The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.
Eduardo R Butelman, Szymon Rus, Thomas E Prisinzano, Mary Jeanne Kreek
Psychopharmacology June 1, 2010 DOI: 10.1007/s00213-009-1771-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Discrimination assay with parallel unconditioned behavioral endpoints Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Adult rhesus monkeys |
| Interventions | Salvinorin A bremazocine U69 593 U50 488 fentanyl SNC80 psilocybin ketamine quadazocine ketanserin |
| Dose | 0.015 mg/kg |
| Topics | Salvia divinorum |
| Keywords | Unique hallucinogen Kappa-opioid compound Kappa-opioid receptors Brain receptors Receptor targets Hallucinogens Psychedelic drugs Psychoactive substances Pharmacology Drug action Pharmacological profile Behavioral effects |
| Citations | 43 |
| Key points | Salvinorin A's discriminative cue and behavioral effects are mediated by kappa-opioid receptor agonism and are mechanistically distinct from serotonergic hallucinogens like psilocybin. |
Abstract
The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans. Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function. Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive. These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 23
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- 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
- Acute and post-acute behavioral and psychological effects of salvinorin A in humans. Psychopharmacology March 1, 2012
- Pharmacological activity of salvinorin A, the major component of Salvia divinorum. Pharmacological Reports 2011
and 18 more in the library
Cites 20
- 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
- Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug and Alcohol Dependence November 8, 2006
- Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans. Neuroimage July 1, 2008
- The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Psychopharmacology March 1, 2004
and 15 more in the library