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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


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 NanoBiTTM 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.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalActa Neuropsychiatrica
Early online date22 Aug 2023
Publication statusE-pub ahead of print - 22 Aug 2023


  • adenosine 2A receptor
  • cannabidiol
  • competitive binding
  • cyclic AMP
  • luminescence-based assays
  • negative allosteric regulation


Dive into the research topics of 'Cannabidiol negatively modulates adenosine A2A receptor functioning in living cells'. Together they form a unique fingerprint.

Cite this