The endocannabinoid system and the ageing brain.

Endocannabinoid signalling shows a dynamic lifespan trajectory—relatively high in early adulthood but functionally declining with ageing—linked to multiple hallmarks of brain ageing.

• Why it matters: Ageing reduces homeostatic resilience, raising risk for chronic disease, disability, and cognitive impairment, yet the mechanisms connecting risk factors to late-life brain dysfunction are not fully understood.
• What they did: This review synthesizes evidence that genetic or pharmacological disruption of endocannabinoid system activity affects neuroinflammatory control, adult neurogenesis, synaptic plasticity, cognitive performance, metabolic regulation, and epigenetic stability.
• The result: Low-dose Δ9-tetrahydrocannabinol (THC) treatment can ameliorate several ageing-related brain phenotypes in old animals, but older-human clinical evidence is limited and cannabinoid intervention potential needs further evaluation.

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