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. Author manuscript; available in PMC: 2018 Mar 15.
Published in final edited form as: Biochem Pharmacol. 2016 Nov 24;128:1–11. doi: 10.1016/j.bcp.2016.11.014

Table 1. Evidence of CB1R functional selectivity.

Ligand Functional selectivity Experimental approach Reference
Endocannabinoids
2-AG No bias towards cAMP inhibition over pERK 1/2 Alphascreen cAMP and SureFire assay with CB1R-expressing CHO cells [60]
Increases CB1R surface expression through Gβγ signaling cAMP accumulation assay in CB1R-expressing CHO cells. [58]
Anandamide Biased towards Gi over Go CB1R urea-extracted from sf9 membranes and reconstituted with varying Ga and Gβγ subunits. [56]
Biased towards Gi over Gs and doesnot signal through Gq cAMP accumulation assay in CB1R-expressing CHO cells. [58]
Biased towards cAMP inhibition over pERK 1/2 Alphascreen cAMP and SureFire assay with CB1R-expressing CHO cells [60]
Eicosanoids
Methanandamide Inverse agonist at Gi1 and Gi2; Agonist at Gi3 CB1R-G protein complex were CHAPS-extracted from N18TG2 cell membrane and quantified by coimmunoprecipitation [57]
Biased towards cAMP inhibition over pERK 1/2 Alphascreen cAMP and SureFire assay with CB1R-expressing CHO cells [60]
Classical Cannabinoids
THC Biased towards cAMP inhibition over pERK 1/2 Alphascreen cAMP and SureFire assay with CB1R-expressing CHO cells [60]
Induces expression of Tyrosine Hydrooxylase mRNA and Protein analysis in mouse neuroblastoma cells N1E-115 [61]
Induced receptor internalization through β-arrestin recruitment CREB phosphorylation in mouse striatal medium spiny projection neurons (STHdhQ7/Q7) [59]
Desacetyl-Levonantradol Agonist at Gi1 and Gi2; Inverse agonist at Gi3 CB1R-G protein complex were CHAPS-extracted from N18TG2 cell membrane and quantified by coimmunoprecipitation [57]
HU210 Non-selective between Gi, Go and Gs pathways cAMP accumulation assay in CB1R-expressing CHO cells. [58]
Biased towards cAMP inhibition over pERK 1/2 Alphascreen cAMP and SureFire assay with CB1R-expressing CHO cells [60]
Decreases Tyrosine Hydroxylase expression unlike CP55940 Tyrosine hydroxylase expression in N1E-115 Neuroblastoma cells [61]
Non-classical Cannabinoids
CP55940 Activates Gs pathway CREB phosphorylation in mouse striatal medium spiny projection neurons (STHdhQ7/Q7) [59]
Biased towards Gi over Gs and does not signal through Go and Gq cAMP accumulation assay in CB1R-expressing CHO cells. [58]
Induced receptor internalization through β-arrestin recruitment CREB phosphorylation in mouse striatal medium spiny projection neurons (STHdhQ7/Q7) [59]
Aminoalkylindole
WIN55212 Activates Gq pathway Intracellular calcium accumulation in CB1R-expressing HEK293 cells and cultured hippocampal neurons. [47]
Non-selective between Gi1, 2 and 3 subtypes CB1R-G protein complex were CHAPS-extracted from N18TG2 cell membrane and quantified by coimmunoprecipitation [57]