Molecular basis for ligand modulation of the cannabinoid CB₁ receptor

The cannabinoid CB₁ receptor is the most abundant G protein coupled receptor (GPCR) in the central nervous system, which mediates the functional response to endocannabinoids and Cannabis compounds. A variety of ligands for CB₁ receptors have been developed as promising drug candidates for the treatment of neurological disorders. New high-resolution structures of CB₁ receptor in different functional states have significantly improved our molecular understanding of CB₁ ligand interactions, selectivity, receptor activation and allosteric modulation. These advances have paved the way for development of novel ligands for different therapeutic applications. In this review, we describe the structural determinants for modulation of CB₁ receptors by different types of ligands, as well as the differences between CB₁ and its homologous, the CB₂ receptor. LINKED ARTICLES: This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc.