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.

Automated summary

The cannabinoid CB1 receptor, as the most abundant G protein coupled receptor in the central nervous system, mediates the response to endocannabinoids and Cannabis compounds. Various ligands targeting CB1 receptors have been developed for the treatment of neurological disorders. High-resolution structures of CB1 receptor in different functional states have enhanced our understanding of CB1 ligand interactions, selectivity, receptor activation, and allosteric modulation, paving the way for the development of novel ligands for therapeutic applications.