Inverse agonist

An inverse agonist is a molecule that binds a receptor and pushes its activity below the resting level, rather than simply blocking it.

Many receptors are not fully silent when unoccupied; a fraction of them sit in the active shape and send a low, steady signal called constitutive activity. A neutral antagonist leaves that baseline alone and only blocks agonists. An inverse agonist stabilizes the inactive shape, so the signal drops beneath baseline, an effect that becomes obvious in cells that express the receptor at high density. Several drugs once labeled antagonists, including some antihistamines and the CB1 blocker rimonabant, were later reclassified as inverse agonists when this distinction became measurable.

The term appears in cannabinoid pharmacology because CB1 and CB2 both show constitutive activity in laboratory systems, and CBD has been described as a weak inverse agonist at CB2 in some cell studies. These are in-vitro classifications used to compare compounds, and they have not been linked to any confirmed effect in people or pets.