THE IMPACT OF CANNABIDIOL (CBD) ON COGNITIVE AND VISUAL SYSTEMS IN HYPERGLYCEMIC ZEBRAFISH (DANIO RERIO)

Diabetes Mellitus (DM) is a serious medical condition that impacts the lives of millions of people around the world. Complications of both micro- (small blood vessels) and macro- (large blood vessels) vascular nature occur later in life due to hyperglycemia. Increased hyperglycemia causes increased inflammation globally throughout the CNS and, more locally, in retinal microvasculature leading to downregulated tight-junction proteins. This leads to cognitive and visual decline later in life in Type 2 DM patients. Cannabidiol (CBD) is a nonpsychoactive cannabinoid with known medicinal properties. CBD has shown potential use in lowering inflammation and blood-glucose levels. Therefore, we wanted to test this agent to see if concurrent use of CBD during hyperglycemic induction would lower the risk for cognitive and visual deficits. Using behavioral (Three-Chamber Choice – Cognition; Optomotor Response – Vision), molecular (RT-qPCR and Western Blot), and physiological (Electroretinograms) techniques, we measured the response of CBD treatment on cognition and vision. Overall, we found that CBD had no impact on preventing cognitive decline, and that there was no significant difference between any of the groups in inflammatory pathways or cytokines in brain tissue. However, CBD successfully increased performance on the optomotor response task in hyperglycemic fish and increased the time to b-wave peak response on electroretinograms. Hyperglycemic fish treated with CBD also had decreased inflammation via the JNK inflammatory pathway and increased response in cell survival pathway AKT in retinal homogenates compared to hyperglycemic fish not treated with CBD. These results therefore suggest, that while CBD does not prevent hyperglycemic insult in the brain, it does have an impact in the retina, protecting against visual-based deficits.