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cc by (c) Sánchez Fernández, Nuria et al., 2024
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/219512

Cannabidiol negatively modulates adenosine A2A receptor functioning in living cells

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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.

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SÁNCHEZ FERNÁNDEZ, Nuria, et al. Cannabidiol negatively modulates adenosine A2A receptor functioning in living cells. Acta Neuropsychiatrica. 2024. Vol. 36, num. 5, pags. 320-324. ISSN 0924-2708. [consulted: 16 of August of 2026]. Available at: https://hdl.handle.net/2445/219512

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