CB2: Therapeutic target-in-waiting

CB2 cannabinoid receptor agonists hold promise as a new class of therapeutics for indications as diverse as pain, neuroinflammation, immune suppression and osteoporosis. These potential indications are supported by strong preliminary data from multiple investigators using diverse preclinical models. However, clinical trials for CB2 agonists, when they have been reported have generally been disappointing. This review considers possible explanations for the mismatch between promising preclinical data and disappointing clinical data. We propose that a more careful consideration of CB2 receptor pharmacology may help move CB2 agonists from “promising” to “effective” therapeutics.

► CB2 cannabinoid receptor agonism is a promising therapeutic approach.
► CB2 is expressed on microglia; its expression on neurons remains controversial.
► Much remains to be learned abourt the regulation of CB2 expression and signaling.
► Development of useful CB2 agonists will require precise attention to its signaling.