Chapter 69 - The Widely Available Hallucinogenic Plant Salvia divinorum and Its Main Component, Salvinorin A: A Unique κ-Opioid Receptor (KOP-r) Agonist with Powerful Behavioral and Neurobiological Effects

Abstract

Salvia divinorum is a hallucinogenic plant originally used in traditional ethnomedical practice in certain cultures, but is now widely available in the industrialized world through a variety of sources. The main active component of Salvia divinorum is salvinorin A, a diterpene shown to be a selective high-efficacy κ-opioid receptor (KOP-r) agonist, without affinity for the site of action of classic hallucinogens (the 5-HT2A receptor). Preparations containing salvinorin A cause robust but short-lasting visual and proprioceptive hallucinations, with commonly reported dissociative effects. These effects may be qualitatively similar to previously reported “psychotomimetic” effects observed in humans with synthetic KOP-r agonists. In preclinical animal models, salvinorin A produces behavioral and neurobiological effects qualitatively similar to those observed with synthetic KOP-r agonists. These effects include a decrease in dopaminergic activation. Activation of KOP-r receptors by synthetic and endogenous neuropeptide agonists (the dynorphins) are known to exert a negative modulatory function on dopaminergic systems. Other salvinorin A–induced effects (similar to those of KOP-r agonists) include aversion, anhedonia, and depressant-like and sedative like-effects. Furthermore, salvinorin A also produces robust prolactin release, a neuroendocrine biomarker measure previously used to study KOP-r agonist effects in humans.