Structural and Functional Insights into Cannabinoid Receptors

Trends Pharmacol Sci. 2020 Sep;41(9):665-677. doi: 10.1016/j.tips.2020.06.010. Epub 2020 Jul 29.

Abstract

Cannabinoid receptors type 1 (CB1) and 2 (CB2) are widely expressed in the human body, and are attractive drug targets in the prevention and management of central nervous system (CNS) and immune system dysfunction, respectively. Recent breakthroughs in the structural elucidation of cannabinoid receptors and their signaling complexes with G proteins, provide the important molecular basis of ligand-receptor interactions, activation and signaling mechanism, which will facilitate the next-generation drug design and the precise modulation of the endocannabinoid system. Here, we provide an overview on the structural features of cannabinoid receptors in different functional states and the diverse ligand binding modes. The major challenges and new strategies for future therapeutic applications targeting the endocannabinoid system (ECS) are also discussed.

Keywords: G-protein-coupled receptor; activation; cannabinoid receptors; endocannabinoid system; signaling; therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Design
  • Endocannabinoids*
  • Humans
  • Ligands
  • Receptors, Cannabinoid
  • Signal Transduction*

Substances

  • Endocannabinoids
  • Ligands
  • Receptors, Cannabinoid