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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding Cannabidiol (CBD), a non-intoxicating compound from cannabis, to Prolonged Exposure therapy can better help military Veterans manage PTSD symptoms. Participants will receive either Prolonged Exposure therapy with CBD or with a placebo to compare outcomes. The study seeks to enhance PTSD treatment and guide future therapy practices. Veterans with PTSD who have not recently used cannabis products and do not have certain mental health conditions may be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering Veterans a chance to contribute to potentially groundbreaking PTSD therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cannabidiol (CBD) is generally safe for people. Studies have found that CBD doesn't cause major health issues when taken in controlled amounts. In one study, participants using CBD didn't report any serious side effects. The most common minor issues included fatigue and changes in appetite.

CBD has been tested in other research settings and has proven safe. It's even approved for treating some medical conditions, suggesting it's safe for general use. However, individual reactions vary, so some might experience mild side effects. Overall, CBD appears safe to use alongside treatments like Prolonged Exposure for PTSD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Most treatments for PTSD focus on traditional psychotherapy and medications like SSRIs or SNRIs. However, the combination of prolonged exposure therapy with cannabidiol (CBD) is unique because it incorporates an active ingredient derived from cannabis, which may offer anxiolytic effects. Researchers are excited about this approach because CBD could potentially enhance the effectiveness of exposure therapy by reducing anxiety and improving emotional regulation, making therapy more tolerable and effective for patients. This is a novel approach compared to standard treatments, which primarily focus on altering neurotransmitter levels.

What evidence suggests that this trial's treatments could be effective for PTSD?

Research has shown that Cannabidiol (CBD) might help reduce PTSD symptoms when combined with Prolonged Exposure therapy (PE). In this trial, some participants will receive Prolonged Exposure therapy with CBD, while others will receive it with a placebo. One study found that 91% of patients experienced fewer PTSD symptoms after using CBD. Another study suggested that people taking CBD likely see more improvement in PTSD symptoms than those who don't. It's important to note that while CBD might provide short-term relief, its long-term benefits for treating PTSD remain unclear. Overall, adding CBD to therapy could potentially enhance treatment results for PTSD. ^{1 2 3 4 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6482919/

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder Results: From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04197102

Use of CBD Oil in the Treatment of Posttraumatic Stress ... We predict that patients receiving CBD oil (CBD isolate or CBD Broad Spectrum) will show significantly greater improvement in PTSD symptoms and functional ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2451865424000176

Design and methodology of a pilot randomized clinical trial Indeed, CBD monotherapy may provide short-term symptom relief, but may not be effective in maintaining long-term PTSD symptom reductions [31]. Collectively, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37529155/

The Effectiveness and Adverse Events of Cannabidiol and ... Conclusions: Formulations of cannabis significantly improved anxiety, depression, fatigue, and the ability to participate in social activities in participants ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04550377

Cannabidiol as a Treatment for PTSD and PTSD Comorbid ... The primary outcome will be change in PTSD symptoms as measured by change in the Clinician-Administered PTSD Scale (CAPS-5) total score. Official ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36154908/

Use of Cannabidiol (CBD) oil in the treatment of PTSD 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 ...