Cannabis for PTSD in Veterans

(CBH Trial)

Overseen By Paula Qefaliaj, B.S.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Wayne State University

Disqualifiers: Hypertension, Psychotic disorder, Bipolar, others

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

Compensation: Varies

Number of Visits: 17

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabinoids (compounds found in cannabis) might assist veterans with PTSD and suicidal thoughts. Participants will be divided into groups receiving different cannabis treatments: one with THC (Tetrahydrocannabinol), one with CBD (Cannabidiol), and one with both. The goal is to determine if these treatments can relieve PTSD symptoms. Veterans who have used cannabis in the past year and have PTSD might be suitable candidates for this study. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you test positive for drugs other than cannabis, nicotine, or mild to moderate alcohol use.

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

Research shows that cannabis, including THC (tetrahydrocannabinol) and CBD (cannabidiol), has been studied for managing PTSD symptoms. Studies have found that THC is generally well-tolerated, with some people experiencing mild side effects like dry mouth and headaches. CBD has also been tested and appears safe to use, with no major issues reported in early studies.

Evidence suggests that using THC and CBD together can help reduce PTSD symptoms. Research on this combination has not commonly reported any severe side effects.

Overall, both THC and CBD are considered to have a reasonable safety profile based on previous research, but individual reactions can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the potential of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), to address PTSD in veterans. Unlike traditional PTSD treatments, which often involve antidepressants and therapy, these treatments use active ingredients derived from cannabis, which may interact with the body’s endocannabinoid system to potentially reduce anxiety and stress. The study also investigates different combinations of THC and CBD, providing unique insights into how these compounds might individually or synergistically benefit those with PTSD.

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

This trial will compare different cannabis treatments for PTSD in veterans. Research has shown that cannabis, which includes THC and CBD, may help reduce PTSD symptoms. Participants in this trial may receive THC, which several studies have found can improve sleep and lessen PTSD symptoms in veterans. Others may receive CBD; one study showed that 91% of patients reported less severe PTSD symptoms after just eight weeks. Some participants will receive a combination of THC and CBD, which might greatly improve anxiety and ease social activities. Overall, these findings suggest that cannabis could be a helpful option for managing PTSD symptoms. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for veterans with PTSD who may also be using cannabis. It's designed to help those struggling with suicidal thoughts. Participants must meet certain health standards, but specific inclusion and exclusion criteria are not detailed here.

Inclusion Criteria

Report using cannabis (no more than 2x in last month and no more than 100 lifetime use episodes)

I have been diagnosed with PTSD and have had symptoms for at least 6 months.

Able to provide informed consent

Exclusion Criteria

Systolic/diastolic BP >140/90 mmHg

At immediate high risk for suicide based on the C-SSRS

Current substance use disorder other than Nicotine Use Disorder and Alcohol Use Disorder (mild or moderate)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomized into one of four groups and undergo a 12-week treatment phase, vaporizing their assigned cannabis dose daily.

12 weeks

12 visits (weekly, in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at multiple intervals.

9 months

4 visits (1 week, 3, 6, and 9 months post-treatment)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol
• Tetrahydrocannabinol

Trial Overview The study tests the effects of Cannabidiol (CBD) and Tetrahydrocannabinol (THC), components of cannabis, against a placebo to see if they can help treat PTSD in veterans. The participants will be randomly assigned to one of these treatments.

How Is the Trial Designed?

Group I: THC Group Experimental Treatment 1 Intervention

Cannabis with 5 mg THC; up to a maximum of 5 doses/day (max dose = 25 mg THC)

Group II: THC & CBD Group Experimental Treatment 2 Interventions

Cannabis with 5 mg THC and 5 mg CBD; up to a maximum of 5 doses/day (max doses = 25 mg THC and 25 mg CBD)

Group III: CBD Group Experimental Treatment 1 Intervention

Cannabis with 5 mg CBD; up to a maximum of 5 doses/day (max dose = 25 mg CBD)

Group IV: Placebo Group Active Control 1 Intervention

Cannabis with \<1mg THC and \<1mg CBD; up to a maximum of 5 doses/day (max dose = \<5 mg THC and \<5 mg CBD)

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

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

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 involving 27 healthy volunteers, a single clinically anxiolytic dose of 300 mg of CBD did not significantly affect the sleep-wake cycle, indicating it does not interfere with normal sleep architecture.

Unlike traditional anxiolytic medications, CBD appears to maintain the natural sleep patterns of individuals, suggesting it may be a safer alternative for anxiety management without disrupting sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. Linares, IMP., Guimaraes, FS., Eckeli, A., et al.[2020]

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]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

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]

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]

This study is the first placebo-controlled clinical trial examining the efficacy of cannabidiol (CBD) for treating PTSD, involving 150 participants over an 8-week period.

The trial compares the effects of two types of CBD (Isolate and Broad Spectrum) on PTSD symptoms, with outcomes measured using the PTSD Checklist for DSM-5, aiming to assess both efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Cannabidiol (CBD) oil in the treatment of PTSD: Study design and rationale for a placebo-controlled randomized clinical trial. Telch, MJ., Fischer, CM., Zaizar, ED., et al.[2023]

A systematic review of 10 studies suggests that medicinal cannabinoids like CBD, Δ9-THC, and nabilone may improve overall PTSD symptoms and specific issues such as sleep disorders and arousal disturbances, potentially enhancing quality of life.

While the results are promising for using cannabinoids as a treatment for PTSD, more research is necessary to fully understand the safety and long-term efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. Steardo, L., Carbone, EA., Menculini, G., et al.[2021]

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 isolate or CBD Broad Spectrum will show significantly greater improvements in PTSD symptoms and functional impairment at ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8222769/

Cannabis in the management of PTSD: a systematic review 77.2% of the patients, had a reduction in PTSD symptoms with the cannabis use (P = 0.0031); whereas 10.5% had not changes in PTSD symptoms. Elms 2019, PCL-5 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04197102

Use of CBD Oil in the Treatment of Posttraumatic Stress ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... No current medical problems that would preclude safe ingestion of CBD oil 11.

7. trialx.com trialx.com/clinical-trials/listings/254606/safety-and-efficacy-of-cannabidiol-cbd-for-symptoms-of-ptsd-in-adults/

Safety and Efficacy of Cannabidiol (CBD) for Symptoms of ... This study is a single-site phase II, double-blind, placebo-controlled study of Nantheia ATL5 for symptoms of Post-Traumatic Stress Disorder ( ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05269459/safety-and-efficacy-of-cannabidiol-cbd-for-symptoms-of-ptsd-in-adults

Safety and Efficacy of Cannabidiol (CBD) for Symptoms ... This study is a single-site phase II, double-blind, placebo-controlled study of Nantheia ATL5 for symptoms of Post-Traumatic Stress Disorder ( ...