Enhancing Prolonged Exposure With Cannabidiol to Treat Posttraumatic Stress Disorder

Phase 1

Completed

Interventions: Drug: Cannabidiol (CBD) oral solution
Drug: Placebo
Behavioral: Massed Prolonged Exposure (mPE)

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.

Recruitment & Eligibility

Inclusion Criteria

Individuals between the age of 18 to 65 years old at time of screening.
Able to write, read, and speak English
PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5)
Stable medication regimen for at least four weeks prior to the onset of study participation.

Exclusion Criteria

History of opiate, cocaine, methamphetamine, benzodiazepine, or cannabis abuse as determined by the National Institute of Drug Abuse Quick Screen (NIDA-Q).
Currently using opiates, cocaine, methamphetamines, benzodiazepines, or cannabis as evidenced by a positive urine drug screen prior to enrollment.
Currently pregnant as determined by a positive urine pregnancy test prior to enrollment.
Current clinically significant alcohol abuse in the past two weeks on the Quick Drinking Screen (QDS).
Currently breastfeeding.
Ongoing illness or physical health problem(s) that may be exacerbated by CBD (e.g., history of liver problems)
History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to cannabinoids.
Concomitant medications with possible CBD-drug interactions
Alanine transaminase (ALT) or Aspartate transaminase (AST) enzyme levels 3x normal limits.
Concurrent engagement in trauma-related psychotherapy for PTSD.
Current or past DSM-5 diagnosis of psychotic disorder or bipolar disorder as determined on the Mini International Neuropsychiatric Interview (MINI 7.0).
Suicide attempt in the last year and/or suicide risk requiring immediate intervention or requiring a higher level of care than can be provided by the study treatment as determined by the Self-Injurious Thoughts and Behaviors Interview (SIT-BI).
Allergy to sesame seed oil.

Arm && Interventions

Group	Intervention	Description
Cannabidiol (CBD)	Cannabidiol (CBD) oral solution	Epidiolex oral solution 500mg (5ml) per day
Cannabidiol (CBD)	Massed Prolonged Exposure (mPE)	Epidiolex oral solution 500mg (5ml) per day
Placebo	Placebo	Placebo oral solution 5ml per day
Placebo	Massed Prolonged Exposure (mPE)	Placebo oral solution 5ml per day

Primary Outcome Measures

Name	Time	Method
Clinician Administered PTSD Scale (CAPS-5)	Baseline and at about 45 days (1 month follow-up visit)	The CAPS-5 is structured interview that assesses the Diagnostic and Statistical Manual of Mental Disorders v5 (DSM-5) criteria for PTSD. Each item is rated on a severity scale ranging from 0 (Absent) to 4 (Extreme/incapacitating) and combines information about frequency and intensity for each of the 20 symptoms.Subscale scores are calculated by summing severity scores for items in the following PTSD symptom clusters: re-experiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. Scores ≥ 25 indicate a probable diagnosis of PTSD. Scores range from 0 to 80. Change in score will be reported.
Posttraumatic Stress Disorder Checklist (PCL-5)	Baseline and at about 45 days (1 month follow-up visit)	The PCL-5 is a 20-item self-report measure update of the PCL designed to assess PTSD symptoms as defined by the DSM-5. The PCL-5 evaluates how much participants have been bothered by PTSD symptoms in the past week (for all assessments during treatment) or the past two weeks (all other assessment time points) as a result of a specific life event. Each item of the PCL-5 is scored on a five-point scale ranging from 0 "not at all") to 4 ("extremely). Scores range from 0 to 80 with a higher score indicating that subjects have been bothered more by PTSD symptoms. Change in score will be reported.

Secondary Outcome Measures

Name	Time	Method
Patient Health Questionnaire-9 (PHQ-9)	Baseline and at about 45 Days (1 month follow-up visit)	It consists of 9 items that assess both affective and somatic symptoms related to depression and depressive disorders; these 9 items correspond to the diagnostic criteria for Diagnostic Statistical Manual of Mental Disorders - Major Depressive Disorder (DSM MDD). Respondents rate the frequency with which they have been bothered by depressive symptoms within the past two weeks on a scale ranging from 0 ("not at all") to 3 ("nearly every day"). Scores on all items are summed to obtain a total severity score between 0 and 27. Scores reflect no significant depressive symptoms (0-4), mild depressive symptoms (5-9), moderate depressive symptoms (10-14), moderately severe depressive symptoms (15-19), and severe depressive symptoms (\>19). Change in score is reported.