# Enhancing massed prolonged exposure with cannabidiol to improve posttraumatic stress disorder: Design and methodology of a pilot randomized clinical trial

## TL;DR

This pilot study explores combining CBD with prolonged exposure therapy to improve PTSD treatment outcomes.

## Contribution

A novel pilot RCT design combining CBD and prolonged exposure therapy for PTSD is presented.

## Key findings

- CBD may decrease hyperarousal and enhance extinction learning in PTSD treatment.
- The study will assess feasibility, safety, and preliminary effects of the CBD intervention.
- Results will guide planning for a larger RCT on this combination therapy.

## Abstract

The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD.

Participants (n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system.

Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims.

Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition.

•Novel treatments for PTSD are critical given that many do not achieve remission after treatment.•CBD may decrease hyperarousal and enhance extinction learning.•The design and methods for a pilot RCT to examine a novel combination intervention are presented.•Findings will inform planning for a larger RCT and an alternative treatment option for PTSD.

Novel treatments for PTSD are critical given that many do not achieve remission after treatment.

CBD may decrease hyperarousal and enhance extinction learning.

The design and methods for a pilot RCT to examine a novel combination intervention are presented.

Findings will inform planning for a larger RCT and an alternative treatment option for PTSD.