CANNABIDIOL PREVENTS COGNITIVE AND SOCIAL DEFICITS AND REDUCES NEUROINFLAMMATION IN A RAT MODEL OF ALZHEIMER’S DISEASE

Progressive cognitive impairment is a hallmark of Alzheimer’s disease (AD), associated with amyloid beta-protein (Aβ) accumulation, tau hyperphosphorylation, neuroinflammation, and neuronal degeneration. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with a favorable safety profile, exhibits immunomodulatory and neuroprotective properties; however, its mechanisms of action in AD are not fully understood.
In this study, we examined the effects of chronic CBD treatment on cognitive, behavioral, and neuropathological alterations in a rat model of sporadic AD induced by intracerebroventricular streptozotocin (ICV-STZ). We further assessed the involvement of neuroinflammatory pathways and cannabinoid receptor signaling in mediating CBD’s effects.
Rats exposed to STZ exhibited marked impairments in object location and object recognition memory, along with reduced social interaction. These deficits were accompanied by increased Aβ levels, enhanced tau phosphorylation, and elevated expression of neuroinflammatory markers, including tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B subunit 1 (NF-κB1). STZ exposure also altered cannabinoid receptor expression, characterized by downregulation of cannabinoid receptor 1 (cnr1) and upregulation of cannabinoid receptor 2 (cnr2). Chronic CBD administration reversed cognitive and social impairments, reduced neuroinflammatory gene expression, and attenuated AD-related neuropathological changes. Notably, pharmacological blockade of CB1 receptors using AM251, but not CB2 receptors using AM630, abolished the beneficial effects of CBD on object location memory and social behavior in STZ-treated rats.
Together, these findings indicate that CBD mitigates cognitive and social deficits in a sporadic AD model through CB1 receptor–dependent mechanisms and modulation of neuroinflammation, supporting its potential as a therapeutic strategy for inflammation-driven AD.