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Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and  in vitro  and limited  in vivo  evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and  APP    Swe    /PS1ΔE9  ( APPxPS1 ) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating.  APPxPS1  mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in  APPxPS1  mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but  APPxPS1  mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated  APPxPS1  mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of  APPxPS1  mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice.

Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice