Adenosine A2A receptor
A2AThe adenosine A2A receptor is a cell-surface protein that responds to adenosine, a signaling molecule involved in blood flow, immune activity and sleep pressure.
Adenosine is produced as cells use energy, and it rises in the brain across a waking day. When it binds the A2A receptor, a G protein-coupled receptor found on blood vessels, immune cells and neurons in regions such as the striatum, the receptor relaxes vascular smooth muscle, damps immune-cell activation and promotes sleepiness. Caffeine produces its alerting effect largely by blocking this receptor, which is why A2A is one of the better known receptors outside the laboratory.
The receptor matters to cannabinoid pharmacology because CBD does not act on it directly but appears, in laboratory studies, to inhibit the transporter that clears adenosine from the space between cells, leaving more adenosine available to reach A2A. Whether that mechanism contributes to any effect in people or animals remains under study, and no clinical conclusion follows from it.