CANNABIDIOL REDUCES NEUROINFLAMMATION CORRELATED WITH CB2 RECEPTOR CHANGES IN AN APP MOUSE MODEL OF ALZHEIMER’S DISEASE.

Alzheimer’s disease (AD) is associated with amyloid beta induced activation of microglia and astrocytes, driving sustained release of pro inflammatory mediators and progressive neurodegeneration. The endocannabinoid system may counteract these responses through CB2 receptor signalling. This study investigates whether CB2 receptors regulate glial activation in AD and whether cannabidiol (CBD) modulates CB2 signalling to attenuate neuroinflammation.

In-vivo dosing was performed using APP^NL-F/NL-F knock- in mouse model of AD, age-matched wild-type mice (12-16 months). Mice were randomly assigned to receive a single treatment of CBD (10 mg/kg), PGN36 (CB2R antagonist; 5 mg/kg), or vehicle, administered once daily for 7 days. Hippocampal sections were analysed using immunofluorescence, confocal microscopy combined with IMARIS analysis, to assess inflammatory glial markers (GFAP and CD68) and CB2 receptor expression.

Z stack confocal analysis revealed increased hippocampal GFAP and CD68 immunoreactivity in APPNL-F/NL-F mice compared with wild type controls, alongside elevated CB2 receptor expression in both astrocytic and microglial populations. CBD treatment reduced GFAP and CD68 levels in the hippocampus of both genotypes relative to vehicle, while generally increasing glial CB2 receptor expression. Colocalisation analysis indicated minimal CB2 overlap with GFAP, whereas CB2 showed substantial colocalisation with CD68, consistent with predominant microglial CB2 localisation.

Our data suggest that CBD influences the expression of CB2 receptors and can enhance their activity in an amyloid model of AD, supporting a potential CB2-mediated therapeutic role for CBD in reducing neuroinflammation.