clinical trial “Leveraging Biomarkers for Personalized Treatment of AUD Comorbid 
with PTSD” (IRB # s18-01405) who are determined to be ineligible will be evaluated for eligibility in this trial. 
Consenting participants’ data will be linked to this study and procedures completed under the Biomarkers trial 
will not be duplicated for this trial except at PI or co-Investigator discretion.  
 
Based on successful recruitment in current and past AUD and PTSD trials at NYULMC, we do not expect any 
significant barriers to recruitment. If recruitment lags, strategies would include altering staffing patterns and 
increasing advertisement and outreach to clinical programs. To maximize rates of completion of the follow-up 
visit, we will follow procedures that have been successful in retaining patients with similar demographics, e.g. 
drug using emergency department patients, for whom we have achieved follow-up rates of 85% at 6 months. If 
follow-up rates at 10 weeks are below 90%, we will reexamine our tracking procedures, and consider altering 
the reimbursement and/or completing community-based follow-ups. 
 
We expect the population to be approximately 50% male, 50% female; 7% Hispanic, 60% Non-Hispanic 
Caucasian, 30% Non-Hispanic African American, and 3% other. 
 
5.5 Duration of Study Participation 
Including screening and follow-up visits, the total duration of participant involvement will be approximately 9 
weeks. Total time of contact during these 9 weeks is estimated at 30-35 hrs. 
 
5.6 Total Number of Participants and Sites 
Recruitment will end when approximately 150 participants are enrolled. It is expected that approximately 48 
participants who fully meet study criteria will be randomized in a 5:3 ratio to receive either 600mg CBD/day (PO) 
or placebo respectively (N=30 participants on CBD and N=18 participants on placebo). 
 
5.7 Participant Withdrawal or Termination 
 
5.7.1 Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator may 
terminate participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the participant 


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• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation 
• 
The participant fails to adhere to protocol requirements 
 
5.7.2 
Handling of Participant Withdrawals or Termination 
Every effort will be made to undertake the protocol-specified safety follow-up procedures to capture AEs, SAEs, 
and UPs. The investigator will attempt to obtain at a minimum safety/survival data on all participants lost to 
follow-up. If a participant is lost to follow-up, they study team will attempt to contact the participant up to 15 
times by telephone, email, or text message. If the participant fails to respond, locators identified by the 
participant at screening will be contacted up to three times in the method specified by the participant. If 
participants withdraw, are terminated, or are lost to follow-up prior to the end of the 6-week treatment phase 
(prior to T8), they will not be replaced to maintain 48 randomized participants to complete the 6-week treatment 
phase (through T8) and their partial data will be handled according to the statistical analysis plan (SAP). 
 
5.8 Premature Termination or Suspension of Study 
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 to Dr. Marmar, NIH/NIAAA, the FDA, the DEA, and the NY State BNE. 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. Circumstances that may warrant termination or suspension include, but are 
not limited to: 
 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance with protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and satisfy 
the sponsor, IRB and/or FDA. 
 
6 Study Agent (Study drug, device, biologic, vaccine etc.) and/or 
Procedural Intervention 
6.1 Study Agent(s) and Control Description 
The TN-C200M2 Oral Capsules and matching placebo for this study are provided by TilrayTM. The CBD is 
derived from cannabis and processed according to CGMP standards (see Quality Overall Summary document 
provided by Tilray). The active capsules will include CBD (the active ingredient) at a quantity of 200mg per 
capsule, as well as a mix of surfactants, co-surfactants, co-solvents and carrier oils. The placebo capsules will 
only include the same excipients, with no CBD. 
 
6.1.1 
Acquisition 
The investigational product, CBD, will be imported from Tilray, which is located at 1100 Maughan Road, 
Nanaimo, British Columbia, Canada V9X 1J2. The IND & DEA schedule I researcher, Michael P. Bogenschutz, 
MD, will acquire a New York State Bureau of Narcotic Enforcement Class 9 license to import controlled 
substances as well as a DEA Schedule I import permit. Tilray will then obtain a DEA export permit that will 
allow them to ship CBD to Michael P. Bogenschutz, MD. Once all permits and licensure is in place, Michael P. 
Bogenschutz will send a DEA 222 form to Tilray requesting the shipment of the investigational product. All 
shipping, importation and exportation of the investigational product will occur in line with local, state and federal 
regulations.  
 
6.1.2 
Formulation, Appearance, Packaging and Labeling 
The drug product to be used in this study (TN-C200LM Oral Capsule) is a formulation of CBD dissolved in a 
mix of surfactants, co-surfactants, co-solvents and carrier oils at a concentration of 400mg/g. The formulation 
is designed to act as a self-emulsifying drug delivery system (SEDDS). Hard gelatin size-zero capsules are 
filled with the formulation to a fill weight of 500mg, providing a single capsule dose of 200mg CBD. This product 
in investigational and will be acquired as described above in 6.1.1. The TN-C200M2 Oral capsules are 
packaged in pharmaceutical grade 100mL polyethylene terephthalate (PET) bottles and lid, with a fill of 20 
capsules. 


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6.1.3 
Product Storage and Stability 
The study drug, CBD, will be stored securely by study personnel under the PI’s individual schedule 1 DEA 
registration and New York Bureau of Narcotics Enforcement (BNE) class 7 license in accordance with all 
applicable laws and regulations. Additionally, a NYS BNE class 9 importer license and a DEA importer permit 
will be obtained prior to importation of study drug and study initiation. CBD will be stored in a double-locked 
refrigerator. The refrigerator is located in a designated research room with limited access to the PI and study 
staff only, within the NYU-HHC CTSI Facility, which is located at 462 1st Avenue, 27th Street, C-D Building 4th 
floor, New York, NY 10016. The drug is to be stored between 2-8 degrees Celsius. It is recommended that the 
investigational product be reassayed at 9-months. The Principal Investigator will oversee the appropriate 
storage, accountability and dispensing of the study medication and all study drug administration to the patients 
will be done by the PI or treating co-investigators. 
 
TilrayTM has provided stability data for RSM-CBD Lots P56/8/116, P56/8/116, p56/17/017 and P56/44/057 at 4, 
25 and 40 degrees Celsius. 12-months data has been generated on the first two batches and 9-months data 
has been generated on the second two batches. There is no evidence of degradation for any of the samples 
stored at 4, 25 and 40 degrees Celsius after 9-months. Additional and detailed stability data can be found in 
the accompanying Quality Overall Summary (QOS) document. 
 
6.1.4 
Preparation 
Because the investigational product is going to be shipped and received in its ready-for-dispensation 
formulation, there will not be any preparation required prior to dispensation. The study drug will be dispensed 
by qualified study personnel. 
 
6.1.5 
Dosing and Administration 
Participants will self-administer CBD vs Placebo twice daily for a total of 600mg/day CBD vs. Placebo for  six-
weeks. Participants will self-administer two 200mg capsules every morning following a light meal at 
approximately the same time of day, and an additional single 200mg capsule approximately 12 hours later 
following a light meal. 
 
6.1.6 
Route of Administration 
CBD will be administered orally in capsules that each contain 200mg CBD vs. Placebo. 
 
6.1.7 
Starting Dose and Dose Escalation Schedule 
All participants will receive 600mg/day CBD vs. Placebo for weeks 1-6 of treatment (T1-T8), unless 
contraindicated. 
 
6.1.8 
Dose Adjustments/Modifications/Delays 
If participants report AEs that are determined by the PI to be treatment-related during administration of study 
medication and are intolerable to the participant or represent a significant risk to the participant, daily 
administration will be reduced by 200mg/day every two days until symptoms are tolerable or clinical 
abnormalities are resolved. For self-described symptoms, tolerability will be determined by a joint decision 
between the PI and the participant, based upon of whether this symptom is tolerable or treatment related. For 
laboratory abnormalities, all values outside of the normal range will be regarded as presenting a risk, as 
evaluated by the PI. All reported AEs will be recorded. Dose will be titrated back up toward the full dose by 200 
mg/day/week as tolerated, based upon a repeat assessment by the PI, including laboratory tests. 
 
Individuals who cannot tolerate the 600mg dose will remain on their maximum tolerable dose for the remainder 
of the study. Treatment will be discontinued immediately if continuing the medication places the participant at 
significant risk in the medical judgement of the PI.  
 
6.1.9 
Duration of Therapy 
The duration of the active treatment portion of the study is 6 weeks, followed by an additional 3-week follow- 
up period. In order for participants to be included in the primary statistical analyses, they must complete the 6- 
week treatment phase of the study (through to T8). 
 
6.2 Study Agent Accountability Procedures 
CBD will be stored by the study personnel securely under the PI’s individual schedule 1 DEA registration and 
New York Bureau of Narcotics Enforcement (BNE) class 7 license in accordance with all applicable laws and 


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regulations. Additionally, a NYS BNE class 9 importer license and a DEA importer permit will be obtained by 
the schedule I license and registration holder prior to importation of study drug and study initiation. CBD will be 
stored in a double-locked refrigerator. The refrigerator is located in a designated research room, with limited 
access to the PI and study staff only, within the NYU-HHC CTSI Facility, which is located at 462 1st Avenue, 
27th Street, C-D Building 4th floor, New York, NY 10016. The Primary Investigator will oversee the appropriate 
storage, accountability and dispensing of the study medication and all study drug administration to the patients 
will be done by the PI or treating co-investigators. In order to preserve the blind, medication will be administered 
in identical capsules containing 0 or 200 mg of CBD dissolved in a mixture of self-emulsifying excipients; 
participants will be delivered multiple 200mg capsules/day for a total of 0 or600 mg CBD/day. 
 
Study medication will be received under a Schedule 1 import license obtained by the PI and will be logged into 
the approved storage facility upon arrival. Study medication will be re-packaged by unblinded study 
personnel from the original Tilray bottles into blinded and appropriately labeled bottles for dispensation. The 
re-bottled, blinded study medication will then be dispensed to participants under the direct supervision of the 
PI or a designated coinvestigator, as approved by the BNE and DEA. Participants will be required to return 
all un-used medication, which will be kept securely at the drug storage site until it is sent to a reverse 
distributor for destruction. 
 
Designated study personnel will keep a log of the study drug accountability and dispensing in accordance with 
New York State Bureau of Narcotic Enforcement and DEA policies (see below). This process will provide strict 
safeguarding and accounting of the agent both for internal and external regulatory agencies. 
 
As per Schedule I drug compliance, a biennial inventory shall be prepared and maintained in accordance with 
New York State and federal statutes. A copy of the inventory will be kept on file with other controlled substance 
records and shall be kept available for inspection for at least 5 years. The number of study drug-containing 
capsules will be checked on a weekly basis by two designated study staff members and it will be recorded on 
a Controlled Substance Accountability Log which includes the following information: 1) date and time of 
recording, 2) name of controlled substance, 3) amount received (number of capsules), 4) amount dispensed, 
and 5) amount returned. All other information will be included in the Study Drug Dispensation Log as each 
individual subject's dose is dispensed. The information included in the Study Drug Dispensation Log is: 1) 
subject initials/number (plus date of birth as a double identifier), 2) date and time of study drug dispensation, 3) 
drug name, 4) lot number, and 5) dose. Two designated study team members will sign the Study Drug 
Dispensation Log. The balance of the remaining medication and any amount returned will be recorded in the 
Controlled Substance Accountability Log (see above). 
 
6.3 Study Behavioral or Social Intervention(s) 
All participants will receive Medical Management by a licensed MD or NP, based on the model developed for 
the NIAAA COMBINE trial [92]. This model provides a low intensity intervention that has some efficacy over no 
intervention, and is designed to enhance compliance in the context of a clinical trial. Brief counselling sessions 
provided by a licensed MD or NP focus on: support for recovery, treatment participation, reporting possible 
adverse effects, and medication compliance. The co-investigator Dr. Bogenschutz has experience adapting 
this model in a prior alcohol pharmacotherapy trial [93]. 
 
6.3.1 
Administration of Intervention 
CBD (or placebo) will be administered daily for 6 weeks. The first administration of CBD vs. placebo (at T1) will 
take place at the study site. Participants will remain at the study site with a study team member for 
approximately 2 hours following the initial administration of each dose of CBD, and participants will not be 
permitted to leave the study site until they are able to pass a standard field sobriety test (a walk-and-turn task, 
one-leg stand, Romberg’s test, finger-finger test, and counting backwards [85]). If there are no AEs during this 
time-period or lasting intoxicating effects of the study drug (i.e. participants are able to pass field sobriety tests 
2-3 hours after study drug administration), participants will be given a 1- or 2-week supply of the study drug 
(CBD or placebo) to self-administer daily at home until the next scheduled study visit. 
 
6.3.2 
Assessment of Subject Compliance with Study Intervention 
To maximize medication compliance, we will implement an optional smartphone-assisted medication 
adherence platform [94] in which the subject takes a video of drug administration at each dose, and transmits 
this to study personnel. This program has been used successfully in previous studies and includes security 
provisions that ensure protection of confidentiality and privacy. If the participant is unable to use the 
smartphone-assisted platform then medication adherence will be ensured using pill counting and meeting with 
the study nurse practitioner at each visit. 


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7 Study Procedures and Schedule 
7.1 Study Procedures/Evaluations 
 
Inclusion/exclusion criteria: 
Medical screening by an NP or MD will include medical history and physical exam, liver function tests, 
complete blood count, urinalysis, menstrual calendar (if female except those menopausal for >1 year since 
last menstrual period and/or had a bilateral oophorectomy), pregnancy test (if female except those 
menopausal for >1 year since last menstrual period, had a hysterectomy, and/or had tubal ligation), and vital 
signs for safety. The licensed provider (NP or MD) will also review participants’ controlled substance 
prescription history using the online Prescription Monitoring Program (PMP) Registry to inform study 
eligibility. The Structured Clinical Interview for DSM-5 (SCID ) will be used to determine substance use 
disorder diagnoses and exclusionary psychiatric disorders {First, 1997 #114}. The Life Events Checklist 
(LEC) and Clinician Administered PTSD Scale (CAPS) for DSM 5 will be used to assess PTSD symptoms 
[101]. The Concussion Symptom Inventory (CSI) and a modified version of the Ohio State University TBI 
Identification Method (TBI OHIO) will be used to assess for Traumatic Brain Injury (TBI). The clinical interviews 
will be conducted by SCID and CAPS trained study clinicians, masters-level study team members and 
bachelors-level study team members with sufficient psych-assessment training as approved by the study PI. 
Individuals will have the option to be audiotaped during the screening interview. If the participant consents, 
audio recordings will be used to ensure quality control and clinical adherence to the protocol. Audio 
recordings will also be used for voice-marker analysis. If a participant voices that he/she is uncomfortable 
with the audiotaped interview, he/she can tell a study team member that he/she does not wish to participate 
in this component of the study. In that case, the participant could still participate in the study but would not 
complete the audiotaped interview. 
 
PhenX Tier 1 measures and a Locator form will be completed at screening to collect contact information, 
demographics, BMI, quality of life, HIV risk and status, and substance use measures (age of onset, past 
30-day 
quantity 
and 
frequency, 
lifetime 
use 
for 
alcohol, 
tobacco, 
and 
other 
substances; 
www.phenxtoolkit.org). The Clinical Institute Withdrawal Scale- Alcohol, revised (CIWA-Ar) will be used to 
verify lack of alcohol withdrawal [95], a urine drug screen (UDS) will be done at every in-person study visit 
(except for visits less than 24 hours from the last visit; i.e. 1 day visit) to verify lack of recent cannabinoid 
and other drug use, and a urine pregnancy test will be done at each in-person study visit (for women of 
childbearing potential: if female except those menopausal for >1 year since last menstrual period, had a 
hysterectomy, and/or had tubal ligation) to verify lack of pregnancy. If subjects are found to have suicidal 
intentions based on screening tests, appropriate referrals to mental health professionals will be made by the 
PI. 
 
7.1.1 
Confirmation of target CBD plasma levels and measurement of THC levels: 
Circulating levels of CBD, THC and THC metabolites (Delta-9 THC, 11-Hydroxy Delta-9 THC and Delta-9 
Carboxy THC) will be obtained from CBD-treated participants baseline (pre-CBD levels), following 45 minutes 
(T1- 45min post-CBD levels), 1 day (T2- 45min post-CBD levels), 1 week (T3- 45min post-CBD and pre-CBD 
levels), 2 weeks (T4- 45min post-CBD and pre-CBD levels), 4 weeks (T6- 45min post-CBD and pre-CBD 
levels),6 weeks (T8- 45min post-CBD and pre-CBD levels), and 7 weeks (T9- pre-CBD levels) after the first 
CBD vs. placebo dose. All of these levels (CBD, THC and THC metabolites) will be determined via High 
Performance Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) at Dr. Thomas Neubert’s Lab at 
the Department of  Cell Biology at NYU Langone Health.. 
 
7.1.2 
Measurement of plasma Anandamide levels: 
Plasma AEA levels will be obtained at baseline (pre-CBD levels), following 45 minutes (T1- 45min post-
CBD levels), 1 day (T2- 45min post-CBD levels), 1 week (T3- 45min post-CBD and pre-CBD levels), 2 weeks 
(T4- 45min post-CBD and pre-CBD levels), 4 weeks (T6- 45min post-CBD and pre-CBD levels),6 weeks (T8- 
45min post-CBD and pre-CBD levels), and 7 weeks (T9- pre-CBD levels) after the first CBD vs. placebo dose. 
Plasma AEA levels will be determined via High Performance Liquid Chromatography/Tandem Mass 
Spectrometry (LC-MS/MS)at Dr. Thomas Neubert’s Lab at the Department of  Cell Biology at NYU Langone 
Health . 
 
7.1.3 
Safety: 


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Safety will be assessed by collection of adverse events using the Systemic Assessment for Treatment of 
Emergent Events (SAFTEE) [103] measure at all visits after treatment is initiated. LFTs will be obtained at 
screening, as well as weeks 2, 6 and 7 to assess the liver function during and after treatment with study 
medication. Risk of suicidality will be assessed by a licensed MD, NP, Psychologist, or C-SSRS certified  study 
team member using the Columbia-Suicide Severity Rating Scale (C-SSRS) [98] as part of each study visit, 
including screening and baseline. If the patient endorses significant suicidality/homicidality,  a safety 
assessment will be conducted, referrals provided, and if indicated, a case report form will be written if indicated, 
a follow-up phone call within 48 business hours of providing referrals will be completed. If and when 
appropriate, the clinicians will then contact the overall study PI (Charles Marmar, MD) for further consultation. 
The appropriate procedures for all study team members to follow in the case of a psychiatric or medical 
emergency are outlined in detail in the Medical and Psychiatric Emergencies SOP. 
 
7.1.4 
Psychomotor and subjective effects of CBD: 
Basic motoric and cognitive function will be evaluated throughout treatment with several established field 
sobriety tests, including a walk-and-turn task, one-leg stand, Romberg’s test, finger-finger test, and counting 
backwards [85]. The Addiction Resource Center Inventory (ARCI), 49-item version [86], will be used as a 
measure of the intoxicating effects and abuse potential of CBD. Breath Alcohol Concentration (BAC) will 
also be measured to ensure participants are not under the influence of alcohol during administration of these 
tasks. 
 
7.1.5 
Cognitive Function: 
Several established neuropsychiatric and cognitive tasks will be administered to evaluate the impact of CBD 
vs. placebo treatment on cognitive domains potentially affected by CBD and/or THC. The Rey Auditory 
Verbal Learning Task (RAVLT) will be used to assess episodic memory [87], the Mental Rotation Task 
(MRT) will evaluate visuospatial ability [88] [89], a Time Reproduction Task (TRT) will measure encoding 
and retrieval of time intervals [67] and several WM Span tasks (OSpan, RSpan, SymSpan, RotSpan) will 
measure working memory capacity [90, 91]. Cognitive function will be assessed one day after CBD or 
placebo treatment and at 6 weeks following treatment. 
 
7.1.6 
AUD-related measures: 
The Penn Alcohol Craving Scale (PACS) [79] will be used to assess craving. This scale has 5 Likert-scaled 
items with excellent internal consistency and evidence of predictive, construct, and discriminant validity. 
Craving will be assessed before CBD or placebo treatment (baseline), at weeks 1, 4 and 6 of treatment, and 
one week after the completion of treatment (week 7). Mood and Anxiety will be measured with the Beck Anxiety 
Inventory (BAI) [99] and Beck Depression Inventory-II (BDI-II) [100] scales before CBD or placebo treatment 
(baseline), at weeks 1, 4 and 6 of treatment, and one week after the completion of treatment (week 7). Self-
efficacy will be assessed using the Alcohol Abstinence Self-Efficacy Scale (AASE) [81], a self-report 
questionnaire which has been used widely in the alcohol treatment research, both as a predictor of 
outcome and as a patient-treatment matching variable [82]. Self-efficacy will be assessed before CBD or 
placebo treatment (baseline), at weeks 1, 4 and 6 of treatment, and one week after the completion of treatment 
(week 7). 
 
7.1.7 
PTSD-related measures: 
PTSD symptoms will be assessed with the PTSD checklist for the DSM-5 (PCL-5) [96]. Baseline PTSD 
symptoms will be defined as the total PCL-5 score at baseline. The primary PTSD outcome is the total score of 
the PCL-5 for each week administered. PTSD symptoms will be assessed before CBD or placebo treatment 
(baseline), at weeks 2, 4 and 6 of treatment, and one week after the completion of treatment (week 7). 
 
7.1.8 
Cue and Traumatic Stress Response Task 
The Cue and traumatic stress Response Task will be performed using methodology developed in Rajita 
Sinha’s lab, similar to that in used in past studies with alcohol dependent patients and AUD+PTSD/subthreshold 
PTSD patients [84].. Imagery scripts will be developed at baseline.Traumatic stress imagery scripts will be based 
on a recent highly stressful situation that the participant identifies as traumatic. Alcohol cue scripts will be 
derived from a recent event that included alcohol-related stimuli and led to alcohol use. Neutral or relaxing 
scripts will also be developed. All scripts will be developed by obtaining specific details of stimulus and 
response, including contextual details, cognitive and verbal content, affective experience, and bodily sensations. 
These details form the basis of a 5-minute imagery script, which will be developed for each of the three 
conditions. Imagery sessions will be structured with a 5-minute pre-imagery period, a 5-minute imagery 
period, and a 5-minute recovery period. Pulse, skin conductance, heart rate variability, and blood pressure 


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will be monitored during each imagery session with an ADInstruments PowerLab 4/30 Galvanic Skin Response 
device and a Contec Patient Monitor. In Human laboratory studies with CBD, skin conductance and 
amygdala activation were reduced by CBD in a closely correlated manner [52], suggesting threat-related 
sympathetic arousal may serve as a proxy for amygdala activation [53]. Participants will complete Likert scale 
ratings of vividness, craving, anxiety, and the 30-item Differential Emotion Scale [84] following each of the three 
periods. After each condition, a progressive relaxation procedure will be implemented to facilitate return to 
baseline of vital signs, craving and anxiety, an approximate period of 10 minutes, as shown in previous research 
from the Sinha lab [97]. The entire imagery protocol will take 120 minutes. The order of the sessions will be 
randomized and counterbalanced among participants. The task will be administered at T6, following 4 weeks 
of treatment with CBD or placebo. At this point, we expect steady- state plasma CBD levels to have been 
reached. 
 
7.1.9 
Alcohol use: 
Alcohol consumption will be assessed with a constellation of measures from Time-line Follow-back (TLFB) 
[78], percent carbohydrate-deficient transferrin (CDT), and breath alcohol concentration (BAC). 
 
 
7.2 Laboratory and Voice-markers Procedures/Evaluations 
Plasma will be collected at baseline before treatment, and 45 minutes, 1 day, 1 week, 2 weeks, 4 weeks 6 
weeks, and 7 weeks  after the first dose of treatment with CBD or placebo. CBD, THC and THC metabolite 
levels will be obtained from the CBD group only. Anandamide levels will be obtained from both the CBD 
and placebo groups. Serum will be collected at baseline, at 4 weeks, and at 6 weeks for measurement of 
CDT. 
 
7.2.1 
Specimen Preparation, Handling, and Storage 
Blood will be drawn at several time points to establish 45 minutes post- and pre-dosing levels of CBD, according 
to the study’s SOP. Briefly, we will measure plasma CBD, THC and THC metabolite levels at baseline, 45 
minutes, 1 day, 1 week, 2 weeks, 4 weeks, 6 weeks, and 7 weeks after treatment with CBD.  Plasma (1ml/sample) 
will be stored at -20 °C for no longer than 6 months, and will be labeled with study number, participant number, 
and timepoint as specified in the MOP.  Plasma CBD levels will be determined via High Performance Liquid 
Chromatography/Tandem Mass Spectrometry (LC-MS/MS) by collaborators at Dr. Thomas Neubert Lab at the 
Department of  Cell Biology at NYU Langone Health.  
 
7.2.2 
Specimen Shipment 
Specimens will be shipped monthly on dry ice with appropriate labeling for shipment of biological specimens on 
dry ice, according to the study’s MOP. Medical screening labs will be labelled according to CTSI protocols and 
processed by LabCorp.  Plasma for anandamide, CBD, THC and THC metabolite testing will be sent to Dr.  
Neubert laboratory  at the Department of Cell Biology at NYU Langone Health. A specimen tracking log will be 
utilized to record dates and times that each specimen was collected and shipped. Specimens may be shipped 
overnight or walked to Dr. Neubert lab between 9:00am and 5:00pm on business days . 
 
7.2.3 Voicemarkers Procedure 
Voice-markers: Clinical interviews (in-person and remote) will be audio and/or video-taped to ensure quality 
control and clinical adherence. De-identified audio recordings of participants who consent to participate in the 
voice-markers analysis will be encrypted and sent via secure sites to HIPAA compliant labs for analysis.  
 
7.2.4 Data Storage and Sharing of Voice-markers Data 
Only the investigator and authorized study personnel will have access to the digital audio recordings to ensure 
quality control, clinical adherence during calibration and to study voice-markers. Under no circumstances will 
any unauthorized personnel listen to or view the tapes without the written permission of the participant. 
 
The study team will collect speech data from audio recordings collected from the clinical interview at the 
screening visit. The digital audio recordings will then be transferred for analysis via encrypted CDs or secure 
NYU sites and stored on secure servers. All the recordings will be de-identified and labeled with a unique study 
code number for each participant in the study. The study team will identify a professional, specialized entity to 
conduct the voice-markers analysis; any authorized entity will only receive de-identified data without any PHI 
or linking information and will store the data on secure servers. 
 
No individual identities will be used in any reports or publications resulting from the study. Study information, 
such as the digital audio recordings will be coded with a code number unique to the study. Only authorized 


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NYUMC study personnel, with the permission of the principal investigator, will have access to the files that links 
the identifying information and study ID codes. Digital audio recordings of interviews will be encrypted and 
pass-code protected while retained on a secure NYU server until the conclusion of the study; at that point they 
will be deleted. Only the investigator and study personnel will have access to the digital audio recordings in 
order to compare the ratings on the standardized interview format. Sessions will be recorded digitally. All files 
will be secured using a digital encryption key. No unauthorized persons will be able to access this key to open 
the audio files. These encrypted audio files will be de-identified , stored and password protected on a secure 
server. Any identifying information embedded in the audio recordings will be deleted during the transcription 
process. Any data sharing will follow all the NYU data security requirements. Identifiable data will not be stored 
on laptops, PDA’s, flash drives or other portable devices.  De-identified data will be shared via mailed encrypted 
CDs, encrypted emails, or via a VPN access and secure access to the secure NYU server. 
 
7.3 Study Schedule 
 
 


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7.3.1 
Screening Visit (S1) (2 Options) 
 
Option 1: Screening Visit – In-Person 
• 
Administer consent quiz (up to 2 administrations) and obtain informed consent of potential participant 
verified either by signature on written informed consent for screening form or through electronic 
signature. 
• 
Obtain consent of participant on audio/visual consent form, either by signature on audio/visual 
consent form or through electronic signature. 
• 
Perform alcohol breathalyzer to obtain BAC 
• 
Review medical and family to determine eligibility based on inclusion/exclusion criteria 
• 
Perform psychiatric assessments to determine eligibility based on inclusion/exclusion criteria 
• 
Audio-record clinical interview (if participant consents to this component) to ensure clinical quality 
control, and study voice-markers for participants that consent to voice-marker analysis. Audio 
recordings can be waived per PI discretion. 
• 
Review concurrent medications to determine eligibility based on inclusion/exclusion criteria 
• 
Perform medical examinations needed to determine eligibility based on inclusion/exclusion criteria 
• 
Obtain demographic information, contact information, alcohol, drug, and tobacco use history and 
quality of life 
• 
Collect urine for urine drug analysis, urinalysis, urine pregnancy test (if applicable) 
• 
Collect blood at either the One Park site or at CTSI for hepatic function panel/liver function tests (LFT), 
complete blood count with differential, basic metabolic panel, and serum pregnancy test (if female) 
• 
Record vital signs 
• 
Schedule study visits for participants who are eligible and available for the duration of the study 
 
NOTE: The in-person screening visit may be split into two or more sessions to accommodate participants’ 
schedules, provider availability, etc. All portions of the screening visit must be complete within 1 month.  
 
Option 2: Screening Visit – Two-part: Clinical Screen Remote; Medical Screen In-Person 
To reduce participant burden and minimize in-person screening visits, we will offer participants the option of 
splitting the screening visit into two or more sessions. The first session will be completed remotely (phone or 
WebEx) to establish that minimal inclusion criteria and no exclusion criteria are met. Participants will be invited to 
a second session, which will be completed in-person, if they meet minimum inclusion/exclusion criteria standards. 
All portions of the screening visit must be complete within 1 month.  
 
Session 1: Clinical Screen – Remote 
• 
Administer consent quiz (up to 2 administrations) and obtain informed consent of potential participant 
verified either by signature on written informed consent for screening form or through electronic signature 
. 
• 
Obtain consent of participant on audio/visual consent form, verified either by signature on audio/visual 
consent form or through electronic signature. 
• 
Review medical and family history to determine eligibility based on inclusion/exclusion criteria 
• 
Perform psychiatric assessments to determine eligibility based on inclusion/exclusion criteria 
• 
Review concurrent medications to determine eligibility based on inclusion/exclusion criteria 
• 
Obtain demographic information, contact information, alcohol, drug, and tobacco use history and 
quality of life 
 
Session 2 – In Person 
• 
Perform alcohol breathalyzer to obtain BAC 
• 
Review medical and family history 
• 
Perform medical examinations needed to determine eligibility based on inclusion/exclusion criteria 
• 
Collect urine for urine drug analysis, urinalysis, urine pregnancy test (if applicable) 
• 
Collect blood at either the One Park site or at CTSI for hepatic function panel/ liver function tests 
(LFT), complete blood count with differential, basic metabolic panel, and serum pregnancy test (if 
female) 
• 
Assess withdrawal using CIWA-Ar 
• 
Record vital signs 
• 
Schedule study visits for participants who are eligible and available for the duration of the study.  
 


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7.3.2 
Enrollment/Baseline (B1) (Day 0, 1-30 days after Screening Visit) 
• 
Perform alcohol breathalyzer to obtain BAC 
• 
Record vital signs, results of examination, other assessments, concurrent medications and menstrual 
calendar (if applicable) 
• 
Record AUD-related and PTSD related measures 
• 
Collect imagery scripts for the cue/traumatic stress response task  
• 
Collect urine for urine drug analysis and urine pregnancy test (if applicable) 
• 
Collect baseline plasma for baseline CBD, THC, and AEA levels (pre-CBD dosing levels) 
• 
Collect blood for carbohydrate deficient transferrin (CDT) test 
• 
Record results of evaluations of safety and psychomotor effects and AUD, PTSD related domains 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Evaluate and record alcohol use 
• 
Administer medical management session 
• 
Provide participants with study medication to administer at visit 
• 
Provide participants with sufficient study medication to administer daily until the next scheduled visit (1 
week), and instructions for how to use the study medication and document their use  
 
7.3.3 
Intermediate Visits 
Intermediate visits that do NOT include safety labs may be conducted remotely via phone or WebEx.  
 
7.2.2.1 Visit 3  
45 minutes +/- 10 minutes (T1) 
• 
Collect blood and plasma for CBD, THC, and AEA levels at 45 minutes post medication (post-CBD 
levels) 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Results of evaluations of safety, and psychomotor effects 
• 
Record participant’s adherence to treatment program 
 
7.2.2.2 Visit 4 (1 day after Baseline/Enrollment Visit +5 days) 
1 day (T2) 
• 
Perform alcohol breathalyzer to obtain BAC 
• 
Collect blood and plasma for CBD, Delta-9 THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy THC and 
Anandamide levels (45 minutes post-CBD levels). 
• 
Collect urine for urine drug analysis  
• 
Record adverse events as reported by participant or observed by investigator 
• 
Record vital signs, concurrent medications, and results of evaluations of safety, cognitive function and 
psychomotor effects 
• 
Record participant’s adherence to treatment program 
• 
Evaluate and record alcohol use 
 
7.2.2.3 Visit 5   
1 week (T3) 
+/- 5 days 
• 
Perform alcohol breathalyzer to obtain BAC  
• 
Collect urine for urine drug analysis and urine pregnancy test (if applicable) 
• 
Collect blood and plasma for CBD, Delta-9 THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy THC and 
Anandamide levels (post- and pre-CBD dosing levels) 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Record vital signs, concurrent medications, menstrual calendar (if applicable), and results of 
evaluations of safety, psychomotor/subjective effects 
• 
Evaluate and record AUD related measures 
• 
Evaluate and record alcohol use 
• 
Provide participants with sufficient study medication to administer daily until the next scheduled visit (1 
week), and instructions for how to use the study medication and document their use 
• 
Record participant’s adherence to treatment program 
• 
Administer medical management session 
 


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7.3.3.2 
Visit 6 
2 weeks (T4) 
+/- 5 days 
• 
Perform alcohol breathalyzer to obtain BAC  
• 
Collect urine for urine drug analysis and urine pregnancy test (if applicable) 
• 
Collect blood and plasma for CBD,  Delta-9 THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy THC and 
Anandamide levels(post- and pre-CBD levels) 
• 
Collect blood for liver function tests (LFT) 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Record vital signs, concurrent medications, menstrual calendar (if applicable), and results of 
evaluations of safety, psychomotor/subjective effects 
• 
Evaluate and record alcohol use 
• 
Evaluate PTSD-related measures 
• 
Provide participants with sufficient study medication to administer daily until the next scheduled visit (2 
weeks), and instructions for how to use the study medication and document their use 
• 
Record participant’s adherence to treatment program 
• 
Administer medical management session 
 
7.3.3.3 
Phone call 1 
3 weeks (T5) 
+/- 5 days 
• 
Record adverse events as reported by participant 
• 
Record participant’s adherence to treatment program 
• 
Record concurrent medications, menstrual calendar (if applicable), and results of evaluations of safety 
 
7.3.3.4 
Visit 7 
4 weeks (T6) 
+/- 5 days 
• 
Perform alcohol breathalyzer to obtain BAC  
• 
Collect urine for urine drug analysis and urine pregnancy test (if applicable) 
• 
Collect blood, plasma and serum for CBD, Delta-9 THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy 
THC and Anandamide levels (post- and pre-CBD levels)  
• 
Collect blood for carbohydrate deficient transferrin (CDT) test 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Record vital signs, concurrent medications, menstrual calendar (if applicable), and results of 
evaluations of safety, psychomotor/subjective effects 
• 
Evaluate and record alcohol use 
• 
Evaluate and record AUD and PTSD-related measures 
• 
Administer the cue/traumatic stress response task and record response 
• 
Provide participants with sufficient study medication to administer daily until the next scheduled visit (2 
weeks), and instructions for how to use the study medication and document their use 
• 
Record participant’s adherence to treatment program 
• 
Administer medical management session 
 
7.3.3.5 
Phone call 2 
5 weeks (T7) 
+/- 5 days 
• 
Record adverse events as reported by participant  
• 
Record participant’s adherence to treatment program 
• 
Record concurrent medications, menstrual calendar (if applicable), and results of evaluations of safety 
 
7.3.3.6 
Visit 8 
6 weeks (T8)  
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• 
Perform alcohol breathalyzer to obtain BAC  
• 
Collect urine for urine drug analysis and urine pregnancy test (if applicable) 
• 
Collect blood, plasma and serum for CBD,  Delta-9 THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy 
THC and Anandamide levels(post- and pre-CBD levels)  
• 
Collect blood for carbohydrate deficient transferrin (CDT) test and liver function tests (LFT) 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Record vital signs, concurrent medications, menstrual calendar (if applicable), and results of evaluations of 
safety, psychomotor/subjective effects 
• 
Evaluate and record alcohol use 
• 
Evaluate and record AUD and PTSD-related measures 
• 
Collect information for cognitive function changes 
• 
Provide participants with morning dose of study medication at the study visit and 1 pill to take in the 
evening.  
• 
Record participant’s adherence to treatment program 
• 
Administer medical management session 
 
7.3.3.7 
Visit 9 
7 weeks (T9) 
+/- 5 days  
• 
Perform alcohol breathalyzer to obtain BAC  
• 
Collect urine for urine drug analysis and urine pregnancy test (if applicable) 
• 
Collect blood and plasma for CBD,  Delta-9 THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy THC and 
Anandamide levels(pre-CBD levels) 
• 
Collect blood for liver function tests (LFT) 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Record vital signs, concurrent medications, menstrual calendar (if applicable), results of evaluations of 
safety, psychomotor/subjective effects  
• 
Evaluate and record alcohol use 
• 
Evaluate and record AUD and PTSD-related measures 
 
7.3.4 
Final Telephone Follow-Up 
9 weeks (T10) 
+/- 5 days 
• 
Record adverse events as reported by participant 
• 
Evaluate and record alcohol use 
• 
Record evaluations of safety 
• 
Administer treatment completion questionnaires 
 
7.3.5 
Unscheduled Visit 
Unscheduled visits will be documented on an unscheduled visit form. 
 
7.3.6 
Clinical Re-Screen  
If there is a delay of ~2-3 months between an eligible participant’s screening visit and baseline visit, the following 
measures/procedures will be administered during a “clinical re-screen” at a separate visit or completed on the 
same day as the baseline visit (prior to baseline procedures) to confirm continued study eligibility as applicable: 
 
The following measures/procedures will be conducted at the clinical re-screen: 
• 
BAC 
• 
Urine toxicology screen and urine pregnancy test (if applicable) 
• 
PCL-5 (past month) 
• 
TLFB (past 30 days) 
• 
CIWA-Ar 
• 
CSSRS (since last visit) 
• 
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• 
Vital signs 
• 
If determined necessary by the study clinicians, we may collect urine for urine analysis and blood at 
either the One Park site or at CTSI for hepatic function panel/liver function tests (LFT), complete blood 
count (CBC) with differential, basic metabolic panel, and serum pregnancy test (if female) 
 
If there is a delay of over 3 months between an eligible participant’s screening visit and their baseline visit, then 
the specific measures/procedures listed above (with the exception of the CSSRS since last visit) will be re-
administered. The LEC/CAPS5, CSSRS baseline/screening, and relevant sections of the SCID5 will also be re-
administered to confirm continued study eligibility and to confirm previously collected data. The TBI Ohio/CSI 
form will also be updated with any new head injuries. Re-screen procedures will be conducted remotely except 
blood draws and urine analysis, if applicable. 
7.4 
Concomitant Medications, Treatments, and Procedures 
All concomitant prescription medications taken during study participation will be recorded on the case report 
forms (CRFs). For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the CRF are concomitant prescription 
medications, over-the-counter medications and non-prescription medications. 
7.5 
Prohibited Medications, Treatments, and Procedures 
Treatment with medications acting on serotonergic pathways, cannabinoids,  treatments for addictions including 
alcohol, and medications metabolized primarily by CYP3A4, CYP3A5, or CYP3A7 will not be permitted unless 
discussed with and approved by the PI. 
 
8 Definitions of Key Terms 
An adverse event (AE; also referred to as an adverse event) is any untoward medical occurrence associated with 
the use of a drug (pharmaceutical investigational product) in humans, which does not necessarily have a causal 
relationship with that treatment. An AE can therefore be any unfavorable and unintended sign (e.g., an abnormal 
laboratory finding or test result), symptom, disease, accident, or worsening (increase in severity or frequency) of 
a pre-existing abnormality, temporally associated with the use of the drug, whether or not considered related to 
the drug. An AE can arise from any use of the drug (e.g., off-label use, use in combination with another drug and 
from any route of administration, formulation, or dose, including overdose). 
A serious adverse event (SAE) is an adverse drug or biologic or device experience occurring during any study 
phase (i.e., screening, admission, treatment, or follow-up), and at any dose of the study drug, comparator or 
placebo, that results in one or more of the following criteria: 
• 
Results in death 
• 
Is life-threatening*  
• 
Requires in-patient hospitalization (i.e., admission) or prolongation of existing hospitalization 
• 
Results in persistent or significant disability** or incapacity 
• 
Is a congenital abnormality or birth defect (in an offspring) 
• 
Is an important medical event that may not result in death, be life-threatening, or require or prolong 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, the event 
may jeopardize the subject or may require medical or surgical intervention to prevent one of the outcomes 
listed above. Examples of important medical events include events requiring intensive treatment in an 
emergency department, convulsions that do not require in-patient hospitalization, or the development of 
drug dependency or drug abuse (see Section 8, Other Significant Adverse Events). 
*Life-threatening: Any AE that places the subject, in the view of the investigator, at immediate risk of death from 
the reaction as it occurred; it does not include a reaction that, had it occurred in a more severe form, might have 
caused death. 
**Disability: A substantial disruption of a person’s ability to conduct normal life functions. 
 


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9 Specification of Safety Variables 
Safety and toxicity monitoring will be performed throughout the study for all subjects. Safety variables to be 
assessed include AEs, vital signs, and safety laboratory values, when collected.  
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and interviews 
of a study participant presenting for medical care, or upon review by a study monitor. At each study visit following 
screening, designated study team members will inquire about the occurrence of AE/SAEs since the last visit.  
 
10 General Guidelines 
All AEs, regardless of causality or severity, must be immediately recorded on the AE CRF when volunteered by 
the subject or solicited through a study assessment questionnaire. The CRC will record all AEs, regardless of 
causality or severity, with start dates occurring any time after informed consent is obtained until 7 (for AEs) or 30 
(for SAEs) days after the last day of study participation on the AE case report forms (CRF). Information to be 
collected includes event description, time of onset, clinician’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization 
of the event.  
Any medical condition that is present at the time that the participant is screened will be considered as baseline 
and not reported as an AE. However, if the study participant’s condition deteriorates at any time during the study, 
it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at each 
level of severity to be performed. AEs characterized as intermittent require documentation of onset and duration 
of each episode. 
At the last scheduled visit, the CRC should instruct each subject to report any subsequent event(s). 
10.1 Solicitation of AEs 
At all follow-up visits occurring after study medication has been administered, the SAFETEE questionnaire 
[Johnson et al., 2005] will be used to assess AEs. The presence or absence of specific AEs should not be solicited 
from subjects. 
10.2 Preplanned Hospitalization or Procedure 
During the study, if a subject has a hospitalization or procedure (e.g., elective surgery) that was due to a 
preexisting condition that has not worsened since enrollment in the study (i.e., since the subject [or the subject’s 
legal representation] signed the informed consent), the hospitalization or procedure is considered a therapeutic 
intervention and not the results of an AE. However, if the event/condition worsens during the study, it must be 
reported as an AE (or SAE, if the event/condition results in a serious outcome, such as hospitalization). 
10.3 Reports of Cancer 
Cancer is no longer considered an FDA criterion for an SAE (unless an event occurs with a serious outcome). If 
a new diagnosis of cancer has a serious outcome, then the reporting time frame for an SAE (48 hours) must be 
met. Progression of disease is not considered new cancer and is therefore not an AE. 
10.4 Specific guidelines for assessing laboratory values as adverse events 
Any laboratory abnormality, including leukopenia, absolute neutropenia, or thrombocytopenia, will not be 
considered an AE unless this abnormal laboratory value results in clinical sequelae, such as infection, bleeding, 
or an intervention. If an abnormal laboratory value results in a clinical event, then the clinical event, not the 
abnormal laboratory value, must be recorded as an AE. The clinical event must be reviewed to determine if it 
meets the criteria for an SAE. 
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The following definitions, developed in accordance with the US Code of Federal Regulations (CFR) and the 
International Committee on Harmonization (ICH), will be used for the purpose of identifying AEs in this clinical 
study. 
11.1 Expectedness 
Unexpected: An AE is considered unexpected if it is not listed in the Investigator Brochure (IB) or is not listed at 
the specificity or severity that has been observed, or not previously observed in animal toxicity studies for 
psilocybin. Unexpected also refers to AEs that are mentioned in the IB as occurring with a class of drugs or as 
anticipated from the pharmacologic properties of the drug, but are not specifically mentioned as occurring with 
psilocybin.  
11.2 Severity 
The determination of severity must be made with the appropriate involvement of a medically qualified investigator. 
The investigator will evaluate the severity of each AE using the following three terms and definitions: 
• 
Minimal: single occurrence that is not distressing and does not limit activities 
• 
Mild: multiple occurrences, awareness of sign or symptom but easily tolerated, usually does not require 
intervention or limit activities 
• 
Moderate: discomfort sufficient to cause interference with normal activities; intervention may be needed 
• 
Severe: incapacitating, with inability to perform normal activities; treatment or other intervention usually 
needed 
11.3 Relatedness 
This category provides the opportunity to indicate the reasons for suspecting a drug-related effect. If no such effect 
is suspected, check “No.” The following reasons for possible relationship to drug are to be assessed by the 
medically qualified investigator. 
• 
Dose-response: indicates that the intensity of the event is related to the dosage level.  
• 
Timing of onset: is used if the onset of the event has some regular relationships to drug administration 
(e.g., it always occurs 1 hour after taking the drug). 
• 
Known drug effect: is another reason for suspecting a drug relationship. 
The relationship of each AE to study drug will be assessed using the following terms and definitions: 
• 
Probable (must have first two): This category applies to AEs that are considered, with a high degree of 
certainty, to be related to the study drug. An AE may be considered probable, if: 
o 
It follows a reasonable temporal sequence from administration of the drug. 
o 
It cannot be reasonably explained by the known characteristics of the subject’s clinical state, 
environmental or toxic factors, or other modes of therapy administered to the subject. 
o 
It follows a known pattern of response to the suspected drug. 
• 
Possible: This category applies to those AEs in which the connection with the study drug administration 
is possible. An AE may be considered possible if, or when, any of the above reasons have been selected.  
• 
Unrelated: This category is applicable to those AEs that are judged to be due only to extraneous causes 
(e.g., disease, environment, etc.) and do not meet any of the criteria for a possible drug relationship. 
The determination of the relationship of the AE to the use of the study drug(s) rests on careful medical 
consideration of the PI.  
12 Monitoring Adverse Events 
The investigator will follow all AEs until the event is resolved, stabilized, or the subject is lost to follow-up. Relevant 


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clinical assessments and laboratory tests may be performed as determined by the PI or a qualified designee, 
appropriate medical intervention should be provided and, if necessary, the subject may be excluded from 
additional treatment with the study drug. 
Any actions taken and follow-up results must be recorded on the appropriate page of the CRF and in the subject’s 
source documentation. Follow-up laboratory results should be filed with the subject’s source documentation. 
For all AEs that require the subject to be discontinued from the study, relevant clinical assessments and laboratory 
tests will be repeated as clinically appropriate, until final resolution or stabilization of the event(s). 
 
13 Known Potential Toxicities of Study Drug 
Overall, no preclinical results have been identified that preclude the development of cannabidiol for the treatment 
of alcohol use disorder, or suggest that serious AEs are likely in clinical studies. Refer to the IB for toxicology 
findings and information on AEs observed to date.  
 
14 Other Significant Adverse Events 
Should any AE occur that is considered significant, but does not meet the criteria for an SAE, the CRC and PI 
should be notified immediately. 
 
15 Reporting Procedures  
15.1 AE Reporting  
To the FDA: In accordance with FDA reporting requirements, all AEs occurring during the course of the clinical 
trial will be collected, documented, and reported by the PI or IND Sponsor. On an annual basis, as part of the 
update to the study IND, the IND Sponsor will submit to the FDA:  
• 
A list of all AEs that have occurred during the reporting period 
• 
A summary of all IND safety reports submitted during the past year 
• 
A list of all subjects who died during the participation in the investigation, listing cause of death for each,  
• 
And a list of subjects who dropped out during the course of the investigation in association with any 
adverse experience, whether or not thought to be drug related. 
To the IRB: In accordance with local IRB requirements, all AEs occurring during the course of the clinical trial 
regardless of relationship to study activities will be collected, documented, and reported by the PI or designee to 
the IRB on an annual basis in the application for the study’s continuation renewal. Staff education, re-training or 
appropriate corrective action plan will be implemented when unreported or unidentified AEs or SAEs are 
discovered, to ensure future identification and timely reporting.  
To the DSMB: All AEs occurring during the course of the clinical trial regardless of relationship to study activities 
will be reported to the DSMB at regular meetings. Prior to each DSMB meeting, the PI will prepare a report to the 
Board including review of aggregate analysis of AEs and SAEs. 
Following each meeting, the board will provide the PI with a report including a recommendation to continue the 
study unchanged, continue with modifications of the protocol and/or the consent form to protect participant safety, 
or terminate the study. This report will then be submitted to the FDA as part of the annual report to the study IND, 
and the IRB in the application for the study’s annual continuation renewal.  
To the Study Sponsors:  
Tilray 
The PI shall promptly inform Tilray of any significant safety issues occurring during the course of the study that 
might affect the performance of the study and of any AEs and SAEs experienced by subjects during the study. 
The PI shall share with Tilray any associated CRFs and source data, safety reports related to such AEs and SAEs, 


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and permit access to anonymized pharmacokinetic data of study subjects. 
PI shall provide all reports issued by the DSMB according to protocol (e.g. annually for the duration of the trial, 
including prior to enrollment of the first participant, following completion of treatment for the first 5 completers, 
after completion of treatment for the first 20 completers, and upon completion of enrollment for the trial).  
NIH/NIAAA 
All AEs occurring during the course of the clinical trial regardless of relationship to study activities will be collected, 
documented, and reported by the PI or designee to NIH/NIAAA on an annual basis in the annual Research 
Performance Progress Report (RPPR). 
15.2 SAE Reporting 
SAEs will be promptly reported to the CRC and PI. The PI or qualified designee will distinguish Serious Adverse 
Events (SAEs) from Adverse Events (AEs). The details of the event will be documented and reported as follows: 
To the FDA: The PI is required to report certain study events in an expedited fashion to the FDA. These written 
notifications of AEs are referred to as IND/IDE safety reports.  
The following describes the IND safety reporting requirements by timeline for reporting and associated type of 
event: 
• Within 7 calendar days (via telephone or facsimile report) 
Any study event that is: 
– associated with the use of the study drug 
– unexpected, and 
– fatal or life-threatening 
 
• Within 15 calendar days (via written report) 
Any study event that is: 
– associated with the use of the study drug, 
– unexpected, and 
– serious, but not fatal or life-threatening 
-or- 
– a previous AE that was not initially deemed reportable but is later found to fit the criteria for reporting 
(reporting within 15 calendar days from when event was deemed reportable). 
Any finding from tests in laboratory animals that:  
– suggest a significant risk for human subjects including reports of mutagenicity, teratogenicity, or 
carcinogenicity. This is not applicable for us as we are not using animals in this study.  
Each written notification must be submitted on an FDA Form 3500A. The PI is also required to identify in IND 
safety reports all previous reports concerning similar AEs and to analyze the significance of the current event in 
light of the previous reports. 
To the IRB: The IRB Chair or Administrator will be notified immediately for SAEs that are at least possibly related 
to study participation only. If the IRB administrator determines that reporting of the incident/issue is required, it will 
be submitted to the IRB within 48 hours of the IRB direction/response.  
The team will also submit summary information related to all SAEs, AEs, and UPs in the annual application for 
continuation to the IRB. 
To the Study Sponsors:  
NIH/NIAAA 
SAEs considered at least possibly related to study participation will be documented and reported to NIAAA within 
48 hours with copies included in the participant’s file. 
Tilray 
If an SAE occurs after the subject signs informed consent through the end of study participation, the PI or a 
qualified designee will complete the Tilray SAE Form and send it via email to contacts designated by Tilray within 


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24 hours of the site becoming aware of the SAE. The form must be completed and submitted to Tilray any time a 
serious medical event has occurred in a participant during the clinical trial, whether or not it is considered related 
to the study treatment, including active comparators and placebo. 
Ensure that an investigator has reviewed and signed the SAE form prior to submission. 
Every exposure during pregnancy (participant) should be reported on an SAE worksheet as a case of special 
interest from the time of study enrolment to the end of study participation. 
The following timelines describe when Tilray, as the manufacturer of IP, has to report ADRs to Health Canada: 
• 
Fatal or life-threatening unexpected ADRs require notification of regulatory agencies as soon as possible 
but no later than 7 calendar days after first knowledge by Tilray that a case qualifies, followed by as 
complete a report as possible within 8 additional calendar days. The report will include an assessment of 
the importance and implication of the findings, including relevant previous experience with the same or 
similar medicinal products. 
• 
All other serious, unexpected ADRs must be filed as soon as possible but no later than 15 calendar days 
after first knowledge by Tilray that the case meets minimum criteria for expedited reporting. 
15.3 UP Reporting 
Incidents or events that meet the OHRP criteria for UPs involving risks to subjects or others require notification of 
the local IRB. The phrase “unanticipated problems involving risks to subjects or others” is found but not defined 
in the HHS regulations at 45 CFR part 46. Any incident, experience, or outcome that meets all of the following 
criteria is considered to be Reportable New Information (RNI) and is required to be promptly reported to the local 
IRB: 
• 
unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the subject population being studied; 
• 
related or possibly related to participation in the research (in this guidance document, possibly 
related means that, in the opinion of the PI, the incident, experience, or outcome was more likely than not 
caused by procedures involved in the research); and 
• 
suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
OHRP recognizes that it may be difficult to determine whether a particular incident, experience, or outcome is 
unexpected and whether it is related or possibly related to participation in the research. OHRP notes that an 
incident, experience, or outcome that meets the three criteria above generally will warrant consideration of 
substantive changes in the research protocol or informed consent process/document or other corrective actions 
in order to protect the safety, welfare, or rights of subjects or others.  
The RNI report will include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
• 
A detailed description of the event, incident, experience, or outcome; 
• 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP; 
• 
A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP. 
UPs must be reported using the following timeline: 
• 
UPs that are SAEs will be reported to the IRB and to the study sponsor according to SAE reporting 
procedures described above (within 48 hours of the investigator becoming aware of the event). 
• 
UPs that meet the requirements for RNI will be reported to the IRB as soon as possible and within 5 
working days of the site becoming aware of the event. 


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• 
All other UPs not related to study activities or that do not result in harm to participants will be reported to 
the IRB annually in the application for the study’s continuation renewal.  
15.4 Pregnancy Reporting 
Pregnancy information on clinical study subjects is collected by the investigator. If a subject should become 
pregnant during the course of the study, the investigator or qualified designee will contact the IRB within 5 working 
days of the PI or qualified designee first becoming aware of the pregnancy.  
Tilray Pregnancy Reporting Requirements: Every exposure during pregnancy (participant) should be reported on 
a Tilray SAE worksheet within 24 hours of the site becoming aware of the pregnancy as a case of special interest 
from the time of study enrollment to the end of study participation. If an SAE occurs in conjunction with the 
pregnancy, then the Tilray reporting timeframe for an SAE (24 hours) must be met. In the event of a pregnancy, 
administration of study medication will be discontinued, but all other follow-up data, including safety data, will be 
collected. 
Pregnancies resulting in congenital abnormalities or birth defects in offspring meet the requirements for an SAE 
and will be collected, documented, and reported according to the procedures outlined above for SAEs. 
 
16 Reporting of Investigational Medicinal Product Quality 
Complaints 
16.1 Defect or Possible Defect in the IP 
Any defect or possible defect in the investigational medicinal product (defined as a pharmaceutical form of an 
active substance or placebo being tested or used as a reference in a clinical trial) must be reported by the PI or 
qualified designee to Tilray within 48 hours of first becoming aware of the possible defect. This report to Tilray 
may be made by telephone or by email. The product and packaging components in question, if available, must be 
stored in a secure area under specific storage conditions until it is determined whether the product is required to 
be returned for investigation of the defect. If the product complaint is associated with an SAE, the SAE must be 
reported separately in accordance with the protocol, and the SAE report should mention the product quality 
complaint. 
16.2 Temperature Deviations 
In the event that the temperature at which the IP is stored is less than 2°C or greater than 8°C, the CRC and PI 
will be notified immediately and a temperature deviation form will be completed and sent via email to contacts 
designated by Tilray as soon as possible. Tilray will provide further guidance on how to proceed on a case-by-
case basis. 
 
17 Study Halting Rules 
When three severe AEs are determined to be “probably related” to the study agent, the DSMB will be informed 
and asked to convene in order to determine whether action should be taken. The Principal Investigator will 
inform the DSMB members within 24 hours of this occurrence and will provide the DSMB with AE listing reports. 
The DSMB will convene an ad hoc meeting by teleconference or in writing as soon as possible. The DSMB will 
provide recommendations for proceeding with the study to the Principal Investigator. The Principal Investigator 
will inform the FDA of the DSMB’s decision and the disposition of the study. If the DSMB finds it is likely that 
CBD is contributing to negative outcomes, they will consider solutions including protocol changes or potentially 
stopping the study. 
 
18 Safety Oversight 
The research team (project manager, coordinators, and research assistants) will submit any adverse events to 
the PI and the Data and Safety Monitoring Board (DSMB). The PI and the DSMB members are responsible for 
reviewing all AEs and serious adverse events (SAEs) reported. All SAEs will be reviewed at the time they are 
reported in the electronic data capture system. Where further information is needed, the DSMB will discuss the 


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event with the research team. All AEs will be reviewed on a weekly basis to observe trends or unusual events. 
 
The PI will generate and present reports for DSMB meetings. The DSMB will receive listings of AEs and 
summary reports of all SAEs at a frequency requested by the DSMB, but at least annually. Furthermore, the 
DSMB will be informed of expedited reports of SAEs. 
 
Data and Safety Monitoring Board (DSMB) 
A Data and Safety Monitoring Board (DSMB) will be established, comprising three to five individuals appointed 
by the PI. The committee will include Dr. Don Goff, Dr. Dan Iosifescu and Dr. Kathlene Tracy. This committee 
will meet (in person or by teleconference) prior to enrollment of the first participant, and at least annually 
thereafter, including meetings following completion of treatment of the first 5 completers, after completion of 
treatment of the first 20 completers, and upon completion of enrollment for the trial. Prior to each meeting, the 
PI will prepare a report to the Board including review of: 
 
• 
Protocol and ICF changes 
• 
Protocol violations and deviations 
• 
Documentation of informed consent 
• 
Enrollment and retention 
• 
Investigator or key personnel changes 
• 
Aggregate analysis of adverse events/serious adverse events 
• 
Protection of confidentiality 
 
Following each meeting, the board will provide the PI with a report including a recommendation to continue the 
study unchanged, continue with modifications of the protocol and/or the consent form to protect participant 
safety, or terminate the study. Reports will be submitted to the IRB on at least an annual basis. 
 
19 Clinical Monitoring 
Site staff will be required to audit source documentation, including informed consent forms and HIPAA forms, 
regulatory documents and case report forms on a biannual basis. Site staff will be responsible for local quality 
assurance and will verify that study procedures are properly followed and that site staff are trained and able to 
conduct the protocol appropriately. If the site staff’s review of study documentation indicates that additional 
training of study personnel is needed, this will be arranged as per the PI. Study team members will review each 
other’s data for completeness, accuracy, and fidelity to the protocol. 
 
20 Statistical Considerations 
 
20.1 Statistical and Analytical Plans (SAP) 
A formal SAP will be developed prior to database lock and unblinding. 
 
20.2 Statistical Hypotheses 
Hypothesis 1a Safety and tolerability: CBD will be safe and well tolerated and will not lead to increased plasma 
THC. No clinically significant cognitive or motoric impairments, CBD-related serious adverse events, persisting 
adverse effects or treatment associated increases in plasma THC will be observed. 
 
Hypothesis 1b: Alcohol use. Relative to the placebo-treated group, CBD-treated participants will have fewer 
drinks per day during the 6 weeks of treatment with CBD vs placebo. 
Hypothesis 2: PTSD symptoms. Relative to the placebo-treated group, CBD-treated participants will lower 
PTSD symptoms during the 6 weeks of treatment with CBD vs placebo. 
Hypothesis 3a: Mechanism, traumatic stress-induced craving: Relative to placebo, CBD will be associated with 
a greater reduction between baseline and end of treatment in trauma induced alcohol craving, negative emotion, 
and psychophysiological arousal in response to the task. 
Hypothesis 3b: Mechanism, AUD and PTSD related measures and cognition: Relative to placebo, CBD will 
improve self-report measures of craving, anxiety, mood, self-efficacy and cognitive performance. 
 
Hypothesis 3c: Mechanism, anandamide: Relative to placebo, CBD will be associated with a greater increase 


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in plasma anandamide levels. 
 
Hypothesis 4: CBD plasma levels. Within-group plasma CBD levels will stabilize within one week, i.e. 45 
minutes post-CBD dosing levels obtained after 1 week of treatment will not differ from those obtained after 4 
weeks of treatment at each dose. 
Exploratory Hypothesis 1: Relationship between effects on PTSD symptoms and alcohol use. The onset of 
reduction in PTSD symptoms will precede the onset of reduction in alcohol use. 
 
20.3 Description of Statistical Methods 
 
20.3.1 General Approach 
We recognize that the relatively small sample sizes proposed in the RCT are not likely to produce statistical 
significance, unless the effect sizes are remarkably high. We will carry out a full Mixed Model Repeated 
Measures (MMRM) statistical analysis in case CBD does perform so well. However, the main focus of the 
statistical analysis of the results of the trial will be to characterize the effect sizes and response rates across 
the various measurement domains and the profiles of individuals who are treatment successes. The intent to 
treat (ITT) population will contain all randomized patients who receive at least one dose of double-blind study 
medication and from whom at least one post-baseline (B1) efficacy measurement is obtained while on study 
medication. The efficacy analysis will be based on the ITT population. Two-sided hypothesis testing will be 
utilized. Tests with p-values less than or equal to 0.05 will be considered statistically significant, while those 
less than equal to 0.10 will be considered suggestive. Since this trial is the first use of this treatment for this 
diagnostic indication, no adjustments of p-values for multiple comparisons will be made. Thus, all control of 
type 1 error is contrast-wise. All confidence intervals will be two-sided with 95% confidence. Mean treatment 
effect, standard errors, and 95% confidence intervals will be derived from fully adjusted models on outcomes 
averaged across the treatment period. Cohen’s d and p-values will be calculated from fully adjusted models 
with appropriately transformed outcome variables. For dichotomous drinking outcomes, prevalence rates will 
be calculated. Odds ratios (ORs) and p-values will be derived from logistic regression models including 
treatment group. 
 
20.3.2 Analysis of the Primary Endpoint(s) 
For Hypothesis 1a, Safety and tolerability, the frequency of adverse events will be analyzed for the entire 
sample at all time points, tabulated for each treatment group, and compared using chi-squared tests. The 
safety analysis will be largely descriptive of outcomes for the entire study population. The incidence of AEs will 
be summarized by system organ class, preferred term, the likelihood of its relationship to the treatment, and 
severity for each treatment group. Clinical laboratory data will be summarized by type of test. Frequency and 
percentage of patients whose values fall outside of reference ranges will be presented for each measurement. 
 
For Hypothesis 1b, Alcohol Use. The Primary outcome measure, number of drinks per day, will be analyzed with 
an MMRM to assess differences in change from baseline. The primary contrast is change from baseline (B1) at 
week 6 (T8). The model at each time point will include terms for treatment, time and treatment by time interaction 
as factors and the baseline value for each score as a covariate. Parameter estimation will be based on REML 
and to begin an unstructured covariate matrix will be used.  If the model fails to converge, the form of the 
covariance matrix will be chosen based on Akaike’s Information Criteria, and Schwarz’ Bayesian Criterion. 
Model-based LS means will be obtained for change from baseline to each time point for each treatment group. 
At each time point, contrasts between CBD and placebo will be obtained. Secondary alcohol use measures will 
be tested with MMRM sequentially in a closed testing union intersection paradigm in the order listed in section 
C.8.3. Validity of the p-value will extend until the first test fails to have a p-value smaller than a two-sided alpha 
of 0.05. The analyses will continue for all measures but the resulting p-value will be nominal. 
 
For Hypothesis 2, PTSD symptoms, the primary outcome measure, total score of the PCL-5, will be analyzed 
in the same way as the primary outcome for alcohol use. The primary contrast is change from baseline (B1) at 
week 6 (T8). 
 
20.3.3 Analysis of the Secondary Endpoint(s) 
For hypothesis 3a: Mechanism, traumatic stress-induced craving: The primary outcome measure will be alcohol 
craving. Alcohol craving outcomes within a session will be examined in terms of a created measure of a 
difference of difference scores: first, the difference score of the alcohol craving response to trauma and to 
neutral challenges calculated for the Pre and for the Post session time points, and second, the difference of the 


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scores between Post and Pre. This difference measure of alcohol craving will be calculated at Baseline, and at 
week 6 of the clinical trial (T8). The outcome analysis will be conducted with an MMRM model that includes 
fixed effects for treatment C, (CBD vs. placebo) and clinical trial time T, a random effect for subjects, and a 
treatment by clinical trial time interaction (C*T). The model will provide least-square mean estimates of 
difference scores at each session for each treatment. Between treatment outcome contrasts will be performed 
at Baseline, as a measure of the equivalence of the groups, and at T6 and for the difference between T6 and 
Baseline. For parameter estimation, the form of the covariance matrix will follow the procedures described for 
the analysis of Aim 1. Secondary outcome measures will be Negative Emotion, and Psychophysiological 
arousal. These outcomes will be analyzed in a similar manner to the primary outcome, alcohol craving. 
 
For Hypothesis 3b: Mechanism, AUD and PTSD related measures and cognition (craving, self-efficacy, anxiety, 
cognitive measures) will be analyzed in the same way as the primary outcome for alcohol use. The primary 
contrast is change from baseline (B1) at week 6 (T8). 
 
For Hypothesis 3c: Mechanism, anandamide, within- and between-group comparisons of plasma anandamide 
levels will be assessed following 45 minutes (T1), 1 day (T2), 1 week (T3), 2 weeks (T4), 4 weeks (T6), 6 weeks 
(T8) of treatment with CBD vs. placebo, and one week (T9) after the completion of treatment. Effects of dose 
will be assessed and the interaction between group and time- point will be evaluated. 
 
For Hypothesis 4, plasma CBD and THC levels will be analyzed in the same manner as anandamide in 
Hypothesis 3c. 
 
20.3.4 Safety Analyses 
Means and standard deviations of plasma CBD and THC levels within the CBD treatment group will be 
presented following 45 minutes (T1), 1 day (T2), 1 week (T3), 2 weeks (T4), 4 weeks (T6),6 weeks (T8) of 
treatment with CBD vs. placebo, and one week (T9) after the completion of treatment to determine whether 
target plasma levels of CBD have been achieved, and whether metabolic transformation of CBD to THC has 
occurred. 
The number of participants within each treatment group that were able to pass a battery of psychomotor field 
sobriety tasks (walk-and-turn task, one-leg stand, Romberg’s test, finger-finger test, and counting backwards 
[85]) within 2 hours of the initial administration of CBD vs. placebo (T1) will be analyzed as summary statistics 
during treatment. 
AEs and SAEs, when present, will be collected on an AE Case Report Form at study visits. The form will 
include an assessment of clinical significance and study relatedness. Serious Adverse Events (SAEs) will be 
documented on an additional SAE form. These CRFs will be based on those used in recent NIDA Clinical Trials 
Network trials. To further assess abuse potential, visual analog scales will be used to assess abuse potential. 
Scales will include desire to use the study medication again, desire to use the study medication again for 
pleasurable intoxication (“to get high”), and craving for the study medication. 
The study may be stopped if there are untoward and concerning levels of Adverse Event (AE) or Serious 
Adverse Event (SAE) outcomes attributable to CBD or study participation. If the DSMB finds it is likely that CBD 
is contributing to negative outcomes, they will consider solutions including protocol changes or potentially 
stopping the study. 
 
The frequency of adverse events will be analyzed for the entire sample tabulated for each treatment group and 
compared using chi-squared tests. The safety analysis will be largely descriptive of outcomes for the entire 
study population. The incidence of AEs will be summarized by system organ class, preferred term, the likelihood 
of its relationship to the treatment, and severity for each treatment group. Clinical laboratory data will be 
summarized by type of test. Frequency and percentage of patients whose values fall outside of reference ranges 
will be presented for each measurement. 
 
20.3.5 Adherence and Retention Analyses 
Adherence to the protocol will be assessed with a smartphone-assisted medication adherence platform [94] in 
which the subject takes a video of drug administration at each dose, and transmits this to study personnel. 
 
This program has been used successfully in previous studies, and includes security provisions that ensure 
protection of confidentiality and privacy. If the participant is unable to use the smartphone-assisted platform 
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at each visit. Plasma concentrations of CBD will also be collected at all in-person visits (T1-T4, T6, and T8) to 
verify treatment adherence.  
 
Number of participants that complete the treatment phase of the study (through T8), complete the follow-up 
phase of the study (through T10), and are lost to follow-up will be collected. Frequency of and reasons for 
discontinuation of the intervention or study follow-up will also be tallied. 
 
20.3.6 Baseline Descriptive Statistics 
Treatment groups will be compared on several baseline characteristics, including sex, age, race/ethnicity, 
education level, baseline measures of alcohol consumption (% drinking days and % heavy drinking days), 
alcohol craving (PACS), anxiety (BAI), mood (BDI-II), CAPS total, and self-efficacy (AASE). Categorical data 
will be tallied, and means and standard deviations of continuous scores will be calculated. 
 
20.3.7 Planned Interim Analysis 
 
20.3.7.1   Safety Review 
The DSMB will meet (in person or by teleconference) at least annually, including prior to enrollment of the first 
participant, following completion of treatment of the first 5 completers, after completion of treatment of the first 20 
completers, and upon completion of enrollment for the trial. Prior to each meeting, the PI will prepare a report 
to the Board including review of the aggregate analysis of adverse events/serious adverse events. 
Following each meeting, the board will provide the PI with a report including a recommendation to continue the 
study unchanged, continue with modifications of the protocol and/or the consent form to protect participant 
safety, or terminate the study. The study may be stopped if there are untoward and concerning levels of AE or 
SAE outcomes attributable to CBD or study participation. If the DSMB finds it is likely that CBD is contributing 
to negative outcomes, they will consider solutions including protocol changes or potentially stopping the study. 
 
20.3.8 Multiple Comparison/Multiplicity 
Because our primary outcomes are safety data, in which we hypothesize a null difference between treatment 
groups, we will not employ a correction for Type I error/alpha inflation. 
 
20.3.9 Tabulation of Individual Response Data 
Aside from AEs/SAEs, individual response data will not be presented. 
 
20.3.10 Exploratory Analyses 
 
For Exploratory Hypothesis 1, relationship between PTSD/subthreshold PTSD and AUD symptom change 
 
Symptom onset is defined to be the first week in which the patient has 50% reduction in the number of drinks 
per day for the primary alcohol outcome and a 30% reduction in the Total Score of the PCL-5 that is sustained 
for at least two weeks. Onset of a positive clinical outcome will be described by a "cure model." The form of a 
cure model is H(t) = 1- p + pS(t); where H(t) is the probability of onset at a time greater than t, p represents  
the probability of success and S(t) is the distribution of time to success, conditional on success occurring. The 
parameters will be estimated based both on Kaplan Meier methods and parametrically. The equality of the 
values of p for the two treatment arms will be tested using a nonparametric likelihood ratio test. For the 
parametric test, a logistic will be used to model p and a Weibull survival distribution will be used to model time 
to failure, S(t). Both allow the use of covariates. The comparison will be based on a likelihood ratio test and  
the median time to onset of S(t). 
 
20.4 Sample Size 
We will phone screen approximately 600 participants, and enroll approximately 150 participants to randomize a 
total of 48 participants (through week 6/T8). In this pilot study sample sizes are obviously quite limited. A simple 
t test of mean differences requires an effect size of .939 to have .8 power. We have chosen an unbalanced 
design with more subjects on CBD to maximize the ability to characterize response to treatment for use in 
planning future confirmatory trials and still have valid hypotheses tests. 
 
20.5 Measures to Minimize Bias 


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20.5.1 Enrollment/Randomization/Masking Procedures 
Enrolled participants that pass screening will be randomized using a 5:3 ratio to receive either 600mg CBD/day 
(PO) or placebo respectively for 6 weeks (N=30 participants on CBD and N=18 participants on placebo). 
Treatment assignment will be known only to a designated unblinded study staff member in charge of 
dispensing study medication under direct PI supervision, but the blind can be broken if necessary, e.g., in case 
of a serious reaction during drug administration. 
 
20.5.2 Evaluation of Success of Blinding 
In order to assess the integrity of the blind, following the treatment portion of the study (T8), participants will be 
asked to guess 1) what medication was administered (CBD or placebo), and 2) degree of confidence in this 
guess. 
 
20.5.3 Breaking the Study Blind/Participant Code 
The blind can be broken for an individual participant if necessary, e.g., in case of a serious reaction during drug 
administration or in the event of a SAE likely to be related to the study medication. 
 
21 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a clinical 
trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source 
documents. Examples of these original documents, and data records include: hospital records, clinical and 
office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, study medication 
dispensing records, recorded data from automated instruments, copies or transcriptions certified after 
verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, 
x-rays, subject files, and records kept at the dispensation site, at the laboratories, and at medico- technical 
departments involved in the clinical trial. It is acceptable to use CRFs as source documents. If this is the case, 
it should be stated in this section what data will be collected on CRFs and what data will be collected from 
other sources. 
The study case report form (CRF) is the primary data collection instrument for the study. All data requested on 
the CRF must be recorded. All missing data must be explained. If a space on the CRF is left blank because 
the procedure was not done or the question was not asked, write “N/D”. If the item is not applicable to the 
individual case, write “N/A”. All entries should be printed legibly in black ink. If any entry error has been made, 
to correct such an error, draw a single straight line through the incorrect entry and enter the correct data above 
it. All such changes must be initialed and dated. DO NOT ERASE OR WHITE OUT ERRORS. For clarification 
of illegible or uncertain entries, print the clarification above the item, then initial and date it. 
Access to study records will be limited to IRB-approved members of the study team. The investigator will permit 
study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government regulatory bodies, 
and University compliance and quality assurance groups of all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data etc.). The investigator will ensure the capability 
for inspections of applicable study-related facilities (e.g. dispensation site, diagnostic laboratory, etc.). 
Participation as an investigator in this study implies acceptance of potential inspection by government regulatory 
authorities and applicable University compliance and quality assurance offices. 
 
22 Quality Assurance and Quality Control 
Data quality assurance (QA) includes all those planned and systematic actions that are established to ensure 
that the trial is performed and the data are generated, documented (recorded), and reported in compliance with 
GCP and the applicable regulatory requirements(s) (ICH E6 1.46). Data quality control (QC) includes the 
operational techniques and activities undertaken within the quality assurance system to verify that the 
requirements for quality of the trial-related activities have been fulfilled (ICH E6 1.47). 
 
QC procedures will be implemented beginning with the data entry system, and data QC checks on the database 
will be generated. Any missing data or data anomalies will be communicated to the site(s) for 
clarification/resolution. 
 
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documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). The 
investigational site will provide direct access to all trial related sites, source data/documents, and reports for the 
purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
 
23 Ethics/Protection of Human Subjects 
23.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the Protection of 
Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or the ICH E6. 
 
23.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant-facing materials will be 
submitted to the IRB for review and approval. Study approval must be obtained before any participant is 
enrolled. Any amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. All changes to the consent form will be IRB approved; a determination will be made 
by the IRB regarding whether previously consented participants need to be re-consented. 
 
23.3 Informed Consent Process 
 
23.3.1 Consent/Assent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study agent, study procedures, and risks are given to the participant 
and written documentation of informed consent is required prior to starting intervention/administering study 
product. 
 
23.3.2 Consent Procedures and Documentation 
An IRB-approved pre-screening form will be used to pre-screen individuals expressing interest in the study, to 
assess whether they are likely to qualify for the study. Interested patients who pass the pre-screening 
(conducted via phone) will be referred for a screening visit.  
 
• 
Participants will be provided with an informed consent form, COVID-19 information sheet, audio and 
video consent form, and health release form at or prior to their screening visit. Understanding of the 
study procedures will be assessed using a consent quiz.  
 
Subjects will be electronically consented via a 21CFR Part 11-compliant electronic consent method. The U.S. 
Food and Drug Administration (FDA)’s MyStudies mobile application is a Part 11-compliant electronic consent 
method which allows our study team to review study informed consent forms with the participants remotely and 
obtain the participant’s electronic signatures on the study’s informed consent forms via the mobile application. 
The app is available in the US in English on both Apple and Android smartphones. Secure registration allows 
participants to enter a unique enrollment code specific to our study to prevent people outside of the study from 
enrolling. The application allows for the storage of signed electronic consent forms on HIPAA and FISMA 
compliant servers; the participant is able to receive secure copies of their electronically signed consent form 
PDF by email directly after they sign the consent. Designated research staff can easily access and download 
all signed consent forms for secure storage on the shared drive by logging into a portal. The FDA MyStudies 
e-consent application will not be used until a link to the informed consent form has been submitted and 
approved by NYU’s IRB. We will also utilize REDCap (accompanied with REDCap Cloud, a Part 11-compliant 
electronic consent method) to obtain the participant’s electronic signatures on the study’s informed consent 
forms remotely. 
Alternatively, remote consent may be obtained via SendSafe email. In this case, a copy of the consent form 
will be sent via SendSafe email. The subject’s signature will be captured electronically on the document 
provided, or the subject may print and sign a physical copy that is scanned and returned via the SendSafe 
method. Subjects who do not have access to email or scanner may choose to have a hard copy of the consent 
mailed to them and return via a self-addressed stamped envelope provided by the study team.  
At or prior to their first visit, participants will be provided with an informed consent form including all pertinent 
details of the study including descriptions of the following: the assessment interview and questionnaires; the 
follow-up interviews; description of experimental treatment; risks and benefits of study procedures; alternatives 


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to participation in the study; confidentiality; emergency treatment and compensation for injury; payment for 
participation; a statement that patients will be informed of any new findings affecting the risks or benefits of the 
study; a statement that participation is voluntary and that the patient may withdraw at any time; and information 
about whom to contact with questions or in case of emergency. The consent form will also include assurances 
of confidentiality and a statement that participation is entirely voluntary, that the decision to participate will in no 
way influence other aspects of the patient’s treatment, and that the participant is free to withdraw participation 
at any time. Study staff will explain the research study to the participant and answer any questions that may 
arise. All participants will receive a verbal explanation in terms suited to their comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research participants. Participants will have 
the opportunity to carefully review the written consent form and ask questions of the study team.  
Participants must pass a consent quiz with a score of 90% or higher prior to signing. Participants who score less 
than 90% may take the quiz a second time after the study team has reviewed content and answered all 
questions. Participants who are unable to score 90% or higher on the quiz after two attempts will be given a 
copy of the consent to take home and may return for a screening visit on a later date. If the participant is unable 
to score 90% or higher on the third attempt, they will be excluded from the study unless otherwise determined 
by senior management or the PI. If a decision is made to retain the subject despite failure to attain a 90% or 
higher on the consent quiz, the rationale will be documented in the subject’s binder via a note to file.   
A copy of the signed informed consent document will be given to the participants for their records. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their medical care 
will not be adversely affected if they decline to participate in this study. The participants may withdraw consent 
at any time throughout the course of the trial. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The consent 
process, including the name of the individual obtaining consent, will be thoroughly documented in the subject’s 
research record. Any alteration to the standard consent process (e.g. use of a translator, consent from a legally 
authorized representative, consent document presented orally, etc.) and the justification for such alteration will 
likewise be documented. 
 
Patients who consent to participate in the study will also be invited to consent to having their remote and/or in-
person screening assessments (i.e. SCID and CAPS) audio-recorded at the initial visit (see Audio Recording 
Consent) for quality control and for voice-markers analysis. If a patient does not sign the Audio Recording 
Consent, then we will not audio-record the patient’s interview. 
 
Re-Contacting Screen Failures 
In the event the protocol inclusion and exclusion criteria are updated, previously screened participants will be 
reconsidered for inclusion in the study. If a previously screened participant is eligible under the updated inclusion 
and exclusion criteria, they will be contacted via phone or email to ascertain whether they are still interested in 
participation. If interested, the participant will be brought in for re-consent and a Clinical Re-Screen or a new 
Screening Visit if 3 months or greater have passed since the initial screening. 
 
Re-Consent 
If the consent is revised (e.g.: new procedures, risk information, compensation, data sharing, etc.), participants 
will be re-consented with the most updated version of the consent form at their next visit. New information that 
could substantially affect a participant’s desire to continue in the study will be communicated via phone, followed 
by re-consent at the next study visit.  
 
23.4 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of the 
Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed 
subject authorization informing the subject of the following: 
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information and why 
• 
Who will use or disclose that information 
• 
The rights of a research subject to revoke their authorization for use of their PHI. 
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains 


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the ability to use all information collected prior to the revocation of subject authorization. For subjects that have 
revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at least 
vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the sponsor(s) 
and their agents. This confidentiality is extended to cover testing of biological samples in addition to the clinical 
information relating to participants. Therefore, the study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the sponsor. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 
records of drug dispensation for the participants in this study. Records will be housed in a secured space in 1 
Park, A, C-D, and H buildings of Bellevue Hospital Center with limited access to study PI and designated study 
staff only. The clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at each clinical site for internal use during 
the study. At the end of the study, all records will continue to be kept in a secure location for as long a period 
as dictated by local IRB and Institutional regulations as described in section 24.2. 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by clinical sites and 
by NYU Langone Medical Center research staff will be secured and password protected. At the end of the 
study, all study databases will be de-identified and archived at the NYU Langone Medical Center. 
Confidentiality of research material will be ensured by storing the research materials in locked cabinets. Material 
will be available only to project staff, and only as needed. All project staff will be thoroughly trained in issues 
relating to confidentiality. Participants will be identified in case report forms (CRFs) by initials and an 
identification code. Data will be entered into TrialMaster™, a program provided by NYU’s Datacore designed 
specifically for clinical trials to protect patient privacy and confidentiality. Published reports will be based on 
group data; no individual data will be reported. 
To further protect the privacy of study participants, a Certificate of Confidentiality will be obtained from the NIH. 
This certificate protects identifiable research information from forced disclosure. It allows the investigator and 
others who have access to research records to refuse to disclose identifying information on research 
participation in any civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, 
or local level. By protecting researchers and institutions from being compelled to disclose information that 
would identify research participants, Certificates of Confidentiality help achieve the research objectives and 
promote participation in studies by helping assure confidentiality and privacy to participants. 
If the study participant has previously participated in a research study at NYU, we will ask the participant’s 
permission to link their previously collected data to the data collected in this research study in order to retain 
longitudinal information on the participant. 
 
23.4.2 Research Use of Stored Human Samples, Specimens, or Data 
• Intended Use: Samples and data collected under this protocol may be used to evaluate study eligibility 
and plasma concentrations of CBD and THC. No genetic testing will be performed. 
• Storage: Access to stored samples will be limited by storing samples in a securely locked area. Samples 
and data will be stored using codes assigned by the investigators. Data will be kept in password-
protected computers. Only investigators will have access to the samples and data. 
• Tracking: Data will be tracked using paper and electronic logs. 
o Disposition at the completion of the study: All stored samples will be sent to GRM Document 
Management. Study participants who request destruction of samples will be notified of 
compliance with such request and all supporting details will be maintained for tracking. 
 
23.5 Future Use of Stored Data 
Data collected for this study will be analyzed and in locked cabinets in NYU space at One Park and within the 
A, C-D, and H buildings of Bellevue Hospital Center. After the study is completed, the de-identified, archived 


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data will be transmitted to and stored at GRM Document Management for use by other researchers including 
those outside of the study. Permission to transmit data to GRM Document Management will be included in the 
informed consent. 
 
When the study is completed, access to study data will be provided through GRM Document Management. 
 
24 Data Handling and Record Keeping 
24.1 Data Collection and Management Responsibilities 
Data collection, interpretation, analysis, review, and reporting is the responsibility of the clinical trial staff at the 
site under the supervision of the site PI. The investigator is responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of data. 
Black or blue ink will be used to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. We will not erase, overwrite or use 
correction fluid or tape on the original.  
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for recording 
data for each participant enrolled in the study. Data reported in the eCRF derived from source documents will 
be consistent with the source documents or the discrepancies will be explained and captured in a progress note 
and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into TrialMaster™ Electronic Data Capture (EDC), a 21 CFR Part 11- compliant 
data capture system. The data system includes password protection and internal quality checks, such as 
automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will 
be entered directly from the source documents. 
 
24.2 Study Records Retention 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication, or 2 years after the last approval of a marketing application is approved for the drug for 
the indication for which it is being investigated or 2 years after the investigation is discontinued and FDA is 
notified if no application is to be filed or if the application has not been approved for such indication. No records 
will be destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor 
to inform the investigator when these documents no longer need to be retained. 
 
24.3 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Manual of Procedures (MOP) 
requirements. The noncompliance may be either on the part of the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. 
 
These practices are consistent with ICH E6: 
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, section 5.1.1 
• 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and report deviations 
within 5 working days of identification of the protocol deviation, or within 5 working days of the scheduled 
protocol-required activity. 
 
All protocol deviations must be addressed in study source documents and reported to NIAAA Program 
Official. 
 
Protocol deviations must be reported to the local IRB per their guidelines. The site PI/study staff is  responsible 


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for knowing and adhering to their IRB requirements. Further details about the handling of protocol deviations 
will be included in the MOP. 
 
24.4 Publication and Data Sharing Policy 
This study will comply with the NIH Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts 
that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. 
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical trials 
registration policy as a condition for publication. The ICMJE defines a clinical trial as any research project that 
prospectively assigns human subjects to intervention or concurrent comparison or control groups to study the 
cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions 
include drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. 
Health outcomes include any biomedical or health-related measures obtained in patients or participants, 
including pharmacokinetic measures and adverse events. The ICMJE policy, and the Section  801 of the Food 
and Drug Administration Amendments Act of 2007, requires that all clinical trials be  registered in a public trials 
registry such as ClinicalTrials.gov, which is sponsored by the National Library of Medicine. Other biomedical 
journals are considering adopting similar policies. For interventional clinical trials performed under NIH IC grants 
and cooperative agreements, it is the grantee’s responsibility to register the trial in an acceptable registry, so 
the research results may be considered for publication in ICMJE member journals. The ICMJE does not review 
specific studies to determine whether registration is necessary; instead, the committee recommends that 
researchers who have questions about the need to register err on the side of registration or consult the editorial 
office of the journal in which they wish to publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal investigator) register 
and report results of certain "applicable clinical trials": 
 
• Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations of a 
product subject to FDA regulation; 
• Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulation (other 
than small feasibility studies) and pediatric postmarket surveillance studies. 
• NIH grantees must take specific steps to ensure compliance with NIH implementation of FDAAA. 
 
25 Study Finances 
25.1 Funding Source 
This study is financed through a grant from the US National Institutes of Health (NIH)/National Institute on 
Alcohol Abuse and Alcoholism (NIAAA). 


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25.2 Costs to the Participant 
Participants will not incur any costs as a result of participating in the study. 
 
25.3 Participant Reimbursements or Payments 
Participants will receive monetary compensation for research assessments as follows: 
 
• Option 1 Screen (S1)= $70 
• Option 2 Screen Session 1 = $50 
• Option 2 Screen Session 2 = $20 
• Baseline (B1)= $70 
• 1-day assessment (T2)= $40 
• 1-week assessment (T3)= $60 
• 2-week assessment (T4)= $60 
• 4-week assessment(T6) = $70 
• 6-week assessment (T8)= $70 
• 7-week assessment (T9)= $40 
 
Participants completing all the assessments would therefore receive a total of $480. Participants will also be 
provided with a gift card or $12 cash compensation for the purchase of a meal for visits that are 5 hours or longer. 
If requested, compensation will also be provided for travel and transportation for study-related visits. Participants 
may receive partial compensation for portions of study visits completed as applicable. Participants may also 
receive a $15 compensation for time/effort spent as a “standby” for a potential screening visit; participants will only 
receive the one-time $15 compensation once the clinical screen visit is completed as part of the study. 
 
In the case of a clinical re-screen or partially completed visits, participants will be compensated $25-$40 depending 
on the length of the visit. The amount is determined by senior management.  
 
Payment may be made in cash, check, or ClinCard.  
 
 
26 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, 
is critical. Therefore any actual conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a way that is appropriate to 
their participation in the trial. The study leadership in conjunction with the NIAAA has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism for 
the management of all reported dualities of interest. 
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study. All 
NYULMC investigators will follow the applicable conflict of interest policies.


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75. 
Babalonis, S., et al., Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana 
smokers. Drug Alcohol Depend, 2016. 172: p. 9-13. 
76. 
Stott, C.G., et al., A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD 
oromucosal spray. Eur J Clin Pharmacol, 2013. 69(5): p. 1135-47. 
77. 
Merrick, J., et al., Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and 
Physiological Fluid. Cannabis Cannabinoid Res, 2016. 1(1): p. 102-112. 
78. 
Sobell, L.C., et al., The reliability of alcohol abusers' self-reports of drinking and life events that occurred 
in the distant past. J Stud Alcohol, 1988. 49(3): p. 225-32. 
79. 
Flannery, B.A., J.R. Volpicelli, and H.M. Pettinati, Psychometric properties of the Penn Alcohol Craving 
Scale. Alcohol Clin Exp Res, 1999. 23(8): p. 1289-95. 
80. 
Ling, W., et al., Buprenorphine tapering schedule and illicit opioid use. Addiction, 2009. 104(2): p. 256-
65. 
81. 
DiClemente, C.C., et al., The Alcohol Abstinence Self-Efficacy scale. J Stud Alcohol, 1994. 55(2): p. 141-
8. 
82. 
Vielva, I. and I. Iraurgi, Cognitive and behavioural factors as predictors of abstinence following treatment 
for alcohol dependence. Addiction, 2001. 96(2): p. 297-303. 
83. 
Hamilton, M., The assessment of anxiety states by rating. Br J Med Psychol, 1959. 32(1): p. 50-5. 
84. 
Seo, D., et al., Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk. 
JAMA Psychiatry, 2013. 70(7): p. 727-39. 
85. 
Burns, M., An overview of field sobriety test research. Percept Mot Skills, 2003. 97(3 Pt 2): p. 1187- 99. 
86. 
Martin, W.R., et al., Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, 
ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther, 1971. 12(2): p. 245-58. 
87. 
Rosenberg, S.J., J.J. Ryan, and A. Prifitera, Rey Auditory-Verbal Learning Test performance of patients 
with and without memory impairment. J Clin Psychol, 1984. 40(3): p. 785-7. 
88. 
Vandenberg, S.G. and A.R. Kuse, Mental rotations, a group test of three-dimensional spatial 
visualization. Percept Mot Skills, 1978. 47(2): p. 599-604. 
89. 
Peters, M., et al., A redrawn Vandenberg and Kuse mental rotations test: different versions and factors 
that affect performance. Brain Cogn, 1995. 28(1): p. 39-58. 
90. 
Conway, A.R., et al., Working memory span tasks: A methodological review and user's guide. 
Psychon Bull Rev, 2005. 12(5): p. 769-86. 
91. 
Unsworth, N., Examining variation in working memory capacity and retrieval in cued recall. Memory, 
2009. 17(4): p. 386-96. 
92. 
Anton, R.F., et al., Combined pharmacotherapies and behavioral interventions for alcohol dependence: 
the COMBINE study: a randomized controlled trial. JAMA, 2006. 295(17): p. 2003-17. 
93. 
Bogenschutz, M.P., et al., Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept 
study. J Psychopharmacol, 2015. 29(3): p. 289-99. 
94. 
Mooney, L.J., et al., Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of 
Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder. J 
Addict Med, 2016. 10(4): p. 236-43. 
95. 
Sullivan, J.T., et al., Assessment of alcohol withdrawal: the revised clinical institute withdrawal 
assessment for alcohol scale (CIWA-Ar). Br J Addict, 1989. 84(11): p. 1353-7. 


 
 
 
 
96. 
Bovin, M.J., et al., Psychometric properties of the PTSD Checklist for Diagnostic and Statistical Manual 
of Mental Disorders-Fifth Edition (PCL-5) in veterans. Psychol Assess, 2016. 28(11): p. 1379- 1391. 
97. 
Sinha, R., Modeling relapse situations in the human laboratory. Curr Top Behav Neurosci, 2013. 13: p. 
379-402. 
98. 
Posner, K., et al., The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency 
findings from three multisite studies with adolescents and adults. Am J Psychiatry, 2011. 168(12): p. 
1266-77 
99. 
Beck, A.T., et al., An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin 
Psychol, 1988. 56(6): p. 893-7. 
100. 
Beck, A. T., Steer, R. A., & Brown, G. K. (1996) Beck depression inventory-II. San Antonio, 78(2), 490-
498.. 
101. 
Weathers, F.W., et al., The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and 
initial psychometric evaluation in military veterans. Psychol Assess, 2018. 30(3): p. 383-395. 
Johsnon, B.A., Ait-Daoud N., & Roache, J.D., The COMBINE SAFTEE: a structured instrument for 
collecting adverse events adapted for clinical studies in the alcoholism field. Journal of studies on 
alcohol, 2005. 14: p. 157-67. 
102. 
Franklin, C. L., Raines, A. M., Chambliss, J. L., Walton, J. L., & Maieritsch, K. P. (2018). Examining 
various subthreshold definitions of PTSD using the Clinician Administered PTSD Scale for DSM-5. 
Journal of affective disorders, 234, 256-260. 
103. 
114. R.H. Pietrzak, R.B. Goldstein, J.C. Malley, D.C. Johnson, S.M. Southwick. Subsyndromal 
posttraumatic stress disorder is associated with health and psychosical difficulties in veterans of 
operations enduring freedom and Iraqi freedom. Depress. Anxiety, 26 (2009), pp. 739-744 
104. 
115. C. Zlotnick, C.L. Franklin, M. Zimmerman. Does “subthreshold” posttraumatic stress disorder have 
any clinical relevance? Compr. Psychiatry, 43 (2002), pp. 413-419 
105. 
116. R.H. Pietrzak, R.B. Goldstein, S.M. Southwick, B.F. Grant. Prevalence and Axis I comorbidity of 
full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National 
Epidemiologic Survey on alcohol and related conditions. J. Anxiety Disord., 25 (2011), pp. 456-465 
 
 
 
 
 
 
 
 

ICF_000.pdf: 
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Research Subject 
Informed Consent Form
Title of Study:
A PHASE I/II RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
TRIAL OF CANNABIDIOL AS A TREATMENT FOR ALCOHOL USE 
DISORDER COMORBID WITH POSTTRAUMATIC STRESS DISORDER 
S17-00949
Principal 
Investigator:
Charles Marmar, MD
NYU School of Medicine, Department of Psychiatry 
One Park Ave.
Charles.Marmar@nyumc.org 
646-754-4855
Emergency 
Contact:
Charles Marmar, MD 
Cell: (415) 299-7472
1. About volunteering for this research study
You are being invited to take part in a research study. Your participation is voluntary which means you can 
choose whether or not you want to take part in this study.
People who agree to take part in research studies are called “subjects” or “research subjects.” These words 
are used throughout this consent form. Before you can make your decision, you will need to know what the 
study is about, the possible risks and benefits of being in this study, and what you will have to do in this 
study. You may also decide to discuss this study and this form with your family, friends, or doctor. If you 
have any questions about the study or about this form, please ask us. If you decide to take part in this 
study, you must sign this form, either by written signature or electronic signature. We will give you a copy 
of this form signed by you for you to keep.
2. What is the purpose of this study?
You are being asked to participate in this study because you have alcohol dependence comorbid with 
PTSD and you want to stop or decrease your drinking and your PTSD symptoms, but are not currently 
receiving any professional alcohol or PTSD treatment. If you are currently participating in a 12-Step 
Recovery program, you may want to speak with your 12- Step Sponsor before enrolling in this research.
The purpose of this research study is to see how safe and effective cannabidiol (CBD) is for the treatment 
of alcohol dependence comorbid with post-traumatic stress disorder (PTSD). We also would like to assess 
its effects on thinking, behavior and habits of people with alcohol use disorder (AUD) and PTSD.
CBD is a naturally occurring, non-psychoactive compound found in the marijuana plant. The United States 
Food and Drug Administration (FDA) has not approved this formulation of CBD as a safe or effective 
treatment for alcohol dependency or PTSD. Therefore, the use of CBD to treat alcohol dependency and 
PTSD is considered experimental. 
CBD works by activating receptors in the brain that might affect the way you respond to stressful situations. 
Even though CBD is found in the marijuana plant, it does not make people feel “high” the same way that 
marijuana does.


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If you agree to participate in this study, you will be randomly assigned (like a flip of a coin) to either a CBD 
or a placebo group. The placebo looks like the study drug but has no CBD or other drugs in it. You are more 
likely to receive the study drug (CBD) than placebo (5:3 ratio).
3. How long will I be in the study? How many other people will be in the study?
After meeting study criteria, approximately 48 subjects will receive medication or placebo in this study at 
NYULMC. ~150 people are expected to be consented in the study in order to randomize 48 participants.
Participation in this study will take a total of about 30-35 hours over a period of 9 weeks; you will receive 
the study drug or placebo for 6 weeks.
4. What will I be asked to do in the study?
The following figure summarizes the visits of the study, which are described in more detail below:


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Below is a list of each study visit that is part of the study. This list includes about how long each visit 
should take and a list of the research tests and procedures to be done at each visit and/or blood 
work to be completed. We may be able to schedule procedures over two separate days within the 
same week if you are unable to stay for an entire visit due to scheduling conflicts.
Screening Visit (~4-6 hours)
If you agree to be in this study, the first visit will be the screening visit. The purpose of the screening visit is to 
make sure that you meet all of the requirements to take part in the study. Procedures marked with an asterisk 
( * ) must be completed in-person. The study investigator will review the results of these tests and procedures 
and we will let you know whether you are eligible to participate in the study. At this visit, the following 
procedures will take place:

Medical history

Family history 

Vital signs (heart rate, blood pressure, and temperature)*

Concurrent medications

Menstrual calendar (if applicable) to minimize the risk of undetected pregnancy during the study

Physical exam*

Your breath alcohol concentration will be measured (breathalyzer test)*

You will be assessed for signs of alcohol withdrawal

We will ask you in detail about your recent use of alcohol and drugs
Blood Sample*:
22 cc of blood (approximately 1.5 tablespoons) will be drawn with a needle from a vein in your arm for safety 
tests. A serum pregnancy test will also be completed for women who may become pregnant.
Urine Samples*:
Urine samples will be collected for urinalysis and to test for the presence of certain drugs, including cocaine, 
methamphetamine, opiates, and marijuana. This test will be performed on-site. You will be able to collect this 
urine in a bathroom without anyone watching you. You will be informed of the results of the laboratory tests 
when they become available. You may be excluded from participating in the study if you test positive for certain 
drugs or substances. Women of child bearing potential without any pregnancy exclusions will also have a 
urine pregnancy test completed; you will be excluded from the study if you are pregnant. We will inform you 
of the results when they become available. The results of the urine drug screen will NOT become part of your 
medical record. These test results WILL become part of your research record.
Questionnaires:
We will ask you to complete forms about your demographics, alcohol and substance abuse, 
psychiatric disorders, quality of life, and alcohol withdrawal. We will also collect contact information 
for yourself, your emergency contact, and primary care physician. 
Diagnostic Interview:
You will receive a diagnostic interview assessing substance use and psychiatric disorders. One of our trained 
staff members will ask questions about your mood, mental health history and diagnoses, assess for traumatic 
brain injury (TBI), post-concussive symptoms (CSI) and suicidality. We will ask you whether we can record 
your diagnostic interview for quality control purposes and voicemarkers analysis on a separate consent form.
Health Release Form: 
We will ask you to sign a health release form so that we can see your personal information in records 
from hospitals, clinics, or doctor’s offices where you may have received care in the past. We may 
also ask to speak with clinicians who have treated you for medical and/or psychiatric conditions, but 
will not reveal the nature of the study without your permission. We will only access this information 
if it is needed to determine your eligibility for the study. 
Locators: 
In order to participate in this study, you will also need to identify at least two people who would know your 


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whereabouts in case study personnel needed to find you during the study. The locator people may be told that 
we are calling from NYU, and may be given the name and phone number of study staff, but will not be given 
any other information about your participation without your permission. If we are unable to reach you with the 
information you have provided on the locator form, we may use publicly available data on the internet, like 
Facebook, in an effort to find updated contact information.
Clinical Re-Screen
If there is a delay between your screening visit and baseline visit, we will conduct a “clinical re-screen” to 
confirm you are still eligible for the study. The following measures will be conducted at the clinical re-screen:

Breath alcohol concentration (BAC)

Urine drug screen

Urine pregnancy test (if applicable) 

Vital signs

Questions about PTSD symptoms, alcohol use, craving, suicidality, and current medications

If deemed necessary by the study clinicians, blood may be collected for safety tests and urine may be 
collected for urinalysis
If the delay between your screening visit and baseline visit is longer than 3 months, a trained staff member 
will also reassess your PTSD, AUD, depression, and suicidality symptoms, ask if you have sustained any new 
head injuries, and check that any drug use has not risen to the level of a disorder diagnosis.  
If you qualify to participate in the study, you will be scheduled for the following visits over the next 9 weeks:
Baseline Visit (5-6 hours)
At the baseline session, the following procedures will be performed:

Vital signs

Menstrual calendar (if applicable)

Your breath alcohol concentration will be measured (breathalyzer test)

We will ask you in detail about your recent use of alcohol and drugs
Questionnaires:
You will be asked to complete a number of questionnaires and interviews, many of which will be repeated at 
later assessment sessions. These include questionnaires about any recent drug and alcohol use (since the 
last visit), problems you may have experienced related to alcohol, your motivation and confidence to cut down 
or stop drinking, your craving for alcohol, and your current mood. 
Urine Sample:
A urine sample will be collected to test for the presence of several drugs, including cocaine, 
methamphetamines and marijuana. You may be excluded from participating in the study if you test positive 
for certain drugs or substances. Women of child bearing potential without any pregnancy exclusions will also 
have a urine pregnancy test completed.
Interview:
We will interview you about an experience you had in the last year that was associated with an urge to drink 
alcohol, an experience you had in the last year that you found traumatic, and an experience you had in the last 
year that you found relaxing. These interviews will be used to create personalized scripts that you will listen to 
at the week 4 visit; if you consent to audio recordings for study purposes, this interview will be audio-recorded. 
Blood Samples: 
We will collect a blood sample (1.5-2 tablespoons) to test for levels of CBD, a marker of alcohol consumption 
called carbohydrate-deficient transferrin (CDT), and several other chemicals related to CBD (delta-9- 
tetrahydrocannabinol (THC), 11-Hydroxy Delta-9 THC, Delta-9 Carboxy THC, and anandamide) prior to your 
first study medication dose. This sample will be sent to outside laboratories for testing, and will be accessible 
only to laboratory personnel. 


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Study Drug (CBD or Placebo):
We will give you the study drug (CBD or placebo) at this visit. We will collect a blood sample (~20 mls or 1.5-
2 tablespoons) to measure your blood levels of CBD, THC and anandamide prior to and after administering 
the first dose of the study drug in the laboratory and you will remain in the laboratory under supervision of 
study staff for 45 minutes following administration of the study drug. 
45 Minutes After You Receive the Study Drug: 
We will collect another blood sample (1.5-2 tablespoons) for safety labs after the first dose of medication. If 
there are no safety concerns after 45 minutes, we will give you instructions on how to use the study drug at 
home, and enough of the study drug to last until your next scheduled visit. You will be given the study drug to 
take home with you, and you will be instructed to take the study drug every day. For the next 6 weeks of the 
study, you will take two capsules in the morning and 1 capsule in the evening with food. Sometimes we will 
ask you to bring your morning dose with you to the research visit to take in the laboratory.
Study Drug Adherence: 
There are two ways that we can make sure you are taking the study drug as instructed:
1.
Optional Emocha App: You may choose to use the Health Insurance Portability and Accountability 
Act (HIPAA)-compliant application “emocha.” If you choose this option, we will show you how to record 
a video of yourself taking the study drug each time you take it. The app will record the time and day 
you took the study drug. The recordings will be used to make sure you are taking the study drug 
correctly and will not be used for any other purpose. The app is available for phones or tablets. You 
can communicate with the principal investigator and study staff on the app if you have any issues. At 
the end of the study, all video records taken using the app will be destroyed. Only the documentation 
of the records will be securely kept for research purposes.
2.
In-Person Pill Count: If you choose not to use emocha, you will be asked to assure medical 
adherence through meeting with the study nurse practitioner/physician at each scheduled visit. The 
study nurse practitioner/physician will ask questions regarding your medication and also count the pills 
you return.
Intermediate Visits (1-4 hours each)
Nine additional assessment sessions will be scheduled. Some will take place in person and some will take 
place over the phone. 
Visit Name
Visit Type
Visit Length
1 Day
In Person
1 to 4 hours
Week 1
In Person
1 to 4 hours
Week 2 
In Person
1 to 4 hours
Week 3
Phone Call
1 hour
Week 4
In Person
1 to 4 hours
Week 5
Phone Call
1 hour
Week 6
In Person
1 to 4 hours
Week 7 
In Person
1 to 4 hours
Week 9
Phone Call
1 hour
In Person Visits (1 Day Visit, Week 1, Week 2, Week 4, Week 6, and Week 7)
At each in-person visit, you will have the following procedures done:

Concurrent medications

Vital signs

Your breath alcohol concentration will be measured (breathalyzer test)

We will review your adherence to the study drug procedures (pill count or emocha)

Evaluate safety, cognitive function, and psychomotor effects

Record your alcohol use


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
Menstrual calendar (if applicable)
Urine Sample:
A urine sample will be collected at each in-person study visit. You may be excluded from participating in the 
study if you test positive for certain drugs or substances or if you become pregnant. 
Blood Draws: 
We will collect one blood sample at the Day 1 Visit and we will collect two samples at weeks 1, 2, 4, and 6. 
On the days that two samples are collected, one sample will be collected before you take the study drug and 
one will be collected 45 minutes after you take the study drug. Each sample is about 1.5-2 tablespoons of 
blood. The samples will be used for liver function tests, CBD, THC, 11-Hydroxy Delta-9 THC, Delta-9 Carboxy 
THC, anandamide, and CDT testing. 
Questionnaires:
You will be asked to complete several questionnaires asking about the effects that you experienced while 
taking the study drug, any desire to use CBD or marijuana in the future, and how satisfied you were with the 
study drug you received in the study. 
Week 4 Script: 
At Week 4, you will listen to recordings based on the interview you gave at your Baseline Visit. Each recording 
is approximately 2-5 minutes long. During these sessions, we will measure your pulse, skin conductance, 
heart rate, and blood pressure. You’ll be recorded before listening to the recordings, during, and after. You’ll 
complete questionnaires about how vivid your memories were, your alcohol craving, and your anxiety and 
emotional response. 
Phone Calls (Week 3, Week 5, and Week 9)
During each phone call, we will:

Review concurrent medications

Review your adherence to the study drug procedures 

Complete menstrual calendar (if applicable)

Ask you about any effects you have experienced while taking the study drug

Ask study drug completion questions to evaluate your safety

Ask questions about your alcohol use
Note: Some of your visits may be conducted remotely, over the phone or over WebEx. 
5. What are the possible risks or discomforts?
Risk of Study Drug
The available evidence suggests that CBD is safe and well tolerated in human participants. Previous studies 
have shown few side effects of CBD orally in doses ranging from 10 mg to 1500 mg per day; there have been 
no reported effects on blood pressure, heart rate, or respiratory rate, no negative mood effects, and no negative 
impacts on coordination or the ability to think or concentrate. The most common side effects reported in studies 
of CBD for Lennox-Gastaut or Dravet Syndrome include:

 Diarrhea

Sleepiness

Mild fever

Decreased appetite

Vomiting

Fatigue

Lethargy (lack of energy)

Convulsion (seizure)

Elevated liver enzymes (seen on blood test result; may not cause physical symptoms)


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It is possible that participation in this research study may involve risks that are currently unforeseeable. For 
more information about risks and side effects, ask a study investigator.
Risk of Placebo: 
There is a chance you will not actually be taking an active drug. In this case, your condition might not improve 
or could get worse. You could miss the benefits or harms (if any) of the study drug.
Blood Draw Risks: 
Drawing blood may cause temporary pain and discomforts from the needle stick, occasional bruising, sweating, 
feeling faint or lightheaded, and in rare cases infection.
Risks of Assessment Procedures: 
There are no known psychological risks associated with the questionnaires used in the study, most of which 
have been used extensively in clinical populations. It is possible that discussion of substance use and 
psychiatric symptoms may cause you some emotional discomfort or temporary stress. One of the investigators 
of the study will be available to meet with you if you become distressed about any aspect of the study and wish 
to discuss it.
Risks to Confidentiality and Potential Legal Consequences:
Information from this study may be submitted to the U.S. Food and Drug Administration (FDA). Medical records 
that identify you and the consent form you signed may be inspected by the FDA and the New York University 
School of Medicine’s Institutional Review Board (the Human Research Protections Office). Because of the 
need to release information to these parties, absolute confidentiality cannot be guaranteed. The results of this 
research project may be presented at meetings or in publications. However, your identity will not be disclosed 
in those presentations.
Incidental Findings:
In some cases, the safety blood draw results may indicate an abnormality with (or without) a clinical 
significance. Every blood draw performed in this study is saved and handled under the standard PHI 
confidentiality restrictions and regulations employed for patients’ information. The results are always reviewed 
by a licensed nurse practitioner or MD, who might then detect an abnormality. If clinically useful information is 
uncovered, we will speak to you in person or on the telephone regarding the new information. A copy of the 
original report will also be provided to you in person and you will be encouraged to follow up on the discovery 
with your treating physician.
6. Can I be in the study if I am pregnant or breastfeeding?
If you are currently pregnant, you will not be able participate in the study. You should not become pregnant 
while you are participating in this study. If you are able to become pregnant, you will be required to use a 
medically accepted method of birth control while you participate in the study. Examples of medically accepted 
methods of birth control are as follows:

Hormonal methods like birth control pills, patches, vaginal rings or implants

Barrier methods such as condoms or a diaphragm used with spermicide (a foam, cream or gel that kills 
sperm)

Intrauterine device (IUD)

Abstinence (no sex)
If you become or you think you have become pregnant during the study, you must tell us right away and must 
tell your obstetrician or other health care provider caring for you during your pregnancy that you took part in 
this study. If you become pregnant, you will have to stop taking part in the study for safety reasons. We may 
ask you to provide information about the outcome of your pregnancy and the health of your baby.
Note to Men: Because the effects of participating in this study on sperm are unknown, you will be required to 
use a medically accepted method of birth control while you participate in the study using one of the methods 
described above.


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7. What if new information becomes available?
During the course of this study we may find more information that could be important to you. This includes 
information that might cause you to change your mind about being in the study. We will notify you as soon as 
possible if such information becomes available.
8. What are the possible benefits of the study?
There may or may not be benefits to you from participating in this study. It is possible that some study subjects 
who receive CBD may experience an improvement in their PTSD symptoms and drinking problems during the 
study. However, if you receive such benefit, because CBD is not FDA-approved for alcohol use disorder, your 
doctor cannot prescribe it after you finish the study. Knowledge gained through this study may aid the 
development of more effective treatments for individuals with alcohol dependence and other addictive 
disorders. 
9. What other choices do I have if I do not participate?
Standard of care for outpatient treatment of alcohol dependence is taking other medications with medication 
monitoring and/or evidence-based psychosocial treatment. These alternatives may be discussed with your 
personal physician.
The FDA-approved treatments for alcohol dependence are disulfiram (Antabuse), naltrexone (ReVia and 
Vivitrol), and acamprosate (Campral). FDA-approved treatments for PTSD include selective serotonin 
reuptake inhibitor (SSRI) drugs. 
Evidence-based psychosocial treatments for alcohol dependence and/or PTSD include methods based on 
motivational interviewing (such as META), cognitive, behavioral, and cognitive-behavioral approaches, 12-
step facilitation therapies, approaches involving the spouse and family, and standardized counseling 
approaches incorporating elements of these various approaches.
10.
Will I be paid for being in this study?
In return for your time and the inconvenience of participating in this study, you will be compensated for the 
study visits you complete. You may be compensated in cash, by check, or ClinCard) 
Visit
Compensation 
Amount
Screening Visit
$70*
Baseline Visit
$70
1 Day
$40
Week 1
$60
Week 2
$60
Week 4
$70
Week 6
$70
Week 7
$40
*If you choose a remote screening visit, you will be compensated $50 for the remote visit and $20 for the in-
person visit. 
In the case of a clinical re-screen, participants will be compensated $25-$40 depending on the length of the 
re-screen.
If you complete all study visits, you will be compensated a total of $480. You may also be provided with a gift card or 
$12 cash compensation for the purchase of a meal for visits that are 5 hours or longer. You may receive partial 
compensation for portions of study visits completed as applicable. You may also receive a $15 compensation for 
time/effort spent as a “standby” for a potential screening visit; you will only receive the $15 compensation once the 
clinical screen visit is completed as part of the study.


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11.
Will I have to pay for anything?
You will not be billed for the cost of tests and procedures directly associated with this study.
You and/or your health insurance may be billed for the costs of medical care during this study if these expenses 
would have happened even if you were not in the study, or if your insurance agrees in advance to pay. If you 
have health insurance, the cost of these services will be billed to your insurance company. If your insurance 
does not cover these costs or you do not have insurance, these costs will be your responsibility.
12.
What happens if I am injured from being in the study?
We will offer you the care needed to treat injuries directly resulting from taking part in this research. We may 
bill your insurance company or other third parties, if appropriate, for the costs of the care you get for the injury, 
but you may also be responsible for some of them.
For medical emergencies contact 911. If you think you have been injured as a result of taking part in this 
research study, tell the principal investigator as soon as possible. The principal investigator’s name and phone 
number are listed at the top of page 1 of this consent form.
There are no plans for the NYU School of Medicine or Medical Center to pay you or give you other 
compensation for the injury. You do not give up your legal rights by signing this form.
13.
When is the study over? Can I leave the Study before it ends?
If you decide to participate, you are free to leave the study at any time. Leaving the study will not interfere with 
your future care, payment for your health care or your eligibility for health care benefits.
You will be informed of any significant new findings that become available during the course of the study, such 
as changes in the risks or benefits resulting from participating in the research or new alternatives to 
participation that might change your mind about participating.
The investigator reserves the right to withdraw you from this study without your consent if it is deemed 
necessary.
This study is expected to end after all participants have completed all visits, and all information has been 
collected. This study may also be stopped or your participation ended at any time by your physician, the study 
sponsor, or the Food and Drug Administration (FDA) without your consent because:

The principal investigator feels it is necessary for your health or safety. Such an action would not 
require your consent, but you will be informed if such a decision is made and the reason for this decision

You have not followed study instructions

The study sponsor, the principal investigator, the Food and Drug Administration (FDA) or other body 
responsible for monitoring the safety of the study has decided to stop the study
14.
How will you protect my confidentiality?
Your medical information is protected health information, or “PHI”, and is protected by federal and state laws, 
such as the Health Insurance Portability and Accountability Act, or HIPAA. This includes information in your 
research record as well as information in your medical record at NYU Langone Health. In compliance with 
NYU Langone Health policies and procedures and with HIPAA, only those individuals with a job purpose can 
access this information.
Medical information created by this research study may become part of your medical record. We may include 
your research information in your medical record for several reasons, including for the billing of services 
provided in connection with the study, to securely document any medical services you receive, and so that 
other members of the NYU Langone Health community who may treat you have access to important 
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You have a right to access information in your medical record. In some cases, when necessary to protect the 
integrity of the research, you will not be allowed to see or copy certain information relating to the study while 
the study is in progress, but you will have the right to see and copy the information once the study is over in 
accordance with NYU Langone Health policies and applicable law.
Certificate of Confidentiality
To help us further protect your confidentiality, this research is covered by a Certificate of Confidentiality from 
the National Institutes of Health (NIH). The NIH has issued a Certificate of Confidentiality for this research. 
This adds special protection for the research information (data, documents, or biospecimens) that may identify 
you.
Research information protected by this Certificate of Confidentiality cannot be disclosed to anyone else who is 
not connected with the research, without your consent. With this Certificate of Confidentiality, the researchers 
may not disclose or use research information that may identify you in any federal, state, or local civil, criminal, 
administrative, legislative, or other action, suit, or proceeding, or be used as evidence, for example, if there is 
a court subpoena, without your consent. However, disclosure, without your consent, is still necessary if there 
is a federal, state, or local law that requires disclosure (such as to report child abuse or communicable 
diseases).
The Certificate of Confidentiality cannot be used to refuse a request for information from appropriate 
government agencies responsible for project oversight.
The Certificate of Confidentiality does not prevent you from releasing information about yourself and your 
involvement in this research, including for your medical treatment. Federal regulations may also allow for the 
use or sharing of information for other scientific research.
By agreeing to be in this research and signing below, you are giving your consent to share research information 
with others at NYU Langone Health. This means that your research information, including lab results, and 
information about the investigational drug used in this study, may be included in your NYU Langone Health 
electronic medical record.
15. HIPAA Authorization
As noted in the Confidentiality section above, federal law requires us, and our affiliated researchers, health 
care providers, and physician network to protect the privacy of information that identifies you and relates to 
your past, present, and future physical and mental health conditions. We are asking for your permission 
(authorization) to use and share your health information with others in connection with this study- in other 
words, for purposes of this research, including conducting and overseeing the study.
Your treatment outside of this study, payment for your health care, and your health care benefits will not be 
affected even if you do not authorize the use and disclosure of your information for this study.
What information may be used or shared with others in connection with this study?
All information in your research record for this study may be used and shared with those individuals listed in 
this section. Additionally, information in your medical record that the research team believes may be important 
to the study may be accessed by those listed here. This includes, for example, results from your physical 
examinations, laboratory tests, procedures, questionnaires, and diaries.
Who may use and share information in connection with this study?
The following individuals may use, share, or receive your information for this research study:

The research team, including the Principal Investigator, study coordinators, and personnel responsible 
for the support or oversight of the study

The study sponsor: The National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Governmental agencies responsible for research oversight (e.g., the Food and Drug Administration or 
FDA)

Health care providers who provide services to you in connection with this study, and laboratories or 


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other individuals who analyze your health information in connection with this study

The Data & Safety Monitoring Board

The data team: DataCore at NYULMC to manage and maintain integrity of study data
Your information may be re-disclosed or used for other purposes if the person who receives your information 
is not required by law to protect the privacy of the information.
What if I do not want to give permission to use and share my information for this study?
Signing this form is voluntary. You do not have to give us permission to use and share your information, but if 
you do not, you will not be able to participate in this study.
Can I change my mind and withdraw permission to use or share my information?
Yes, you may withdraw or take back your permission to use and share your health information at any time for 
this research study. If you withdraw your permission, we will not be able to take back information that has 
already been used or shared with others. To withdraw your permission, send a written notice to the principal 
investigator for the study noted at the top of page 1 of this form. If you withdraw your permission, you will not 
be able to stay in this study.
How long may my information be used or shared?
Your permission to use or share your personal health information for this study will never expire unless you 
withdraw it.
16. 21 CENTURY CURES ACT
What is an Electronic Medical Record? 
An Electronic Medical Record (EMR) is an electronic version of your medical chart within NYU Langone Health. 
An EMR is simply a computer version of a paper medical record. 
If you are or have been a patient at NYU Langone Health in the past, you have an EMR at NYU Langone Health. 
Information from your research participation will be added to this EMR. 
If you have never been a patient at NYU Langone Health, you may not have an EMR at NYU Langone Health. 
In connection with your participation in this study, an EMR will be created for you. The purpose of your EMR at 
NYU Langone Health will be to facilitate this research study and allow the researchers to maintain information 
arising from your participation in this research study. The creation of this EMR is a requirement of your 
participation in this study. In order to create your EMR, the study team will need to obtain basic information 
about you that would be similar to the information you would provide the first time you visit a hospital or medical 
facility, for example, your name, the name of your primary doctor, the type of insurance you have, your date of 
birth and other health-related information. 
What may be placed in the EMR? 
Information related to your participation in the research (e.g., laboratory tests, research-related notes, imaging 
studies, and clinical procedures, etc.) will be placed in your EMR maintained by NYU Langone Health.
This information will be accessible to other members of the NYU Langone workforce that are not part of the 
research team. Information within your EMR may also be shared with others who NYU Langone Health has 
determined may appropriately have access to your EMR (e.g., Health Insurance Company, disability provider, 
etc.). 
Will I have access to research-related information within the Electronic Medical Record? 
In this study, research-related information in your EMR will not be available to you until the end of the study. 
This information will not be accessible in your EMR immediately in order to protect the integrity of the research 
trial results. The researchers will provide you access to this research-related information in your EMR when 
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
Results in the medical record that will not be immediately accessible: hepatic function panel test 
results, liver function test (LFT) results, complete blood count (CBC) with differential test results, basic 
metabolic panel test results, urinalysis test results, serum pregnancy test results (if female), and 
carbohydrate deficient transferrin (CDT) test results
Test results and other study information (e.g., progress notes and research notes) will be withheld until the 
end of the study unless the research clinicians determine that the results require follow-up with your medical 
provider. 
Additionally, some research-related information will never be made available to you in your EMR. This 
information will not be accessible in your EMR because the information is specific to this research and is not 
part of your medical history and clinical care. 
 

Results that will not be placed in the medical record: pharmacokinetic blood test results 
(concentrations of CBD, THC, and anandamide)
17.
Optional Parts of Research
1.
Option to Store, Use, and Share Health Information for Future Research 
NYULMC would also like to store, use, and share your health information from this study in research 
databases or registries for future research conducted by NYULMC or its research partners. To give this 
additional permission, check the box below and write your initials where indicated. You may still participate 
in this study even if you do not give us this additional permission.
NYULMC will continue to protect the confidentiality and privacy of this information as required by law and our 
institutional polices. If you give this additional permission, you will continue to have the rights described in 
this form. You have the right to take back this additional permission at any time.
I agree to allow the study team to store, use, and share my health information from this study 
in research databases or registries for future research conducted by NYULMC or its research 
partners.
I DO NOT allow/s the study team to store, use, or share my health information from this 
study in research databases or registries for future research conducted by NYULMC or its 
research partners.
Signature of participant
 Date
2.
Option to Use the Emocha App
To ensure medication adherence during your participation in this study, we ask that you use the emocha app 
on a smartphone or smart device. If you do not agree to this then medication adherence will be comprised 
of an interview with the nurse practitioner/physician who will also count the pills returned at each study visit.


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I agree to use emocha for the duration of this study, and have adequate device access and 
internet access to use it.
I do not agree to use emocha for the duration of this study for the following reason(s):
□
I do not have adequate device access 
□
I do not have adequate internet access to use it.
□
Other 
_____________________________________________________
______________
Signature of participant
Date
3.
Option to Link Study Information to Other NYULMC Psychiatry Department Studies
If you participate in another research study with the NYULMC Psychiatry Department, such as the 
cannabidiol as a treatment for alcohol use disorder study (#s17-01001), the investigators are interested in 
accessing the information obtained from you and linking it to the information collected from this study for 
further analyses. All confidentiality and safety procedures will still apply. Your signature below indicates your 
permission to access and link data collected.
I agree to allow the study team to link information collected as part of this study with
information collected in other NYULMC Psychiatry department research studies.
I do not allow the study team to link information collected as part of this study with 
information collected in other NYULMC Psychiatry department research studies.
Signature of participant
Date
4.
Option to Receive Reimbursement via ClinCard
A new reimbursement program was introduced by the NYU Finance Department in 2016 called 
Greenphire. Greenphire uses reloadable debit cards, called “ClinCards” for reimbursement. 
Study staff will add funds to the ClinCards for compensation and travel reimbursement through 
a secure web-based portal. Access to the portal is granted to NYULMC designated staff by the 
vendor or NYU administrator. 
ClinCards can be used to withdraw cash from a bank or ATM, as a PIN-based transaction, or as 
a credit card. No bank account is required. The system is in compliance with the HIPAA Act and 
stores your information securely using appropriate administrative, physical, and technical 
safeguards. 
If a ClinCard is lost or damaged, we can de-activate the lost/damaged card and issue you a new 
card. You and designated NYU staff will be able to check your balance online at any time. We 
will not have access to information regarding where or how the card is issued. 


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I agree to receive study reimbursement through the NYU ClinCard system.
I do not want to receive study reimbursement through the NYU ClinCard system. I prefer to 
receive reimbursement by cash or check. 
Signature of participant
    Date
5.
Option to be contacted about future research
We would like your permission to contact you in the future to tell you about new research 
opportunities. If you are contacted, you can decide whether or not you are interested in participating 
in the particular study. You will then have the opportunity to contact the researcher to schedule an 
appointment to be fully informed about the research project.
I agree to allow the study team to contact me in the future about new research opportunities 
at NYU’s Department of Psychiatry.
I DO NOT allow the study team to contact me in the future about new research 
opportunities at NYU’s Department of Psychiatry.
Signature of participant
    Date
18.
The Institutional Review Board (IRB) and how it protects you
The IRB reviews all human research studies – including this study. The IRB follows Federal Government rules 
and guidelines designed to protect the rights and welfare of the people taking part in the research studies. The 
IRB also reviews research to make sure the risks for all studies are as small as possible. The NYU IRB Office 
number is (212) 263-4110. The NYU School of Medicine’s IRB is made up of doctors, nurses, non-scientists, 
and people from the community.
19.
Who can I call with questions, or if I’m concerned about my rights as a 
research subject?
If you have questions, concerns or complaints regarding your participation in this research study or if you have 
any questions about your rights as a research subject, you should speak with the Principal Investigator listed 
on top of the page 1 of this consent form. If a member of the research team cannot be reached or you want 
to talk to someone other than those working on the study, you may contact the Institutional Review Board 
(IRB) at (212) 263-4110.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. 
This Web site will not include information that can identify you. At most, the Web site will include a summary 
of the results. You can search this website site at any time.


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When you sign this form, you are agreeing to take part in this research study as described to you. 
This means that you have read the consent form, your questions have been answered, and you have 
decided to volunteer.
Name of Subject (Print)
Signature of Subject
Date
Name of Person Obtaining Consent (Print)
Signature of Person Obtaining Consent
Date