Salvinorin A analogs and other κ-opioid receptor compounds as treatments for cocaine abuse.
Bronwyn M Kivell, Amy W M Ewald, Thomas E Prisinzano
Advances in pharmacology (San Diego, Calif.) 2014 DOI: 10.1016/b978-0-12-420118-7.00012-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Salvia divinorum |
| Keywords | Drug abuse Kappa-opioid receptor |
| Key findings | Salvinorin A and its analogs show anti-addictive effects with reduced side effects compared to traditional kappa-opioid agonists, though Salvinorin A's rapid metabolism hinders clinical development. |
Abstract
Acute activation of kappa-opioid receptors produces anti-addictive effects by regulating dopamine levels in the brain. Unfortunately, classic kappa-opioid agonists have undesired side effects such as sedation, aversion, and depression, which restrict their clinical use. Salvinorin A (Sal A), a novel kappa-opioid receptor agonist extracted from the plant Salvia divinorum, has been identified as a potential therapy for drug abuse and addiction. Here, we review the preclinical effects of Sal A in comparison with traditional kappa-opioid agonists and several new analogs. Sal A retains the anti-addictive properties of traditional kappa-opioid receptor agonists with several improvements including reduced side effects. However, the rapid metabolism of Sal A makes it undesirable for clinical development. In an effort to improve the pharmacokinetics and tolerability of this compound, kappa-opioid receptor agonists based on the structure of Sal A have been synthesized. While work in this field is still in progress, several analogs with improved pharmacokinetic profiles have been shown to have anti-addictive effects. While in its infancy, it is clear that these compounds hold promise for the future development of anti-addictive therapeutics.
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 29
- Models of psychedelic drug action: modulation of cortical-subcortical circuits Brain October 22, 2021
- Ligand and G-protein selectivity in the κ-opioid receptor. Nature May 1, 2023
- Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase The Plant Journal November 19, 2016
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain Scientific Reports October 2, 2020
and 24 more in the library
Cites 44
- 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
- Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents British Journal of Pharmacology May 5, 2009
- Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology March 1, 2013
and 39 more in the library