Cannabidiol improves the cognitive function of SAMP8 AD model mice involving the microbiota-gut-brain axis

J Toxicol Environ Health A. 2024 Jun 2;87(11):471-479. doi: 10.1080/15287394.2024.2338914. Epub 2024 Apr 9.


Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aβ). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.

Keywords: Alzheimer’s disease; Cannabidiol; Lipopolysaccharide (LPS); SAMP8 mouse; cognitive impairment; gut microbiota; microglia.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Animals
  • Brain-Gut Axis
  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cognition
  • Cognitive Dysfunction* / drug therapy
  • Disease Models, Animal
  • Mice


  • Cannabidiol