Cannabidiol and Prolonged Exposure (CBD-PE)

• ClinicalTrials.gov Identifier: NCT03518801
• Recruitment Status: Recruiting
• First Posted: May 8, 2018
• Last Update Posted: September 7, 2022
• Sponsor: VA Office of Research and Development
• Collaborator: University of California, San Diego
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

The trial will include a randomized control trial to evaluate the efficacy of using Cannabidiol (CBD), a non-intoxicating cannabinoid, as an adjunctive to Prolonged Exposure therapy (PE). The trial will compare PE + CBD to PE + placebo in a sample of 136 military Veterans with PTSD at the VA San Diego Medical Center. The study represents the logical and innovative next step for augmenting existing treatments and developing novel pharmacotherapy for PTSD. Findings from the proposed RCT will inform clinical practice and policy by investigating whether administration of CBD in the context of PE therapy will improve treatment outcomes for military Veterans with PTSD.

Condition or disease	Intervention/treatment	Phase
PTSD	Behavioral: Prolonged Exposure; Drug: Cannabidiol; Drug: placebo	Phase 2

Detailed Description:

Prolonged exposure therapy (PE) is among the most efficacious treatments for PTSD and is designated as a VA/DoD frontline treatment. However, PE does not always lead to clinically meaningful symptom reductions in Veterans with PTSD. Successful PE treatment relies on extinction learning, which is often impaired in patients with PTSD. Cannabidiol (CBD) is a non-intoxicating phytocannabinoid. Administration of specific phytocannabinoids, like CBD, increase extinction learning in patients with PTSD, and could increase the speed and effectiveness of PE therapy. CBD also modulates 5-HT1A, which may directly improve hyperarousal/insomnia symptoms, and improve engagement and retention in treatment. Given these findings, adjunctive administration of CBD+PE could improve response rates to PE and reduce the number of sessions of PE needed to reach clinically meaningful change. The proposed study is designed to test the efficacy of using CBD in conjunction with PE for the treatment of PTSD in US Military Veterans. A randomized, controlled, double-blind study will compare Veterans who receive PE+CBD to PE+placebo. Participants will include 136 male and female Veterans from all service eras with PTSD. The primary hypothesis is that PE+CBD will reduce PTSD symptoms to a greater degree than PE+placebo.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants randomly assigned to one of two treatment conditions.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind study. Only pharmacist will have access to randomization table.
• Primary Purpose: Treatment
• Official Title: Cannabidiol as an Adjunctive to Prolonged Exposure for the Treatment of PTSD
• Actual Study Start Date: March 1, 2019
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: September 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Prolonged Exposure + Cannabidiol; Psychotherapy plus active medication	Behavioral: Prolonged Exposure; psychotherapy; Other Name: PE; Drug: Cannabidiol; active medication; Other Name: CBD
Active Comparator: Prolonged Exposure + Placebo; Psychotherapy plus placebo medication	Behavioral: Prolonged Exposure; psychotherapy; Other Name: PE; Drug: placebo; non-active medication

Outcome Measures

Primary Outcome Measures :

1. Clinician-Administered PTSD Scale DSM 5 (CAPS-5) [ Time Frame: Baseline, Post Treatment (16-weeks), 1-Month Follow-up (20-weeks), 3-Month Follow-up (28-weeks) ]
   Change in PTSD Symptoms will be assessed by change in Total Severity Score (summed severity ratings on items 1-20) on the Clinician-Administered PTSD Scale DSM 5 (CAPS-5); CAPS-5 Total Severity scores range from 0 to 80; Higher scores indicate higher severity.

Secondary Outcome Measures :

1. PTSD Checklist (PCL-5) [ Time Frame: Baseline, Weekly (up to 16-weeks) ]
   Rate of PTSD symptom reduction will be assessed by comparing the time-to-event of clinical response to treatment. The time-to-event is defined by number of PE sessions completed before patient achieves a 10-point reduction from baseline in total (summed) PTSD Checklist scores (PCL-5). PCL-5 Total Scores range from 0 to 80; Higher scores indicate worse functioning.

Other Outcome Measures:

1. UKU Side Effects Rating Scale, Patient Version (UKU-SERS-Pat) [ Time Frame: Weekly (up to 16 weeks) ]
   Total Adverse Events (AEs) will be tallied numerically by condition using the UKU Side Effects Rating Scale, Patient Version (UKU-SERS-Pat)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Over the age of 18 at the time of screening.
• Judged by the study physician to be in generally good health.
• Meet clinical criteria for Posttraumatic Stress Disorder (PTSD) on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).
• Negative urine pregnancy test.

Exclusion Criteria:

• History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to cannabinoids.
• Used cannabis, synthetic cannabinoid, cannabinoid analogue, or any CBD or THC-containing product within 30 days of eligibility screening.
• Patient has had a change in psychopharmacotherapy regimen in the last 4 weeks, or has any plans to change regimen over the course of the study.
• Patient is engaged in trauma-related psychotherapy for PTSD.
• Current or past DSM-5 diagnosis of dissociative identity disorder, eating disorder with active purging, personality disorders, primary psychotic disorder, or bipolar affective disorder type 1.
• Patient is currently prescribed medications with possible CBD-drug interactions.
• History of actual suicide attempt in the last 5 years.
• Unmanaged obstructive sleep apnea.
• Positive drug screen for THC, barbiturates, amphetamines (if not prescribed), benzodiazepines, and/or opiates.
• History of treatment for, or evidence of, moderate to severe alcohol or drug abuse within the past year or regular alcohol consumption exceeding recommended limits.
• Lifetime history of Cannabis Use Disorder.
• Pregnant or breastfeeding.

Contacts and Locations

Contacts

Contact: Julie M Holcomb, MS BS; (858) 552-8585 ext 2712; julie.holcomb@va.gov

Contact: Catherine R Ayers, PhD; (858) 642-2976; Catherine.Ayers1@va.gov

Locations

United States, California

VA San Diego Healthcare System, San Diego, CA; Recruiting

San Diego, California, United States, 92161

Contact: Julie M Holcomb, MS BS 858-552-8585 ext 2712 julie.holcomb@va.gov

Principal Investigator: Brian Martis, MD

Principal Investigator: Catherine R Ayers, PhD

Sponsors and Collaborators

VA Office of Research and Development

University of California, San Diego

Investigators

• Principal Investigator: Catherine R Ayers, PhD; VA San Diego Healthcare System, San Diego, CA
• Principal Investigator: Brian Martis, MD; VA San Diego Healthcare System, San Diego, CA

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT03518801
• Other Study ID Numbers: MHBB-001-17F
• First Posted: May 8, 2018
• Last Update Posted: September 7, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:

cannabidiol; CBD; PTSD; Veterans

Additional relevant MeSH terms:

Cannabidiol; Anticonvulsants