Use of Cannabidiol (CBD) oil in the treatment of PTSD: Study design and rationale for a placebo-controlled randomized clinical trial

Background: The burden of illness for PTSD is staggering and confers significant interference in work, social functioning, as well as increased risk for other physical and mental health problems. Recently, there's been considerable attention paid to the potential therapeutic use of cannabidiol (CBD) products in the treatment of a variety of physical and mental health problems. The endocannabinoid system (ECS) is a logical therapeutic target for combating PTSD and other fear-based disorders given that cannabinoid receptors and other molecular me-diators crucial for ECS signaling are richly expressed in a variety of brain regions that govern the regulation of learned fear and defensive behavior. Methods: This is an 8-week single-site Phase II randomized double-blind placebo-controlled fixed dose clinical trial. Participants recruited throughout the United States (N = 150) meeting DSM-5 criteria for posttraumatic stress disorder are randomly assigned to one of three treatment arms: (a) 300 mg CBD Isolate; (b) 300 mg CBD Broad Spectrum; and (c) Placebo oil. The primary outcome is PTSD symptom severity as indexed by the PTSD Checklist for DSM-5 (PCL-5) assessed at post treatment (Week 9) and follow-up (Week 13). Secondary outcomes including patient-rated depression, overall disability, anxiety, quality of life, and alcohol use are assessed weekly throughout the trial. Safety and CBD adherence are assessed daily throughout the trial.Conclusion: This is the first placebo-controlled clinical trial investigating (a) CBD for the treatment of PTSD; and (b) the first study to test the relative efficacy of CBD Isolate vs CBD Broad Spectrum.Trial registrationClinicalTrials.gov registered (12/12/2019), trial identifier NCT04197102. Protocol version: issued 08/04/2022, protocol amendment number #2019-05-0123.