**Abstract**

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.

**Keywords:** cannabinoid agonist, inflammation, infection, endocannabinoids, phytocannabinoids, synthetic cannabinoids

## **1. Introduction**

Neutrophils have been classically recognized as the most relevant cell during acute inflammatory responses and, more recently, in chronic inflammation [1]. On the one hand, neutrophils produce bactericidal molecules and coordinate the accumulation of pro-resolving cells. On the other hand, neutrophil over activation leads to tissue damage. In this context, several approaches have been proposed to regulate the accumulation and the activity of neutrophils in pathological conditions.

In parallel, the findings concerning the importance of the endocannabinoid system as the endogenous immunoregulatory mechanism raise questions on how it could be therapeutically used to treat inflammatory diseases. In this chapter, we discuss how the endocannabinoid system can be used to modulate the activity of neutrophils in sterile and infectious inflammatory diseases.
