Cannabis Compounds for PTSD

(CAPER Trial)

Not yet recruiting at 2 trial locations

Overseen By Karen Tucker

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Wayne State University

Must not be taking: Daily severe interactions

Disqualifiers: Bipolar, Schizophrenia, Severe alcohol, others

Compensation: Varies

Number of Visits: 23

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabis compounds like THC and CBD might help treat PTSD, a condition affecting many veterans. Participants will receive one of several treatments: CBD only, THC only, a mix of THC and CBD, or a placebo. The goal is to determine if these compounds can improve mental health symptoms such as anxiety and depression. Veterans with PTSD as their main concern who are not currently receiving psychotherapy for it are a good fit. This research could lead to new treatment options for managing PTSD symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on daily medication that has severe interactions with cannabis.

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

Earlier studies have found that CBD is well-tolerated by people with PTSD, meaning they didn't stop using it due to side effects. Research shows that THC can also reduce PTSD symptoms, but some people might need more over time to achieve the same effect.

When using THC and CBD together, studies suggest they can help with PTSD symptoms. However, the results are mixed, and there's insufficient information to fully confirm their safety.

This trial is in its early stages and primarily focuses on assessing the safety of these treatments. So far, both CBD and THC are generally considered safe, but individual reactions can differ. Participants should consult their healthcare provider about any concerns before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for PTSD because they explore the potential of cannabis compounds like CBD and THC, which are thought to interact with the body’s endocannabinoid system, potentially influencing stress and fear responses. Unlike standard PTSD treatments, which often include antidepressants or therapy, these cannabis-based options offer a unique mechanism by directly targeting pathways associated with memory and emotion regulation. Particularly intriguing is the combination treatments, THC:CBD 1:1 and THC:CBD 1:10, which aim to balance the psychoactive effects of THC with the calming properties of CBD, possibly offering a more tailored approach to managing PTSD symptoms.

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

Research has shown that cannabidiol (CBD) alone can help reduce PTSD symptoms. In one study, 91% of participants noticed improvements in their PTSD symptoms over eight weeks. In this trial, some participants will receive only CBD. Delta-9-tetrahydrocannabinol (THC) has also been found to ease PTSD symptoms and improve quality of life, making it another treatment option in this trial. When used together in equal amounts (1:1 ratio), CBD and THC have reduced PTSD symptoms in most patients. This trial will also test a mix of THC and CBD in a 1:10 ratio, which has been reported to help with PTSD symptoms, although the specific effects compared to other ratios remain less clear. Overall, these cannabis compounds show potential for helping with PTSD, but their effectiveness can vary. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for veterans with PTSD who use little to no cannabis currently but are open to trying it for anxiety, depression, PTSD, or suicidal thoughts. Specific eligibility criteria were not provided.

Inclusion Criteria

Veteran who has served in a branch of the US armed forces

Report using cannabis at least once, or using cannabis no more than once a week within the past 3 months and fewer than 100 times lifetime

Agree to comply with requirements and procedures

Exclusion Criteria

Risk of harm to self or others that requires immediate intervention

Current severe alcohol use or any substance use other than cannabis or nicotine

Lack of fluency in English

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-Treatment Assessments

Participants undergo physical examination, neurocognitive assessments, and fear acquisition tasks

2 weeks

5 visits (in-person)

Treatment

Prolonged exposure therapy sessions with cannabis or placebo administration

18 weeks

11 visits (in-person)

Post-Treatment Assessments

Participants undergo post-treatment behavioral tests and MR scans

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for therapeutic gains and relapse prevention

9 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol (CBD) only
• Delta-9-tetrahydrocannabinol (THC) only
• Placebo only
• THC:CBD 1:1
• THC:CBD 1:10

Trial Overview

The study tests different ratios of THC and CBD (1:10, 1:1), CBD alone, THC alone, and a placebo in managing PTSD symptoms in veterans. The goal is to find out if these treatments can help improve mental health.

How Is the Trial Designed?

Group I: THC:CBD 1:10 Experimental Treatment 1 Intervention

In a double-blind, placebo and active-controlled, between-subjects design, the investigators will administer drugs using a vaporizer containing THC (2.5mg), CBD (2.5mg,25mg) or PBO (0mg THC/CBD). Drug is administered immediately prior to exposure therapy sessions 3-6. 75 participants will be randomly assigned to each treatment arm. All participants will receive prolonged exposure therapy.

Group II: THC:CBD 1:1 Experimental Treatment 1 Intervention

In a double-blind, placebo and active-controlled, between-subjects design, the investigators will administer drugs using a vaporizer containing THC (2.5mg), CBD (2.5mg,25mg) or PBO (0mg THC/CBD). Drug is administered immediately prior to exposure therapy sessions 3-6. 75 participants will be randomly assigned to each treatment arm. All participants will receive prolonged exposure therapy.

Group III: Delta-9-tetrahydrocannabinol (THC) only Experimental Treatment 1 Intervention

In a double-blind, placebo and active-controlled, between-subjects design, the investigators will administer drugs using a vaporizer containing THC (2.5mg), CBD (2.5mg,25mg) or PBO (0mg THC/CBD). Drug is administered immediately prior to exposure therapy sessions 3-6. 75 participants will be randomly assigned to each treatment arm. All participants will receive prolonged exposure therapy.

Group IV: Cannabidiol (CBD) only Experimental Treatment 1 Intervention

In a double-blind, placebo and active-controlled, between-subjects design, the investigators will administer drugs using a vaporizer containing THC (2.5mg), CBD (2.5mg,25mg) or PBO (0mg THC/CBD). Drug is administered immediately prior to exposure therapy sessions 3-6. 75 participants will be randomly assigned to each treatment arm. All participants will receive prolonged exposure therapy.

Group V: Placebo (PBO) only Placebo Group 1 Intervention

In a double-blind, placebo and active-controlled, between-subjects design, the investigators will administer drugs using a vaporizer containing THC (2.5mg), CBD (2.5mg,25mg) or PBO (0mg THC/CBD). Drug is administered immediately prior to exposure therapy sessions 3-6. 75 participants will be randomly assigned to each treatment arm. All participants will receive prolonged exposure therapy.

Who Is Running the Clinical Trial?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

Published Research Related to This Trial

In a study of 198 participants with anxiety disorders, treatment with various cannabis formulations significantly improved quality of life outcomes, including reductions in anxiety, depression, and fatigue, as well as enhanced social functioning.

Common adverse events reported included dry mouth, somnolence, and fatigue, with gastrointestinal issues more prevalent in formulations containing THC, indicating a need for careful consideration of cannabis formulation in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study. Stack, SK., Wheate, NJ., Moloney, NC., et al.[2023]

Cannabidiol (CBD) shows promise as a therapeutic option for treating COVID-19-related anxiety and post-traumatic stress symptoms, supported by small randomized controlled trials that demonstrate its anxiolytic effects in various populations.

Pre-clinical studies indicate that CBD interacts with specific receptors in the brain, such as cannabinoid receptors and serotonin receptors, which may help reduce anxiety and improve sleep quality, making it a potential candidate for further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders? O'Sullivan, SE., Stevenson, CW., Laviolette, SR.[2022]

In a study of 11 adults with PTSD, 91% experienced a reduction in symptoms after 8 weeks of oral CBD treatment, with an average decrease in PTSD Checklist scores of 28%.

CBD was well tolerated by patients, with no discontinuations due to side effects, suggesting it may be a safe adjunct treatment for PTSD alongside standard psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. Elms, L., Shannon, S., Hughes, S., et al.[2020]

In a mouse model of PTSD, cannabidiol (CBD) significantly reduced PTSD-like symptoms by affecting trauma-related fear memory and anxiety behaviors, showing its potential as a treatment option.

Unlike the antidepressant sertraline, which was only effective when given before exposure to fear, CBD was effective regardless of when it was administered, indicating a broader mechanism of action in fear memory processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between cannabidiol and sertraline for the modulation of post-traumatic stress disorder-like behaviors and fear memory in mice. Han, X., Song, X., Song, D., et al.[2022]

In a study of 33 PTSD patients, administering 300 mg of cannabidiol (CBD) before recalling a nonsexual traumatic event significantly reduced anxiety and cognitive impairment compared to a placebo.

However, CBD did not show a significant effect on anxiety or cognitive impairment in patients recalling sexual trauma, suggesting that the efficacy of CBD may depend on the nature of the traumatic event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event. Bolsoni, LM., Crippa, JAS., Hallak, JEC., et al.[2022]

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.

tandfonline.com

tandfonline.com/doi/full/10.1080/14737175.2022.2155139

analysis from the UK Medical Cannabis Registry

Significant improvements were observed in PTSD symptoms, sleep, and anxiety across all follow-up periods (p < 0.050). There were 220 (135.8%) adverse events ...

5.

vfw.org

vfw.org/media-and-events/latest-releases/archives/2021/9/federal-study-finds-cannabis-beneficial-for-ptsd-treatment

Federal Study Finds Cannabis Beneficial for PTSD Treatment

Over the course of a year, the study found that cannabis users reported a greater decrease in the severity of their PTSD symptoms. They also ...

6.

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 ...

7.

ptsd.va.gov

ptsd.va.gov/professional/treat/cooccurring/marijuana_ptsd_vets.asp

Cannabis Use and PTSD Among Veterans

Results showed a significant reduction in PTSD symptoms in the THC+CBD group only; however, because there was no placebo group in this phase, it is not possible ...

8.

frontiersin.org

frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00502/full

Cannabidiol as a Therapeutic Alternative for Post-traumatic ...

In addition, exposure to traumatic stress is essential for the development of PTSD, and CBD is effective in reducing both the cardiovascular responses and ...