Reply To: How does Salvia divinorum act?
The principal psychoactive constituent of the plant Salvia divinorum is Salvinorin A (see – what is Salvia divinorum?). Salvinorin A is reported to be the most potent natural hallucinogen. Salvinorin A is a unique hallucinogen as it is a highly selective κ-opioid receptor (KOR or KOPr) agonist with no activity at the 5-HT2A serotonin receptor. The principal site of activity of classic hallucinogens is at the 5-HT2A serotonin receptor. Salvinorin A has been shown to be a highly selective kappa opioid agonist or kappa opioid receptor agonist both in vitro (see – what is in vitro?) and in vivo studies (see – what is in vivo?). Thus, the mechanism of action (MOA) underlying the hallucinogenic effects of Salvia divinorum has been attributed to the kappa opioid agonist activity of Salvinorin A. Kappa opioid receptors are found widely distributed in the regions of brain involved in interoception, pain, reward, emotion, and memory.