Cannabidiol as a Treatment for PTSD and PTSD Comorbid With TBI

Study Overview
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Brief Summary
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This will be a randomized placebo controlled study to test the efficacy of cannabidiol (CBD) as a treatment for symptoms of post-traumatic stress disorder (PTSD). Subjects, 120 in total, will be males and females with PTSD, half of which will have comorbid mild traumatic brain injury (TBI). There will be three study arms, each with 40 subjects: 1) Oral CBD 400 mg daily; 2) Oral CBD 800 mg daily, and 3) Placebo daily. Treatment duration will be 8 weeks. The primary outcome will be change in PTSD symptoms as measured by change in the Clinician-Administered PTSD Scale (CAPS-5) total score.

Official Title
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Cannabidiol for Treating PTSD Symptoms and Neurocognitive Impairment in PTSD and PTSD Comorbid With TBI: A Placebo-controlled RCT With Neural-circuit Centered Precision Medicine Prediction of Response.

Conditions
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Post Traumatic Stress Disorder, Traumatic Brain Injury

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets clinical criteria for Posttraumatic Stress Disorder (PTSD) as per Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) TBI present (for PTSD+TBI subjects only) as per American Congress of Rehabilitation Medicine (ACRM) definition Mild TBI (for PTSD+TBI subjects only) as per Ohio State University Identification Screener Able to provide at least 2 locators Able to provide informed consent Confirmation that the participant is reliably domiciled Agreement to abstain from all other cannabinoid use for the duration of the study Willingness to use contraception if of childbearing potential. Exclusion Criteria: History of open head injury TBI within the last 6 months Moderate or Severe TBI SUD in the last 12 months other than mild AUD or nicotine use Use of any cannabinoid containing product within the last 1 month Positive urine drug screen (Positive for cannabinoids, amphetamine, cocaine, opioids) Currently prescribed medications with possible CBD-drug interactions Lifetime history of any psychiatric disorder with psychotic features, bipolar disorder Exposure to trauma in the last 30 days, including police duty or military service Psychotherapy for PTSD or other psychiatric conditions initiated within 2 months of screening Not stable for at least 2 months on psychiatric medication, anticonvulsants, antihypertensive medication, sympathomimetic medication, estrogen replacement therapy, medications associated with neurogenesis, or steroid medication Active suicide attempt within the past year Current significant suicidality (assessed using the C-SSRS), any significant suicidal behavior in the past 12 months, or any history of serious suicide attempts requiring hospitalization, or current significant homicidality. Neurologic disorder or systemic illness affecting CNS function (apart from TBI) Major medical illness (i.e. cancer or infectious disease.) Clinical diagnosis of anemia, advised by physician to avoid blood draws Significant laboratory abnormalities, significantly impaired hepatic function, abnormalities in complete blood count or metabolic panel Significant allergic reactions to the drug including cannabinoids or sesame oil Pregnancy or lactation Contraindication to MRI Males and females who plan to conceive a child during or two weeks following the study Active legal problems likely to result in incarceration within 12 weeks of treatment initiation Has a high risk of adverse emotional or behavioral reaction (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, and lack of meaningful social support). Inpatient psychiatric treatment in past 12 months, with the exception of detox and extended ED stays.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cannabidiol Group 1<br>40 participants will be titrated to a maximum dose of oral cannabidiol 800 mg daily over 2 weeks for a total of 8 weeks treatment. | Drug: Cannabidiol<br>* The drug product to be used in this study is an oral formulation of CBD<br>* Other names: A1002N5S;|
| Active Comparator: Cannabidiol Group 2<br>40 participants will be titrated to a maximum dose of oral cannabidiol 400 mg daily over 2 weeks for a total of 8 weeks treatment. | Drug: Cannabidiol<br>* The drug product to be used in this study is an oral formulation of CBD<br>* Other names: A1002N5S;|
| Placebo Comparator: Placebo Group<br>40 participants will be given a placebo for a total of 8 weeks treatment. | Drug: Placebo<br>* non-active medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PTSD symptoms | Baseline - Week 8 change in Clinician-Administered PTSD Scale (CAPS-5) total score. The CAPS-5 is the gold standard clinician administered interview for diagnosing PTSD and assessing symptom severity. Total CAPS-5 scores range from 0-80. Higher scores indicate greater symptom severity. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PTSD symptoms measured with PTSD Checklist (PCL-5) total score. | The PCL-5 is a 20-item self-report measure that assesses DSM-5 symptoms of PTSD. Higher scores indicate greater symptom severity. | Weekly over Weeks 1 to 8. | 
| Safety and tolerability of cannabidiol | Frequency of adverse events collected at all visits following randomization for active arms. The specific tool that will be used to document adverse events is the SAFTEE (Parts A and B). | All visits | 
| Change in CAPS-5 symptom cluster severity score for Criterion B, Reexperiencing. | The Criterion B (reexperiencing) severity score is the sum of the individual severity scores for CAPS-5 items 1-5. | Baseline, Week 8. | 
| Change in CAPS-5 symptom cluster severity score for Criterion C, Avoidance. | The Criterion C (Avoidance) severity score is the sum of the individual severity scores for CAPS-5 items 6 and 7. | Baseline, Week 8. | 
| Change in CAPS-5 symptom cluster severity score for Criterion D, Negative alterations in cognitions and mood. | The Criterion D (Negative alterations in cognitions and mood) severity score is the sum of the individual severity scores for CAPS-5 items 8-14. | Baseline, Week 8. | 
| Change in CAPS-5 symptom cluster severity score for Criterion E, Hyperarousal. | The Criterion E (Hyperarousal) severity score is the sum of the individual severity scores for CAPS-5 items 15-20. | Baseline, Week 8. | 
| Frequency of substantial reduction in PTSD symptoms | Number of subjects per arm with a reduction in Baseline - Week 8 CAPS-5 total score equal to or greater than 30%. | Baseline, Week 8 | 
| Change in plasma CBD levels | Peak and trough levels (Cmax) of plasma CBD will be determined via High Performance Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) | Day 1 (post first dose), Week 2, Week 8. |