Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders
Mary Jeanne Kreek, Eduardo R Butelman
Frontiers in Pharmacology September 8, 2015 DOI: 10.3389/fphar.2015.00190 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Hallucinogen Κ-opioid receptor Pharmacology Dynorphin Partial agonist |
| Citations | 77 |
| Key findings | Salvinorin A is a selective high-efficacy kappa-opioid receptor agonist that produces aversion and anhedonia in preclinical models, and its unique non-nitrogenous structure provides a new scaffold for developing therapeutic analogs with reduced side effects. |
Abstract
Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.
Comparable studies
Other narrative reviews on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. General (review of novel psychoactive substances) | 2012 | Review | |
| Opioid receptors and legal highs:Salvia divinorumand Kratom | 2008 | Review | |
| Salvinorin A: the "magic mint" hallucinogen finds a molecular target in the kappa opioid receptor. | 2003 | Review | |
| Salvia divinorum and the unique diterpene hallucinogen, Salvinorin (divinorin) A. | 1994 | Review | |
| Drug models of schizophrenia. General (review of drug models of schizophrenia) | 2015 | Review |
Citations in the library
Cited by 21
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Pivotal mental states Journal of Psychopharmacology April 1, 2021
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action. Journal of Pain Research 2019
- Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology July 12, 2017
and 16 more in the library
Cites 39
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Psychopharmacology May 1, 2005
- Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). Journal of Ethnopharmacology May 1, 1983
- Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology March 1, 2013
and 34 more in the library