Advances in the Research on Biased Ligands of Cannabinoid Receptors

Cannabinoid receptors, class A family of G protein-coupled receptors (GPCR) that have been proposed as potential therapeutic targets for varieties of diseases, have two main subtypes, CB₁ and CB₂, which are expressed in different tissues and organs. Most existing studies have been focused on the selectivity of the two subtypes of receptors rather than that of the specific signal pathways, but it has been found that drug addiction is related to the selectivity of signal pathways. Activation of CB₁ and CB₂ receptors leads to different effects on each downstream signal transduction pathway, which is called biased agonism. GPCRs show multiple conformations when bound with different agonists, and biased agonists can selectively stabilize a subset of conformations and activate a specific downstream signaling pathway, thereby reducing side effects. This paper focuses on the structural characteristics of cannabinoid receptors, biased signals and research advances of biased ligands, in order to provide reference for related research.