The plant-derived hallucinogen, salvinorin A, produces κ-opioid agonist-like discriminative effects in rhesus monkeys

@article{Butelman2004ThePH,
  title={The plant-derived hallucinogen, salvinorin A, produces $\kappa$-opioid agonist-like discriminative effects in rhesus monkeys},
  author={Eduardo R Butelman and Todd J. Harris and Mary Jeanne Kreek},
  journal={Psychopharmacology},
  year={2004},
  volume={172},
  pages={220-224}
}
RationaleSalvinorin A is the active component of the hallucinogenic plant Salvia divinorum. The potential mode of action of this hallucinogen was unknown until recently. A recent in vitro study detected high affinity and efficacy of salvinorin A at κ-opioid receptors. It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy κ-agonist (U69,593) in rhesus monkeys.MethodsMonkeys were previously trained to discriminate U69,593 (0.0056 or… 
The discriminative effects of the κ-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects
TLDR
These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at κ-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.
Unconditioned Behavioral Effects of the Powerful κ-Opioid Hallucinogen Salvinorin A in Nonhuman Primates: Fast Onset and Entry into Cerebrospinal Fluid
TLDR
These are the first studies documenting rapid unconditioned effects of salvinorin A in a primate species, consistent with descriptive reports of rapid and robust effects of this powerful hallucinogen in humans.
Effects of Salvinorin A, a κ-Opioid Hallucinogen, on a Neuroendocrine Biomarker Assay in Nonhuman Primates with High κ-Receptor Homology to Humans
TLDR
It is indicated that the hallucinogen salvinorin A acts as a high-efficacy κ-agonist in nonhuman primates in a translationally viable neuroendocrine biomarker assay, including particular C-terminal residues thought to be involved in receptor desensitization and internalization.
Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats
TLDR
These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors, and future studies may assist in the development and screening of salvinegorin A analogs for potential pharmacotherapy.
Kappa-opioid receptor-mediated effects of the plant-derived hallucinogen, salvinorin A, on inverted screen performance in the mouse
TLDR
In the mouse, salvinorin A disrupted climbing behavior on an inverted screen task, indicating a rapid, but short-lived induction of sedation/motor incoordination and the possibility that the development of other diterpene-based opioids may yield important therapeutic compounds.
Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents
TLDR
These findings suggest that similarities in the pharmacological effects of salvinorin A and those of cannabinoids are mediated by its activation of KOR rather than by any direct action of salvia divinorum A on the endocannabinoid system.
Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement
TLDR
Results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior.
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