Salvinorin A, the active ingredient in Salvia divinorum, produced both anxiety-reducing and antidepressant-like effects in rats and mice. These effects were prevented by blocking either kappa-opioid or CB1 cannabinoid receptors. Salvinorin A reduced fatty acid amide hydrolase activity in the amygdala but showed very weak binding to CB1 receptors. The findings suggest that both kappa-opioid and endocannabinoid systems mediate these mood-altering effects, which may help explain subjective experiences reported by recreational users.
Salvinorin A, a drug from the plant Salvia divinorum, produces rewarding effects in rats at low to moderate doses but becomes aversive at the highest doses tested. In conditioned place preference tests, doses between 0.1 and 40 micrograms per kilogram given subcutaneously were rewarding, while 160 micrograms per kilogram was aversive. In self-administration tests, doses of 0.1 to 0.5 micrograms per infusion given intracerebroventricularly were rewarding, but 1 microgram per infusion was aversive. The rewarding effect was blocked by pretreatment with either a cannabinoid CB1 receptor antagonist or a kappa-opioid receptor antagonist. Salvinorin A also increased dopamine levels in the shell of the nucleus accumbens by about 150 percent. These findings indicate that the rewarding effects involve interaction between kappa-opioid and endocannabinoid systems.