Oral Administration of CBD Improves Histopathological and Cognitive Outcomes Following Traumatic Brain Injury

Meghan Blaya
University of Miami

Objective: Traumatic brain injury (TBI) is a leading cause of death and disability with 69 million individuals sustaining TBI each year. Long-term complications, such as cognitive impairment, headache, sleep disturbances, and neurological comorbidities are primary complaints. Currently, there is a severe lack of treatment options to lessen the negative impact injury-induced disorders have on quality of life. Cannabidiol (CBD) is a nonpsychoactive, plant-derived compound that has beneficial outcomes in several nervous system disorders due to its anti-inflammatory and anti-apoptotic properties. Thus, we sought to evaluate a clinically-relevant oral administration of CBD to investigate its potential to reverse TBI-induced pathology in a preclinical model of TBI.

Methods: Adult rats were exposed to a moderate fluid-percussion pulse over the right parietal cortex. CBD was orally administered (5 mg/kg) in 1 ml of peanut oil 1 hour post-surgery followed by 1x/day for 6 subsequent days via oral gavage. Outcome measures included spatial memory acquisition/retention and short-term memory via the Morris water maze. We also investigated whether CBD was cytoprotective through volumetric analyses of cortical contusion and quantifying cortical atrophy. Immunohistochemistry was utilized to assess microglia reactivity in various brain structures.

Results: After TBI, cognitive assessment revealed no CBD effect on spatial memory acquisition/retention, however short-term working memory skills trended towards uninjured levels. Histological assessment revealed reduced cortical atrophy and decreased contusion volume in animals treated with CBD. Furthermore, in the hippocampus and cortical penumbra, preliminary analyses showed CBD administration significantly decreased activated microglia phenotypes and reduced overall microglia numbers, two hallmark indicators of TBI-induced neuroinflammation.

Conclusion: CBD has been shown to mediate neuroprotection and inflammatory pathways. We anticipated oral administration would mitigate some of the behavioral deficits and loss of cytoarchitecture after TBI. While positive trends were present, there was a lack of strong significance. However, because of preliminary analyses showing reduction in microglial reactivity and overall numbers, we propose that a higher oral dose may be more efficacious in reversing neuropathological sequelae. While the therapeutic potential of CBD after brain injury has yet to be fully elucidated, its neuroprotective, anti-apoptotic, and anti-inflammatory properties make it a promising

Co-authors: William Moreno¹, Yoandy Ferrer-Marcelo¹, Juliana Sanchez¹, Michael Hoffer¹, Helen Bramlett^1
1_{University of Miami}