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Review
. 2017:80:169-206.
doi: 10.1016/bs.apha.2017.03.007. Epub 2017 Jun 12.

CB1 and CB2 Receptor Pharmacology

Allyn C Howlett  1 , Mary E Abood  2
Affiliations
Review

CB1 and CB2 Receptor Pharmacology

Allyn C Howlett et al. Adv Pharmacol. 2017.

Abstract

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.

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

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Conflict of interest statement

Conflict of Interest

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Biased agonism
Upon agonist binding, G-proteins dissociate into α and βγ subunits and intracellular signaling pathways commence. Phosphorylation of the receptor (by one or more GRKs, not shown) recruits β-arrestin, which, in addition to directing internalization, can also initiate intracellular signaling.
See this image and copyright information in PMC

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