Clinical trial NCT05132699
Conditions: Posttraumatic Stress Disorder Stress Disorders, Post-Traumatic
Sponsor: The University of Texas Health Science Center at San Antonio
Start date: 2022-04-04; Completion date: 2023-06-30
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary goal of this pilot project is to demonstrate the safety and feasibility of using Cannabidiol (CBD) in combination with standard of care prolonged exposure (PE) psychotherapy to reduce PTSD symptoms.

Detailed description:
This study is an early Phase II double-blind, pilot randomized controlled clinical trial. The study team will use a permuted block randomization design stratified by a Posttraumatic Stress Disorder (PTSD) severity median score on the PTSD Checklist (PCL-5) derived from a recently completed STRONG STAR repository. Participants will be up to 24 individuals with PTSD to investigate the safety, feasibility, and PTSD symptom change associated with CBD 250mg taken twice a day for 18 days (n=up to 12) vs. placebo (n=up to12) in combination with a standard of care, 10-sessions massed PE psychotherapy administered over 2 weeks. Aims 2 and 3 will evaluate biochemical and physiological outcomes associated with the brain endocannabinoid (eCB) and PTSD that may be affected by CBD. Permuted block randomization is advantageous in small clinical trials to ensure equal allocation of participants in each condition. Participant randomization will be subdivided into randomized blocks of four, two patients in each block will be assigned to CBD and two will be assigned to placebo.

Arms: arm 1: Epidiolex oral solution 500mg (5ml) per day arm 2: Placebo oral solution 5ml per day
Interventions: intervention 1: Cannabidiol (CBD) oral solution intervention 2: Placebo intervention 3: Massed Prolonged Exposure (mPE)
Intervention descriptions: intervention 1: An oral strawberry flavored liquid, taken as a 2.5ml (250mg) dose twice a day intervention 2: An inert strawberry flavored oral solution, taken as a 2.5ml dose twice a day intervention 3: mPE, delivered daily Monday through Friday over two weeks, utilizes exposure-based interventions to target psychological mechanisms (i.e., experiential and behavioral avoidance; maladaptive cognitive changes) that are thought to maintain trauma-related symptoms.

Protocol documents:
Prot_SAP_001.pdf: 
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COVER PAGE  
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Official Study Title: Enhancing Prolonged Exposure with Cannabidiol to 
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Treat PTSD 
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NCT number: NCT05132699 
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IRB Approval Date: 11-15-2022 
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Unique Protocol ID: HSC20210711H 
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HUMAN SUBJECTS RESEARCH PROTOCOL 


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1.  PROTOCOL TITLE:  Enhancing Prolonged Exposure with Cannabidiol to Treat PTSD 
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2.  ABSTRACT   
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Posttraumatic stress disorder (PTSD) is considered a signature psychiatric disorder among military populations. When left 
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untreated, the symptoms of PTSD can cause significant health and functional impairments. While established treatments 
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for PTSD exist, there remains room for improvement in outcomes since almost half of military patients fail to benefit from 
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treatment. Epidiolex (Cannabidiol [CBD]) is an FDA-approved, non-controlled prescription medication with promising 
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potential for the treatment of PTSD.1,2 To date, there are no published clinical trials investigating CBD in reducing PTSD, 
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and existing literature in humans with PTSD only includes healthy individuals or case study data. Greater research is 
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needed to fully understand the benefits of CBD for PTSD and to better understand biological mechanisms for its effect. 
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The primary goal of this pilot project is to demonstrate the safety and feasibility of using CBD in combination with standard 
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of care prolonged exposure (PE) psychotherapy to reduce PTSD symptoms (Aim 1). We will also assess possible 
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biochemical and physiological outcomes associated with treatment (Aim 2) and evaluate the relationship between 
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changes in biochemical/physiological measures with PTSD symptom reductions (Aim 3). To address study aims, we will 
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enroll 24 individuals with PTSD to be randomized to CBD (n=12) or placebo (n=12) and all participants will receive 10 
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daily sessions of PE. 
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3.  OBJECTIVES/SPECIFIC AIMS/RESEARCH QUESTIONS 
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This project will be a pilot, double-blind randomized controlled trial of CBD effects to pursue three goals: (1) to 
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demonstrate the safety and feasibility of using CBD to reduce PTSD symptoms in conjunction with massed PE (mPE); (2) 
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to assess biochemical and physiological outcomes associated with PTSD treatment; and (3) to evaluate the possible 
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relationship between changes in biochemical/physiological measures with PTSD symptom reductions. 
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Aim 1: To examine the safety, feasibility, and PTSD symptom reductions associated with CBD (n=12) vs. placebo (n=12) 
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in 24 individuals receiving 10 daily sessions of mPE as a standard of care for PTSD. 
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Hypothesis 1: Combining CBD with mPE will be safe based on minimal (< 5%) adverse events and no serious adverse 
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events related to treatment in the study. 
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Hypothesis 2: A CBD vs. placebo trial design will be feasible defined as 75% or more of assessed individuals meeting 
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all eligibility criteria and 80% or more of CBD participants completing all 10 mPE sessions. 
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Hypothesis 3: Participants in the CBD condition will have greater treatment-related PTSD reductions than placebo as 
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measured by the Clinician Administered PTSD Scale (CAPS-5)3 and PTSD Checklist (PCL-5).4 
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Aim 2: To evaluate biochemical and physiological levels associated with the eCB system and stress response in CBD vs. 
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placebo. 
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Hypothesis 4: Participants in the CBD condition will have higher levels of AEA and 2-AG, and lower levels of cortisol 
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than placebo following treatment. 
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Hypothesis 5: Participants in the CBD condition will have lower average heart rate during exposure therapy sessions 
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than placebo. 
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Aim 3: To determine the association between changes in biomarker levels (cortisol, AEA, 2-AG), physiology (heart rate), 
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and PTSD symptom reduction following treatment. 
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Hypothesis 6: Reductions in cortisol and increases in AEA and 2-AG will be associated with PTSD symptom reductions 
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following treatment. 
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Hypothesis 7: Lower average heart rate observed during exposure therapy sessions will be associated with PTSD 
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symptom reductions following treatment. 
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4.  MILITARY RELEVANCE 
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As compared to civilians, the rate of PTSD is particularly elevated among military populations, with approximately 23% of 
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military vs. 6-8% of civilians meeting criteria for PTSD.5 PTSD has been identified as the signature deployment-related 
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psychiatric condition among service members. The functional impact of PTSD can cost service members their military 
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careers and veterans with PTSD are at increased risk of unemployment and homelessness following military separation.6 
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Notwithstanding evidence that PE is an effective treatment for PTSD, there remains room for improvement in outcomes 
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given that a large proportion of patients (~50%) fail to significantly benefit from treatment.7 This issue is especially 
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problematic among military populations who generally demonstrate poorer treatment gains from first-line psychotherapies 
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for PTSD including PE.8,9 Given that almost three million U.S. military service members have deployed to Afghanistan, 
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Iraq, and surrounding locations in support of military combat operations since September 11, 2001, the need for effective 
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treatment for PTSD is critical.  Research dedicated to target mechanisms associated with PTSD symptomatology has the 
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potential to promote greater PTSD treatment efficacy that will lead to greater symptom reductions, positive well-being, and 
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improved functioning in civilians and military veterans. 
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5. BACKGROUND AND SIGNIFICANCE 
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PTSD Prevalence and Impact. PTSD is a chronic and debilitating condition triggered by exposure to a traumatic event. 
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Symptoms of PTSD can include anxiety, negative mood, sleep disruption, nightmares, and negative, uncontrollable 
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thoughts about the event. When left untreated, it can lead to detriments in mental health and psychosocial functioning.10,11 
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The overall impact of PTSD is substantial and often leads to significant burdens on the individual, their family, and the 
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community.12 The sequalae of PTSD not only impacts an individual’s immediate environment but also places significant 
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burden on society due to increased work sick days and greater healthcare utilization.6,11 The rate of PTSD is particularly 
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elevated among military populations, with approximately 23% of military meeting criteria for PTSD annually.5 PTSD has 
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been identified as the signature deployment-related psychiatric condition among service members. The functional impact 
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of PTSD can cost service members their military careers and veterans with PTSD are at increased risk of unemployment 
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and homelessness following military separation. Given that almost three million U.S. military service members have 
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deployed to Afghanistan, Iraq, and surrounding locations in support of military combat operations since September 11, 
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2001, the need for effective treatment for PTSD is critical. 
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Behavioral Therapy Approaches to PTSD Treatment. Evidence-based treatments for PTSD exist and are well-
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established.13 PE is a type of Cognitive Behavioral Therapy (CBT) and one of the most widely used first-line interventions 
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for PTSD. PE has been validated across various populations and trauma types.e.g.,14–16 Preliminary evidence suggests that 
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PE can even be effectively delivered in deployed settings, potentially helping service members return to duty without 
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being aeromedically evacuated out of theater.17 PE aims to reduce trauma-related distress and PTSD symptomatology 
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through extinction learning interventions (i.e., repeated exposure) to internal (e.g., trauma memory) and external (e.g., 
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environmental stimuli) trauma cues under objectively safe conditions. Notwithstanding evidence that PE is an effective 
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treatment for PTSD, there remains room for improvement in outcomes given that a large proportion of patients (~50%) fail 
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to significantly benefit from treatment.7 This issue is especially problematic among military populations who generally 
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demonstrate poorer treatment gains from first-line psychotherapies for PTSD including PE.9 Based on the rising number of 
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service members returning from combat deployments to Afghanistan, Iraq, and surrounding areas, there is a high priority 
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need for the most effective treatments for PTSD. Research dedicated to target mechanisms associated with PTSD 
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symptomatology has the potential to promote greater PTSD treatment efficacy that will lead to greater symptom 
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reductions, positive well-being, and improved functioning in civilians and military veterans. 
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Medication Approaches to PTSD Treatment. Despite the benefits of first-line CBT interventions for PTSD treatment, 
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pharmacotherapy remains the most commonly used approach to treat PTSD in civilians and military veterans.18 The only 
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pharmacological interventions for PTSD approved by the Food and Drug Administration (FDA) are the selective serotonin 
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reuptake inhibitors (SSRIs) fluoxetine and sertraline. Although approved by the FDA for PTSD treatment, these drugs 
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have relatively modest benefits to reduce PTSD and often fail to help patients reach PTSD remission.19,20 Based upon 
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expert panel psychological trauma recommendation guidelines21, no medication treatments have been determined to be a 
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first-line option for treatment of PTSD. Unfortunately, this state of pharmacotherapy for PTSD has prompted many 
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providers to use polypharmacy in which patients are prescribed a combination of medications with little to no empirical 
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guidance on either the benefits or adverse reactions.22 
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Endocannabinoid System and PTSD. One potential reason for the low efficacy of SSRIs and the use of 
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polypharmacotherapy is that these medications do not directly target PTSD symptomatology. A rapidly growing body of 
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evidence has highlighted the endocannabinoid (eCB) system as a critical regulator of the stress response.23 Further, it has 
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been suggested that psychological trauma can lead to long-term alterations in the eCB system.24 The eCB system is a 
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neuromodulatory system comprised of two primary receptors (CB1 and CB2), two main neurotransmitters (anandamide 
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[AEA] and 2-arachidonylglycerol [2-AG]), and several enzymes that synthesize and degrade these neurotransmitters.25 
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Most research has focused on CB1 receptors, which are primarily located in the central nervous system and have the 
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highest densities in brain regions associated with anxiety and fear learning (e.g., cortex, amygdala, and hippocampus). 
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Preclinical animal models have shown that CB1 antagonists increase anxiety, while agonists produce anxiolytic effects.26 
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AEA and 2-AG are the two primary endogenous eCBs that act as agonists at CB1 receptors.27,28 These eCBs are critical 
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nerve signaling chemicals shown to regulate mood, memory, perception, and sleep.29. Overall, novel pharmacological 
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approaches targeting the eCB system have promising potential to improve anxiety, mood, and sleep problems, while 
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facilitating extinction learning, all of which characterize PTSD symptoms and seem particularly important to compliment 
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first-line psychotherapy interventions. 
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Cannabidiol for Augmentation of PE Treatment for PTSD. Based on growing evidence on the synergistic relationship 
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between the eCB system and PTSD, increasing efforts have been devoted to pharmacotherapy options. The recently 
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FDA-approved prescription medication, Epidiolex (Cannabidiol [CBD]) is a cannabis-derived, non-controlled drug that may 
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be beneficial for PTSD. Existing research has shown that CBD may facilitate extinction learning, decrease anxiety, and 
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improve mood and sleep, all of which might enhance the effectiveness of mPE for PTSD.30,31 Furthermore, CBD is well 
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tolerated, even in large doses, and has not been shown to produce adverse side effects associated with other cannabis-
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derived medications (e.g., dependence, withdrawal, psychoactive effects, increased anxiety, memory and concentration 
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difficulties, slowed reaction time, coordination problems, and elevated heart rate). Thus, CBD may be able to maximize 
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the positive benefits associated with the eCB system, while mitigating adverse events that occur with other cannabis-
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derived drugs. 
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Most of the existing literature indicating the benefits of CBD for PTSD treatment has involved preclinical animal studies, 
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case studies, and a few proof-of-concept trials with healthy humans. Preclinical animal models have used a fear-based 
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conditioning paradigme.g.,32 designed to parallel the impact of trauma in humans with PTSD to investigate the effects of 
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CBD. Animal models have shown that CBD can reduce cardiovascular and anxiogenic effects of stress.30,31 CBD has 
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been found to decrease retrieval and acquisition of fear memories33,34 and even block reconsolidation of the trauma 
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memory in animal models.30 The most promising outcome of preclinical PTSD research is evidence that CBD can facilitate 
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and enhance the extinction learning process, a key component of exposure-based psychotherapies for PTSD.35,36 
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Consistent with preclinical animal research, Das et al.37 found that CBD facilitated extinction learning and decreased cue-
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based fear response in a sample of healthy humans. 
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Only a few studies have been completed in humans. A case report found that daily use of CBD was associated with 
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reduced anxiety and improved sleep in a child with treatment resistant PTSD despite the fact that standard 
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pharmacotherapy for PTSD had produced only limited and acute symptom relief.38 In a retrospective case series analysis 
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of adults (N=11) with PTSD, participants received oral CBD in combination with routine psychiatric and psychotherapy 
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care over 8 weeks.2 Results suggested that CBD was associated with a 28% decrease in PTSD symptom and was well 
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tolerated (with no discontinuation due to side effects) among participants. Though these findings suggest that CBD may 
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be used for the treatment of PTSD, there is a paucity of research on the safety, feasibility, and efficacy of CBD as a 
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treatment for PTSD in human trials. 
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Furthermore, although preliminary evidence suggests CBD may benefit PTSD symptom reduction, the specific 
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mechanisms of action of CBD on the eCB remains unclear. One possible mechanism may include modulation of the eCB 
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system since research has shown that CBD may have low affinity for CB receptors, but nonetheless is able to bind to 
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CB1.39 CBD may also act as an antagonist to other agonists due to effects at different prejunctional sites and indirect 
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interactions with non-cannabinoid receptors.40 In turn, this may explain possible effects on eCB metabolism including 
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inhibition of the uptake and degradation of critical eCBs associated with stress response including AEA and 2-AG. 
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Innovation. Additional research is warranted to fully understand the benefits of CBD for PTSD. Currently, there are no 
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published clinical trials investigating the efficacy of CBD in reducing PTSD and existing PTSD literature in humans only 
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includes healthy individuals or case study data. Research on cannabinoids and PTSD remains in the early stages of 
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development and more research is needed to understand how CBD modulates the eCB system. Based on existing 
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research, the next logical step is to investigate CBD as an augmentation treatment for an established psychotherapy that 
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targets extinction learning mechanisms for PTSD symptom reduction. This proposal will examine CBD as an adjunct for 
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mPE and explore potential biological mechanisms for its effect, making it the first study of its kind. Findings from this study 
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have the potential to improve outcomes among military and civilians with PTSD and mitigate the personal, social, and 
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economic costs of this debilitating, chronic condition. This study will also expand understanding of the relationship 
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between PTSD, CBD, and the eCB system. 
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6.  RESEARCH DESIGN 
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This study is an early Phase II double-blind, pilot randomized controlled clinical trial. We will use a permuted block 
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randomization design stratified by PTSD severity median score of 51 on the PCL-5 and population type (military or 
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civilian). The median score stratification was derived from a recently completed STRONG STAR randomized clinical trial 
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of military veterans seeking treatment for PTSD (manuscript in press). The decision to stratify by population was based on 
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existing literature that has found differences in treatment response between military and civilian samples (e.g., Steenkamp 
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et al., 2015; Straud et al., 2019). Participants will be 24 individuals with PTSD to investigate the safety, feasibility, and 
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PTSD symptom change associated with CBD 250mg taken twice a day for 18days (n=12) vs. placebo (n=12) in 
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combination with a standard of care, 10-sessions mPE psychotherapy administered over 2 weeks. Aims 2 and 3 will 
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evaluate biochemical and physiological outcomes associated with eCB and PTSD that may be affected by CBD. 
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Permuted block randomization is advantageous in small clinical trials to ensure equal allocation of participants in each 
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condition. Participant randomization will be subdivided into randomized blocks of four, two patients in each block will be 
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assigned to CBD and two will be assigned to placebo. Randomization will occur after the participant consents to the study 
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and eligibility is determined. John Roache, PhD (Co-Mentor on this KL2) will determine randomization codes and 
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coordinate with the compounding pharmacy (Oakdell Pharmacy) providing the medication and placebo for this trial to 
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ensure blocking procedures are appropriately carried out. All other study team members will be blinded to randomization. 
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The study assessments and the timing for repeated assessments conducted are described in detail in section 7.3. 
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7.  RESEARCH PLAN 
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7.1 Selection of Subjects 
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Number of subjects to be screened for eligibility: 40 
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Target number randomized: 28 
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Target enrollment number for completers: 24 
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7.1.1. Subject Population.  
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Individuals between 18-65 years old recruited from the San Antonio community will be invited to participate in this research. 
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Efforts will be tailored to equally recruit diverse individuals across sex, gender/sexual orientation, race, age, disability, 
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socioeconomic status, national origin, and branch of military service. 
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7.1.2. Inclusion and Exclusion Criteria.  
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Inclusion Criteria 
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1. Individuals between the age of 18 to 65 years old at time of screening. 
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2. Able to write, read, and speak English  
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3. PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5) 
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4. Stable medication regimen for at least four weeks prior to the onset of study participation. 
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Exclusion Criteria 
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1. History of opiate, cocaine, methamphetamine, benzodiazepine, or cannabis abuse as determined by the National 
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Institute of Drug Abuse Quick Screen (NIDA-Q). 
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2. Currently using opiates, cocaine, methamphetamines, benzodiazepines, or cannabis as evidenced by a positive 
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urine drug screen prior to enrollment. 
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3. Currently pregnant as determined by a positive urine pregnancy test prior to enrollment. 
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4. Current clinically significant alcohol abuse in the past two weeks on the Quick Drinking Screen (QDS). 
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5. Currently breastfeeding. 
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6. Ongoing illness or physical health problem(s) that may be exacerbated by CBD (e.g., history of liver problems) 
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7. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to 
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cannabinoids. 
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8. Regular use of the following concomitant medications because of the possible interaction with CBD  
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The anti-convulsant/anti-epileptics Carbamazepine and Phenytoin 
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The atypical antipsychotics Olanzapine, Quetiapine, and Risperidone 
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The entire class of barbiturates (Sedative-Hypnotics) 
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Chronic, daily use of any class of benzodiazepines.  Intermittent or as needed dose of a benzodiazepine will 
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be allowed. 
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The miscellaneous hypnotics Zaleplon, Zolpidem, Eszopiclone, Ramelteon, and Suvorexant 
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The herbal supplement St. John's Wort. 
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The entire class of glucocorticoids 
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Use of platelet inhibitors Clopidogrel and Warfarin unless the participant is on a stable dose. 
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The antiretrovirals Ritonavir and Indinavir  
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The antifungals Itraconazole and Ketoconazole (topical not exclusionary) 
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The antibiotics Clarithromycin, Erythromycin, and Rifampin  
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Chronic, daily use of opioids. 
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Patients taking the antidepressants Trazodone and Mirtazapine can be enrolled with additional monitoring as 
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outlined below under Section 8.0 Risk Benefit. 
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9. Alanine transaminase (ALT) or Aspartate transaminase (AST) enzyme levels 3x normal limits. 
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10. Concurrent engagement in trauma-related psychotherapy for PTSD. 
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11. Current or past DSM-5 diagnosis of psychotic disorder or bipolar disorder requiring immediate stabilization or 
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hospialization (as determined by clinical judgement) 
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12. Suicide attempt in the last year and/or suicide risk requiring immediate intervention or requiring a higher level of 
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care than can be provided by the study treatment (as determined by the SIT-BI). 
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13. Allergy to sesame seed oil 
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7.1.3. Description of the Recruitment and Prescreening Process.  
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Potential participants will be between 18-65 years old recruited from recruitment events, flyers and provider referrals from 
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the community,   Providers can give their patients contact information for the study staff so that interested individuals may 
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contact STRONG STAR directly. Alternatively, providers can obtain consent to contact from their patients that allows the 
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study staff to contact the potential participant directly.  Individuals who are not eligible or interested in other IRB-approved 
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STRONG STAR protocols will be told about this study. Study information will be posted on the STRONG STAR website 
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and social media to gain self-referrals for treatment-seeking patients. Under an IRB approved HIPAA Waiver of 
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Authorization, study personnel will initially conduct a brief telephone interview where the basic study inclusion/exclusion 
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criteria will be reviewed to help determine if the individual likely meets study criteria. This will mitigate unnecessary travel 
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and more in-depth screening. Participants who appear eligible after telephone pre-screening will be invited into the 
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STRONG STAR clinic to provide written informed consent and undergo more rigorous assessment for study eligibility. 
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7.1.4. Consent Process. 
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During the consent appointment, potential participants will have the study explained to them in a private location in-person 
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at the UT Health San Antonio (UTHSA) STRONG STAR offices located at 7550 IH10 West, Suite 1325, San Antonio, TX 
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78229. The potential participant will be given a copy of the informed consent document (ICD) to read. After the potential 
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participant has read the ICD, and a member of the study team has reviewed the risks and benefits of the study to ensure 
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the participant understands the research, the participant will be given the opportunity to discuss the research with family 
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and friends. The research team will be available to answer any questions about the research. Once the potential 
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participant has reached a decision, the participant will sign the consent form. A copy of the signed ICD will be given to the 
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participant. 
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7.1.5. Subject Screening Procedures  
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Following consent, screening assessment will take place to determine participant eligibility. The entire screening process 
will take approximately 4 hours. This will include the completion of the questionnaires, interviews, and screening tests 
outlined in the Table of Assessments below (see section 7.3). The baseline assessment may occur in-person using paper 
forms, or the participant will be logged into the STRONG STAR eCAP online data capture system to complete self-report 
questionnaires. For individuals not meeting study inclusion criteria, the study staff will assist coordinating appropriate care 
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If the participant has been referred from another STRONG STAR study and already undergone baseline testing within the 
past 30 days, the participant will be asked as part of the consent process to use these assessments rather than repeating 
the assessment battery.  If the participant is newly referred to this study, if it has been more than 30 days since baseline 
testing for another study, or the participant declines use of previously completed assessments, he or she will meet with an 
evaluator and complete the full baseline assessment per protocol. 
 
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7.1.6. Source of Research Material.  
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All measures will be administered for research purposes. For a complete list of measures see Section 7.3. 
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Source of Research Material 
 
Conducted for Clinical 
Purposes(Y/N) 
Conducted for Research 
Purposes (Y/N) 
 
Clinician Rating Scales 
No 
Yes 
 
Self-Report Questionnaires 
No 
Yes 
 
Biological Samples 
No  
Yes 
 
Heart Rate Monitoring 
No 
Yes 
 
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7.1.7. Compensation for participation 
Participants will be paid for each blood draw as follows for a total of up to $100: 
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$10 pre-treatment medication appointment 
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$20 Interim Assessment 1 
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$30 Interim Assessment 2 
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$40 Interim Assessment 3 
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Payment will be provided via a rechargeable MasterCard® ClinCard. The MasterCard® ClinCard is a debit card issued to 
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the study participant. Funds are loaded onto card through the ClinCard website at www.clincard.com.  Only authorized 
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users will be able to access the ClinCard website to add funds with a username and password. The ClinCard funds will be 
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available to recipients within 1 business day and can be used as the participant chooses. The participant will be notified 
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that their name, address, and date of birth will be shared with a third-party (ClinCard) solely for the purposes of payment 
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processing. This information will only be used for the administration of the payment and will be kept strictly confidential.   
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7.2 Study Drug Overview 
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7.2.1 Epidiolex will be the active intervention used in this study. Epidiolex is an FDA approved non-controlled prescription 
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medication indicated for the treatment of seizure disorders. Prior research has demonstrated the safety and early positive 
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benefits of off-label use of Epidiolex for Anxiety and Trauma-Related symptoms in humans. 
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• 
Complete names and composition of drugs:  
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Epidiolex is a clear, colorless yellow oral solution containing cannabidiol at a concentration of 100 mg/mL. 
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Cannabidiol is the active ingredient in Epidiolex and naturally occurs in the Cannabis sativa L. plant. 
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Cannabidiol is a natural cannabinoid designated chemically as 2-[(1R,6R)-3-Methyl-6-(1-methylethenyl)-
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2cyclohexen-1-yl]-5-pentyl-1,3-benzenediol (IUPAC/CAS). Its empirical formula is C21H30O2 and its 
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molecular weight is 314.46. Inactive ingredients of Epidiolex include dehydrated alcohol, sesame seed oil, 
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strawberry flavor, and sucralose. 
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The Placebo liquid solution will be compounded by Oakdell Pharmacy using the inactive ingredients of 
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Epidiolex to match the composition and blind participants and team members to the medication. 
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Source of the product(s): Oakdell Pharmacy (7220 Louis Pasteur Dr. San Antonio, TX 78229) will obtain Epidiolex 
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from Manufacturer and prepare oral solution bottles of Epidiolex and matching placebo under the prescription 
320 
authority of physician collaborator, Van King, MD. 
321 
• 
Location where study product(s) will be stored: The medication will be received from Oakdell Pharmacy by a 
322 
trained study team member and transported to the STRONG STAR clinic where it will be stored in a locked 
323 
cabinet until the participant arrives to receive the medication at the medication review appointment. 
324 
• 
Dose range, schedule, and administration route of study product(s): 2.5 mL (250mg) taken twice daily in the 
325 
morning and evening after meals for (500mg per day) for 18 consecutive days beginning three days prior to the 
326 


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start of mPE. Epidiolex and placebo will be prepared by Oakdell Pharmacy in a strawberry-flavored liquid solution 
327 
administered using an oral syringe. 
328 
• 
Plan for disposition of unused study product(s): Any unused study products will be disposed of in accordance with 
329 
the STRONG STAR Drug Accountability and Storage SOP. 
330 
• 
FDA status: The FDA has approved the use of Epidiolex for seizure disorders. Prior research has demonstrated 
331 
the safety and early positive benefits of off-label use of Epidiolex for Anxiety and Trauma-Related symptoms in 
332 
humans. We are not seeking a new indication with this research project. 
333 
 
334 
7.3. Research Interventions/Study Procedures. 
335 
Interventions.  
336 
Participants will be randomized to either Epidiolex (CBD) or placebo. All participants will receive 10 sessions of mPE 
337 
administered weekdays over 2 weeks.  
338 
 
339 
Epidiolex (CBD) is an FDA approved, non-controlled prescription medication indicated for the treatment of seizure 
340 
disorders. Prior research has demonstrated the safety and early positive benefits of off-label use of CBD for Anxiety and 
341 
Trauma-Related symptoms in humans. CBD comes in a 100-mL bottle containing 100 mg of CBD per ml of strawberry-
342 
flavored liquid solution that is taken using an oral syringe. Strawberry-flavored liquid solution is also available for Oakdell 
343 
pharmacy to create a comparable placebo to maintain the blind. Starting recommended dose is 2.5 mL (250mg) taken 
344 
twice daily (total = 5 mL/500mg) in the morning and evening after meals.1 We will employ this dosing recommendation for 
345 
this study for 18 consecutive days. Steady state has been shown to occur in 2 days.41 To ensure maintenance on an 
346 
adequate steady state dose for all randomized participants, we will begin medication 3 days prior to the start of mPE. CBD 
347 
and matching placebo for this study will be obtained through Oakdell Pharmacy which will obtain a sufficient supply of 
348 
CBD for 12 participants from their supplying manufacturer. They will then prepare CBD (n = 12) and matching placebo (n 
349 
=12) dosage for 24 participants in blinded containers that will be numbered per the randomization design. The medication 
350 
and placebo will be dispensed to a trained study team member and transported in a locked container to the STRONG 
351 
STAR Clinic where it will be stored in a locked cabinet until the participant arrives to receive the medication at the 
352 
medication review appointment 3 days prior to beginning mPE.  
353 
 
354 
Massed Prolonged Exposure (mPE). Prolonged Exposure (PE) is a first-line, empirically supported cognitive behavioral 
355 
treatment for PTSD and serves as the foundation for mPE.16 mPE, delivered daily Monday through Friday over two 
356 
weeks, utilizes exposure-based interventions to target psychological mechanisms (i.e., experiential and behavioral 
357 
avoidance; maladaptive cognitive changes) that are thought to maintain trauma-related symptoms. Ten 90-minute 
358 
sessions of mPE, which has been found to be non-inferior to ten 90-minute spaced PE delivered once or twice a week 
359 
over eight weeks, helps minimize military-specific treatment barriers, and decreases treatment dropout rates.14 For this 
360 
study, each participant will receive ten 90-minute mPE daily over two weeks. Up to 19 days following initiation of the 
361 
medication regimen will be allowed to complete the ten sessions of mPE to accommodate scheduling constraints. 
362 
Consistent with the standard spaced PE therapy manual, mPE includes four primary treatment components: (1) 
363 
psychoeducation on common reactions to trauma; (2) relaxation training; (3) in vivo exposure; and (4) imaginal exposures. 
364 
In vivo exposure involves approaching avoided situations, people, places, and/or objects that are realistically safe.  With 
365 
imaginal exposure, participants repeatedly and systematically revisit their trauma memory and related thoughts and 
366 
feelings. Participants also will be asked to complete homework, including reviewing treatment materials, listening to 
367 
recordings of their imaginal exposure, and completing in vivo exposures. Since mPE requires considerable time and 
368 
effort, the study team will work with the participant to receive a release from work while participating in the treatment. 
369 
 
370 
Study Procedures. 
371 
 
Visit / Follow Up (F/U) Interval 
Study Procedure 
Base-
line 
Medi-
cation 
Review* 
(Day 1) 
PE 1 
PE 2 
PE 3-4 
Interi
m 
Asses
s (PE 
5) 
PE  
5-9 
Interi
m 
Asses
s (PE 
10) 
PE 10 
18 days 
following 
medicatio
n review 
1 Month 
from 
completio
n of 
treatment 
Follow-up 
Study Days 
 
1 
4 
5 
6-7 
8 
8, 11-
14 
15 
15 
18 
45 
Informed Consent 
R 
 
 
 
 
 
 
 
 
 
 
1. 
Demographics and Military Service 
Characteristics Form 
S,R 
 
 
 
 
 
 
 
 
 
 
2. 
Life Events Checklist-5 
S,R 
 
 
 
 
 
 
 
 
 
 
3. 
Deployment Risk and Resilience 
Inventory-2 
S,R 
 
 
 
 
 
 
 
 
 
 
4. 
STRONG STAR Health Questionnaire 
S,R 
 
 
 
 
 
 
 
 
 
R 


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5. 
Prior and Concomitant Medications 
Interview 
S,R 
 
 
 
 
 
 
 
 
 
 
6. 
Self-Injurious Thoughts and Behaviors 
Interview short form 
S,R 
 
 
 
 
 
 
 
 
 
R 
7. 
Depressive Symptom Index – 
Suicidality Subscale 
S,R 
 
R 
 
 
R 
 
R 
 
 
R 
8. 
Clinician-Administered PTSD Scale 
for the DSM-5(CAPS-5) 
S,R 
 
 
 
 
 
 
 
 
 
R 
9. 
PTSD Checklist for the DSM-5 (PCL-
5) 
R 
 
R 
 
 
R 
 
R 
 
 
R 
10. 
Patient Health Questionnaire-9 
S,R 
 
R 
 
 
R 
 
R 
 
 
R 
11. 
Generalized Anxiety Disorder-7 
R 
 
R 
 
 
R 
 
R 
 
 
R 
12. 
Brief Inventory of Psychosocial 
Functioning 
R 
 
 
 
 
 
 
 
 
 
R 
13. 
Veterans RAND 12 Item Short Form 
Health Survey 
R 
 
 
 
 
 
 
 
 
 
R 
14. 
Quick Drinking Screen 
S,R 
 
 
 
 
 
 
 
 
 
R 
15. 
National Institute of Drug Abuse-Quick 
Screen 
S,R 
 
 
 
 
 
 
 
 
 
R 
16. 
Insomnia Severity Index 
R 
 
 
 
 
 
 
 
 
 
R 
17. 
Posttraumatic Cognitions Inventory 
R 
 
R 
 
 
R 
 
R 
 
 
R 
18. 
Credibility and Expectancy 
Questionnaire for PE 
 
 
 
R 
 
 
 
 
 
 
 
19. 
Credibility and Expectancy 
Questionnaire for CBD 
 
 
 
R 
 
 
 
 
 
 
 
20. 
AEA, 2-AG (Blood Draw Collection) 
 
R 
R 
 
 
R 
 
R 
 
 
 
21. 
Cortisol (Saliva Collection) 
 
R 
R 
 
 
R 
 
R 
 
 
 
22. 
HR Monitoring During Exposure (PE 
3, 5, 10) 
 
 
 
 
R 
 
R 
 
R 
 
 
23. 
Adverse Event Monitoring 
 
R** 
R 
R** 
R** 
R 
R** 
R 
R** 
R** 
R 
24. 
Urine Pregnancy/Drug Screen  
S 
 
 
 
 
 
 
 
 
 
 
25. 
Liver Function Tests Labs*(LFTs) 
S 
 
 
 
 
 
 
 
 
 
 
26. 
Massed Prolonged Exposure 
 
 
 R 
R 
 R 
  
 R 
 
 R 
 
 
27. 
CBD 500mg/daily or placebo daily+ 
  
 Rstart 
 R 
R 
 R 
  
 R 
 
R 
Rend 
  
Table Notes. S=screening purposes; R= Research purposes; *Medication Review Appointment will occur three days prior to beginning Massed Prolonged Exposure. Start 
and End superscripts represent beginning and end of medication/placebo use. CBD=Cannabidiol; AEA=Anandamide; 2-AG=Arachidonoylglycerol; HR= Heart Rate; *All 
potential study candidates will be required to complete LFTs or provide a copy of recent LFT labs (completed within 90 days of  baseline) and bring their lab results prior to 
randomization.  
+CBD or placebo to be administered daily days 1-18. 
** Daily Adverse Event monitoring to occur if participant taking one of the identified medications warranting additional monitoring.  See Section 
 
372 
7.3.1 Collection and Storage of Human Biological Specimens.  
373 
Urine drug and pregnancy screen tests will be conducted at baseline for screening eligibility purposes.  
374 
 
375 
Blood will be collected at four time points for a study total of about 28mLs. Approximately, 7mL of blood will be collected 
376 
by venous puncture using a 7 mL EDTA blood collection tube immediately prior to the pretreatment medication review, 
377 
and at interim assessments 1 (prior to PE session 1), 2 (prior to PE session 5), and 3 (prior to PE session 10). Blood will 
378 
be immediately chilled in a cooler filled with ice.  
379 
 
380 
Saliva will also be collected at four time points via passive drool. At the medication review appointment participants will be 
381 
given a kit with salivette test tubes and instructions on how to collect early waking saliva samples (cortisol) upon waking. 
382 
Saliva collections will be completed upon waking the day after the medication review appointment, and the day of 
383 
sessions 1, 6, and 10. Participants will be instructed to immediately refrigerate the sample and bring it to the next 
384 
scheduled appointment. Saliva samples will be collected from the participant by study staff when the participant arrives for 
385 
their appointment and immediately chilled in a cooler filled with ice. Samples will be frozen at or below -20oC upon arrival 
386 
at the Biological Psychiatry Analytic Laboratory (BPAL). 
387 
 
388 
Biological specimens will be coded when collected from the participant by the study staff with a digital bar code that can 
389 
be linked to the study and subject only by key-codes maintained by the STRONG STAR Data and Statistics Services. 
390 
 
391 
Heart rate will be monitored using a wearable device placed on the right wrist, and elevations will be recorded 
392 
continuously during sessions 3, 6, and 10 to obtain an objective measure of arousal to assess possible within- and 
393 
between- session extinction learning in response to rehearsal of the individual’s primary traumatic event. This data can be 
394 
beneficial for individuals who report subjectively being more aroused during the exposure or behaviorally appear to be 
395 
more activated.  
396 
 
397 
All biospecimen samples will be transported to the BPAL in the UTHSA Department of Psychiatry and Behavioral 
398 
Sciences at the UT Health-Long School of Medicine in room 727F for processing and storage. This location is monitored 
399 
24-7 by a wireless monitoring system on the Isensix system.  
400 


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401 
7.3.1.1 Laboratory evaluations and special precautions:  
402 
All biospecimen collection procedures will be carried out by trained team members and appropriately transported, stored, 
403 
and disposed of in accordance with STRONG STAR Biomarkers and Genomics Services SOP, International Air Transport 
404 
Association (IATA), and UTHSA IRB guidelines.  All samples will be labeled with coded subject numbers and dates to 
405 
protect the identities of participants. 
406 
 
407 
At the times designated in Section 7.3 Table, 7mL of venous blood will be drawn into one purple top tube for 
408 
measurement of AEA, 2-AG, and CBD levels.  Immediately upon collection, blood will be labeled, mixed, and chilled on 
409 
ice. This blood will be transported to the BPAL as soon as possible, where it will be processed to separate out the plasma. 
410 
Plasma will be aliquotted into two cryovials, labeled, and placed in the STRONG STAR-CAP biorepository for long-term 
411 
storage at -800 C.  Samples will be later analyzed in batches using HPLC/Tandem Mass Spectrometry. 
412 
 
413 
On the days designated in Section 7.3 Table, saliva samples will be collected by participants immediately upon awakening 
414 
in the morning.  Samples are collected by passive drool saliva collection into saliva sample tubes labeled only by coded 
415 
subject number and Day number.  Participants will be instructed to refrigerate the sample upon collection and to bring the 
416 
salivette to their next scheduled appointment. Saliva samples will be collected from the participant by study staff when the 
417 
participant arrives for their appointment and immediately chilled in a cooler filled with ice and then brought to the BPAL for 
418 
storage at -200 C as soon as possible. Subjects will bring these samples to their visit appointment and staff will receive 
419 
them and transport them to the BPAL for long-term storage until later analysis for cortisol levels. 
420 
 
421 
7.3.2 Data Collection.   
422 
See Table in Section 7.3 for a summary of the assessments and timing of administration. The data collected in the study 
423 
will be coded using an assigned number. Hard copies of data collected during the study will be securely stored in locked 
424 
cabinets at the STRONG STAR offices. Data will be entered into the STRONG STAR database by a member of the 
425 
research team.  
426 
 
427 
7.3.2.1. Instrumentation.  
428 
See the table in Section 7.3 for a summary of the assessments and timing of administration.  A description of each of the 
429 
assessments can be found at the end of this protocol.  Assessments will be administered in person whenever possible.  
430 
However, to accommodate participant schedules and/or instances in which a participant does not reside in the local area 
431 
at the time of a follow-up assessment, we may collect full or partial assessments in person or via phone, video 
432 
conferencing, and/or electronic data capture using a secure link to the encrypted STRONG STAR database.  Reasonable 
433 
efforts will be made to collect all data as described in this protocol, but we expect some participants may not be able to 
434 
complete part or all of any given follow up assessment. 
435 
  
436 
7.3.2.2 Data Storage, Access, and Protection.  
437 
Study files containing hard copies of data collected during study participation will be kept securely at the STRONG STAR 
438 
offices in San Antonio. Files will be placed into locked cabinets and stored securely in a locked room by a STRONG STAR 
439 
staff member.  
440 
 
441 
Data will be coded using an assigned number. Local study sites will maintain a list of assignment numbers for the purpose 
442 
of linking subsequent research materials. 
443 
 
444 
Data will be entered into the STRONG STAR password protected database housed on a secure UTHSA server by 
445 
member of the research team. Electronic data will be stored, managed, and analyzed by the STRONG STAR Data and 
446 
Statistics Services staff of the STRONG STAR consortium. The overall PI and named collaborators will have access to 
447 
identifiable data through the STRONG STAR website and UTHSA server via direct request to STRONG STAR Data and 
448 
Statistics Services.  
449 
 
450 
All UTHSA STRONG STAR network connectivity is segmented with Access Control Lists and is not accessible to any 
451 
other UTHSA network segments. The STRONG STAR data server is physically located at the Advanced Data Center 
452 
(ADC), which has 24x7 onsite security, card key, biometric access controls and video surveillance. UTHSA ADC facility 
453 
also maintains Gen 2 firewall devices to protect and prohibit any unauthorized access to UTHSA data. All UTHSA network 
454 
devices are monitored by state-of-the-art monitoring applications that include configuration audit, management, and 
455 
availability 24x7.  
456 
 
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The UTHSA STRONG STAR data server is currently a VMware Instance running Windows Server 2016 Enterprise 
458 
Standard with daily backup services and vSphere Business Continuity Advanced Failover. 
459 
 
460 
Only select STRONG STAR Data and Statistics Services personnel have direct access to the data on a “need to access 
461 
basis”; for example (but not limited to) detecting and repairing data corruption and producing reports not currently within 
462 
the STRONG STAR system. STRONG STAR Data and Statistics Services also follows the Principals Of Least Privilege 
463 
(POLP).  All user activity is tracked and recorded within the system so if any records are added, altered, or viewed the 
464 
action is recorded and can be recalled for auditing purposes. Access to this information will require a password-protected 
465 
login available only to authorized STRONG STAR Data and Statistics Services staff.  
466 
 
467 
Every member of the Research Team will be trained and monitored about how to handle and protect both medical and 
468 
research records.  Furthermore, the Research Team strictly controls access to study data.  
469 
 
470 
The STRONG STAR Data Safety and Monitoring Plan (DSMP) that has been developed in accordance with the National 
471 
Institutes of Health Office of Human Research Protection to assure the appropriate clinical safety monitoring of study 
472 
subjects participating in research will be used to monitor this study.  
473 
 
474 
7.4. Statistical Consideration  
475 
 
476 
7.4.1. Sample Size Estimation. 
477 
Estimate Required Sample Size (Completed / Evaluable) 
24 
Estimate Participant Drop Out / Withdrawal after Randomization/Inclusion 
4 (17%) 
Total Required to Randomize / Include 
28 
Estimate Participant Screen Fail / Exclusion 
12 (30%) 
Total Required to Consent 
40 
 
478 
7.4.2. Primary (i.e., primary outcome variables) and secondary endpoints  
479 
Health Questionnaire and Self-Report Measures: The primary aim of this pilot is to explore the potential feasibility, 
480 
safety, and effect of CBD in reducing PTSD symptoms compared to placebo in retired service members receiving mPE. 
481 
Therefore, the primary outcome variables will be the CAPS-5 total score, the PCL-5 total score, and adverse event 
482 
monitoring. Secondary endpoints are listed in the table in Section 7.3 and include associated psychopathology, such as 
483 
severity scores on measures of depression, general anxiety, disability, and PTSD-related cognitions. 
484 
Biospecimens & Heart Rate Monitoring Measures: We will also assess possible biochemical and physiological 
485 
outcomes associated with treatment (Aim 2) and evaluate the relationship between changes in biochemical/physiological 
486 
measures with PTSD symptom reductions (Aim 3). To address these aims we will collect blood and saliva samples and 
487 
heart monitoring data via a wearable device as described in 7.3.1 
488 
7.4.3. Data analysis.  
489 
This pilot study was not powered for formal efficacy or mechanistic hypotheses testing.42 Our primary interests are to evaluate 
490 
the safety and feasibility of the proposed recruitment, assessment, and treatment protocols; and to detect a signal of possible 
491 
PTSD symptom reductions associated with CBD in preparation for a larger trial. To inform future studies, we will calculate 
492 
conventional effect sizes with 95% confidence interval limits. Hedges’ g will be used to calculate continuous outcome effect 
493 
sizes (e.g., CAPS-5, PCL-5). Hedges’ g has been recommended over Cohen’s d for small samples based on sample size 
494 
adjustments yet can be interpreted using the same conventional recommendations as Cohen’s d.43  
495 
Although the statistical power of this study is limited, we will perform statistical analyses appropriate for an adequately 
496 
powered study to identify data analysis issues germane to future planning (e.g., data management and scoring, missing 
497 
data, data distributions, outliers, trends over time, covariance structures). Statistical analyses will be intent to treat. We will 
498 
complete descriptive statistics to describe the study sample and address the feasibility and safety hypotheses. Continuous 
499 
outcome measures related to symptom changes and comparison of baseline and posttreatment means will be done with 
500 
general or generalized linear mixed effects regression models with repeated measures, with fixed effects of time, group, 
501 
and the group by time interaction. Measures with data collected during treatment will also be included in models. Little’s44 
502 
missing completely at random analysis will be completed to confirm likelihood-based model assumptions. Pearson 
503 
correlation analyses will be used to examine associations between change in PTSD symptoms, biochemical markers, and 
504 


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physiology. To address attrition and missing data, participants will have frequent follow-up to maintain contact with the 
505 
study team. Participants who discontinue treatment will be asked their reasons at the point of drop-out. 
506 
 
507 
7.5. Confidentiality. 
508 
PE sessions, interview assessments, and blood draws will be delivered in private offices at the STRONG STAR Clinic at the 
509 
UTHSA. When travel to the STRONG STAR clinic is not feasible, Interview Assessments and PE sessions via video 
510 
teleconferencing will be made available to mitigate missed appointments. Data will be stored by an assigned participant code 
511 
number so that data records can be viewed by password-authenticated, authorized investigators and Consortium personnel. 
512 
Every member of the research study team will be trained and monitored on how to handle and protect both medical and 
513 
research records. Only authorized study staff, and members of the STRONG STAR Data and Statistics Services staff will 
514 
have access to either the raw data or electronic study data. 
515 
7.6. Long Term Data Storage.  
516 
A STRONG STAR Repository has been approved by the UTHSA (HSC20100475H) IRB to enable the STRONG STAR 
517 
Consortium to store specimens and data for future use. The STRONG STAR Repository is a large comprehensive 
518 
database of information, biological specimens and neuroimages related to the identification, assessment, and treatment of 
519 
posttraumatic stress disorder (PTSD), insomnia, pain, and related behavioral health conditions. All information entered 
520 
into the STRONG STAR Repository will be extracted from primary datasets collected as part of IRB-approved studies, 
521 
including this study, being conducted and /or supported in collaboration with the UTHSA STRONG STAR Consortium.  
522 
Study databases are established and maintained by the STRONG STAR Data and Statistics Services.  A unique, 
523 
sequential alpha-numeric STRONG STAR ID will be assigned to each participant at the time of recruitment into this study. 
524 
However, all Repository data will be identified with a different code number that can be cross linked to the original study 
525 
code only through records maintained by the STRONG STAR Data and Statistics Services.  At the conclusion of this 
526 
study, participants who signed the consent to have their data placed in the STRONG STAR Repository will be maintained 
527 
under the UTHSA IRB-approved Repository protocol.  For participants who decline participation in the STRONG STAR 
528 
Repository, their data will be de-identified, and the data maintained in the Repository without identifiers at the conclusion 
529 
of the study. 
530 
 
531 
8.0. RISKS/BENEFITS ASSESSMENT 
532 
 
533 
8.1. Risks. 
534 
 
535 
Likely, but Not Serious Risks: 
536 
 
537 
Epidiolex (CBD): CBD is well tolerated in human subjects and is considered a safe drug, with minimal adverse events 
538 
(AEs) and low abuse potential.1,41,45–47 However, like almost all medications, toxicity and AEs are possible with CBD. The 
539 
most common side effects of CBD can include fatigue, drowsiness, feeling weak, malaise, loss of appetite, diarrhea, skin 
540 
rash, insomnia, and viral/fungal infections.  
541 
 
542 
PTSD & Prolonged Exposure (PE): Potential risks associated with PTSD assessment and PE therapy can include 
543 
temporary increase in distress, becoming emotionally upset or experiencing an initial increase of PTSD symptoms due to 
544 
the consideration of traumatic events. Studies with PE suggest that a small minority experience an increase in symptoms 
545 
of PTSD after the initiation of imaginal exposure and for this minority, the distress and increased symptoms are 
546 
temporary, are not predictive of poor outcome, and are not associated with increased likelihood of dropout.46 
547 
 
548 
Biospecimen Collection: Potential risks associated with blood draw may include pain, bruising, infection, lightheadedness, 
549 
fainting, blood clots, and bleeding or other discomforts at the blood draw site. 
550 
 
551 
Rare, but Serious Risks: 
552 
CBD: Serious side effects of CBD are very rare but can occur. Serious side effects include liver problems, sedation (e.g., 
553 
sleepiness, loss of coordination, and difficulty with concentration), severe allergic reaction (skin rash, itchiness, flushed 
554 
skin, angioedema, difficulty breathing), and in very rare circumstances ( < 1%) suicidal thoughts or behavior.1 
555 
 
556 
Biospecimen Collection: More rare risks of blood draw may include swelling and/or infection at the needle site, and 
557 
thrombosis of the vein due to trauma. Proper training of study team members on biospecimen collection safety 
558 
procedures can reduce the risk of contamination, clerical error, infection, injury, misuse of appropriate blood-sampling 
559 
devices, and risk when transporting laboratory samples.  
560 
 
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Risks to Confidentiality 
562 
With the handling of medical and research records there is always the possibility of a breach of confidentiality. We will 
563 
maintain patients’ names, contact information (i.e. Identifiers), and all PHI (protected health information) in an encrypted 
564 
computer database and all PHI identifiers will be removed in the database during data analysis. Every member of the 
565 
Research Team is carefully trained and monitored about how to store, handle, and protect participant records. 
566 
 
567 
Risks of PTSD Diagnosis regardless of Treatment: 
568 
Possibility of increased suicidal risk. One of the risks of PTSD both in and out of treatment is attempted suicide, which can 
569 
result in death. 
570 
 
571 
Safeguards for Protecting Participants:  
572 
CBD: Participants will be required to complete a liver function test (LFT) or provide a copy of recent LFT lab results 
573 
(completed within the last 90 days) to the study team prior to randomization to be considered for study eligibility. To 
574 
mitigate unnecessary LFTs, candidates will complete the full assessment to determine eligibility. If the candidate is 
575 
deemed eligible, the final step of the assessment process will be to complete an LFT or provide a copy of a recent (LFT).  
576 
The study team will work with the candidate to obtain LFTs and pay for them if necessary.  All LFT labs will be reviewed 
577 
by Dr. King to determine study eligibility. Participants with enzyme levels 3x the normal limit will be excluded from the 
578 
study. 
579 
 
580 
CBD, like most drugs, can lead to AEs and has drug-drug interactions. To safeguard against potential risk, we have 
581 
developed exclusionary criteria related to the individual’s medical history and concomitant medication regimen. 
582 
Participants prescribed medications listed in the exclusion criteria will be excluded . Exceptions will be made for 
583 
participants taking the antidepressants Trazodone and Mirtazapine, a benzodiazepine just as needed, and/or stable doses 
584 
of the platelet inhibitors Clopidogrel or Warfarin.  These participants will be monitored for AEs on a more frequent basis 
585 
(daily at each session). Additionally, consultation between the study team and Dr. King may occur on a more regular basis 
586 
regarding potential medication/health risk and additional risk management procedures. Individuals on medications with 
587 
known drug-drug interactions may also complete an additional LFT during study participation. 
588 
 
589 
All participants will complete the STRONG STAR Health Questionnaire and the Prior and Concomitant Medications 
590 
Interview at the baseline assessment. These measures assess medical and psychiatric diagnoses, current prescription 
591 
and over the counter medication use, and caffeine use. Prior to enrollment in the study, Van King, MD (physician 
592 
collaborator) and Casey Straud, PsyD (principal investigator) will review participants’ Health Questionnaire and 
593 
Medication Interview to determine potential for risk and confirm eligibility based on self-reported health history, current 
594 
prescribed medications, and current substance use.  
595 
 
596 
For participants identified as having low to moderate risk of AE or drug-drug interaction, the patient will be maintained on 
597 
protocol and additional risk management procedures will be implemented within the context of the study treatment. All 
598 
enrolled participants will be monitored for AEs by the study therapist on Day 1 (beginning of mPE), Day 5-Interim 
599 
Assessment, Day 10-Interim Assessment, and at the 1-month follow-up. For participants identified as being at high risk for 
600 
a health/medication-related AE or drug-drug interaction, ineligibility will be considered if it is unlikely that standard 
601 
treatment plus additional risk management procedures (i. e., adverse event monitoring at every visit) will maintain safety. 
602 
Dr. King, Casey Straud, PsyD (PI), and study team members will meet each week to review reported AEs. AE meetings 
603 
will involve consultation with Dr. King on potential medication/health risk and additional risk management procedures as 
604 
described above. For urgent issues, whether potentially related to CBD or mPE, participants will be instructed to get help 
605 
immediately by going to the nearest emergency room.  
606 
 
607 
All participants will also be given a medication emergency department wallet card at the beginning of the study. 
608 
Participants will be instructed to keep this card on their person throughout the study. The wallet card briefly describes the 
609 
study intervention (Epidiolex vs. Placebo) and drug dose (250mg b.i.d), and provides a study team contact number. 
610 
 
611 
 
612 
PTSD & PE: Psychological distress experienced by participants is expected to be temporary and participants will be 
613 
provided immediate coping tools and techniques to manage distressing emotions by the study therapist.  Any indication 
614 
that the participant is considering suicide, endorses active psychosis/mania, or other harm to self/others will be handled 
615 
using evidence-based procedures and policies developed by the STRONG STAR Consortium. Participants who endorse 
616 
mania/psychotic symptoms will prompt a clinical interview with a licensed clinical provider to assess current risk and risk 
617 
of active mania/psychosis during study participation. Individuals with active mania/psychosis will be excluded from study 
618 
participation. Trained clinicians and evaluators will assess history of suicide and current suicidal ideation using the 
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Suicidal Ideation Thoughts and Behaviors Interview at the baseline assessment.  For participants identified as having low 
620 
to moderate risk for suicide based on the assessment results, the patient will be maintained on protocol and additional risk 
621 
management procedures will be implemented within the context of the study treatment. For participants identified as being 
622 
at high risk for suicide based on the assessment results, disenrollment will be considered if it is unlikely that standard 
623 
treatment plus additional risk management procedures will maintain safety.  High risk participants who are disenrolled 
624 
from the study will be referred for more intensive treatment (outpatient or inpatient).  
625 
 
626 
If the research team feels that hospitalization should be considered, the participant’s primary care provider or unit will be 
627 
contacted to escort the individual to the ED.  If a participant reports experiencing psychotic or mania symptoms, or reports 
628 
dangerous amounts of alcohol and/or substance use, additional assessment by a licensed provider for consideration of 
629 
referral for clinical care and for disenrolling participants from the study will be conducted.   
630 
 
631 
Enrolled participants will be monitored for AEs by the study therapist at Interim Assessment 1 (PE Session 1), Interim 
632 
Assessment 2 (PE Session 5), Interim Assessment 3 (PE Session 10), and at the 1-month follow-up. Dr. Straud and study 
633 
team members will meet each week to review reported AEs and to consult on potential behavior health risks. For urgent 
634 
issues, whether potentially related to psychotherapy or CBD, participants will be instructed to get help immediately by 
635 
going to the nearest emergency room. 
636 
 
637 
Biospecimen Collection: To reduce the risk of AEs for study participants, all staff members collecting biospecimens will be 
638 
trained in procedures to reduce the risk of contamination, clerical error, infection, injury, use of appropriate blood-sampling 
639 
devices, and safe transportation of laboratory samples via IATA guidelines. When collecting or handling biospecimens, 
640 
staff members will wear well-fitting, non-sterile gloves, and carry out hand hygiene before and after each patient 
641 
procedure, before putting on gloves and after removing them. To reduce the risk of environmental contamination with 
642 
pathogens, the blood draw room will be appropriately sanitized before and after each blood draw and saliva collection. To 
643 
prevent infections and other AEs, health workers should follow the guidelines on patient identification, hand hygiene, use 
644 
of gloves, skin disinfection, use of appropriate blood-sampling devices and safe transportation of laboratory samples. 
645 
 
646 
8.2 Potential Benefits.   
647 
Potential benefits of participation in this study may include a reduction in, or amelioration of, PTSD symptoms over the 
648 
course of therapy.  Collectively, the possible risks (i.e., temporary increase in distress and severity) associated with 
649 
participation are low and reasonable within this context given the level of participant monitoring and access to research 
650 
and clinical staff. We believe that the possible benefits from participating in this study significantly outweigh the possible 
651 
risks. The knowledge gained from this study will serve to inform the most effective early interventions for the prevention 
652 
and treatment of PTSD. 
653 
 
654 
8.3 Alternatives. 
655 
Other choices to participating in this study include: not participating in this study; receiving psychotherapy or medications 
656 
in the community; or participation in other research studies involving experimental treatments. 
657 
 
658 
9.0  ADVERSE EVENTS, UNANTICIPATED PROBLEMS, AND DEVIATIONS 
659 
9.1. Adverse Events will be assessed and monitored according to the established STRONG STAR SOP and the IRB of 
660 
record’s policies and procedures.  
661 
9.2. Reporting Unanticipated Problems Involving Risks to Subjects or Others, Serious Adverse Events and Deaths to 
662 
the IRB Office.  All adverse events, unanticipated problems involving risk to subjects or others, and deviations will be 
663 
reported to the Institutional Review Board (IRB) in accordance with current IRB policy. UPIRSOs and recurrent non-
664 
compliance with study procedures will be reported promptly to the IRB.  All adverse events that do not meet the UPIRSO 
665 
criteria and deviations that are not non-compliance will be summarized at Continuing Review per the IRB of record’s policy. 
666 
10.0. WITHDRAWAL FROM STUDY PARTICIPATION. 
667 
Participation in the study may be discontinued by the principal investigator if continued participation is considered a 
668 
danger to a participant’s welfare. Reasons for discontinuation include: 1) a serious AE such that continued participation 
669 
would be a danger to the participant; 2) clinical worsening for any reason that is deemed to necessitate non-study 
670 
psychological or medical treatment; 3) exacerbation of PTSD, anxiety, or depressive symptoms that the participant cannot 
671 
tolerate; or 4) drug interactions from concomitant medications that the participant cannot tolerate or would be a danger to 
672 
the participant; or 5) discontinuation would be in the participant's best interest. Participants deemed candidates for 
673 
discontinuation will be discussed in conference calls with relevant study team members and will be brought to the 
674 
attention of the PI and mentor committee for final decision. Participants who are discontinued from the study for any 
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reason will be scheduled for a final evaluation within one week and given appropriate treatment referrals. If participants 
676 
are discontinued due to a serious AE, they will continue to be followed clinically by the therapist and/or member of the 
677 
research staff until the AE is resolved or becomes stable. The reason the participants are discontinued from the study will 
678 
be documented for future study planning. 
679 
11.0. TIME REQUIRED TO COMPLETE THE RESEARCH (including data analysis). 
680 
The following table provides an overview of activities that the research team plans to accomplish. We anticipate recruiting 
681 
and treating two eligible service members per month to meet study goals. We anticipate that the study will be completed 
682 
by July 1, 2023. 
683 
 
684 
Study Activities (Months) 
Year 1 
Year 2 
0-
3 
4-6 
7-9 
10-
12 
13-15 
16-
18 
19-21 
22-
24 
IRB Approvals, Prepare Materials, Train Staff 
 X 
 
 
 
 
 
 
 
Recruit, Screen, and Treat 24 Participants  
 
 X 
X  
 X 
X 
 
 
 
Follow-up Assessments 
 
 
X  
 X 
 X 
X 
 
 
Data Cleaning 
 
 
 
 
 X 
X 
 
 
Data Analysis 
 
 
 
 
 
 X 
X 
X 
 
685 
12.0. STUDY CLOSURE PROCEDURES.  
686 
At the conclusion of the study all data will be stripped of identifiers. De-identified (anonymized) data will be maintained 
687 
indefinitely in the STRONG STAR Repository. Informed consent documents will be stored securely for a minimum of three 
688 
years following completion of the research in accordance with 45 CFR 46. HIPAA authorizations will be stored for a minimum 
689 
of six years in accordance with HIPAA regulations. A Final Report will be submitted to the IRB to request inactivation of the 
690 
study.  
691 
13. FUNDING. 
692 
This project is funded through the Institute for Integration of Medicine and Science Clinical and Translational Research 
693 
Scholars Mentored Research Career Development Program at UTHSA (KL2 TR002646; PI: Casey Straud, PsyD). 
694 
14.0 DESCRIPTION OF ASSESSMENTS. 
695 
The majority of the measures listed below is commonly used, have adequate to good psychometrics, and are part of the 
696 
Consortium common data elements (CDE). As outlined in the National Research Action Plan, evidence-based CDEs and 
697 
measures for STRONG STAR studies will ensure comparability of results across the consortium as well as other clinical trials 
698 
and epidemiological studies of PTSD.  
699 
 
700 
1. Demographics and Military Service Characteristics Form:  The Demographics Form measures standard demographics 
701 
(race, gender, age) and military service information (e.g., rank).  This measure will be administered at the baseline 
702 
assessment. 
703 
 
704 
2. Life Events Checklist-5 (LEC-5).48 The LEC includes a list of 24 potentially traumatic life events commonly associated with 
705 
PTSD symptoms. The instrument was designed to facilitate the diagnosis of PTSD. In this study, the LEC-5 will also be 
706 
used to identify the index event and focus of the PTSD treatment. For each potentially traumatic life event, respondents 
707 
rate their experience of that event on a 5-point nominal scale (1 = happened to me, 2 = witnessed it, 3 = learned about it, 
708 
4 =part of my job, 5= not sure, and 6 = does not apply). Each nominal point will be scored separately, as either 0 (=not 
709 
endorsed by participant) or 1 (=endorsed by participant). This measure will be administered at the baseline assessment. 
710 
 
711 
3. Deployment Risk and Resilience Inventory-2 (DRRI-2) Combat Experience and Post-battle -Scales.49,50 High- and low-
712 
intensity deployment stress exposure will be assessed using scales from the DRRI-2. The DRRI-2 is an update of the 
713 
original DRRI, which was developed and tested in three separate national samples of veterans of the first Gulf War. It has 
714 
been revised and tested with OEF/OIF/OND returnees. The DRRI-2 provides an update of the DRRI’s assessment of 
715 
deployment-related factors to ensure the instrument’s applicability across a variety of deployment circumstances (e.g., 
716 
different eras of service) and military subgroups (e.g., men and women), as well as to validate updated measures in a 
717 
contemporary Veteran cohort. High intensity stressor exposures will be assessed using the DRRI Combat Experiences 
718 
and Aftermath of Battle subscales. Responses to these scales are on a 6-point Likert scale. The total score is the sum of 
719 
the item scores, where higher scores signify greater exposure to combat or exposure to the consequences of combat, 
720 
respectively. Both subscales have very good internal consistency (α = .90 to .92) and construct validity. This measure will 
721 
be administered at the baseline assessment and only among participants who identify as a military veteran. 
722 
 
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724 
4. Health Questionnaire. The Health Questionnaire includes items regarding physical and mental health history, diagnoses, 
725 
utilization of services, and military medical board evaluation/VA disability. Participants are also asked about current 
726 
medications being used and provide information on how long they have been taking the medication. The Health 
727 
Questionnaire also asks about caffeine use and frequency of use in the past month.  Overall, this measure provides a 
728 
brief, yet comprehensive overview of the patient’s medical and psychiatric history as well as relevant information 
729 
regarding caffeine use and medications. This measure will be administered at the baseline assessment and 1-month 
730 
follow-up. 
731 
 
732 
5. Prior and Concomitant Medications Interview. The Prior and Concomitant Medication Interview is a brief, semi-structured 
733 
interview to assess medication use, dose, frequency, route of administration, and course of medication use in the past 30 
734 
days prior to the assessment. The interview also assesses if medication use is ongoing and the indication for the 
735 
medication use. This measure will be administered at the baseline assessment. 
736 
 
737 
6. Self-Injurious Thoughts and Behaviors Interview (SITBI).51 The SITBI is a structured interview assessing the presence, 
738 
frequency, and characteristics of self-injurious and suicidal thoughts and behaviors. The SITBI will be administered by an 
739 
Independent Evaluator, who will instruct the participants to answer the questions based on their entire lifetime of 
740 
experience. The SITBI has shown high interrater reliability, test-retest reliability, and concurrent validity. This measure will 
741 
be administered at the baseline assessment and the one-month follow-up assessment. 
742 
 
743 
7. Depressive Symptoms Index-Suicidality Subscale (DSI-SS).52  The DSI-SS will be used to assess current suicidal 
744 
ideation. The DSI-SS is a 4-item self-report measure of suicidal ideation that focuses on ideation, plans, perceived control 
745 
over ideation, and impulses for suicide. It is being used as a core measure in the Military Suicide Research Consortium. 
746 
Scores on each item range from 0 to 3, with higher scores reflecting greater severity of suicidal ideation. Instructions will 
747 
instruct the participants to respond based on the past two weeks. A systematic review of measures of suicidal ideation 
748 
and behaviors found that the DSI-SS had evidence of excellent internal consistency and concurrent validity. This measure 
749 
will be administered at the baseline assessment, interim assessments, and the one-month follow-up assessment. 
750 
 
751 
8. The Clinician Administered PTSD Scale for DSM-5 (CAPS-5).3 The CAPS-5 is structured interview that assesses the 
752 
DSM-5 criteria for PTSD. Each item is rated on a severity scale ranging from 0 (Absent) to 4 (Extreme/incapacitating) and 
753 
combines information about frequency and intensity for each of the 20 symptoms. Additional items that are not included in 
754 
the total score evaluate overall symptom duration, distress, impairment, dissociative symptoms, and global ratings by the 
755 
interviewer. Validation studies are nearly complete to establish the psychometric properties of the CAPS-5 and findings 
756 
will be reported in peer-reviewed publications. This interview is very similar to its predecessor, the CAPS for DSM-IV, 
757 
which has been considered the gold standard for evaluating PTSD and demonstrated good reliability and validity. In 
758 
addition to reflecting diagnostic changes for PTSD in DSM-5, the CAPS-5 differs from the CAPS in that frequency and 
759 
intensity ratings for each symptom are no longer scored separately, so the severity rating for each item determines 
760 
whether a symptom is present or not. Subscale scores are calculated by summing severity scores for items in the 
761 
following PTSD symptom clusters: re-experiencing, avoidance, negative alterations in cognitions and mood, and 
762 
hyperarousal. Scores ≥ 25 indicate a probable diagnosis of PTSD. This measure will be administered at the baseline 
763 
assessment and the one-month follow-up assessment. 
764 
 
765 
9. PTSD CheckList-5 (PCL-5).4 The PCL-5 is a 20-item self-report measure update of the PCL designed to assess PSTSD 
766 
symptoms as defined by the DSM-5. The PCL-5 is currently available and has been shown to have good psychometric 
767 
properties. The PCL-5 evaluates how much participants have been bothered by PTSD symptoms in the past week (for all 
768 
assessments during treatment) or the past two weeks (all other assessment time points) as a result of a specific life event.  
769 
Each item of the PCL-5 is scored on a five-point scale ranging from 0 “not at all”) to 4 (“extremely). This measure will be 
770 
administered at the baseline assessment, the interim assessments, and the one-month follow-up assessment. 
771 
 
772 
10. Patient Health Questionnaire-9 (PHQ-9).53 The PHQ-9 is a widely used and well-validated instrument for measuring the 
773 
severity of depressive symptoms. It consists of 9 items that assess both affective and somatic symptoms related to 
774 
depression and depressive disorders; these 9 items correspond to the diagnostic criteria for DSM MDD. Respondents rate 
775 
the frequency with which they have been bothered by depressive symptoms within the past two weeks on a scale ranging 
776 
from 0 (“not at all”) to 3 (“nearly every day”). Scores on all items are summed to obtain a total severity score. Scores 
777 
reflect no significant depressive symptoms (0-4), mild depressive symptoms (5-9), moderate depressive symptoms (10-
778 
14), moderately severe depressive symptoms (15-19), and severe depressive symptoms (>19). Respondents also 
779 
indicate the degree to which their depressive symptoms have made it difficult for them to do their work, take care of things 
780 
at home, or get along with other people, from “not difficult at all” to “extremely difficult.” The PHQ-9 has high internal 
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consistency (e.g., alpha ranging from .83 to .92) and correlates strongly with other measures of depression. This measure 
782 
will be administered at the baseline assessment, the interim assessments, and the one-month follow-up assessment. 
783 
 
784 
11. Generalized Anxiety Disorder Screener (GAD-7).54 The GAD-7 will be used to assess generalized anxiety symptomology. 
785 
This is a 7-item measure that asks participants to rate the frequency with which they have been bothered by anxiety 
786 
symptoms within the past two weeks on a scale ranging from 0 (“not at all”) to 3 (“nearly every day”). Scores on all items 
787 
are summed to obtain a total severity score.  Scores reflect no significant anxiety symptoms (0-4), mild anxiety symptoms 
788 
(5-9), moderate anxiety symptoms (10-14), and severe anxiety symptoms (>15).  Respondents also indicate the degree to 
789 
which their anxious symptoms have made it difficult for them to do their work, take care of things at home, or get along 
790 
with other people, from “not difficult at all” to “extremely difficult.” The GAD-7 has been shown to have high internal 
791 
consistency (e.g., α = .89) and has been shown to reliably discriminate between anxious and non-anxious diagnostic 
792 
groups. This measure will be administered at the baseline assessment, interim assessments, and the one-month follow-
793 
up assessment. 
794 
 
795 
12. Brief Inventory of Psychosocial Functioning (BIPF).55 The BIPF is a 7-item self-report instrument measuring respondents’ 
796 
level of functioning in seven life domains: romantic relationship, relationship with children, family relationships, friendships 
797 
and socializing, work, training and education, and activities of daily living. Respondents indicate the degree to which they 
798 
had trouble in the last 30 days in each area on a 7-point scale ranging from “0 = Not at all” to “6 = Very much.” This 
799 
measure will be administered at the baseline assessment, and the one-month follow-up assessment. 
800 
 
801 
13. Veterans Rand 12-Item Health Survey (VR-12).56 Because a certain level of PTSD symptoms is an occupational hazard 
802 
among service members redeployed for combat, it is critical to pay close attention to functional capacities as an important 
803 
index of intervention efficacy.  The Veterans SF-36 (VR-36) was adapted from the RAND SF-36 Version 1.0 
804 
questionnaire, and spans the range of health domains from physical to psychological health status. It includes two 
805 
modifications.  The first modification is an increase in the number of response choices for the role physical (RP) and role 
806 
emotional (RE) items from a two point yes/no choice to a five-point likert scale (no, none of the time, yes, a little of the 
807 
time, yes, some of the time, yes, most of the time, yes, all of the time).  The second modification is the use of two items to 
808 
assess health change, one focusing on physical health and one on emotional problems, in contrast to the one general 
809 
change item in the RAND SF-36.56 The VR-36 has been widely used, distributed and documented in the Veterans Health 
810 
Administration (VHA) with close to 2 million questionnaires administered nationally in six national surveys since 1996. The 
811 
changes to the survey have increased the overall precision of the instrument and the discriminant validity of the physical 
812 
and mental component summary scales.57 The VR-36 is comprised of 37 items and eight scales:  physical functioning, 
813 
role limitations due to physical problems, bodily pain, general health perceptions, energy/ vitality, social functioning, role 
814 
limitations due to emotional problems, and mental health. Also, there are two summary scales:  a physical component 
815 
summary (PCS) and mental component summary (MCS). Higher scores indicate better health. Each summary is 
816 
expressed as a T score, which facilitates comparisons between the VA patients and the general U.S. population. The PCS 
817 
and MCS scores provide at least 90% of the reliable variance in the eight SF-36 concepts. The Veterans SF-12 was 
818 
developed from the Veterans SF-36 and adapted from the MOS SF-36. It includes fewer items for seven of the eight 
819 
scales and provides 90% of the reliable variance in the two component summary measures using the Veterans SF-36. 
820 
Using independent results from the Veterans Health Study and the 1996 National Survey of Ambulatory Care Patients, the 
821 
results for the Veterans SF-12 corresponded very closely with the results for the Veterans SF-36 (average differences of 
822 
0.06 points between them for PCS and 0.31 points for MCS). This measure will be administered at the baseline 
823 
assessment and the one-month follow-up assessment and only among participants who identify as a military veteran.  
824 
 
825 
14. Quick Drinking Screen (QDS).58 The QDS will be used to assess hazardous or harmful patterns of alcohol consumption in 
826 
the past two weeks. The QDS is a four-item screener that assesses average number of drinking days, average number of 
827 
drinks on drinking days, number of heavy drinking days, and greatest number of drinks in a day over the past two weeks. 
828 
The average total drinks consumed per week can also be calculated by multiplying items 1 (average number of drinking 
829 
days per week) and 2 (average drinks per day). This measure will be administered at the baseline assessment and the 
830 
one-month follow-up assessment. At the baseline assessment, the PI (Casey Straud, PsyD) and physician collaborator 
831 
(Van King, MD) will review QDS scores to determine if the screened individual demonstrates clinically significant alcohol 
832 
abuse that warrants exclusion from the study. This measure will be administered at the baseline assessment and the one-
833 
month follow-up assessment.  
834 
 
835 
15. National Institute of Drug Abuse Quick Screen (NIDA-Q).59 The NIDA-Q will be used to identify individuals with a history of 
836 
or current substance abuse. The NIDA-Q is a brief interview to assess history and current alcohol, tobacco, and other 
837 
substances. Each substance involves seven questions to determine a substance involvement score with scores ranging 
838 
from 0-27 per substance. Scores greater than or equal to 27 indicate high risk and scores between 4-26 suggest 
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moderate risk. Participants are first asked about the frequency of substance use in the past year. If the patient reports 
840 
none, then screening in this section for the past year is complete. If the participant endorses use in the past year, 
841 
additional follow-up questions are asked to determine the frequency and severity of use for each substance. Part two of 
842 
the NIDA-Q assesses lifetime substance use. If the participant responds “no” then screening for part two is complete. If 
843 
the participant endorses a history of substance use, additional questions are asked to assess frequency and severity in 
844 
the past three months. For the purposes of this study, participants who endorse current use (or a history of abuse) of the 
845 
five listed substances described in the exclusion criteria section will be excluded from the study. This measure will be 
846 
administered at the baseline assessment and 1-month follow-up. 
847 
 
848 
16. Insomnia Severity Index (ISI).60 The ISI is a 7-item self-report measure that assesses perceived severity of insomnia. 
849 
Each item uses a 4-point Likert type scale from 0 (not at all satisfied) to 4 (very much satisfied). The items sum to produce 
850 
a total score (range 0 – 28). The ISI has an internal consistency alpha coefficient of 0.74, and has shown convergent 
851 
validity with other measures such as the Pittsburgh Sleep Quality Index (r = 0.67), the Dysfunctional Beliefs and Attitudes 
852 
about Sleep (r = 0.55), and sleep diaries (r ranges from 0.32-0.91). This measure will be administered at the baseline 
853 
assessment and the one-month follow-up assessment. 
854 
 
855 
17. Posttraumatic Cognitions Inventory (PTCI).61 The PTCI is a 36-item questionnaire that was developed to determine how 
856 
an individual views the trauma and its sequelae in an attempt to understand both how PTSD develops and is maintained. 
857 
Using an emotional processing theory, Foa and her colleagues have suggested that PTSD is a consequence of 
858 
disruptions in the normal processes of recovery when an individual has excessively rigid concepts about self and world 
859 
rendering the person vulnerable if a traumatic event occurs. Thus, the PTCI was developed as a measure of trauma-
860 
related thoughts and beliefs.  It is comprised of three subscales (Negative Cognitions about the Self, Negative Cognitions 
861 
about the World, and Self-Blame).  The measure was tested in almost 600 adult volunteers recruited from two university 
862 
PTSD treatment clinics as well as a university community.  Approximately 65% (n=392) of individuals reported having 
863 
experienced a trauma in which their own life or that of another person was perceived to be in danger and their response at 
864 
the time included intense terror, horror, or helplessness (Criterion A event).  The remaining 35% (n=162) denied such a 
865 
traumatic experience.  Of those who had experienced a trauma, 170 had PTSD symptoms of at least moderate severity 
866 
while the remaining 185 reported a low symptom severity.  The three subscales of the PTCI demonstrated internal 
867 
consistency with alpha coefficients ranging from 0.86 to 0.97.  Convergent validity was demonstrated comparing the PTCI 
868 
to appropriate subscales of the World Assumptions Scale and Personal Beliefs and Reactions Scale.  Significant 
869 
correlations between the appropriate subscales ranged from 0.20 to 0.85.  The PTCI was able to differentiate individuals 
870 
with and without PTSD demonstrating discriminate validity (sensitivity = 0.78, specificity = 0.93).  Test–retest reliability for 
871 
each of the three subscales at a 1-week interval ranged from 0.75 to 0.89 and for a 3-week interval ranged from 0.80 to 
872 
0.86. This measure will be administered at the baseline assessment, the interim assessments, and the one-month follow-
873 
up assessment. 
874 
 
875 
18. Credibility/ Expectancy Questionnaire (CEQ) for PE.62  The CEQ is a 6-item measure that was designed to assess 
876 
treatment expectancy and rationale credibility for use in clinical outcomes studies.  This measure has been utilized across 
877 
a number of STRONG STAR treatment trials and can be easily adapted to assess the target intervention(s). For the 
878 
current proposed study, the CEQ will be adapted to assess the credibility and expectancy for PE and CBD separately will 
879 
be assessed separately from the credibility and expectancy for Cannabidiol.  The 6-item CEQ assesses both whether the 
880 
person cognitively understands how the therapy works (credibility) as well as whether the person affectively believes that 
881 
the therapy will work for them personally (expectancy).  The 6-item CEQ has been tested in 217 individuals including 68 
882 
male Vietnam veterans and 58 female spouses, 69 individuals diagnosed with general anxiety disorder who had received 
883 
treatment, and 22 individuals who had received either Cognitive Based Therapy (CBT) or Eye Movement Desensitization 
884 
and Reprocessing (EMDR) for the treatment of PTSD.  The scale demonstrated high internal consistency (alpha 
885 
coefficients ranged from 0.84 to 0.85).   Test-retest reliability over a one-week period was found to be 0.82 for expectancy 
886 
and 0.75 for credibility. The CEQ was able to differentiate between two treatment rationales in one study, one with and 
887 
one without an encompassing theory while maintaining equivalence between three rationales in another study.  
888 
Responses to four questions are scored using a 9-point Likert scale (1= not at all, 9= extremely).  Responses to two of the 
889 
questions are scored using an 11-point Likert Scale (0% to 100%).  The combined responses are used to generate a 
890 
score for credibility and another score for expectancy. This measure will be administered prior to the second PE session 
891 
following Session 1 which will review the PE rationale for the treatment of PTSD. 
892 
 
893 
19. Credibility/ Expectancy Questionnaire (CEQ) for CBD. The CEQ is a 6-item measure that was designed to assess 
894 
treatment expectancy and rationale credibility for use in clinical outcomes studies.  The CEQ has been utilized across a 
895 
number of STRONG STAR treatment trials and can be easily adapted to assess the target intervention(s). For the current 
896 
proposed study, the CEQ will be adapted to assess the credibility and expectancy for PE and CBD separately will be 
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assessed separately from the credibility and expectancy for Cannabidiol.  The 6-item CEQ assesses both whether the 
898 
person cognitively understands how the therapy works (credibility) as well as whether the person affectively believes that 
899 
the therapy will work for them personally (expectancy).  The 6-item CEQ has been tested in 217 individuals including 68 
900 
male Vietnam veterans and 58 female spouses, 69 individuals diagnosed with general anxiety disorder who had received 
901 
treatment, and 22 individuals who had received either Cognitive Based Therapy (CBT) or Eye Movement Desensitization 
902 
and Reprocessing (EMDR) for the treatment of PTSD.  The scale demonstrated high internal consistency (alpha 
903 
coefficients ranged from 0.84 to 0.85).   Test-retest reliability over a one-week period was found to be 0.82 for expectancy 
904 
and 0.75 for credibility. The CEQ was able to differentiate between two treatment rationales in one study, one with and 
905 
one without an encompassing theory while maintaining equivalence between three rationales in another study.  
906 
Responses to four questions are scored using a 9-point Likert scale (1= not at all, 9= extremely).  Responses to two of the 
907 
questions are scored using an 11-point Likert Scale (0% to 100%).  The combined responses are used to generate a 
908 
score for credibility and another score for expectancy. This measure will be administered prior to the second PE session 
909 
following Session 1 which will review the CBD rationale as an augmentation to PE for the treatment of PTSD. 
910 
 
911 
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ICF_000.pdf: 
Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
21-711H, Straud, Form D Civilian, 03-25-22, AMD.docx 
 
 
Page 1 of 12 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
Updated by STRONG STAR on 03/25/22 
COVER PAGE  
 
 
 
 
 
Official Study Title: Enhancing Prolonged Exposure with Cannabidiol to Treat 
Posttraumatic Stress Disorder: A Pilot Study 
 
NCT number: NCT05132699 
 
IRB Approval Date: 03-25-2022 
 
 
Unique Protocol ID: HCS20210711H 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Page 2 of 12 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
Updated by STRONG STAR on 03/25/22 
 
Concise Summary 
Important Information  
This information gives you an overview of the research. More information about these topics may be found in the 
pages that follow. You may choose not to take part in the study or may choose to leave the study at any time. 
Deciding not to participate, or deciding to leave the study later, will not result in any penalty or loss of benefits to 
which you are entitled and will not affect your relationship with us. 
1. What problem is this study trying to solve? 
You are being asked to participate in a research study. Scientists do research to answer important questions which 
might help change or improve the way we do things in the future. In this study, we are evaluating whether 
cannabidiol (CBD) can be combined with Prolonged Exposure (PE), an evidence-based, gold standard talk therapy 
for posttraumatic stress disorder (PTSD) to improve treatment response. For more information see the Why is this 
study being done section in the next pages. 
2. What will happen to me during the study and how is this different from continuing with usual care? 
What are all my options for treatment, including the pros and cons? 
After consenting to be in the study, you will be asked to complete a baseline assessment of your psychological 
and physical health that will determine whether you are able to participate in the study. Following the baseline, 
you will be randomly assigned to receive 18 consecutive days of CBD (Epidiolex®) or placebo. Everyone will 
also participate in 10 PE therapy sessions (90 minutes each) provided over 2 consecutive weeks. At the first 
treatment session and at the end of each treatment week, you will be asked to complete additional 
assessments. Finally, you will be asked to complete a follow-up assessment 1-month after you finish with 
treatment. In addition to questionnaires and interviews, assessments will include a blood draw, saliva 
collection, and wearing a watch to monitor your heartrate.  Not all assessments will be done at every 
assessment time.   
Comparison to Usual Care:  PE is care typically provided to treat PTSD and is considered a standard 
treatment. Other treatments for PTSD can include other talk therapies or medications that may help manage 
PTSD symptoms. It may be possible that a community physician will prescribe CBD (Epidiolex®), but this is not 
currently a usual practice. Additionally, there may be other research studies that treat PTSD. For more 
information, see the What will be done if you decide to be in the research section in the next pages. 
3. How much time will I spend on the study? 
You will be asked to complete a total of 13 visits, which includes 2 assessment visits (up to 4 hours each), 1 
medication review appointment (up to 60 minutes), and 10 PE treatment visits (90 minutes each day) 3 of 
which will also include some assessments. Altogether, you will spend up to 26 hours in this study over the next 
one to two months. 
4. Could taking part in the study help me and are there risks?  
Participating in this study may help you reduce your PTSD symptoms. Research on CBD has found that is safe 
and well-tolerated by most individuals. Common risks of CBD may include diarrhea or drowsiness. Other side 
effects that can occur are reduced appetite, dry mouth, vomiting, weight loss, and elevated liver function. Risks 
of PE talk therapy may include temporary increases in emotional distress, PTSD, depression, or anxiety 
symptoms. For more information, please see How could you or others benefit from your taking part in this 
study section in the next pages. For details and a list of risks you should know about, please see the What are 
the risks of participation in the research section in the next pages. 
5. What else should I consider before I make my decision? 
The daily format of therapy in this study can be time intensive. It is helpful to select a two-week period in which you 
can minimize outside appointments and obligations. 
Please review the rest of this document for additional details about these topics and other information you 
should know before making a decision about participating in this research. 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Page 3 of 12 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
Updated by STRONG STAR on 03/25/22 
Consent to be part of a Research Study 
To be conducted at  
The University of Texas Health Science Center at San Antonio (UT Health San Antonio) 
 
Information about this form 
You may be eligible to take part in a research study. This form gives you important information about the study. 
Please take time to review this information carefully. You should talk to the researchers about the study and 
ask them any questions you have. You may also wish to talk to others (for example, your friends, family, or a 
doctor) about your participation in this study. If you decide to take part in the study, you will be asked to sign 
this form. Before you sign this form, be sure you understand what the study is about, including the risks and 
possible benefits to you. Please tell the researchers or study staff if you are taking part in another research 
study. 
 
Voluntary Participation - You do not have to participate if you don't want to. You may also leave the study at 
any time. If you leave the study before it is finished, there will be no penalty to you, and you will not lose any 
benefits to which you are entitled.  
 
General Information – “Who is conducting this research?” 
 
Principal Investigator 
The Principal Investigator (PI) is the researcher directing this study; the PI is responsible for protecting your 
rights, safety, and welfare as a participant in the research. The PI for this study is Casey Straud, PsyD, a 
board-certified psychologist who is part of the faculty of the Division of Behavioral Medicine, Department of 
Psychiatry and Behavioral Sciences, UT Health San Antonio. 
 
Partnering Senior Investigator 
The grant award supporting this study supports early career investigators. The Partnering Senior Investigator is 
the primary mentor for the PI on this this study. The Partnering Senior Investigator for this study is Alan 
Peterson, PhD, a board-certified psychologist who leads the Division of Behavioral Medicine, Department of 
Psychiatry and Behavioral Sciences, UT Health San Antonio. 
 
Study Physician  
The Study Physician Investigator on this study is Van King, MD, who is a Professor in the  Department of 
Psychiatry and Behavioral Sciences, UT Health San Antonio.  Dr. King will be prescribing the study drug. 
 
Funding  
This project is supported by the National Center for Advancing Translational Sciences, National Institute of 
Health, a non-profit, federal government organization. 
 
Purpose of this study – “Why is this study being done?” 
This study is being done to see if cannabidiol (CBD) can be combined with Prolonged Exposure (PE), an 
evidence-based, gold standard talk therapy for posttraumatic stress disorder (PTSD) to improve treatment 
response. CBD (Epidiolex®) comes in an oil-based solution and is taken orally using a dropper. The use of 
CBD in combination with PE may reduce hyperarousal symptoms associated with PTSD and help process the 
traumatic event more effectively during therapy.  
 
The researchers hope to learn if the combination of CBD+PE is safe and effective. We also hope to identify 
biomarkers that explain how CBD interacts with the body to reduce PTSD symptoms. 
 
Investigational Use of Procedures & Drug for PTSD: This study involves the use of an investigational drug 
(CBD-Epidiolex®) to augment treatment for PTSD. “Investigational” means that this drug has not yet been 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Page 4 of 12 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
Updated by STRONG STAR on 03/25/22 
approved by the U.S. Food & Drug Administration (FDA) for treating PTSD; however CBD is FDA-approved for 
the treatment of some types of seizure disorders. The safety of this drug in humans has been tested in prior 
research studies; however, the amount of benefit of CBD to treat PTSD above and beyond placebo in 
combination with PE therapy has not been determined. 
 
This trial will be registered on www.ClinicalTrials.gov, a publicly available registry of clinical trials. This web site 
will not include information that can identify you. At most, the Web site will include a summary of the study 
results. You can search this web site at any time.  
 
Information about Study Participants – “Who is participating in this research?” 
You are being asked to take part in this research study because you are experiencing trauma-related 
symptoms consistent with posttraumatic stress disorder (PTSD). This pilot study will enroll up to 24 study 
participants. 
 
Information about Study Procedures – “What will be done if you decide to be in the research?” 
The preferred method of assessment and therapy is face-to-face in San Antonio. However, there may be 
circumstances when you can complete some of the assessments electronically or over the telephone and part 
of the therapy through telebehavioral health (i.e., by phone or using a HIPAA-compliant video calling platform 
like Zoom). Decisions will be made on a case-by-case basis as issues arise for individuals (e.g., childcare) and 
in discussion with the treatment team. Patients who do not have internet access may need to receive treatment 
in person if a phone call is not sufficient for the type of visit.  You will need to be seen in person to receive the 
medication. 
 
Baseline/Screening: After you sign this consent to participate, you will be asked to complete a series of 
questionnaires and then meet with an evaluator who will assess your mental and physical health. All 
participants will complete a urine drug test and females who are able to become pregnant will complete a urine 
pregnancy test. You cannot take part in this study if you are pregnant or breastfeeding. You will also be asked 
to complete liver function blood tests (LFTs) and provide them to the study team for review prior to 
randomization. The baseline/screening process will take approximately 3-4 hours. The results of these 
screening procedures will be reviewed to determine whether it is appropriate for you to continue in the study. If 
at any point during the baseline process it is determined that it would not be appropriate for you to continue in 
the study OR if you choose not to enroll, then the researcher will discuss the reasons with you and coordinate 
appropriate follow-up outside of this study.  
 
You have my permission to use assessments collected as part of the screening for another UT Health San 
Antonio STRONG STAR study or program as baseline data for my participation in this study.  
 
Circle one:  N/A    YES    NO     ________________            _____________________                                      
                                                   Initials of Participant                              Date 
 
Study Procedures: As a participant, you will be asked to: 
• 
Meet with a member of the research team to review your assessment findings and discuss treatment. 
• 
Participate in a medication review appointment (up to 60 minutes) prior to beginning CBD/placebo and 
Prolonged Exposure (PE). This appointment will include a blood draw and saliva collection participants will 
be given materials for a saliva collection the following morning 
• 
Participate in 10 PE sessions on weekdays over two consecutive weeks. Sessions will be held weekdays 
at the UT Health San Antonio STRONG STAR offices or by telebehavioral/telemedicine health and will 
each last approximately 90 minutes. At sessions 3, 5, and 10, you will also wear a hear rate monitor 
wristwatch during the 90 minute session. 
• 
Complete three interim assessments during treatment to complete blood draw and psychological self-report 
measures. 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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• 
You will receive instructions for collecting 2 saliva (spit) samples at home before each interim 
assessment.  You will be given plastic vials to store the samples in and an insulated lunch bag with an ice 
pack to bring the samples into the research office with you.  
• 
Complete out-of-session treatment assignments daily. (e.g., listen to session audio recording and complete 
a real world exposure). 
• 
Complete 18 consecutive days of the medication regimen of CBD or placebo taking two liquid doses orally 
twice a day, morning and evening. 
• 
Refrain from or postpone changing your medications or working with another provider on problems related 
to PTSD while you are in the study. This will help us better understand how the treatment in this study 
impacts you. However, if you feel that you do need to work with another provider on your PTSD, please be 
sure to let us know so that we can coordinate your care accordingly. Also, if you and your prescriber feel 
that a change in your medication is needed please let a member of the research team know so that we can 
record the change in your research file. 
 
Since the study is examining an outpatient treatment for PTSD, you have the option of having the study team 
coordinate with you and your employer to ensure you have the time to attend all of the treatment and 
assessment sessions. With your permission, one of the members of the research team will contact your 
supervisor to get his or her support for you to participate in this study. If you choose to have the research team 
contact your supervisor, supervisor will be told that you have agreed to participate in a research study and will 
be given your treatment and assessment schedule. 
 
Assignment to Study Groups: When it is determined that you are eligible for the study, you will be assigned 
by chance (like flipping a coin) to receive 18 consecutive days of either CBD or placebo. You will have a 50% 
chance of being in the placebo group. A placebo is an inactive, harmless substance that looks like the study 
drug. Randomization will be double blinded which means that neither you nor the researchers will know 
whether you are receiving the study drug or placebo. In the event of an emergency, there is a way for the 
researcher to find out which drug you are receiving. All participants will receive 10 sessions of PE regardless of 
which group they are randomized to for the study. 
 
Assessments: In addition to the treatment sessions, you will be asked to complete interim assessments prior 
to the first PE session, halfway through treatment, and at your final treatment session. These assessments will 
include a blood draw, saliva collection, wearing a watch to monitor heart rate, and self-report questionnaires 
and will add up to 30 minutes to your therapy appointment to complete. One month after you have completed 
treatment, you will be asked to complete a longer, more comprehensive assessment similar to what you did for 
the assessment prior to starting treatment.  
 
Even if you choose to stop treatment, we will ask that you complete the 1-month assessment visit. This will 
help us understand how the treatment works even if you do not receive the full dose. Your participation in all 
parts of this study is very important.  
 
Recordings: As part of PE treatment, you will be asked to listen to an audio recording of the session prior to 
your next session. Therefore, all therapy sessions will be audio-recorded using an independent recording 
device These recordings are only for the purpose of therapy and will be deleted once you have reviewed the 
session. We will not store any recordings for future purposes for this study. If you do not have an audio 
recording device, we can provide one for you during study participation. By signing this consent, you are giving 
your permission for recordings. 
 
Time Commitment: While you are taking part in this study, you will be asked to attend approximately 13 visits, 
which includes 2 assessment visits (up to 4 hours each), 1 medication review appointment (up to 60 minutes), 
and 10 PE treatment visits (90 minutes each day). You will also complete 3 assessment visits prior to PE 
sessions 1, 5, and 10 for a blood draw, saliva collection, and completion of self-report psychological measures 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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that will add up to 30 minutes to each of these 3 appointments. You will take the medication every day for 18 
consecutive days; however, therapy sessions will be completed on weekdays during regular business hours. 
Altogether, you will spend up to 26 hours in this study over the next one to two months. 
 
Future Use of Your Information or Biospecimens Collected as Part of Your Participation 
The researchers will be asking your permission to store your questionnaire answers and any left-over blood 
samples with your personal identifying information after this study is completed in the STRONG STAR 
Repository. The Repository is designed to be used for research investigating the causes, consequences, and 
treatment of PTSD and related conditions. Your consent to allow us to store your information will be given in a 
separate consent document. Your participation in the current study does not depend on your decision to 
participate or not in the Repository. Please note however that if you decide not to participate in the Repository, 
the researchers intend to keep and use the information collected as part of this study, but your personal 
identifiers (such as name, SSN, and contact information) will be permanently destroyed so that it can never be 
linked to you again. 
 
The de-identified information or biospecimens could be used for future research studies or distributed to 
another investigator for future research studies without additional informed consent from you or your legally 
authorized representative.  
 
Information about Optional Procedures – “What are other research activities that may be done but 
are not required for your participation?” 
 
E-mail Authorization Agreement  
The research team would like to communicate with you regarding your research visits via email.  If you agree 
to receive emails about your research visits, we will ask that you sign a separate Email Authorization 
Agreement. You do not have to consent to receive emails. 
 
Ending Participation Early – Could your participation end early? There are several reasons why the 
researchers may need to end your participation in the study (early withdrawal). Some reasons are: 
• 
The researcher believes that it is not in your best interest to stay in the study. 
• 
You become ineligible to participate. 
• 
Your condition changes and you need treatment that is not allowed while you are taking part in the study. 
• 
You do not follow instructions from the researchers. 
• 
The study is stopped. 
 
Risks – “What are the risks of participation in the research?” 
Risks from the research 
There are risks to taking part in this research study. One risk is that you may have side effects while in the 
study. Everyone taking part in the study will be watched carefully for any side effects. However, the study staff 
do not know all of the side effects that may happen. Be sure to tell your study therapist immediately about any 
side effects that you have while taking part in the study. The frequency that people experience a certain side 
effect can range from many (likely), few (less likely) or only one or two (rarely).  
 
The following section will describe the risks related to your participation in this research study, including your 
participation in the psychological assessments, the Prolonged Exposure therapy, the medications, and the 
blood draw. These risks apply whether you complete the treatment program in person or by 
telebehavioral/telemedicine health. You should talk to your study doctor about any side effects or other 
problems that you have while taking part in the study.  
 
 
 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Risks related to Cannabidiol (Epidiolex®): 
Likely but Not Serious (expected to occur in less than 20 out of 100 participants): 
• 
Fatigue 
• 
Drowsiness 
• 
Feeling weak 
• 
Malaise 
• 
Loss of appetite 
• 
Diarrhea 
• 
Skin rash 
• 
Insomnia 
• 
Viral/fungal infections 
Rare, but Serious Risks (expected to occur in less than 5 out of 100 participants): 
• 
Liver problems 
• 
Sedation (e.g., elevated somnolence, loss of coordination, and difficulty with concentration) 
• 
Severe allergic reaction (skin rash, itchiness, flushed skin, angioedema, difficulty breathing) 
• 
Suicidal thoughts or behavior (< 1%) 
Risks related to Prolonged Exposure Therapy and Psychological Assessments:  
Likely but Not Serious (expected to occur in less than 20 out of 100 participants): 
• 
Emotional distress including experiencing an initial increase of PTSD symptoms due to the discussion 
of traumatic events.  
 
Rare, but Serious Risks (expected to occur in less than 5 out of 100 participants): 
• 
A temporary or occasional increase in symptoms of depression, anxiety, or other pre-existing 
psychiatric symptoms. 
 
Risks related to the Blood Draw:  
Likely Risks, but Not Serious (expected to occur in more than 20 subjects out of 100): 
• 
You may experience discomfort, bruising or both, at the site of the needle puncture during blood 
sample collection.   
 
Less Likely, and Not Serious (expected to occur in 5-20 subjects or less out of 100) 
• 
Some people experience fainting, the formation of a small blood clot or swelling of the vein and 
surrounding tissue, or bleeding from the puncture site. 
 
Rare, but Serious Risks (expected to occur in <5 subjects out of 100):   
• 
There could be infection at the site where the blood was drawn, but this risk is reduced because the 
trained staff drawing your blood will use procedures to reduce this risk. 
 
Risks to Confidentiality 
• 
Although efforts are made to protect your research study records, there is always a risk that someone 
could get access to the personal information in your medical records or other information researchers 
have stored about you. 
• 
If you use of online conferencing systems there is a possibility for someone to overhear your 
discussions or our conferencing systems to be accessed, your privacy and confidentiality is not 
guaranteed. 
 
 
 
 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Updated by STRONG STAR on 03/25/22 
Reproductive Risks 
 
Concerns for sexually active men and women:  Women should not become pregnant and men should not 
father a baby while taking part in this study because we do not know how the study drugs/procedures could 
affect a man's sperm (for some drugs/procedures, the concern may be that the sperm might be affected and in 
some cases, drugs could being carried by the semen into the vagina and cause harm) or a fetus, if a woman 
becomes pregnant during the study.  It is important that you talk to your study doctor about avoiding pregnancy 
during this study.  If you think you might have become pregnant or if you believe your female partner has 
become pregnant while you are in this study, you must tell one of the study doctors right away so that 
management of the pregnancy and the possibility of stopping the study can be discussed.   
 
If you are a woman who is pregnant or could be pregnant, you cannot take part in this study because we do 
not know how CBD might affect a developing fetus.  We will do a pregnancy test before you start treatment to 
make sure you are not pregnant.    
 
Risks to babies who are being breastfed:  Women who are breastfeeding cannot take part in this study 
because we do not know what effect CBD might have on their breast milk and the baby. 
 
Risks whether you participate in this research or not: 
Individuals with PTSD may have suicidal thoughts or attempt suicide. This is a risk to you whether you are 
being treated for PTSD or not. Therefore, the risk of suicide is not any higher in the study than it would be if 
you were not in this study. Your treatment may require you to talk about some things that might be painful or 
uncomfortable for you, which could cause increased emotional distress and the possibility of increased suicide 
risk, which can result in death. In the event that you are thinking about hurting yourself, please tell your 
therapist. Your therapist will work with you to develop a plan of specific steps for you to follow when in crisis. If 
we believe that you are at high risk for hurting yourself, we might also decide to include your family and social 
support network in your care to maintain your safety.  
 
If at any time you are feeling significant distress or if you are having thoughts of hurting yourself or someone 
else, please notify your therapist or come into the clinic as soon as possible. You can also be seen in a 
Hospital Emergency Room after business hours and on weekends and holidays at any time.  
 
We will tell you about any significant new findings which develop during the course of this research which may 
influence your willingness to continue to take part. For more information about risks and side effects, ask one 
of the researchers or study staff.  
 
Are there Risks related to withdrawing from the study?  
If you decide to withdraw from this study early, please discuss your decision with the research team. If you 
decided to withdraw, we may ask you if you are willing to participate in a brief assessment with a study clinician 
either in-person or by phone just to assess your condition and make appropriate referrals if necessary. We are 
also interested in following up with you at the times you would have been assessed if you had completed all of 
the sessions to answer some questionnaires. However, your participation in the follow-up assessments is 
completely your choice. There is no risk to you if you do not complete the final withdrawal procedures, and you 
can choose not to participate in them.  
 
Are there risks if you also participate in other research studies? 
Being in more than one research study at the same time may affect the results of the studies. You should not 
take part in more than one study without discussing it with the researchers of both studies. 
 
 
 
 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Updated by STRONG STAR on 03/25/22 
What if a research-related injury occurs?  
The researchers have taken steps to minimize the known or expected risks. However, you may still experience 
problems or side effects, even though the researchers are careful to avoid them. In the event of a research-
related injury or if you experience an adverse reaction, please immediately contact your study doctor. See the 
section “Contact Information” for phone numbers and additional information. You may also need to tell your 
regular doctors. 
 
If you are injured or made sick from taking part in this research study, medical care will be provided. This care 
may be billed to you or your insurance. Depending on the circumstances, this care may be provided at no cost 
to you. We have no plans to give you money if you are injured. The investigator can provide you with more 
information. 
 
If you sign this form, you do not give up your right to seek additional compensation if you are harmed as a 
result of being in this study. 
 
Benefits – “How could you or others benefit from your taking part in this study?” 
The possible benefit of your participating in this study is a potential reduction in your symptoms associated with 
PTSD, which may positively affect your overall health and well-being. There is no guarantee or promise that 
you will receive any benefit from this study. We hope the information learned from this study will benefit other 
people with similar conditions in the future. 
 
Alternative procedures or course of treatment – “What other options are there to participation in this 
study?” 
There are other options available to you. Your other choices may include: 
• 
Not participating in the study.  
• 
Receiving another form of psychotherapy (talk therapy) from another therapist. 
• 
Other medications, such as antidepressants. 
• 
A community physician may be willing to prescribe you CBD (Epidiolex®), but this is not their usual 
practice for PTSD.  
• 
There may be other research studies involving experimental treatments that could be helpful for your 
conditions.  
 
Payments – Will there be any payments for participation? 
Participants will be paid for each blood draw as follows for a total of up to $100: 
• 
$10 pre-treatment medication appointment 
• 
$20 Interim Assessment 1 
• 
$30 Interim Assessment 2 
• 
$40 Interim Assessment 3 
 
The researchers will provide you with a ClinCard MasterCard®. Compensation will be automatically credited 
after completion of each blood draw. Your name, address, date of birth, and social security number will be 
shared with a third-party solely for the purposes of compensation processing. This information will only be used 
for the administration of the compensation (ClinCard MasterCard®) and will be kept strictly confidential.  
 
In addition to the compensation on the card, you may also elect to receive messages (text and/or email) that 
money has been loaded onto your card. Please indicate your willingness to receive study-related messages: 
□ Yes, I would like to participate (please select the best method(s) for communication) 
o Cell Phone (text messages) 
o Email 
□ No, I choose not to participate 
 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Costs – Will taking part in this study cost anything? 
 
CBD (Epidiolex®) will be provided to you free of charge during this study. 
 
You will be required to complete a blood test for liver function tests (LFTs) or provide a copy of LFT lab results 
completed within the last 90 days.  A study team member will work with you to obtain and pay for your LFTs, if 
necessary.  We do not guarantee that there will be no additional costs for LFTs, but if there are additional costs 
we will work with you to cover those costs. 
 
Confidentiality – How will your records be kept confidential? 
 
Information we learn about you in this study will be handled in a confidential manner, within the limits of the 
law. If we publish the results of the study in a scientific journal or book, we will not identify you. The Institutional 
Review Board and other groups that have the responsibility of monitoring research may want to see study 
records which identify you as a subject in this study.  
 
Research policies require that private information about you be protected and this is especially true for your 
health information. However, the law sometimes allows or requires others to see your information. The 
information below describes how your privacy and the confidentiality of your research records will be protected 
in this study. 
 
What is Protected Health Information (PHI)?  
Protected Health Information is information about a person’s health that includes information that would make it 
possible to figure out who it is. According to the law, you have the right to decide who can see your protected 
health information. If you choose to take part in this study, you will be giving your permission to the 
investigators and the research study staff (individuals carrying out the study) to see and use your health 
information for this research study. In carrying out this research, the health information we will see and use 
about you will include: name, address, phone numbers, and email address to be able to contact you and make 
follow-up appointments; social security number for medical history to be sure we understand your medical and 
treatment history as well as any ongoing care that you receive while participating in this study; and 
questionnaire answers that you provide us as part of this study. We will get this information by asking you. 
 
How will your PHI be shared?  
Because this is a research study, we will be unable keep your PHI completely confidential. We may share your 
health information with people and groups involved in overseeing this research study including: 
• 
Members of the STRONG STAR research team at UT Health San Antonio 
• 
The STRONG STAR Data & Safety Monitoring Board, which is a committee that checks the study data 
on an ongoing basis, to determine if the study should be stopped for any reason. 
• 
Oakdell Pharmacy, responsible for distributing the CBD (Epidiolex®) and compounding the placebo. 
• 
The Institutional Review Board and the Compliance Office of the University of Texas Health Science 
Center at San Antonio, and other groups that oversee how research studies are carried out. 
• 
The Food and Drug Administration (FDA) and other U.S. State and Federal Government agencies 
when required by law.  
 
If you decide to participate in this study, you will be giving your permission for the groups named above to 
collect, use and share your health information within the limits of the law. If you choose not to let these groups 
collect, use and share your health information as explained above, you will not be able to participate in the 
research study. 
 
Parts of your PHI may be photocopied and sent to a central location or it may be transmitted electronically, 
such as by e-mail or fax. You need to be aware that some parties receiving your protected health information 
may not have the same obligations to protect your protected health information and may re-disclose your 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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protected health information to parties not named here. If your protected health information is re-disclosed, it 
may no longer be protected by state or federal privacy laws. 
 
How will your PHI be protected?  
In an effort to protect your privacy, the study staff will use code numbers instead of your name to identify your 
health information. These code numbers will be used on any copy of our study records and other study 
materials containing health information. If the results of the study are reported in medical journals or meetings, 
you will not be identified.  
 
STRONG STAR strictly controls access to study data only allowing researchers associated with this study to 
review your data. However, complete confidentiality cannot be promised because information regarding your 
health may be required to be reported to appropriate medical authorities. For example, if you indicate you have 
thoughts of harming yourself of others the research team will want to immediately work with you to get you 
help.  
 
Do you have to allow the use of your health information? 
You do not have to allow (authorize) the researchers and other groups to see and share your health 
information. If you choose not to let the researchers and other groups use your health information, there will be 
no penalties but you will not be allowed to participate in the study.  
 
After you enroll in this study, you may ask the researchers to stop using your health information at any time. 
However, you need to say this in writing and send your letter to: 
 
Dr. Casey Straud  
University of Texas Health Science Center at San Antonio 
Department of Psychiatry and Behavioral Sciences – Mail Code 7747 
7550 IH10 West, Suite 1325, San Antonio, Texas 78229 
 
How long will your PHI be used?  
By signing this form, you agree to let us use and disclose your health information for purposes of the study until 
the end of the study. This permission to use your personal health information expires when the research ends 
and all required study monitoring is over. If you also decide to participate in the STRONG STAR Repository 
with a separate consent, you will agree to let us use and disclose your health information in accordance with 
the Repository’s authorization. 
 
Contact Information – Who can you contact if you have questions, concerns, comments or 
complaints? 
If you have questions now, feel free to ask us. If you have additional questions, concerns, comments or 
complaints later or you wish to report a problem which may be related to this study please contact: 
 
Primary contact: 
Principal Investigator: Casey Straud, PsyD, ABPP who can be reached at 210-562-6742.  
 
If primary is not available, you can contact: 
Partnering Senior Investigator: Alan Peterson, PhD, ABPP who can be reached at 210-562-6700. 
 
The University of Texas Health Science Center committee that reviews research on human subjects 
(Institutional Review Board) will answer any questions about your rights as a research subject, and take any 
concerns, comments or complaints you may wish to offer. You can contact the IRB by calling 210-567-8250, or 
by mail to IRB, UTHSCSA, Mail Code 7830, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. 
 
 


Title of Study: Enhancing Prolonged Exposure with Cannabidiol to Treat Posttraumatic Stress Disorder: A 
Pilot Study 
 
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Research Consent & Authorization Signature Section 
The lawyers at the UT Health San Antonio require patients participating in research studies who are receiving 
part of their research by phone or a video platform to read and sign this form voluntarily requesting UT Health 
San Antonio and such research associates, residents, research assistants and other research health care 
providers as needed (“UT Health San Antonio Telemedicine/Telebehavioral Providers”) to participate in your 
research care through the use of telemedicine. You understand that UT Health San Antonio (i) may practice in 
a different location than where you present for medical care, (ii) may not have the opportunity to perform an in-
person interview, and (iii) will rely on information provided by you. You acknowledge that UT Health San 
Antonio research Telemedicine/Telebehavioral Providers’ will not provide advice, recommendations about your 
routine health care. No decisions or recommendations for your care outside of this research project will be 
made. You acknowledge that it is your responsibility to provide information about your medical history, 
condition and care that is complete and accurate to the best of your ability, you understand that the practice of 
medicine is not an exact science and that no warranties or guarantees are made to you as to result or cure. If 
UT Health San Antonio Telemedicine/Telebehavioral Providers determine that the telemedicine services do not 
adequately address your medical needs, they may require an in-person psychological evaluation. In the event 
the telemedicine session is interrupted due to technological problem or equipment failure, alternative means of 
communication may be implemented, or an in-person psychological evaluation may be necessary. If you 
experience an urgent matter, such as a bad reaction to any treatment after a telemedicine session, you should 
alert your primary care provider and, in case of emergencies dial 911 or go to the nearest hospital emergency 
department. 
 
If you agree to participate in this research and agree to the use of your protected health information in this 
research sign this section. You will be given a copy of this form to keep. You do not waive any of your legal 
rights by signing this form.  
 
SIGN THIS FORM ONLY IF THE STATEMENTS LISTED BELOW ARE TRUE 
• 
You have read the above information. 
• 
Your questions have been answered to your satisfaction about the research and about the collection, use 
and sharing of your protected health information.  
 
Adult Signature Section 
• 
You have voluntarily decided to take part in this research study. 
• 
You authorize the collection, use and sharing of your protected health information as described in this form. 
 
 
 
 
 
 
 
 
AM 
PM 
Printed Name of Subject 
 
 
 
Signature of Subject 
 
 
Date 
 
Time 
 
 
 
 
 
 
 
 
AM 
PM 
Printed Name of Person Obtaining 
Consent and Authorization 
 
Signature of Person Obtaining Consent 
and Authorization 
 
 
Date 
 
Time 
Consent and authorization was obtained from this individual who is unable to read and/or write but can otherwise communicate and/or comprehend 
English.  The method used for communication with the subject was: ______________________.  
The specific means by which the subject communicated agreement to participate was: 
____________________________________