Cannabidiol negatively modulates adenosine A 2A receptor functioning in living cells.

Objectives: Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A _2A receptors (A _2A Rs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A _2A R.
Methods: We used HEK-293T cells transfected with the cDNA encoding the human A _2A R and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A _2A R ligand binding using an A _2A R NanoLuciferase sensor. Next, we evaluated whether CBD modified A _2A R coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on A _2A R intrinsic activity by recording agonist-induced cAMP accumulation.
Results: CBD did not bind orthosterically to A _2A R but reduced the coupling of A _2A R to Gαs protein and the subsequent generation of cAMP.
Conclusion: CBD negatively modulates A _2A R functioning.