Cannabinoid receptors type 2: Function and development in agonist discovery from synthetic and natural sources with applications for the therapy of osteoporosis

Type-2 cannabinoid receptor (CB2R) is a member of the G protein-coupled receptor superfamily with various biological activities in pain regulation, anti-inflammation, anti-fibrosis, and bone metabolism regulation. CB2R modulators have been demonstrated to have significant regulatory effects on bone metabolism with no significant psychoactive adverse effects. In this article, we present a comprehensive review of the molecular mechanism of CB2R in regulating bone metabolism and summarize virtual screening and experimental screening methods for CB2R modulators from natural and synthetic products. Knowing that some botanical compounds are CB2R modulators involved in the regulation of bone metabolism, we also review the botanical and synthetic compounds currently known to be potential CB2R and summarize their regulatory effects on bone metabolism based on the results of animal, osteoblasts (OBs) and osteoclasts (OCs) experimental studies presently available, hoping that the findings and conclusions in this review could provide a scientific basis for the discovery of new CB2R regulators and the development of new anti-osteoporosis drugs.