Cannabinoid Receptors as Regulators of Neutrophil Activity in Inflammatory Diseases

Cannabinoids are compounds present in Cannabis sativa (phytocannabinoids), endogenously produced (endocannabinoids) or synthesized, that bind to G protein-coupled receptors named cannabinoid receptors B1 and B2. They were first described as psychotropic compounds; however, cannabinoids are also potent immunoregulatory agents. Cannabinoids can modulate neutrophil activity in sterile and infectious inflammatory diseases. Concerning sterile inflammatory diseases as arthritis, ischemic diseases, and colitis, the use of CB2 agonist impairs the intracellular signaling pathways involved in the production of inflammatory mediators and expression of adhesion molecules. As a consequence, neutrophils did not release metalloproteinases either to adhere to endothelial cells, resulting in reduced tissue damage. A similar anti-inflammatory CB2 agonist mechanism of action in sepsis and mycobacterial infection models is observed. However, it is not clear if inflammation resolution promoted by cannabinoid treatment during infection is also related to microbial viability. Despite the growing literature showing the effects of cannabinoids on neutrophils, there are still some gaps that should be filled before proposing cannabinoid-based drugs to treat neutrophil-dependent diseases