Kappa opioid receptor (KOR) agonists have preclinical antipsychostimulant effects; however, adverse side effects have limited their therapeutic development. In this preclinical study, conducted in Sprague Dawley rats, B6-SJL mice, and non-human primates (NHPs), we evaluated the G-protein-biased analogue of salvinorin A (SalA), 16-bromo salvinorin A (16-BrSalA), for its anticocaine effects, side...
The kappa (κ) opioid receptor/dynorphin system modulates depression-like states and anhedonia, as well adaptations to stress and exposure to drugs of abuse. Several relatively short-acting small molecule κ-receptor antagonists have been synthesized, and their behavioral profile has been examined under some conditions. The hypothesis of this study is that pharmacological manipulations of the...
Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available...
In the original review, we placed an incorrect citation in a sentence. The correct sentence and citation are as follows: "Also, salvinorin A can act as a “punisher” to self-administration of cocaine or a short-acting MOPr agonist in primates (when given contingently; Freeman et al., 2014).” The authors apologize for the mistake. This error does not change the scientific conclusions of the...
Active blood-brain barrier mechanisms, such as the major efflux transporter P-glycoprotein (mdr1), modulate the in vivo/central nervous system (CNS) effects of many pharmacological agents, whether they are used for nonmedical reasons or in pharmacotherapy. The powerful, widely available hallucinogen salvinorin A (from the plant Salvia divinorum) is a high-efficacy, selective κ-opioid agonist...
Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as...
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...
Salvinorin A is the main active component of the widely available hallucinogenic plant, Salvia divinorum. Salvinorin A is a selective high-efficacy kappa-agonist in vitro, with some unique pharmacodynamic properties. Descriptive reports show that salvinorin A-containing products produce robust behavioral effects in humans. However, these effects have not been systematically characterized in...
This study focused on the in vivo effects of the kappa-opioid hallucinogen salvinorin A, derived from the plant Salvia divinorum. The effects of salvinorin A (0.0032-0.056 mg/kg i.v.) were studied in a neuroendocrine biomarker assay of the anterior pituitary hormone prolactin in gonadally intact, adult male and female rhesus monkeys (n = 4 each). Salvinorin A produced dose- and time-dependent...
Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8...
Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class...
Salvinorin A is a naturally occurring hallucinogen derived from the plant Salvia divinorum. Salvinorin A is also a potent and selective kappa opioid receptor agonist in vitro. It has been shown that kappa agonists decrease dopamine levels in the caudate putamen and nucleus accumbens and cause conditioned place aversion in rodents. To study the effects of salvinorin A on basal dopamine levels in...
Salvinorin 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 kappa-opioid receptors. It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy kappa-agonist...