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.
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