Cannabinoid CB2 receptor mechanism of Cannabis sativa L.

Abstract

Cannabinoids and many other compounds are constituents in Cannabis sativa L., (cannabaceae) and endocannabinoids (eCBs) are the endogenous marijuana-like substances found in animals and humans. Endocannabinoids, phy- tocannabinoids and marijuana use activate two cannabinoid receptors (CBRs), CB1Rs and CB2Rs that are encoded in human chromosomes 6 and 1 respectively. New understanding in the science of cannabis botany along with medical and biotechnological advances demonstrate that phytocannabinoids and eCBs acting on CBRs are important regulators of various aspects of physiological, behavioral, immunological and metabolic functions. CB2Rs were previously thought to be predominantly expressed in immune cells in the periphery and were traditionally referred to as peripheral CB2Rs. The neuronal and functional expression of CB2Rs in the brain had been controversial and have been less well characterized in comparison with the expression of the ubiquitous CB1Rs. We and others have now demonstrated the expression of CB2Rs in neuronal, glial and endothelial cells in the brain, and this warrants a re-evaluation of the CNS effects of CB2Rs. In this chapter we focused on the neurobiology of CB2Rs and describe its gene structure, regulation, variation, CNS distribution and its emerging role in immuno- endocannabinoid interactions with novel knowledge and deeper insight from the genetic and epigenetic manipulation of CB2Rs. With the rapidly shifting landscape on recreational, medicalization, and legalization of marijuana use, further research will certainly provide the scientific basis to unravel the mode of action of marijuana use and its implication on its neurological and psychiatric effects in human health and disease. We conclude that CB2 cannabinoid receptor signaling plays an important role in neuro-immuno-cannabinoid activity and beyond with potential therapeutic targets in neurological and mental diseases.