The endocannabinoid system in sepsis – a potential target to improve microcirculation?

Abstract

During the last decade, research has identified the endocannabinoid system (ECS) as a key regulator of essential physiological functions, including the regulation of microvascular and immune function. Indeed, increasing evidence now suggests that release of endocannabinoids and activation of cannabinoid receptors occurs during sepsis and that manipulation of the ECS may represent an important therapeutic target to improve microcirculation in sepsis. In this review, the pharmacology and physiology of the ECS and the involvement of cannabinoids, cannabinoid receptors and non-CB1R/CB2R pathways related to ECS activation will be described. This information will increase our comprehension of the role of lipid signaling pathways in sepsis and may lead to the identification of new drug targets for the treatment of impaired microcirculation.

Anti‐inflammatory effects of cannabinoid CB2 receptor activation in endotoxin‐induced uveitis

“…Recently, several studies have reported that modulating CB 2 receptors in experimental models of sepsis decreased inflammation (Lehmann et al ., 2011; 2012), and deleting these receptors reduced survival (Tschop et al ., ). Attenuation of the inflammatory response by activation of CB 2 receptors has also been reported in the brain.…”

Neutrophil to Lymphocyte ratio of Synthetic Cannabinoid Intoxication

“…In contrast, CB2 are localized primarily in immune cells such as lymphocytes, macrophages and neutrophils and are responsible for immunomodulatory effects of cannabinoids. (1,3,4) While THC is a low-efficacy partial agonist of cannabinoid receptors, the synthetic cannabinoids are high-potency full agonists for CB1 receptors. (5) Most synthetic cannabinoids are not currently found using routine toxicology screening as they contain synthetic cannabinoids from different chemical classes.…”