“This study aimed to determine if orally administered cannabidiol (CBD) lessens the cortical over-release of glutamate induced by a severe traumatic brain injury (TBI) and facilitates functional recovery. The short-term experiment focused on identifying the optimal oral pretreatment of CBD. Male Wistar rats were pretreated with oral administration of CBD (50, 100, or 200 mg/kg) daily for 7 days. Then, extracellular glutamate concentration was estimated by cortical microdialysis before and immediately after a severe TBI. The long-term experiment focused on evaluating the effect of the optimal treatment of CBD (pre- vs. pre- and post-TBI) 30 days after trauma. Sensorimotor function, body weight, and mortality rate were evaluated. In the short term, TBI induced a high release of glutamate (738% ± 173%; p < 0.001 vs. basal).
Oral pretreatment with CBD at all doses tested reduced glutamate concentration but with higher potency at when animals received 100 mg/kg (222 ± 33%, p < 0.01 vs. TBI), an effect associated with a lower mortality rate (22%, p < 0.001 vs. TBI). In the long-term experiment, the TBI group showed a high glutamate concentration (149% p < 0.01 vs. SHAM). In contrast, animals receiving the optimal treatment of CBD (pre- and pre/post-TBI) showed glutamate concentrations like the SHAM group (p > 0.05). This effect was associated with high sensorimotor function improvement. CBD pretreatment, but not pre-/post-treatment, induced a higher body weight gain (39% ± 2.7%, p < 0.01 vs. TBI) and lower mortality rate (22%, p < 0.01 vs. TBI).
These results support that orally administered CBD reduces short- and long-term TBI-induced excitotoxicity and facilitated functional recovery. Indeed, pretreatment with CBD was sufficient to lessen the adverse sequelae of TBI.”
https://pubmed.ncbi.nlm.nih.gov/36015236/
“CBD administration decreases short- and long-term glutamate over-release after severe TBI, an effect associated with improvement of sensorimotor activity and body weight gain, as well as lower mortality. Future studies are essential to elucidate the mechanisms via which CBD exerts these effects and whether other mechanisms, such as antiinflammation, antioxidative stress, and neuroprotection, are involved. Our study suggests a neuroprotective effect of CBD short- and long-term after a severe TBI. These findings support orally administered CBD as a therapeutic strategy to prevent long-term consequences after TBI in the high-risk population, such as military personnel and contact sport athletes. It will also be interesting to determine if CBD neuroprotection is sufficient to prevent the development of long-term disorders following TBI, such as Alzheimer’s disease, Parkinson’s disease, and post-traumatic epilepsy.”
“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. 
“Despite the high incidence of traumatic brain injury (TBI), there is no universal treatment to safely treat patients. Blunt brain injuries destroy primary neural tissue that results in impaired perfusion, excessive release of glutamate, inflammation, excitotoxicity, and progressive secondary neuronal cell death. 
“The hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF) is well known to stimulate proliferation of blood stem/progenitor cells of the leukocyte lineage, but is also recognized as a neurotrophic factor involved in brain self-repair processes. G-CSF administration has been shown to promote recovery from experimental models of traumatic brain injury (TBI) and to modulate components of the endocannabinoid system (eCS). Conversely, Δ9-tetrahydrocannabinol (
“There is not a single pharmacological agent with demonstrated therapeutic efficacy for traumatic brain injury (TBI). With recent legalization efforts and the growing popularity of medical cannabis, patients with TBI will inevitably consider medical cannabis as a treatment option.
“The prevalence of mild traumatic brain injury is highest amongst the adolescent population and can lead to complications including neuroinflammation and excitotoxicity.