The Multiple Waves of Cannabinoid 1 Receptor Signaling

Abstract The cannabinoid 1 receptor (CB1R) is one of the most abundant G protein–coupled receptors (GPCRs) in the central nervous system, with key roles during neurotransmitter release and synaptic plasticity. Upon ligand activation, CB1Rs may signal in three different spatiotemporal waves. The first wave, which is transient (<10 minutes) and initiated by heterotrimeric G proteins, is followed by a second wave (>5 minutes) that is mediated by β-arrestins. The third and final wave occurs at intracellular compartments and could be