Pattern of use and subjective effects of Salvia divinorum among recreational users

González, Débora; Riba, Jordi; Bouso, José Carlos; Gómez-Jarabo, Gregorio; Barbanoj, Manel J.

doi:10.1016/j.drugalcdep.2006.04.001

Cited by 148 publications

(190 citation statements)

References 23 publications

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“…These results could be expected given modafinil's complex pharmacological profile and may be indicative of commonality with opioids in terms of their histaminergic effects (Ishizuka et al, 2008;Chikai et al, 1994;Barke and Hough, 1992). Salvinorin A, a k-agonist (Roth et al, 2002;Chavkin et al, 2004) with psychotomimetic properties (Gonzalez et al, 2006;Dalgarno, 2007), was an interesting compound to test as it had the potential to fall into two classifications (opioid and psychotomimetic). Interestingly, PA classified it along its predominant psychopharmacological property, namely psychotomimetic ( Figure 9).…”

Section: Discussionmentioning

confidence: 93%

A Data Mining Approach to In Vivo Classification of Psychopharmacological Drugs

Kafkafi

Yekutieli

Elmer

2008

Neuropsychopharmacol

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Data mining is a powerful bioinformatics strategy that has been successfully applied in vitro to screen for gene-expression profiles predicting toxicological or carcinogenic response ('class predictors'). In this report we used a data mining algorithm named Pattern Array (PA) in vivo to analyze mouse open-field behavior and characterize the psychopharmacological effects of three drug classesFpsychomotor stimulant, opioid, and psychotomimetic. PA represents rodent movement with B100 000 complex patterns, defined as multiple combinations of several ethologically relevant variables, and mines them for those that maximize any effect of interest, such as the difference between drug classes. We show that PA can discover behavioral predictors of all three drug classes, thus developing a reliable drug-classification scheme in small group sizes. The discovered predictors showed orderly dose dependency despite being explicitly mined only for class differences, with the high doses scoring 4-10 standard deviations from the vehicle group. Furthermore, these predictors correctly classified in a dose-dependent manner four 'unknown' drugs (ie that were not used in the training process), and scored a mixture of a psychomotor stimulant and an opioid as being intermediate between these two classes. The isolated behaviors were highly heritable (h 2 450%) and replicable as determined in 10 inbred strains across three laboratories. PA can in principle be applied for mining behaviors predicting additional properties, such as within-class differences between drugs and within-drug dose-response, all of which can be measured automatically in a single session per animal in an open-field arena, suggesting a high potential as a tool in psychotherapeutic drug discovery.

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Section: Discussionmentioning

confidence: 93%

A Data Mining Approach to In Vivo Classification of Psychopharmacological Drugs

Kafkafi

Yekutieli

Elmer

2008

Neuropsychopharmacol

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“…k-Opioid agonists are aversive, and cocaine, opioid, and ethanol withdrawal is associated with increased dynorphin in the nucleus accumbens and/or amygdala (Koob, 2008). An exception is salvidorin A, which is a k-agonist abused by humans, but this may reflect its hallucinogenic effects rather than any pleasurable properties (Gonzalez et al, 2006).…”

Section: Withdrawal/negative Affect Stagementioning

confidence: 99%

Erratum: Neurocircuitry of Addiction

Koob¹,

Volkow²

2010

Neuropsychopharmacol

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Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: 'binge/intoxication', 'withdrawal/negative affect', and 'preoccupation/anticipation' (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.

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“…In view of anecdotal reports and survey studies indicating that this substance tends to produce dysphoria (Gonzalez et al 2006), the abuse liability of S. divinorum and its extracts may be relatively low compared to other recreational drugs. However, given the paucity of controlled scientific research, this conclusion may be a bit premature.…”

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confidence: 99%

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

et al. 2009

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Background and rationale Research interests regarding the psychopharmacology of salvinorin A have been motivated by the recreational use and widespread media focus on the hallucinogenic plant, Salvia divinorum. Additionally, kappa opioid (KOP) receptor ligands may have therapeutic potential in the treatment of some neuropsychiatric conditions, including drug dependence and mood disorders. Salvinorin A is a selective KOP agonist, but only a few studies have explored the discriminative stimulus effects of this compound. Objective This study compared the discriminative stimulus effects of salvinorin A and two synthetic derivatives of salvinorin B to the KOP agonists, U69,593 and U50,488. Materials and methods Sixteen male Sprague-Dawley rats trained to discriminate U69,593 (0.13 mg/kg, s.c., N=8) or U50,488 (3.0 mg/kg, i.p., N=8) under a fixed-ratio 20 schedule of food reinforcement were administered substitution tests with salvinorin A (0.125-3.0 mg/kg, i.p.). The animals trained to discriminate U69,593 were also administered substitution tests with salvinorin B ethoxymethyl ether (0.005-0.10 mg/kg, i.p.) and salvinorin B methoxymethyl ether (0.03-0.10 mg/kg, i.p.). Another eight rats were trained to discriminate 2.0 mg/kg salvinorin A and tested with U69,593 (0.04-0.32 mg/kg) and U50,488 (0.4-3.2 mg/kg). Results Salvinorin A and both synthetic derivatives of salvinorin B substituted completely for U69,593. Additionally, cross-generalization was observed between salvinorin A and both KOP agonists.Conclusion These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors. Future studies may assist in the development and screening of salvinorin A analogs for potential pharmacotherapy.

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Pattern of use and subjective effects of Salvia divinorum among recreational users

Cited by 148 publications

References 23 publications

A Data Mining Approach to In Vivo Classification of Psychopharmacological Drugs

A Data Mining Approach to In Vivo Classification of Psychopharmacological Drugs

Erratum: Neurocircuitry of Addiction

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

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