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.
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.