Evidence from in vitro and in vivo studies have demonstrated the deleterious pathological effects of a dysregulated endocannabinoid system. Increased stimulation of the cannabinoid receptor 1 (CB₁ ) and subsequent downstream cellular signalling, are both causative in the deleterious pathological effects observed in a number of diseases. When the CB₁ cell signalling cascade is blocked, this results in whole body weight-loss, leading to a reduction in obesity and associated co-morbidities. In the central nervous system however CB₁ antagonism results in adverse psychological side effects. Blockade of CB₁ via peripheral acting compounds that do not cross the blood brain barrier have been determined to have beneficial effects in metabolic tissues such as the liver and skeletal muscle. These results support the notion that peripheral blockade of CB₁ using pharmacological antagonists is a viable target for the treatment of the current epidemic of obesity and its associated co- morbidities.
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PMID:

 

23782485

 

[PubMed – as supplied by publisher]