Salvinorin A, the active compound in Salvia divinorum, slows intestinal movement by activating kappa-opioid receptors (KORs). In mice with croton oil-induced intestinal inflammation, this effect also involves cannabinoid CB1 receptors, as the CB1 antagonist rimonabant blocked the motility delay. In healthy mice, rimonabant did not affect salvinorin A's action. Binding tests showed salvinorin A has very weak affinity for CB1 and CB2 receptors and does not inhibit endocannabinoid breakdown or uptake. The findings suggest a functional interaction between CB1 receptors and KORs occurs specifically in the inflamed gut, not in the normal gut.
An extract from the hallucinogenic plant Salvia divinorum and its active ingredient salvinorin A reduce gut motility in mice, but only during intestinal inflammation. In healthy mice, salvinorin A slowed motility only at high doses, and this effect did not involve kappa-opioid receptors (KOR). Inflammation made salvinorin A more potent at lower doses, and this effect was blocked by KOR antagonists, indicating a switch to KOR-mediated action. A standard KOR agonist did not share this enhanced potency, suggesting salvinorin A may act through additional targets in the inflamed gut.