Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders
Frontiers in Pharmacology September 8, 2015 Mary Jeanne Kreek, Eduardo R. Butelman 77 citations
Salvinorin A, a hallucinogen from the plant Salvia divinorum, selectively activates kappa-opioid receptors (KOPr) in the brain, which are normally stimulated by endogenous dynorphins. This activation counterbalances dopamine-driven reward and mood systems, producing aversion and anhedonia in animal models. Unlike other opioid ligands, salvinorin A is a non-nitrogenous neoclerodane, offering a novel chemical scaffold for drug development. Ongoing research aims to create semi-synthetic analogs with partial or biased KOPr agonism to achieve therapeutic effects—such as for pain or mood disorders—while reducing the undesirable effects seen with salvinorin A itself.