Cannabinoid Receptor (CB1) Plays Crucial Role in Alzheimers Disease - Dr. Dave Hepburn

Tuesday, 9 October 2018

Article recommend by Dr. Dave Hepburn:

Genetic deletion of CB1 cannabinoid receptors exacerbates the Alzheimer-like symptoms in a transgenic animal model.

Activating CB1 cannabinoid receptor has been demonstrated to produce certain therapeutic effects in animal models of Alzheimer's disease (AD). In this study, we evaluated the specific contribution of CB1 receptor to the progression of AD-like pathology in double transgenic APP/PS1 mice. A new mouse strain was generated by crossing APP/PS1 transgenic mice with CB1 knockout mice. Genetic deletion of CB1 drastically reduced the survival of APP/PS1 mice. In spite that CB1 mutant mice bearing the APP/PS1 transgene developed normally, they suddenly died within the first two months of life likely due to spontaneous seizures. This increased mortality could be related to an imbalance in the excitatory/inhibitory transmission in the hippocampus as suggested by the reduced density of inhibitory parvalbumin positive neurons observed in APP/PS1 mice lacking CB1 receptor at 7 weeks of age. We also evaluated the AD-like phenotype of APP/PS1 mice heterozygous for the CB1 deletion at 3 and 6 months of age. The memory impairment associated to APP/PS1 transgene was accelerated in these mice. Neither the soluble levels of Aβ or the density of Aβ plaques were modified in APP/PS1 mice heterozygous for CB1 deletion at any age. However, the reduction in CB1 receptor expression decreased the levels of PSD-95 protein in APP/PS1 mice, suggesting a synaptic dysfunction in these animals that could account for the acceleration of the memory impairment observed. In summary, our results suggest a crucial role for CB1 receptor in the progression of AD-related pathological events.

“Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, now a crucial role of CB1R has become evident. One of the more exciting areas of cannabis and endocannaboid research.”

Dr. Dave Hepburn

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