“Cognitive decline is a hallmark of Alzheimer’s disease (AD). Cannabidiol (CBD), a non-intoxicating phytocannabinoid with immunomodulatory properties, shows promise in alleviating AD symptoms.
This study examined the effects of chronic CBD treatment in a male rat model of sporadic AD induced by intracerebroventricular streptozotocin (ICV-STZ) and explored its impact on neuroinflammatory genes and cannabinoid signaling.
STZ rats showed impaired performance in object location and recognition tasks, along with reduced social behavior. STZ exposure also affected AD-related hippocampal markers, leading to increased levels of amyloid β-protein (Aβ) and tau phosphorylation (p-Tau) and elevated mRNA levels of triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E4 (APOEε4). Additionally, STZ increased hippocampal neuroinflammatory markers, including mRNA levels of Tumor Necrosis Factor α (TNF-α), nuclear factor kappa B subunit 1 (NF-κB1), and interleukin (IL)-1β. It also altered cannabinoid receptor expression, with cannabinoid receptor 1 (cnr1) and 2 (cnr2) genes upregulated in the dentate gyrus (DG), whereas in the CA1, cnr2 was upregulated and cnr1 downregulated.
Chronic CBD treatment restored the STZ-induced behavioral deficits, reduced neuroinflammatory marker expression, and mitigated AD-associated changes. Importantly, the CB1 receptor antagonist AM251, but not CB2 antagonist AM630, blocked the beneficial effects of CBD on performance in object location and social tasks in STZ-treated rats, highlighting CB1 receptor activation as a key mechanism.
These findings suggest that CBD holds promise as a therapeutic agent for inflammation-induced AD, with the potential to ameliorate cognitive deficits and prevent disease onset through mechanisms involving CB1 receptor activation and modulation of neuroinflammation.”
https://pubmed.ncbi.nlm.nih.gov/40859005/
“Our findings suggest that CBD protects against STZ-induced cognitive and social deficits, hippocampal neuroinflammation, and AD-related pathology, with CB1r playing a key role in its therapeutic effects. As current AD treatments are limited, our study highlights CBD as a promising candidate, demonstrating for the first time that a low dose can prevent behavioral and molecular deficits in a rodent model of sporadic AD. By targeting neuroinflammation and endocannabinoid pathways, CBD may help prevent cognitive decline and neuropathological changes in AD.”