Cannabidiol negatively modulates adenosine A 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 receptors (ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of AR.

METHODS

We used HEK-293T cells transfected with the cDNA encoding the human AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on AR ligand binding using an AR NanoLuciferase sensor. Next, we evaluated whether CBD modified AR coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on AR intrinsic activity by recording agonist-induced cAMP accumulation.

RESULTS

CBD did not bind orthosterically to AR but reduced the coupling of AR to Gαs protein and the subsequent generation of cAMP.

CONCLUSION

CBD negatively modulates AR functioning.