Salvia divinorum

Generic name: Salvia Divinorum Epl. & Jativa-M.
Brand names: Diviner's Sage, Hojas De Maria, Magic Mint, Mystic Mint, Purple Sticky, Sally D, Ska Maria Pastora, Yerba De La Pastora, Yerba Maria

Usage of Salvia divinorum

CNS effects

The discovery of salvinorin A as responsible for the hallucinogenic activity of the leaves sparked interest in its mechanism of action. While lysergic acid diethylamide, mescaline, and psilocybin all act through serotoninergic pathways, salvinorin A acts as a potent agonist at the kappa-opioid receptor(Roth 2002) while having no effect at the mu- and delta-opioid receptors. It was more effective than several other kappa agonists.(Chavkin 2004) Analysis of activity with mUTAted kappa-receptors identified key binding sites on the receptor.(Yan 2005)

Animal data

Salvinorin A was active in a mouse tail-flick analgesia model, and the effect was blocked by a kappa-opioid antagonist, but not by mu- or delta-antagonists.(John 2006) Similarly, in a kappa-opioid knockout mouse, salvinorin A had no analgesic or hypothermic effects. The kappa-1 receptor suBClass was affected in preference to kappa-2.(Ansonoff 2006) Behavioral studies in mice using inverted screen climbing performance also found kappa-agonism involvement.(Fantegrossi 2005)

Salvinorin A produced reduction in striatal dopamine levels in mice, consistent with a kappa-opioid effect, and these reductions were linked to reduced locomotor activity and conditioned place aversion. Effects were blocked by the kappa-antagonist nor-binaltorphimine.(Zhang 2005) In rats, extracellular levels of dopamine were decreased in the nucleus accumbens without affecting serotonin levels. Effects in forced-swimming tests and intracranial self-stimulation were found as well.(Carlezon 2006)

Like another kappa-opioid agonist, salvinorin A potentiated the effect of the dopamine D2/D3 agonist quinpirole in rats in high doses, but had an opposite effect at low doses.(Beerepoot 2008) Rat studies demonstrated an effect on the cannabinoid reward system with salvinorin A, which was blocked by a cannabinoid receptor type 1 antagonist (rimonabant) and a kappa-opioid antagonist.(Braida 2008)

Salvinorin A modulated the behavioral and molecular effects of cocaine in rats, suggesting that it interfered with dopamine 1 receptor signaling in the striatum.(Chartoff 2008) Other studies found that salvinorin A blocked cocaine-induced drug-seeking in rats, similar to other kappa-agonists.(Morani 2009)

Hallucinogens are extraordinarily difficult to study in animals; however, the measurement of discriminative stimulus effects is capable of sorting drugs into congruent categories. That is, experimental animals are trained to recognize the cues produced by a particular standard drug, and further experiments with other drugs can define the similarity in response to the standard. Thus, in rats, salvinorin A was a sufficient substitute for the kappa-opioid agonist U69593.(Willmore-Fordham 2007) A second group found the SAMe effect in rats with U69593 and U50488.(Baker 2009) In rhesus monkeys, the same substitution was obtained with U69593 and salvinorin A.(Butelman 2004) Biochemical studies by the same group found that salvinorin A and U69593 produced increases in serum prolactin levels, and these effects were blocked by kappa-antagonism. The effect was more robust in females than in males.(Butelman 2007) The reported rapid onset and short duration of action of S. divinorum in humans(Siebert 1994) was paralleled in baboons. Positron emission tomography showed rapid salvinorin A brain uptake and a clearance half-life of 8 minutes. The labeled drug was administered intravenously (IV), and the highest concentrations were found in the cerebellum and visual cortex.(Hooker 2008) Unconditioned responses to IV salvinorin A in rhesus monkeys (facial relaxation, ptosis) were of a similarly rapid onset and short duration.(Butelman 2009) Some of the previously mentioned effects have also been observed in zebrafish.(Braida 2007)

Clinical data

Observational studies of the plant and pure compound have been published(Siebert 1994) while salvinorin A was detected in urine and saliva after plant consumption.(Pichini 2005) Small double-blind, randomized, placebo-controlled trials have been conducted using the Hallucinogen Rating Scale and other similar scales. Marked changes in auditory, visual, and interoceptive sensory input are reported in addition to other effects as could be expected with a mechanism of opioid agonsim by salvinorin A.(Addy 2015, MacLean 2013, Ranganathan 2012)

Other uses

S. divinorum and pure salvinorin A inhibited cholinergic transmission in guinea pig ileum.(Capasso 2006) This may account for traditional use as an antidiarrheal. Several recent reviews have appeared.(Grundmann 2007, Prisinzano 2005, Vortherms 2006)

In mice, salvinorin A inhibited bronChial hyperReactivity comparable to those of non-sensitized controls via significant inhibition of allergen-induced leukotriene and cytokine production as well as inhibition of pulmonary mast cell degranulation.(Rossi 2017)

Salvia divinorum side effects

A case report was published showing persistent psychosis associated with S. divinorum use.Przekop 2009 A second report found that self-administered S. divinorum was effective in moderate depression.Hanes 2001 Potential for addiction is considered to be muted due to the lack of euphoric effects.Ranganathan 2012

Before taking Salvia divinorum

Use in pregnancy and lactation is not recommended.

How to use Salvia divinorum

The pure compound salvinorin A is estimated to be psychoactive at doses of 200 to 500 mcg when smoked. Several whole leaves are typically chewed or smoked for a similar effect; however, the leaves must be held in the mouth, because absorption through the oral mucosa is superior to GI absorption.Siebert 1994, Prisinzano 2005, Vortherms 2006

Warnings

Salvinorin A produced no toxicity in mice in a 2-week, subchronic toxicology study.Mowry 2003 Limited clinical studies suggest a low level of toxicity within certain dosages and a short duration of intoxication effect.Casselman 2014, Dueweke 2015

What other drugs will affect Salvia divinorum

The activation of numerous cytochrome P450 enzymes has been noted in vitro, but not explored, in herb-drug interactions.(Teksin 2009)

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