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  • Cannabidiol negatively modulates adenosine A2A receptor functioning in living cells

  • Nuria Sánchez-Fernández, Laura Gómez-Acero, Laura I. Sarasola, Josep Argerich, Andy Chevigné, Kenneth A. Jacobson, Francisco Ciruela, Víctor Fernández-Dueñas, Ester Aso
  • Journal:
    Acta Neuropsychiatrica / Volume 36 / Issue 5 / October 2024
    Published online by Cambridge University Press:
    22 August 2023, pp. 320-324
    • Article
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  • 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 A2A receptors (A2ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A2AR.

    Methods:

    We used HEK-293T cells transfected with the cDNA encoding the human A2AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A2AR ligand binding using an A2AR NanoLuciferase sensor. Next, we evaluated whether CBD modified A2AR coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on A2AR intrinsic activity by recording agonist-induced cAMP accumulation.

    Results:

    CBD did not bind orthosterically to A2AR but reduced the coupling of A2AR to Gαs protein and the subsequent generation of cAMP.

    Conclusion:

    CBD negatively modulates A2AR functioning.