CBD for Traumatic Brain Injury

Overseen By Raeghan Mueller, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Epidiolex contraindicated drugs

Disqualifiers: Schizophrenia, Bipolar, Epilepsy, Autism, others

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: Unknown

Duration: 12 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two types of cannabidiol (CBD) in improving thinking skills and other symptoms related to traumatic brain injuries (TBI). Participants will receive either full-spectrum CBD, broad-spectrum CBD, or a placebo (a pill with no active ingredients) for 12 weeks. The trial aims to determine if these CBD treatments can improve issues like memory, mood, pain, or sleep problems related to TBI. Individuals who have experienced a mild or moderate TBI, serious enough to require a hospital visit, and who continue to have symptoms such as anxiety or sleep troubles, might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

You can continue taking your current medications as long as they have been stable in type, dose, and frequency for the four weeks before joining the study, and you must not change them during the study. However, you cannot participate if you are taking medications that are not allowed with Epidiolex, such as buprenorphine or clobazam.

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

Research has shown that cannabidiol (CBD) is generally safe for people. Studies have found that both broad spectrum CBD, which lacks THC, and full spectrum CBD, which contains a small amount of THC, are usually well-tolerated. Most people do not experience serious side effects, though some might feel slightly tired or notice changes in appetite.

Previous research suggests that CBD might aid brain injuries by protecting the brain and reducing swelling. While researchers continue to study the safety of CBD, its approval for other uses indicates it is likely safe. However, consulting a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of cannabidiol (CBD) for traumatic brain injury because it introduces a novel approach compared to conventional treatments like rest, physical therapy, and medications that target symptoms. Unlike these standard options, CBD is derived from cannabis and may offer neuroprotective properties by reducing inflammation and oxidative stress in the brain. The trial features both broad spectrum CBD, which contains no THC, and full spectrum CBD, which has trace amounts of THC, potentially offering different therapeutic effects. This innovative approach could lead to more effective management of brain injuries with fewer side effects than traditional treatments.

What evidence suggests that this trial's treatments could be effective for traumatic brain injury?

Research suggests that cannabidiol (CBD) may help treat traumatic brain injury (TBI). Studies have shown that CBD can lower the release of glutamate, a chemical that harms brain cells after a TBI. In this trial, participants will receive either Broad Spectrum CBD or Full Spectrum CBD, both of which might help protect brain cells from damage. Additionally, CBD reduces inflammation, aiding recovery from brain injuries. Overall, early findings suggest that CBD could improve cognitive function and lessen TBI-related symptoms, offering hope for those affected by such injuries. ^{1 2 3 6 7}

Who Is on the Research Team?

Kent Hutchison, PhD

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with mild to moderate traumatic brain injury (TBI) who have been evaluated in a hospital setting. Participants should not be involved in other TBI treatment studies, must have stable treatments for four weeks prior, and cannot change these during the study. Exclusions include severe mental illness, unstable medical conditions, high liver enzymes, current heavy cannabis or CBD use, certain neurological disorders, substance abuse issues, and pregnancy.

Inclusion Criteria

Ability to provide valid informed consent

TBI event must have resulted in hospital evaluation or evaluation within a clinical setting, except in cases in which the TBI was acquired in a military deployment context

Not currently in another treatment study for TBI-related symptoms or co-occurring conditions

Exclusion Criteria

Vision, hearing, or communication impairments that preclude valid completion of study assessments

Pregnant or unwilling to commit to two forms of contraception throughout the study

Evidence of poor effort on neuropsychological testing at baseline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Full Spectrum CBD, Broad Spectrum CBD, or placebo for 12 weeks to assess effects on cognition and TBI-related symptoms

12 weeks

In-person visits at Weeks 0, 1, 6, and 12; remote contact each remaining week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol

Trial Overview The study tests two forms of cannabinoids (fsCBD and bsCBD) against a placebo to see if they can improve cognition and symptoms related to TBI. Participants are randomly assigned to one of these options for a duration of 12 weeks in this double-blind trial where neither the researchers nor participants know who receives the actual drug or placebo.

How Is the Trial Designed?

Group I: Broad Spectrum Cannabidiol Active Control 1 Intervention

Broad Spectrum Cannabidiol (0.0% THC) Oral softgel capsule, 210mg/day

Group II: Full Spectrum Cannabidiol Active Control 1 Intervention

Full Spectrum Cannabidiol (\<0.3% THC) Oral softgel capsule, 210mg/day

Group III: Hemp Seed Oil Placebo Group 1 Intervention

Placebo Oral softgel capsule, 210mg/day

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Colorado State University

Collaborator

Trials

138

Recruited

38,200+

Published Research Related to This Trial

Administering cannabidiol (CBD) directly to the site of a brain injury, combined with systemic delivery, significantly reduced neuronal damage and improved neurological outcomes in a rat model of traumatic brain injury (TBI).

The dual treatment approach (CBD infused in a gelfoam matrix at the injury site plus systemic CBD injection) not only decreased lesion volume and neuronal loss but also restored cognitive functions and motor performance, suggesting it may be a more effective strategy than using either method alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol reduces lesion volume and restores vestibulomotor and cognitive function following moderately severe traumatic brain injury. Friedman, LK., Peng, H., Zeman, RJ.[2021]

Oral administration of cannabidiol (CBD) significantly reduced the over-release of glutamate caused by severe traumatic brain injury (TBI) in male Wistar rats, with the most effective dose being 100 mg/kg, which also correlated with a lower mortality rate (22%).

In the long-term, CBD pretreatment improved sensorimotor function and body weight gain, showing that it can effectively mitigate both short- and long-term effects of TBI, while pre- and post-treatment did not yield the same benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery. Santiago-Castañeda, C., Huerta de la Cruz, S., Martínez-Aguirre, C., et al.[2023]

Cannabidiol (CBD) shows promise as a neuroprotective agent for recovery from mild traumatic brain injuries (TBIs) like concussions, influencing various physiological processes such as inflammation reduction and neurogenesis.

While CBD has demonstrated potential benefits in enhancing recovery and protecting brain function, further validation through double-blind randomized controlled trials is necessary to confirm its efficacy as a treatment for concussions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotection Following Concussion: The Potential Role for Cannabidiol. Singh, J., Neary, JP.[2021]

A systematic review of 51 clinical studies indicates that cannabidiol (CBD) is generally well tolerated in humans, with most adverse events (AEs) being mild to moderate, such as diarrhea and sedation.

While serious AEs are rare, they can occur, particularly when CBD is taken with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Cannabidiol Clinical Toxicity and Adverse Effects: A Systematic Review. Madeo, G., Kapoor, A., Giorgetti, R., et al.[2023]

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

In a study using a mild traumatic brain injury (TBI) mouse model, 10% Cannabidiol (CBD) oil treatment effectively restored behavioral changes associated with chronic pain, anxiety, and depression, indicating its potential as a therapeutic option.

The research revealed that TBI led to specific neurotransmitter changes in the brain, and CBD treatment helped to partially normalize these biochemical alterations, suggesting a mechanism for its efficacy in improving neurological dysfunctions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury. Belardo, C., Iannotta, M., Boccella, S., et al.[2020]

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 rat model of traumatic brain injury (TBI), cannabidiol significantly reduced brain edema and improved neurological function, indicating its potential as a protective treatment for TBI.

Cannabidiol administration led to decreased levels of proinflammatory cytokines and improved the integrity of the blood-brain barrier, suggesting it helps mitigate inflammation and maintain brain health after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats. Jiang, H., Li, H., Cao, Y., et al.[2022]

Cannabidiol (CBD) shows promise as a neuroprotective treatment for traumatic brain injury (TBI) due to its anti-inflammatory, antioxidative, and antiepileptic properties, which could help mitigate the damaging effects that occur after the initial injury.

Pre-clinical research supports CBD's potential effectiveness in treating TBI, and upcoming clinical trials, particularly in professional sports, aim to evaluate its efficacy in real-world head injury treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol's neuroprotective properties and potential treatment of traumatic brain injuries. Aychman, MM., Goldman, DL., Kaplan, JS.[2023]

Purified cannabidiol (CBD), specifically the product Epidiolex, is approved for treating seizures in certain syndromes, and there is growing evidence supporting its use for anxiety, psychosis, PTSD, and substance abuse, based on numerous clinical studies.

However, while there is some positive data for other conditions like sleep quality and Parkinson's disease, the overall evidence is limited, and large-scale phase 3 trials are needed to confirm CBD's efficacy across various indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic potential of purified cannabidiol. O'Sullivan, SE., Jensen, SS., Nikolajsen, GN., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05632627?term=AREA%5BConditionSearch%5D(%22Brain%20Injuries,%20Traumatic%22)&rank=9

Cannabinoids and Traumatic Brain Injury: A Randomized ... The current study will directly test the hypothesis that a moderate dose of CBD leads to improvements in cognition, TBI-related symptoms, pain, sleep, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9932048/

Cannabidiol's neuroprotective properties and potential ... The mechanistic evidence provided by pre-clinical research shows great potential for CBD as a much-needed improvement in the clinical treatment of TBI. Upcoming ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05632627

Cannabinoids and Traumatic Brain Injury: A Randomized ... This is a double-blind, placebo-controlled, parallel group study designed to assess the tolerability and efficacy of fsCBD and bsCBD, compared to a placebo ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10999198/

Traumatic Brain Injury Outcomes After Recreational ... Basic science data indicate potential neuroprotective effects of cannabinoids in traumatic brain injury (TBI).

5. withpower.com withpower.com/trial/phase-2-brain-injuries-traumatic-11-2022-110bb

CBD for Traumatic Brain Injury Oral administration of cannabidiol (CBD) significantly reduced the over-release of glutamate caused by severe traumatic brain injury (TBI) in male Wistar rats, ...

6. jneuroinflammation.biomedcentral.com jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02734-9

Cannabinoids in traumatic brain injury and related ... Cannabinoids interact with neurons, microglia, and astrocytes, and exert anti-inflammatory and neuroprotective effects which are highly desirable for the ...

7. journals.sagepub.com journals.sagepub.com/doi/full/10.1089/neu.2023.0539

Cannabidiol Alleviates Neurological Deficits After ... CBD improves the drainage of MLVs in acute TBI mice. Recent studies have identified MLVs in the dura mater that communicate with dCLNs, playing a pivotal role ...