Cannabinoids and Traumatic Brain Injury: A Randomized, Placebo Controlled Trial

Eligibility Criteria

• 1. Ability to provide valid informed consent
• 2. 18-60 years old
• 3. Current or history of TBI as identified by the Ohio Identification Method
• 4. TBI severity is mild or moderate based on the VA/DoD Classification of TBI Severity
• 5. TBI event must have resulted in hospital evaluation (emergency department or other hospital-based assessment) or evaluation within a clinical setting, except in cases in which the TBI was acquired in a military deployment context in which medical services were not immediately available
• 6. Ongoing neuropsychiatric symptoms (i.e., depressive, anxiety, pain, cognitive complaints, or sleep complaints) that are plausibly associated with TBI and not better accounted for by co-occurring medical or psychological health conditions
• 7. Not currently in another treatment study for TBI-related symptoms or co-occurring medical or psychological health conditions
• 8. Co-occurring treatments must be stable in type, dose, and frequency for the four weeks preceding study enrollment and participants must commit to making no changes in these co-occurring treatments during the study
• 1. Currently incarcerated, paroled, or on probation
• 2. Participant has retained an attorney in relation to the TBI
• 3. Pregnant at the time of study enrollment or unwilling to commit to the use of two forms of contraception throughout the duration of the study
• 4. Vision, hearing, or communication impairments that preclude valid completion of study assessments
• 5. History of autism spectrum disorders, intellectual disability, and/or serious neurological or central nervous system disease that would be expected to affect cognition (e.g., epilepsy, tumors, multiple sclerosis)
• 6. Evidence of poor effort (TOMMe \< 8) on neuropsychological testing at baseline/Week 0
• 7. Current or lifetime diagnosis of a schizophrenia spectrum disorder, psychotic disorder, bipolar disorder type I \& II, cluster B personality disorders (antisocial, borderline, narcissistic, histrionic), eating disorders, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revised (DSM-5-TR, APA 2022)
• 8. Meets criteria for major depressive episode as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revised (DSM-5-TR, APA 2022) and with a Beck Depression Inventory-2 score \> 24;
• 9. Current suicidal ideation, as indicated by Beck Depression Inventory-2 item #9 score \> 0, or C-SSRS endorsement of item #2, or verbal or written report of current suicidal ideation by the participant to any study team member
• 10. History of significant systemic illness or unstable medical condition
• 11. Alcohol use disorder score of 5 or greater, or substance use disorder, based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revised (DSM-5-TR, APA 2022), in the six months preceding study enrollment
• 12. Reported use of other drugs (cocaine, opiates, methamphetamine, MDMA) in the past 60 days or test positive on a urine test for those drugs of abuse at baseline;
• 13. Currently taking medications known to be contraindicated with Epidiolex (buprenorphine, leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib, propoxyphene, sodium oxybate, teriflunomide, clobazam, lamotrigine, valproate).
• 14. Current diagnosis of a seizure disorder or epilepsy
• 15. Report using cannabis once daily or more than once daily over the last 12 months
• 16. Report current use of CBD for medical reasons or TBI symptoms
• 17. Liver function enzymes (AST, ALT) that are greater than 2x normal