Use of CBD Oil in the Treatment of Posttraumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT04197102
• Recruitment Status: Recruiting
• First Posted: December 12, 2019
• Last Update Posted: August 3, 2021
• Sponsor: University of Texas at Austin
• Information provided by (Responsible Party): Michael J. Telch, University of Texas at Austin

Tracking Information

• First Submitted Date: December 10, 2019
• First Posted Date: December 12, 2019
• Last Update Posted Date: August 3, 2021
• Actual Study Start Date: January 15, 2020
• Estimated Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2019)

• CAPS-5 [ Time Frame: Post-treatment (week 9), one month (week 13), and three month (week 21) follow-up assessments ]
  Change from baseline in clinician-rated PTSD severity.
• CGI [ Time Frame: Post-treatment (week 9), one month (week 13), and three month (week 21) follow-up assessments ]
  Change from baseline in clinician-rated global impressions.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 10, 2019)

• PCL-5 [ Time Frame: Post-treatment (week 9), one month (week 13), and three month (week 21) follow-up assessments ]
  Change from baseline in patient-rated symptoms of PTSD.
• QIDS [ Time Frame: Post-treatment (week 9), one month (week 13), and three month (week 21) follow-up assessments ]
  Change from baseline in patient-rated symptoms of depression.
• SDS [ Time Frame: Post-treatment (week 9), one month (week 13), and three month (week 21) follow-up assessments ]
  Change from baseline in overall disability.
• WHOQOL-BREF [ Time Frame: Post-treatment (week 9), one month (week 13), and three month (week 21) follow-up assessments ]
  Change from baseline in quality of life.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Use of CBD Oil in the Treatment of Posttraumatic Stress Disorder
• Official Title: Use of Cannabidiol (CBD) Oil in the Treatment of PTSD: A Placebo-Controlled Randomized Clinical Trial

Brief Summary

The overarching objective of the proposed project is to test the clinical efficacy of CBD in the treatment of post-traumatic stress disorder using a rigorous double-blind randomized clinical trial methodology. Participants (n=150) meeting full DSM-5 criteria for post-traumatic stress disorder (PTSD) will be randomized to one of 3 treatment arms: (a) CBD -Isolate; (b) CBD-Broad Spectrum; (c) Placebo oil.

We predict that patients receiving CBD isolate or CBD Broad Spectrum will show significantly greater improvements in PTSD symptoms and functional impairment at the posttreatment, one month, and three month follow-up assessments relative to patients receiving placebo oil. Additionally, we expect that patients receiving CBD Broad Spectrum will show significantly greater improvements relative to patients receiving CBD Isolate.

Detailed Description

Background and Significance of the Proposed Project

Over 80% of Americans are exposed to a significant trauma sometime during their lifetime and approximately 7% will meet for a threshold diagnosis of posttraumatic stress disorder. PTSD is the most costly anxiety-related disorder and confers significant interference in work, social functioning, increased risk for other physical and mental health problems, and a four-fold increase in suicide rates compared to the general population.

Over the past two decades, trauma-focused psychotherapies for PTSD have been shown to outperform more traditional supportive psychotherapy or pharmacotherapy and have become the first line treatment for PTSD. Despite these advances, trauma focused treatments such as prolonged exposure therapy (PE) are associated with high rates of treatment refusal, and among those who do enter treatment, approximately 25% drop-out. These data highlight the need to develop PTSD treatment strategies that are both effective and more palatable to patients.

More recently, there's been considerable excitement in the press over the potential therapeutic use of cannabidiol (CBD) products in the treatment of a variety of physical and mental health problems.( Delta-9-tetrahydrocannabinol (delta-9 THC) is still illegal in most states because of its psychoactive abuse potential. In contrast, cannabidiol (CBD) does not convert to THC in the body and has negligible side effects relative to main stream psychiatric drugs (benzodiazepines and antidepressants) commonly prescribed for the treatment of PTSD. Mounting evidence from studies with rodents suggests that CBD may confer significant promising health-related benefits including anti-inflammatory, pain-relieving, anti-cancer, memory enhancement, and facilitation of fear extinction (see White for a recent review).

The biggest success story for CBD use in humans to date comes from controlled randomized clinical trials demonstrating a 50% or more reduction in previously intractable seizures in children suffering from Dravet syndrome and Lennox-Gastaut syndrome. Moreover, several controlled clinical trials have shown promising findings in reducing psychotic symptoms among patients with schizophrenia and among young adults displaying THC-induced psychosis.

Preliminary Evidence that CBD may offer promise in the treatment of anxiety-related disorders has started to emerge. A small pilot trial with 24 patients presenting with social anxiety disorder found that relative to placebo, a single dose of 100 mg of CBD oil led to lower levels of anxiety, cognitive impairment, and discomfort in their actual speech performance as well as their anxiety before the speech. Unfortunately, human treatment studies for anxiety-related problems is limited almost exclusively to single dose effects on an anxiety challenge task. Studies are clearly needed to assess the effects of multi-dose CBD treatments across the full spectrum of trauma and anxiety-related disorders such as posttraumatic stress disorder.

PROJECT AIMS

The overarching objective of the proposed project is to test the clinical efficacy of CBD in the treatment of posttraumatic stress disorder using a rigorous double-blind randomized clinical trial methodology.

Specific aims of the project include:

1. Compare the efficacy of an 8-week multi-dose regimen of two CBD oil formulations (CBD Isolate (300 mg/day) and CBD Broad Spectrum) relative to placebo oil in reducing clinician and patient-rated PTSD symptoms at the posttreatment and one month follow-up assessments.

   We predict that patients receiving CBD oil (CBD isolate or CBD Broad Spectrum) will show significantly greater improvement in PTSD symptoms and functional impairment at post-treatment and one month follow-up relative to patients receiving placebo oil.

   We also predict that patients receiving the CBD Broad Spectrum formulation will show significantly greater improvement in PTSD symptoms and functional impairment relative to patients receiving CBD Isolate.

2. Examine predictors of patients' clinical response to the various treatment combinations.

   We expect that the superiority of CBD relative to placebo will be more pronounced for patients showing more severe PTSD symptoms at baseline and for those showing significant sleeping difficulties.

3. Examine the perceived acceptability and patients' side effects profile of 8 weeks of daily CBD oil ingestion.

We expect that CBD-treated patients will show equivalent levels of side effects as those receiving placebo oil.

STUDY METHODS AND PROCEDURES

Participant Recruitment: 150 participants between the ages of 18 and older will be recruited through several outlets including notices posted on campus, announcements on our research laboratory website and national organizations related to PTSD and its treatment.

Participant Screening: Participants will undergo a two-stage screening procedure. Stage 1 will be a brief structured web-based screening interview. Stage 2 will be a telephone-administered structured clinical interview (CAPS-5). Participants meeting the following inclusion and exclusion enrollment criteria will be invited to take part in the study (see below).

NOTE: ALL STUDY PROCEDURES ARE COMPLETED AT PARTICIPANTS' HOMES. NO VISITS TO OUR RESEARCH LABORATORY ARE REQUIRED.

Inclusion/Exclusion Criteria:

1. Meets for a current DSM-5 diagnosis of PTSD as their "primary" mental disorder
2. Age between 18 to 70
3. Fluent in English
4. Willingness to provide signed informed consent online
5. No history of a suicide attempt in the past 6 months
6. No history of psychosis with the past 6 months

9. No history of current alcohol or substance use disorder within the past 6 months.

10. No current medical problems that would preclude safe ingestion of CBD oil 11. Willingness to refrain from other forms of Cannabis use during the 8-week treatment phase of the study.

12. Has home access to the internet.

Participant Informed Consent:

All study participants will be consented by the study coordinator or a doctoral student research assistant during the screening visit conducted over the phone. The online informed consent document will provide participants with information regarding the aims of the project, what they will be asked to do, any anticipated risks or benefits associated with participating in the study, as well as a clear statement that their participation is voluntary and that they may discontinue participation at any time.

Study Design Overview: The research plan is to conduct a Phase II double-blind placebo controlled randomized clinical trial comparing the efficacy of two CBD oil (300 mg./day) versus Placebo Oil.

CBD/Placebo Dosing:

Nightly dosing of a hemp-derived formulation of purified CBD isolate (300 mg), CBD Broad Spectrum (300 mg.) or matching placebo oil daily for 8 weeks. Individual doses of both CBD formulations and placebo oil will be provided in identical individual plastic syringes. All patients, PI, and staff who interact with study participants will be blind to participants' assigned treatment condition.

Clinical Assessment Schedule:

Week 0 - Pre-Treatment Screening Visit: All enrolled study participants will complete from their home a clinical assessment battery consisting of (a) self-report rating scales over the Internet (see measures); and (b) a structured clinical interview (CAPS-5).

Treatment Visits (Weeks 1 - 8) : During this phase, all study participants will (a) receive via Fed-Ex their weekly allotment of CBD/Placebo oil; (b) complete weekly clinical status assessments via the Internet (see measures).

Posttreatment Assessment Visit (Week 9): All participants will complete an online battery of clinical outcome measures identical to those administered during their pre-treatment visit (see outcome measures).

1-Month Follow-up Assessment Visit (Week 13) - All participants will be re-administered the complete battery of primary and secondary outcome measures (see outcome measures).

Outcome Measures

Primary Clinical Outcomes: The primary clinical outcomes will be (a) scores on the Clinician Administered PTSD Scale (CAPS-5) and (b) independent evaluator ratings of clinical status using the Clinical Global Improvement Scale administered at each of the three posttreatment assessment periods (Week 9, Week 13).

Secondary Clinical Outcomes: Several additional psychiatric outcomes will be assessed at each of the three follow-up assessment visits. These clinical outcomes and their respective measures appear below. Additional information on these measures is available in the accompanying cited publication for each measure.

• Patient-rated PTSD symptoms using the PCL-5
• Depression - Patient Health Questionnaire (PHQ-9)
• Life Impairment - Sheehan Disability Scale (SDS)
• Quality of Life - World Health Organization (WHOQOL-BREF)
• Substance Use Disorders - NIDA-Modified Alcohol, Smoking, and Substance Involvement Screening Test (NIDA M-ASSIST)
• Pittsburgh Sleep Quality Index (PSQI)

Data Management Data Management involves development of methods for ensuring that data collection instruments are programmed; data are properly collected; participants are tracked and monitored over the course of the study; data sets are documented and maintained; variables are created and documented; and main analyses are conducted. To enhance quality control, all data for the current study including demographic information, diagnoses, and participant and clinician rated measures will be directly entered into a HIPPA compliant electronic case report form (eCRF) using Qualtrics - a secure cloud-based platform designed exclusively for supporting HIPPA compliant data capture and storage. Qualtrics provides: (a) An intuitive interface for data entry with data validation; (b) Audit trails for tracking data manipulation and export procedures; (c) Procedures for importing data from external sources; (d) Automated export procedures for seamless data downloads to common statistical packages (SPSS, SAS, Stata, R) to facilitate data analysis; (e) automated and secure data back-up and storage to servers housed at the University of Texas Population Research Center (PRC). Dr. Telch in his role as Principal Investigator will serve as the Senior data manager and will meet bi-weekly with the biostatistician and research staff on issues related to data management.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Each nightly dose of CBD/Placebo oil will be tagged with a code # on the plastic syringe containing the CBD oil or placebo oil. Both oils will have identical color and mint flavor. Two independent staff not connected to the study will be unblinded to the participants' assignment to condition.

Primary Purpose: Treatment

• Condition: Post Traumatic Stress Disorder

Intervention

• Drug: CBD Isolate
  A fixed dose of 300-mg of a hemp-derived formulation of purified 99.9% CBD isolate oil will be taken once daily for 8 weeks for participants randomized to the CBD arm.
  Other Name: CBD Isolate Oil
• Other: CBD Broad Spectrum
  A fixed dose of 300-mg of a hemp-derived formulation of purified 99.9% CBD Broad Spectrum oil will be taken once daily for 8 weeks for participants randomized to the CBD - Broad Spectrum arm.
  Other Name: CBD Broad Spectrum Oil
• Other: Placebo oil
  Placebo solution will be taken once daily for 8 weeks by participants randomized to the placebo arm.
  Other Name: PLBO

Study Arms

• Active Comparator: CBD Isolate
  300 mg/day of CBD isolate
  Intervention: Drug: CBD Isolate
• Active Comparator: CBD Broad Spectrum
  300 mg/day of CBD Broad Spectrum Oil
  Intervention: Other: CBD Broad Spectrum
• Placebo Comparator: Placebo oil
  Matched Placebo Oil
  Intervention: Other: Placebo oil

Publications *

• Shalev AY, Gevonden M, Ratanatharathorn A, Laska E, van der Mei WF, Qi W, Lowe S, Lai BS, Bryant RA, Delahanty D, Matsuoka YJ, Olff M, Schnyder U, Seedat S, deRoon-Cassini TA, Kessler RC, Koenen KC; International Consortium to Predict PTSD. Estimating the risk of PTSD in recent trauma survivors: results of the International Consortium to Predict PTSD (ICPP). World Psychiatry. 2019 Feb;18(1):77-87. doi: 10.1002/wps.20608.
• Powers MB, Gillihan SJ, Rosenfield D, Jerud AB, Foa EB. Reliability and validity of the PDS and PSS-I among participants with PTSD and alcohol dependence. J Anxiety Disord. 2012 Jun;26(5):617-23. doi: 10.1016/j.janxdis.2012.02.013. Epub 2012 Mar 3.
• Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007 May;64(5):543-52. Erratum in: Arch Gen Psychiatry. 2007 Sep;64(9):1039.
• Powers MB, Halpern JM, Ferenschak MP, Gillihan SJ, Foa EB. A meta-analytic review of prolonged exposure for posttraumatic stress disorder. Clin Psychol Rev. 2010 Aug;30(6):635-41. doi: 10.1016/j.cpr.2010.04.007. Epub 2010 May 2.
• White CM. A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential. J Clin Pharmacol. 2019 Jul;59(7):923-934. doi: 10.1002/jcph.1387. Epub 2019 Feb 7. Review.
• Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.
• Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631.
• McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018 Mar 1;175(3):225-231. doi: 10.1176/appi.ajp.2017.17030325. Epub 2017 Dec 15.
• Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schröder N, Nardi AE, Martín-Santos R, Hallak JE, Zuardi AW, Crippa JA. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011 May;36(6):1219-26. doi: 10.1038/npp.2011.6. Epub 2011 Feb 9.
• Berk M, Ng F, Dodd S, Callaly T, Campbell S, Bernardo M, Trauer T. The validity of the CGI severity and improvement scales as measures of clinical effectiveness suitable for routine clinical use. J Eval Clin Pract. 2008 Dec;14(6):979-83. doi: 10.1111/j.1365-2753.2007.00921.x. Epub 2008 May 2.
• Pinto-Meza A, Serrano-Blanco A, Peñarrubia MT, Blanco E, Haro JM. Assessing depression in primary care with the PHQ-9: can it be carried out over the telephone? J Gen Intern Med. 2005 Aug;20(8):738-42.
• Leon AC, Olfson M, Portera L, Farber L, Sheehan DV. Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med. 1997;27(2):93-105.
• Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychol Med. 1998 May;28(3):551-8.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 27, 2021): 150
• Original Estimated Enrollment (submitted: December 10, 2019): 120
• Estimated Study Completion Date: May 2024
• Estimated Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Meets for a current DSM-5 diagnosis of PTSD as their "primary" mental disorder
2. Age between 18 to 70
3. Fluent in English
4. Able to arrange transportation to our laboratory
5. Has access to the internet
6. Willingness to provide signed informed consent
7. Willingness to refrain from all non-study cannabis use during the study period

Exclusion Criteria:

1. History of a suicide attempt within the past 6 months
2. History of psychosis with the past 6 months
3. History of current alcohol or substance use disorder within the past month
4. Any medical problems that would preclude participating in the study
5. History of adverse reaction to CBD oil or other CBD products

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michael J. Telch, PhD; 5125604100; telch@austin.utexas.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04197102
• Other Study ID Numbers: 2019-05-0123
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Michael J. Telch, University of Texas at Austin
• Original Responsible Party: Michael J. Telch, University of Texas at Austin, Dr.
• Current Study Sponsor: University of Texas at Austin
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael J Telch, Ph.D.; University of Texas at Austin

• PRS Account: University of Texas at Austin
• Verification Date: July 2021