Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A.
Christopher W Cunningham, Richard B Rothman, Thomas E Prisinzano
Pharmacological Reviews June 1, 2011 DOI: 10.1124/pr.110.003244 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Compound Unique mechanism Nitrogen-free activation Biological processes Therapeutic potential Pain treatment Mood disorder treatment Substance abuse treatment Gastrointestinal treatment Hallucinogens |
| Citations | 109 |
| Key findings | Salvinorin A is the first non-nitrogenous opioid receptor agonist, activating KOP receptors to produce its psychoactive effects, and has therapeutic potential for pain, mood disorders, substance abuse, and gastrointestinal disturbances. |
Abstract
Salvia divinorum is a perennial sage native to Oaxaca, Mexico, that has been used traditionally in divination rituals and as a treatment for the "semimagical" disease panzón de borrego. Because of the intense "out-of-body" experiences reported after inhalation of the pyrolized smoke, S. divinorum has been gaining popularity as a recreational hallucinogen, and the United States and several other countries have regulated its use. Early studies isolated the neoclerodane diterpene salvinorin A as the principal psychoactive constituent responsible for these hallucinogenic effects. Since the finding that salvinorin A exerts its potent psychotropic actions through the activation of KOP receptors, there has been much interest in elucidating the underlying mechanisms behind its effects. These effects are particularly remarkable, because 1) salvinorin A is the first reported non-nitrogenous opioid receptor agonist, and 2) its effects are not mediated by the 5-HT(2A) receptor, the classic target of hallucinogens such as lysergic acid diethylamide and mescaline. Rigorous investigation into the structural features of salvinorin A responsible for opioid receptor affinity and selectivity has produced numerous receptor probes, affinity labels, and tools for evaluating the biological processes responsible for its observed psychological effects. Salvinorin A has therapeutic potential as a treatment for pain, mood and personality disorders, substance abuse, and gastrointestinal disturbances, and suggests that nonalkaloids are potential scaffolds for drug development for aminergic G-protein coupled receptors.
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 47
- 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. Journal of Medical Toxicology March 1, 2012
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology March 1, 2013
- Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Journal of Medicinal Chemistry December 26, 2014
- New psychoactive substances of natural origin: A brief review Journal of Food and Drug Analysis April 18, 2017
and 42 more in the library
Cites 104
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Opioid receptors and legal highs:Salvia divinorumand Kratom Clinical Toxicology 2008
- 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
and 99 more in the library