Kappa Opioids, Salvinorin A and Major Depressive Disorder.
George T Taylor, Francesca Manzella
Current Neuropharmacology 2016 DOI: 10.2174/1570159x13666150727220944 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Salvia divinorum |
| Key findings | Salvinorin A has a complex pharmacological profile beyond kappa agonism, making it an ideal candidate for MDD treatment research. |
Abstract
Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.
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 10
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics Trends in Neurosciences December 21, 2020
- DARK Classics in Chemical Neuroscience: Salvinorin A. ACS Chemical Neuroscience December 2, 2020
- Addressing blinding in classic psychedelic studies with innovative active placebos. The International Journal of Neuropsychopharmacology April 1, 2025
- Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs. Frontiers in Psychiatry 2019
and 5 more in the library
Cites 33
- 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
- Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug and Alcohol Dependence November 8, 2006
- 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
- Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Drug and Alcohol Dependence May 1, 2011
and 28 more in the library