A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics.

Salvinorin A, the active compound in the plant Salvia divinorum, is the most potent natural hallucinogen known, with as little as 200-500 μg of smoked leaves producing intense hallucinations. It acts as a highly selective agonist of the kappa-opioid receptor. Originally used only by the Mazatec people of Oaxaca, Mexico, it has become a globally accessible drug of abuse. Scientific interest has grown due to its unique structure and properties; studies have demonstrated antinociceptive, antidepressant, in some circumstances pro-depressant, and anti-addictive effects, opening potential new avenues for therapeutic applications.

Study at a glance

Abstract

Until the mid-60s, only the Mazatecs, an indigenous group from Oaxaca, Mexico, used Salvia Divinorum (S. divinorum) due to its hallucinogen properties. Later it was found that the hallucinogen effects of this plant were caused by the presence of a neoclerodane diterpene Salvinorin A (salvinorin A), which is a highly selective agonist of kappa-opioid receptor (KOR) that cause more intense hallucinations than the common hallucinogens as lysergic acid, mushrooms, ecstasy and others. In fact, smoking of only 200-500 μg of S. divinorum leaves is enough to produce these effects thus making it the most potent natural occurring hallucinogen known. Due to its legal status in various countries, this compound has gained a worldwide popularity as a drug of abuse with an easy access through smartshops and internet. Furthermore, salvinorin A gathered an increased interest in the scientific community thanks to its unique structure and properties, and various studies demonstrated that salvinorin A has antinociceptive, antidepressant, in some circumstances pro-depressant and anti-addictive effects that have yielded potential new avenues for research underlying salvinorin A and its semi-synthetic analogs as therapeutic agents.