CBD + Prolonged Exposure for PTSD

(CBD-PE Trial)

Overseen By Brian Martis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: CBD-interacting drugs

Disqualifiers: Cannabis use, Psychotic disorders, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 16 weeks

136 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you have changed your medication regimen in the last 4 weeks or plan to change it during the study. Also, you cannot be on medications that might interact with CBD.

What data supports the effectiveness of the treatment for PTSD?

Prolonged Exposure (PE) therapy has been shown to significantly reduce PTSD symptoms in veterans, with studies reporting reductions in PTSD and depression symptoms and improvements in quality of life. This suggests that PE is an effective treatment for PTSD, which may support its use in combination with CBD for enhanced outcomes. ^{1 2 3 4 5}

Is Prolonged Exposure therapy safe for treating PTSD?

Prolonged Exposure (PE) therapy is considered safe and effective for treating PTSD, with extensive research supporting its use in various populations, including veterans and military personnel. ^{4 5 6 7 8}

How is Prolonged Exposure Therapy for PTSD different from other treatments?

Prolonged Exposure Therapy is unique because it involves patients confronting their trauma-related memories and situations in a safe and controlled way, which helps reduce the power these memories have over them. This approach is different from other treatments that might focus more on medication or avoiding trauma reminders. ^{9 10 11 12 13}

Research Team

Catherine R Ayers, PhD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Brian Martis, MD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Eligibility Criteria

This trial is for military Veterans over 18 with PTSD, as confirmed by a specific clinical scale. They must be in good health and not pregnant. Participants cannot have used cannabis products recently, be on certain medications, or be undergoing other trauma-related psychotherapy.

Inclusion Criteria

I have been diagnosed with PTSD by a professional.

Negative urine pregnancy test

I am over 18 years old.

Exclusion Criteria

I have not changed my mental health medication in the last 4 weeks and do not plan to change it during the study.

I am currently in therapy for PTSD related to trauma.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Prolonged Exposure therapy with either Cannabidiol or placebo for PTSD

16 weeks

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

1-month and 3-month follow-up visits

Treatment Details

Interventions

• Cannabidiol
• Prolonged Exposure

Trial Overview The study tests if Cannabidiol (CBD) can improve the effectiveness of Prolonged Exposure therapy for PTSD when compared to a placebo. It's conducted at the VA San Diego Medical Center with 136 participants who are randomly assigned to either the CBD group or placebo group.

Participant Groups

Group I: Prolonged Exposure + Cannabidiol Experimental Treatment 2 Interventions

Psychotherapy plus active medication

Group II: Prolonged Exposure + Placebo Active Control 2 Interventions

Psychotherapy plus placebo medication

Prolonged Exposure is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Prolonged Exposure Therapy for:

• Post-traumatic Stress Disorder (PTSD)

Approved in European Union as Prolonged Exposure Therapy for:

• Post-traumatic Stress Disorder (PTSD)

Approved in Canada as Prolonged Exposure Therapy for:

• Post-traumatic Stress Disorder (PTSD)

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Findings from Research

Prolonged exposure (PE) therapy for PTSD was effective in reducing PTSD symptoms and trauma-related beliefs in all four participants before they started a 5-week multidisciplinary cognitive behavioral therapy (CBT) program for chronic pain.

While PE therapy showed significant improvements in PTSD, it did not lead to notable reductions in pain intensity or interference, suggesting that treating PTSD and chronic pain may require different approaches tailored to individual needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged exposure for pain and comorbid PTSD: a single-case experimental study of a treatment supplement to multiprofessional pain rehabilitation. Åkerblom, S., Perrin, S., Fischer, MR., et al.[2022]

Prolonged Exposure (PE) therapy led to a significant 42% reduction in PTSD symptoms and a 31% reduction in depression symptoms among 115 veterans, indicating its effectiveness as a treatment for PTSD in this population.

Veterans not taking psychotropic medications experienced greater reductions in PTSD symptoms compared to those who were, suggesting that PE may be particularly beneficial for veterans seeking non-pharmacological treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Prolonged Exposure therapy for veterans with posttraumatic stress disorder. Goodson, JT., Lefkowitz, CM., Helstrom, AW., et al.[2022]

In a study involving 10 veterans with chronic PTSD treated at a VHA clinic, prolonged exposure therapy (PE) led to significant reductions in total PTSD symptoms from before to after treatment.

The therapy was effective across different groups of veterans, including those from recent conflicts in Afghanistan and Iraq, as well as Vietnam veterans and those with military sexual trauma, and it also resulted in significant reductions in depression symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged exposure for PTSD in a Veterans Health Administration PTSD clinic. Rauch, SA., Defever, E., Favorite, T., et al.[2009]

Prolonged exposure (PE) therapy was found to be effective in reducing PTSD and depression symptoms in a small group of 10 Veterans with mild to moderate traumatic brain injury (TBI) and chronic PTSD, showing large effect sizes from pre- to posttreatment.

The therapy was safely adapted for Veterans with cognitive impairments, indicating that PE can be a viable treatment option for this population, with significant symptom improvements observed after 8 to 18 sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary examination of prolonged exposure therapy with Iraq and Afghanistan veterans with a diagnosis of posttraumatic stress disorder and mild to moderate traumatic brain injury. Wolf, GK., Strom, TQ., Kehle, SM., et al.[2022]

Prolonged exposure (PE) therapy is an effective first-line treatment for PTSD in Veterans and military personnel, significantly reducing symptoms and comorbid issues like anger and depression, supported by extensive research and clinical guidelines.

The PE protocol includes key components such as psychoeducation and exposure techniques, and the Veterans Health Administration has trained over 1,300 mental health providers to deliver this therapy, indicating a strong commitment to improving PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of exposure therapy: a gold standard for PTSD treatment. Rauch, SA., Eftekhari, A., Ruzek, JI.[2021]

Providers who received post-workshop consultation after a 4-day prolonged exposure therapy (PE) training reported significantly higher self-efficacy and used more components of PE, leading to better treatment delivery.

Patients treated by providers with post-workshop consultation experienced faster reductions in PTSD symptoms and lower severity at follow-up assessments, indicating that ongoing support for providers can enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of a prolonged exposure workshop with and without consultation on provider and patient outcomes: a randomized implementation trial. Foa, EB., McLean, CP., Brown, LA., et al.[2022]

A hybrid treatment combining group and individual Prolonged Exposure (PE) therapy was effective in reducing PTSD and depression symptoms in veterans, based on a 12-week program involving 67 participants across 12 cohorts.

Both completers and those analyzed by intent-to-treat showed significant symptom reductions, highlighting the potential of group therapies to efficiently provide care for veterans with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged Exposure for PTSD in a Veteran group: a pilot effectiveness study. Smith, ER., Porter, KE., Messina, MG., et al.[2019]

A study involving 160 active-duty military personnel with PTSD found that 60-minute prolonged exposure (PE) therapy sessions are just as effective as the standard 90-minute sessions, making treatment more accessible in settings that typically use shorter appointment times.

Both the Clinician Administered PTSD Scale (CAPS-5) and the PTSD Checklist (PCL-5) showed that the efficacy of 60-minute sessions was noninferior to 90-minute sessions, suggesting that shorter sessions can be effectively implemented without compromising treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of 90-min versus 60-min sessions of prolonged exposure for PTSD: A randomized controlled trial in active-duty military personnel. Foa, EB., Bredemeier, K., Acierno, R., et al.[2022]

In pediatric Crohn's disease, both standard (5 weeks) and rapid (3 days) food reintroduction after 6 weeks of exclusive enteral nutrition resulted in similar clinical remission rates (80% for standard and 76% for rapid).

The study found that the type of food reintroduction did not significantly affect relapse rates or duration of remission, suggesting that rapid reintroduction is a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard versus rapid food reintroduction after exclusive enteral nutritional therapy in paediatric Crohn's disease. Faiman, A., Mutalib, M., Moylan, A., et al.[2022]

Exclusive enteral nutrition (EEN) significantly improved weight recovery and reduced disease activity in a murine model of colitis, indicating its clinical efficacy in treating conditions like pediatric Crohn's disease.

EEN therapy was associated with beneficial changes in gut microbiota, including increased levels of mucin-degrading bacteria, which suggests that enhancing mucin production may play a key role in the healing effects of EEN on the gut barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model. Jang, S., Kim, Y., Lee, C., et al.[2022]

In a pilot study involving 44 children with severe acute malnutrition and environmental enteric dysfunction (EED), treatment with mesalazine was found to be safe, showing no increase in adverse events or negative effects on nutritional recovery over 28 days.

Mesalazine treatment led to modest reductions in inflammatory markers, suggesting that targeting intestinal inflammation may help improve growth outcomes during nutritional rehabilitation for children with EED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial. Jones, KD., Hünten-Kirsch, B., Laving, AM., et al.[2021]

In a study of 11 adults with active Crohn's disease undergoing exclusive enteral nutrition (EEN) for 12 weeks, 9 patients achieved clinical remission, indicating EEN's effectiveness in managing this condition.

EEN treatment led to significant changes in plasma lipid profiles, with alterations in lipid classes linked to anti-inflammatory effects, suggesting that lipid metabolism plays a crucial role in the therapeutic mechanism of EEN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipidomics reveals significant alterations associated with exclusive enteral nutrition treatment in adult patients with active Crohn's disease. Yang, Q., Huang, Z., Diao, N., et al.[2022]

In a study of 32 adult patients with Crohn's disease, the Crohn's disease exclusion diet (CDED) achieved clinical remission in 76.7% of patients after 6 weeks and 82.1% after 12 weeks, demonstrating its effectiveness as a treatment.

The CDED also significantly reduced calprotectin levels, a marker of inflammation, indicating its potential to improve intestinal health in adults with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. Szczubełek, M., Pomorska, K., Korólczyk-Kowalczyk, M., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Prolonged exposure for pain and comorbid PTSD: a single-case experimental study of a treatment supplement to multiprofessional pain rehabilitation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Prolonged Exposure therapy for veterans with posttraumatic stress disorder. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Prolonged exposure for PTSD in a Veterans Health Administration PTSD clinic. [2009]

4. United States pubmed.ncbi.nlm.nih.gov

A preliminary examination of prolonged exposure therapy with Iraq and Afghanistan veterans with a diagnosis of posttraumatic stress disorder and mild to moderate traumatic brain injury. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Review of exposure therapy: a gold standard for PTSD treatment. [2021]

6. England pubmed.ncbi.nlm.nih.gov

The effects of a prolonged exposure workshop with and without consultation on provider and patient outcomes: a randomized implementation trial. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Prolonged Exposure for PTSD in a Veteran group: a pilot effectiveness study. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

The efficacy of 90-min versus 60-min sessions of prolonged exposure for PTSD: A randomized controlled trial in active-duty military personnel. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Standard versus rapid food reintroduction after exclusive enteral nutritional therapy in paediatric Crohn's disease. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial. [2021]

12. China pubmed.ncbi.nlm.nih.gov

Lipidomics reveals significant alterations associated with exclusive enteral nutrition treatment in adult patients with active Crohn's disease. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. [2021]