Introduction: Using nanoparticle (NP) drugs can have better effects on the target tissue in various diseases. Alzheimer’s disease (AD) is one of the degenerative neurological diseases that due to its high prevalence, requires the use of more appropriate treatments. Therefore, the aim of this study was consideration of the effect of cannabidiol (CBD) coated by nano-chitosan on learning and memory, hippocampal cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 1 (CB2) levels, and amyloid plaques in an AD rat model. Material and Methods: Thirty-five male Wistar rats were randomly divided into 5 groups (n = 7 in each): control, Alzheimer’s disease model that received the beta-amyloid (Aβ) peptide (Alz), Alz + nano-chitosan (NP) Alz + CBD, and Alz + NP + CBD. Alz was induced by injection of the Aβ1-42 peptide into the hippocampal area cornu ammonis1. After confirmation of Alz, 1 μL of CBD and NP + CBD were administered by oral gavage daily in rats for 1 month. The Morris water maze (MWM) test was used to assess learning and memory of animals. Cresyl violet staining was used for consideration of dead cells. Gene and protein expression of CB1 and CB2 was performed by real-time PCR and immunohistochemistry methods. Results: Induction of Alz significantly increased Aβ plaques and dead cells compared to the control group (p < 0.001). Results of MWM in the day test show that Alz + NP + CBD significantly decrease escape latency (p < 0.01), travelled distance (p < 0.001), and significantly increased spending time (p < 0.001) compared to the Alz group. Protein expression of CB1 and CB2 significantly increased in Alz + CBD and Alz + NP + CBD compared to the Alz group (p < 0.05). Conclusion: It seems that CBD coated by nano-chitosan has good potential for reducing Aβ plaques, increasing brain CB1 and levels CB2, and improving learning and memory in Alz rats.
