Background:To understand the differential response to cannabinoids, we examined the functional selectivity of type 1 cannabinoid receptor (CB 1 ) agonists in a cell model of striatal neurons. Results: 2-Arachidonylglycerol, ⏠9 -tetrahydrocannabinol, and CP55,940 were arrestin2-selective; endocannabinoids and WIN55,212-2 activated G⣠i/o , Gâ€â„, and G⣠q ; and cannabidiol activated G⣠s independent of CB 1 . Conclusion: Cannabinoids displayed functional selectivity. Significance: CB 1 functional selectivity may be exploited to maximize therapeutic efficacy.