Cannabinoid CB₁ and CB₂ Receptor Signaling and Bias

An agonist that acts through a single receptor can activate numerous signaling pathways. Recent studies have suggested that different ligands can differentially activate these pathways by stabilizing a limited range of receptor conformations, which in turn preferentially drive different downstream signaling cascades. This concept, termed "biased signaling" represents an exciting therapeutic opportunity to target specific pathways that elicit only desired effects, while avoiding undesired effects mediated by different signaling cascades. The cannabinoid receptors CB₁ and CB₂ each activate multiple pathways, and evidence is emerging for bias within these pathways. This review will summarize the current evidence for biased signaling through cannabinoid receptor subtypes CB₁ and CB₂.