The effects of chronic cannabidiol administration on brain pathology and behavioral deficits found in the tau P301s-line PS19 mouse model of Alzheimer's disease

BackgroundCompounds derived from the plant <i>Cannabis</i> demonstrate many therapeutic properties suggesting that they could delay the onset and progression of Alzheimer's disease (AD).ObjectiveThe goal of the present experiment was to observe the effects of chronic cannabidiol (CBD) administration on the behavior and brain pathology of an AD tauopathy mouse model, Tau P301S-Line PS19 mice.MethodsMice were orally given CBD (20 mg/kg) or vehicle, daily, beginning around 3 months of age. At 6 months old, mice were tested on a battery of tasks to assess object recognition, motor function, and spatial learning and memory. The mice were retested at 9 months old on the behavioral tasks and the fear conditioning paradigm was added. Following completion of behavioral testing, the mice were perfused for histological analysis.ResultsChronic CBD treatments did not appear to affect the behavior nor restore the reduced hippocampal volume of Tau P301S mice. However, a deeper assessment of the changes in inflammatory markers showed a treatment effect on a measure of microglia reactivity. Robust sex differences were revealed with Tau P301S males showing more severe pathology relative to females. Finally, daily treatments of CBD did not negatively impact the behavior or brain of any of the experimental groups suggesting that its chronic administration was relatively safe.ConclusionsTaken together, the results suggested that CBD can have beneficial effects on some of the pathology associated with AD, even in an aggressive model of this neurodegenerative disease, but the impacts on impaired behavior were minimal.