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

Trial Summary

What is the purpose of this trial?

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 control, to improve cognition and traumatic brain injury-related symptoms. If eligible for the study, subjects will be randomized to receive one of the conditions for 12 weeks.

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.

What data supports the effectiveness of the drug Cannabidiol (CBD) for treating traumatic brain injury?

Research suggests that CBD may help protect the brain after a traumatic brain injury by reducing inflammation, oxidative stress, and excessive glutamate release, which can damage brain cells. Studies in animals have shown that CBD can improve brain function and reduce brain damage after injury, indicating its potential as a treatment for traumatic brain injuries. ^{1 2 3 4 5}

Is CBD safe for human use?

CBD is generally well tolerated in humans, but it can cause some side effects like diarrhea, decreased appetite, and sleepiness. Serious side effects are rare but can include liver issues, especially when taken with other medications. More research is needed to fully understand its safety, especially outside of specific conditions like childhood epilepsy. ^{4 5 6 7 8}

How does the drug CBD differ from other treatments for traumatic brain injury?

CBD is unique because it targets multiple pathways involved in traumatic brain injury, such as reducing inflammation, oxidative stress, and excitotoxicity (damage caused by excessive stimulation of nerve cells). Unlike other treatments, CBD can be administered directly to the injury site and systemically, potentially offering a more comprehensive approach to protecting brain tissue and improving neurological outcomes. ^{1 4 5 9 10}

Research Team

Kent Hutchison, PhD

Principal Investigator

[e-mail]

Eligibility Criteria

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

I am between 18 and 60 years old.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Cannabidiol reduces lesion volume and restores vestibulomotor and cognitive function following moderately severe traumatic brain injury. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Neuroprotection Following Concussion: The Potential Role for Cannabidiol. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol's neuroprotective properties and potential treatment of traumatic brain injuries. [2023]

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Update on Cannabidiol Clinical Toxicity and Adverse Effects: A Systematic Review. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The therapeutic potential of purified cannabidiol. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury. [2020]