Cannabidiol Regulates Amyloid-β Plaque Deposition and Astrogliosis in the 5xFAD Transgenic Mouse Model.

Ng S.; Somvanshi R.; Kumar U. · Journal of molecular neuroscience : MN · 2026

**Background & Methods** This study investigated cannabidiol (CBD) effects on Alzheimer's Disease pathology using 5xFAD transgenic mice compared to age-matched wild-type controls. Researchers employed immunohistochemistry and immunoblotting to analyze receptor expression and pathological markers in AD-affected brain regions (cortex and hippocampus). **Key Findings** • CBD treatment significantly reduced amyloid-beta (Aβ) plaque burden and glial fibrillary acidic protein (GFAP)-positive astrocyte accumulation in 5xFAD transgenic mice, indicating reduced neuroinflammation and plaque pathology. • CBD induced selective changes in cannabinoid receptor expression: CB1R was upregulated in transgenic mice cortex (compared to controls), while CB2R expression remained unchanged between groups but significantly increased following CBD treatment. • PPAR-gamma (PPARγ) co-localized with Aβ plaques in transgenic mice, and CBD treatment enhanced this co-expression; additionally, CBD ameliorated dysregulation of the PI3K signaling pathway observed in untreated transgenic mice. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This review article presents preclinical evidence from a transgenic mouse model of Alzheimer's Disease. Significant limitations include: (1) findings are restricted to animal models and may not translate to human disease; (2) the abstract does not specify CBD dosing, treatment duration, or administration route, limiting reproducibility; (3) no pharmacokinetic or toxicity data are provided; (4) the mechanism of action appears multifactorial (CB2R, PPARγ, PI3K pathway), making it difficult to identify the primary therapeutic target; and (5) as a 2026 publication date suggests this is a recent or future publication, peer review status and citation history remain to be established. The study provides valuable mechanistic insights into CBD's potential neuroprotective effects but represents preliminary preclinical evidence requiring validation through human clinical trials before therapeutic recommendations can be established.

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