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Szymon Rus

2 papers in the library · 110 citations · publishing 2009-2010

Papers

Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospinal fluid.

The Journal of pharmacology and experimental therapeutics February 1, 2009 Eduardo R Butelman, Thomas E Prisinzano, Haiteng Deng et al. 67 citations

Salvinorin A, the main active component of the hallucinogenic plant Salvia divinorum, produces rapid behavioral effects in nonhuman primates, including sedation and postural relaxation, similar to synthetic kappa-agonists. These effects occur within 1 to 2 minutes of intravenous injection and can be blocked by the opioid antagonist nalmefene. The drug enters the central nervous system within 1 minute at concentrations matching its affinity for brain kappa-receptors. This is the first systematic documentation of such rapid unconditioned effects in a primate species, consistent with human reports of the drug's fast and powerful effects.

The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

Psychopharmacology June 1, 2010 Eduardo R Butelman, Szymon Rus, Thomas E Prisinzano et al. 43 citations

Salvinorin A, a plant-derived hallucinogen, selectively activates kappa-opioid receptors and produces effects distinct from classic hallucinogens like psilocybin or dissociatives like ketamine. In adult rhesus monkeys trained to discriminate salvinorin A from vehicle, the compound's discriminative cue generalized to other kappa-opioid agonists (bremazocine, U69,593, U50,488) but not to mu- or delta-opioid agonists, psilocybin, or ketamine. The opioid antagonist quadazocine blocked these effects, while the serotonin antagonist ketanserin did not. Unconditioned behavioral measures (facial relaxation, ptosis) confirmed kappa-receptor mediation. These results demonstrate that salvinorin A's interoceptive effects are mediated specifically by kappa-opioid receptor agonism, mechanistically distinct from serotonergic hallucinogens.