Patent review of cannabinoid receptor type 2 (CB2R) modulators (2016-present).

Introduction: Cannabinoid receptor type 2 (CB₂R), predominantly expressed in immune tissues, is believed to play a crucial role within the body's protective mechanisms. Its modulation holds immense therapeutic promise for addressing a wide spectrum of dysbiotic conditions, including cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, and autoimmune diseases, as well as lung disorders, cancer, and pain management.

Areas covered: This review is an account of patents from 2016 up to 2023 which describes novel CB₂R ligands, therapeutic applications, synthesis, as well as formulations of CB₂R modulators.

Expert opinion: The patents cover a vast, structurally diverse chemical space. The focus of CB₂R ligand development has shifted from unselective dual-cannabinoid receptor type 1 (CB₁R) and 2 agonists toward agonists with high selectivity over CB₁R, particularly for indications associated with inflammation and tissue injury. Currently, there are at least eight CB₂R agonists and one antagonist in active clinical development. A better understanding of the endocannabinoid system (ECS) and in particular of CB₂R pharmacology is required to unlock the receptor's full therapeutic potential.