Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats

“The number of activated microglia increase during normal aging. Stimulation of endocannabinoid receptors can reduce the number of activated microglia, particularly in the hippocampus, of young rats infused chronically with lipopolysaccharide (LPS). In the current study we demonstrate that endocannabinoid receptor stimulation by administration of WIN-55212-2 (2 mg/kg/day) can reduce the number of activated microglia in hippocampus of aged rats and attenuate the spatial memory impairment in the water pool task. Our results suggest that the action of WIN-55212-2 does not depend upon a direct effect upon microglia or astrocytes but is dependent upon stimulation of neuronal cannabinoid receptors. Aging significantly reduced cannabinoid type 1 receptor binding but had no effect on cannabinoid receptor protein levels. Stimulation of cannabinoid receptors may provide clinical benefits in age-related diseases that are associated with brain inflammation, such as Alzheimer’s disease.”

“Our results are consistent with the hypothesis that CB receptors on hippocampal neurons modulate glutamatergic and GABAergic function and this leads to reduced microglia activation. This mechanism may underlie the neuroprotective effects of cannabinoids”.

“Importantly, the benefits of cannabinoid receptor stimulation occurred at a dose that did not impair performance in a spatial memory task, indeed the performance of aged rats was significantly improved. This finding is particularly relevant for elderly for patients suffering with diseases associated with brain inflammation, e.g. AD, Parkinson’s disease or multiple sclerosis. The current report is the first to our knowledge to demonstrate the anti-inflammatory actions of cannabinoid therapy in aged animals and strongly advocate an cannabinoid-based therapy for neuroinflammation-related diseases, as well as a potential tool to reduce the impairment in memory processes occurring during normal aging.”

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Can the benefits of cannabinoid receptor stimulation on neuroinflammation, neurogenesis and memory during normal aging be useful in AD prevention?



Alzheimer’s disease has become a growing socio-economical concern in developing countries where increased life expectancy is leading to large aged populations. While curing Alzheimer’s disease or stopping its progression does not appear within reach in a foreseeable future, new therapies capable of delaying the pathogenesis would represent major breakthroughs.

Presentation of the hypothesis

The growing number of medical benefits of cannabinoids, such as their ability to regulate age-related processes like neuroinflammation, neurogenesis and memory, raise the question of their potential role as a preventive treatment of AD.

Testing the hypothesis

To test this hypothesis, epidemiological studies on long term, chronic cannabinoid users could enlighten us on the potential benefits of these compounds in normal and pathological ageing processes. Systematic pharmacological (and thus more mechanistic) investigations using animal models of Alzheimer’s disease that have been developed would also allow a thorough investigation of the benefits of cannabinoid pharmacotherapy in the pathogenesis of Alzheimer’s disease.

Implications of the hypothesis

The chronic administration of non-selective cannabinoids may delay the onset of cognitive deficits in AD patients; this will dramatically reduce the socio-economic burden of AD and improve the quality of life of the patients and their families.”

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