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      Salvia divinorum Epling & Játiva (Maria Pastora) e Salvinorina A: crescente uso recreacional e potencial de abuso Translated title: Salvia divinorum Epling & Játiva ("ska María Pastora") and Salvinorin A: increasing recreational use and abuse potential

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          Abstract

          A planta Salvia divinorum Epling & Játiva (SDI), da família Lamiaceae, tem sido usada por séculos pela cultura mazateca e vem ganhando popularidade como droga recreacional nos últimos anos. Seu princípio ativo - Salvinorina A (SA) - é agonista dos receptores opióides kappa, com potencial psicotrópico. A utilização da planta vem crescendo na Europa e na América do Norte, apesar de ainda não existirem provas concretas sobre abuso. A presente revisão da literatura contemporânea aborda as evidências sobre o potencial de abuso de SDI, bem como o crescente uso recreacional, ainda que seja alucinógeno permitido legalmente e de fácil compra em muitos países.

          Translated abstract

          The plant Salvia divinorum Epling & Játiva (SDI), of the Lamiaceae family, has been used for centuries by the Mazateca culture and has gained popularity as a recreational drug in the last years. Its active principle, Salvinorin A (SA), is a potentially psychotropic agonist of the kappa opioid receptors. The use of SDI has increased in Europe and North America, although there are no concrete proofs about abuse. The present review discusses current evidence on potential SDI abuse, as well as its increasing recreational use, although it is considered a legalized hallucinogen easily acquired in many countries.

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          Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.

          Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited (3)H-bremazocine binding to cloned kappa opioid receptors. Salvinorin A had no significant activity against a battery of 50 receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent kappa opioid agonist at cloned kappa opioid receptors expressed in human embryonic kidney-293 cells and at native kappa opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT(2A) serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for kappa opioid receptors, kappa opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception.
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            Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats.

            Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of kappa-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A (SalvA), a potent and highly selective kappa-opioid agonist, would produce depressive-like effects in the forced swim test (FST) and intracranial self-stimulation (ICSS) test, which are behavioral models often used to study depression in rats. We extracted, isolated, and purified SalvA from Salvia divinorum plant leaves and examined its effects on behavior in the FST and ICSS test across a range of doses (0.125-2.0 mg/kg) after systemic (intraperitoneal) administration. SalvA dose dependently increased immobility in the FST, an effect opposite to that of standard antidepressant drugs. Doses of SalvA that produced these effects in the FST did not affect locomotor activity in an open field. Furthermore, SalvA dose dependently elevated ICSS thresholds, an effect similar to that produced by treatments that cause depressive symptoms in humans. At a dose that caused the depressive-like effects in both the FST and ICSS assays, SalvA decreased extracellular concentrations of dopamine (DA) within the nucleus accumbens (NAc), a critical component of brain reward circuitry, without affecting extracellular concentrations of serotonin (5-HT). These data provide additional support for the hypothesis that stimulation of brain kappa-opioid receptors triggers depressive-like signs in rats and raise the possibility that decreases in extracellular concentrations of DA within the NAc contribute to these effects.
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              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.

              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 the caudate putamen and nucleus accumbens, and to determine whether salvinorin A induces conditioned place preference or aversion and changes in locomotor activity in the mouse. In the first experiment, changes in dopamine levels in these brain regions after administration of salvinorin A were measured with in vivo microdialysis. In the second experiment, we examined whether salvinorin A led to conditioned place preference or aversion, and changes in locomotor activity during conditioning sessions. The higher doses of salvinorin A studied (1.0 mg/kg and 3.2 mg/kg, i.p.) significantly decreased dopamine levels in the caudate putamen, but not in the nucleus accumbens, and this effect was completely blocked by pre-injection with 10 mg/kg of the kappa opioid receptor antagonist nor-binaltorphimine. The same doses of salvinorin A caused conditioned place aversion and decreased locomotor activity. The inhibitory effect of salvinorin A on striatal dopamine levels may contribute to its induction of conditioned place aversion and decreases in locomotion in mice. These findings are consistent with the in vitro characterization of salvinorin A as a kappa opioid receptor agonist. It is of interest that a compound such as salvinorin A, that lowers striatal dopamine levels and leads to conditioned place aversion in rodents, is self-administered by humans under certain conditions.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                rbpm
                Revista Brasileira de Plantas Medicinais
                Rev. bras. plantas med.
                Sociedade Brasileira de Plantas Medicinais (Botucatu )
                1983-084X
                September 2010
                : 12
                : 3
                : 358-362
                Affiliations
                [1 ] Centro Universitário Feevale Brazil
                [2 ] Instituto de Ciências da Saúde Brasil
                Article
                S1516-05722010000300014
                10.1590/S1516-05722010000300014
                bbf7136e-e5de-43fb-93f7-f974430df7b1

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1516-0572&lng=en
                Categories
                PHARMACOLOGY & PHARMACY

                Pharmacology & Pharmaceutical medicine
                Salvia divinorum,Salvinorin A,abuse potential,recreational use,Salvinorina A,potencial de abuso,uso recreacional

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