Cannabis Compounds for PTSD

(CAPER Trial)

Recruiting at 2 trial locations

Overseen By Christine A Rabinak, PhD

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

350 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall strategy is to recruit veterans with PTSD who report minimal current cannabis use but are interested in or considering therapeutic cannabis to manage mental health symptoms (anxiety, depression, PTSD and/or suicidality). The information gained from this study could lead to the development of new treatments for persons who suffer from post-traumatic stress disorder and maintain better mental health.

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 cannabis safe for treating PTSD?

Cannabis compounds like CBD and THC have been studied for safety in treating anxiety and PTSD. Common side effects include dry mouth, sleepiness, and fatigue, with THC sometimes causing stomach issues like nausea. Overall, these compounds are generally considered safe, but side effects can vary depending on the formulation. ^{1 2 3 4 5}

How does the drug cannabidiol (CBD) differ from other treatments for PTSD?

Cannabidiol (CBD) is unique because it is a compound from the cannabis plant that does not cause a 'high' and works by interacting with the body's endocannabinoid system, which may help regulate fear and anxiety. Unlike traditional PTSD medications, CBD is being explored for its potential to specifically modulate fear memory and anxiety without the psychotomimetic effects (mind-altering effects) associated with other cannabis compounds. ^{1 2 3 5 6}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

References

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

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. [2020]

2. Brazil 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. [2022]

3. Germany 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. [2022]

4. United States 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. [2023]

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

The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial. [2023]

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

Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders? [2022]