Abstract
BACKGROUND: Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is characterized by progressive cognitive decline. Among the approved clinical treatments for AD, acetylcholinesterase (AChE) inhibitors are widely used to alleviate symptoms by increasing acetylcholine (ACh) levels in the basal forebrain. Cannabidiol (CBD), a major phytocannabinoid derived from Cannabis sativa, has also been demonstrated to enhance ACh levels and alleviate cognitive deficits. AIMS & OBJECTIVES: This study aimed to evaluate the therapeutic potential of CBD in addressing cognitive impairments associated with AD using a mouse model. METHOD: We applied the Nine-month-old 3xTg-AD mice as the AD mouse model, while B6129s mice as the normal cognitive control group. To investigate the potential cognitive improvements following administration, 3xTg-AD mice were treated either with vehicle or CBD (10 mg/kg/day, i.p.), Cognitive function was assessed through behavioral tests, including the Morris water maze, Object Location Test (OLT), and Open Field Test (OFT). For aging-related analysis, senescence-associated β-galactosidase (SA-β-gal) staining was performed in the hippocampus of 3xTg-AD mice. RESULTS: Compared to vehicle-injected 3xTg-AD mice, those treated with CBD (10 mg/kg/day, intraperitoneally, for 21 days) exhibited significantly improved cognitive performance, as evidenced by increased time spent in the target zone (%) in the Morris water maze and a higher object discrimination index (DI) in the object location test. Moreover, CBD treatment reduced senescence-associated β-galactosidase (SA-β-gal)-positive cells in the hippocampus of 3xTg-AD mice. DISCUSSION & CONCLUSIONS: These findings highlight the potential of CBD to mitigate cognitive deficits in AD, offering a novel perspective on its clinical application as a therapeutic agent.