CB1 and CB2 Receptor Pharmacology

The CB₁ and CB₂ cannabinoid receptors (CB₁R, CB₂R) are members of the G protein-coupled receptor (GPCR) family that were identified over 20 years ago. CB₁Rs and CB₂Rs mediate the effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the principal psychoactive constituent of marijuana, and subsequently identified endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonoyl glycerol. CB₁Rs and CB₂Rs have both similarities and differences in their pharmacology. Both receptors recognize multiple classes of agonist and antagonist compounds and produce an array of distinct downstream effects. Natural polymorphisms and alternative splice variants may also contribute to their pharmacological diversity. As our knowledge of the distinct differences grows, we may be able to target select receptor conformations and their corresponding pharmacological responses. This chapter will discuss their pharmacological characterization, distribution, phylogeny, and signaling pathways. In addition, the effects of extended agonist exposure and how that affects signaling and expression patterns of the receptors are considered.

Biased agonism; Cannabinoid; G protein; GPCR; Human; Polymorphism; Rodent; Splice variant; Tissue selectivity.