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Club drugs and "other" abusable substances are briefly overviewed as a reminder about the wide variety of known and unknown substances used by adolescents, the high potential for direct and interactive substance use effects to manifest acutely and chronically, and the vigilance needed to anticipate and recognize the new effects and drug-drug interactions arising as novel substances continue to be custom "designed," manufactured, and marketed to meet substance use trends. This article discusses dextromethorphan, flunitrazepam (Rohypnol), gamma-hydroxybutyrate, inhalants, ketamine, lysergic acid diethylamide, methylenedioxymethamphetamine, phencyclidine, Salvia divinorum (salvia), synthetic cannabinoids, and synthetic cathinones (bath salts).

Until the mid-60s, only the Mazatecs, an indigenous group from Oaxaca, Mexico, used Salvia Divinorum (S. divinorum ) due to its hallucinogen properties. Later it was found that the hallucinogen effects of this plant were caused by the presence of a neoclerodane diterpene Salvinorin A (salvinorin A), which is a highly selective agonist of kappa -opioid receptor (KOR) that cause more intense hallucinations than the common hallucinogens as lysergic acid, mushrooms, ecstasy and others. In fact, smoking of only 200–500 μg of S. divinorum leaves is enough to produce these effects thus making it the most potent natural occurring hallucinogen known. Due to its legal status in various countries, this compound has gained a worldwide popularity as a drug of abuse with an easy access through smartshops and internet. Furthermore, salvinorin A gathered an increased interest in the scientific community thanks to its unique structure and properties, and various studies demonstrated that salvinorin A has antinociceptive, antidepressant, in some circumstances pro-depressant and anti-addictive effects that have yielded potential new avenues for research underlying salvinorin A and its semi-synthetic analogs as therapeutic agents.

In many forensic science disciplines, mass spectrometry is used for the analysis and comparison of case samples to reference materials. To increase confidence in identifications made from such comparisons, our laboratory previously developed a method for the statistical comparison of unabbreviated mass spectra. The method uses the unequal variance t-test to statistically compare ion abundances across the mass scan range. In the current work, the method was applied for the comparison of mass spectra of salvinorin A, the hallucinogenic compound in the plant Salvia divinorum. S. divinorum samples collected from eight locations in the United States and Canada were extracted and analyzed by gas chromatography-mass spectrometry (GC–MS). Mass spectra of salvinorin A from three replicate extracts of S. divinorum were statistically associated with those of an authentic salvinorin A reference material at various concentrations at the 99.9% confidence level. Salvinorin A was distinguished from spectra of salvinorins B, C, and D, also at the 99.9% confidence level. For S. divinorum samples from different locations, statistical association of salvinorin A spectra was possible at the 99.9 to 98.0% confidence levels. Finally, 441 different Salvia species and varieties were screened for salvinorin A and mass spectra of compounds with similar retention times were statistically discriminated from salvinorin A at the 99.9% confidence level. Overall, spectra of salvinorin A were associated to each other and discriminated from other compounds in plant materials obtained from different locations, extracted using different procedures, and analyzed using different GC–MS instruments and methods over a three-year period.

Salvia divinorum (Lamiaceae) is a herb native to Mexico where it is used by Mazatec shamans for spiritual and divination purposes. S. divinorum products are easily available to consumers and are used worldwide as legal highs because of the hallucinogenic effects caused mainly by salvinorin A. Highly popular videos and websites on the internet depicting the use of S. divinorum products have contributed to an increase in their consumption. Recent reports have highlighted the potential of these products to induce psychosis in consumers. In Mexico, dried leaf extracts of S. divinorum are sold in different strengths, claiming to correlate with increasing amounts of salvinorin A. In order to determine the variability of salvinorin A content between brands and to investigate possible correlation between brand strengths, this study sought to quantify salvinorin A in commercial products available in Mexico using an HPLC method. The HPLC analytical method showed a correlation coefficient R 2 >0.99, with LOD of 0.44μg/mL and LOQ of 1.34μg/mL. The retention time for salvinorin A was 23.09±0.95min and the measured concentrations ranged between 8.32±0.65 and 56.52±3.77mg/g dried leaf. The results for brand c did not show an agreement between the declared and the calculated amount of salvinorin A. Additionally, the emergence in Mexico of high strength salvia products (100×), the lack of regulation and the observed variability of salvinorin A content between brands of commercial legal highs products of S. divinorum could result in a health problem for consumers.

Objectives: The archaeological, ethno-historical and ethnographic evidence of the use of hallucinogenic substances in Mesoamerica is reviewed. Results: Hallucinogenic cactus, plants and mushrooms were used to induce altered states of consciousness in healing rituals and religious ceremonies. The Maya drank balché (a mixture of honey and extracts of Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and other psychoactive substances were also used to induce states of trance. Olmec, Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl: Psilocybe spp.) and the seeds of ololiuhqui (Turbina corymbosa), that contain mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad Bufo spp. contains bufotoxins with hallucinogenic properties, and was used during the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their psychoactive effects. Mushroom stones dating from 3000 BC have been found in ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagún, described their effects in the sixteenth century. Conclusions: The use of psychoactive substances was common in pre-Columbian Mesoamerican societies. Today, local shamans and healers still use them in ritual ceremonies in Mesoamerica. Resumen: Introducción: El continente americano es rico en hongos y plantas psicoactivas, y numero-sas culturas precolombinas mesoamericanas las emplearon con fines mágicos, terapéuticos y religiosos. Objetivos: Se revisan las evidencias arqueológicas, etnohistóricas y etnográficas del uso de sustancias alucinógenas en Mesoamérica. Resultados: Cactus, plantas y hongos alucinógenos se utilizaron para provocar estados altera-dos del nivel de conciencia en ceremonias rituales y curativas. Los mayas ingerían el balché (hidromiel y extracto de Lonchocarpus) en ceremonias grupales para lograr la embriaguez. También emplearon enemas rituales con sustancias psicoactivas para inducir estados de trance. Olmecas, zapotecas, mayas y aztecas usaron el peyote, los hongos alucinógenos (teonanacatl: Psilocybe spp.) y las semillas de ololiuhqui (Turbina corymbosa), que contienen mescalina, psilocibina y amida del ácido lisérgico, respectivamente. La piel del sapo Bufo spp. contiene bufotoxinas, con propiedades alucinógenas y fue usado desde el periodo olmeca. El toloache (Datura estramonio), el tabaco silvestre (Nicotiana rustica), el lirio de agua (Nymphaea ampla) y la hoja de la pastora (Salvia divinorum) se utilizaron por sus efectos psicotropos. Piedra fún-gicas de 3.000 ãnos de antigüedad se han encontrado en contextos rituales en Mesoamérica. Las evidencias arqueológicas del uso del peyote se remontan a más de 5.000 ãnos. Diversos cronistas, entre ellos Fray Bernardino de Sahagún, relataron sus efectos en el siglo xvi. Conclusiones: El empleo de sustancias psicotrópicas fue muy común en las sociedades preco-lombinas mesoamericanas. En la actualidad chamanes y curanderos locales las siguen usando en ceremonias rituales. Keywords: Hallucinogens, Hallucinogenic fungi, Peyote, Pre-Columbian culture, Psilocybe spp., Turbina corymbosa, Palabras clave: Alucinógenos, Culturas precolombinas, Hongos, Peyote, Psilocybe spp., Turbina corymbosa

Ethnopharmacological relevance In 1962 ethnopharmacologists, Hofmann and Wasson, undertook an expedition to Oaxaca, Mexico. These two researchers were the first scientists to collect a flowering specimen of Salvia divinorum allowing the identification of this species. While the species' traditional use is confined to a very small region of Mexico, since Hofmann and Wasson's expedition 50 years ago, Salvia divinorum has become globally recognized for its main active constituent, the diterpene salvinorin A, which has a unique effect on human physiology. Salvinorin A is a kappa-opioid agonist and the first reported psychoactive diterpene. Methods This review concentrates on the investigation of Salvia divinorum over the last 50 years including ethnobotany, ethnopharmacology, taxonomy, systematics, genetics, chemistry and pharmacodynamic and pharmacokinetic research. For the purpose of this review, online search engines were used to find relevant research. Searches were conducted between October 2011 and September 2013 using the search term “ Salvia divinorum ”. Papers were excluded if they described synthetic chemical synthesis of salvinorin A or analogues. Results Ethnobotanically there is a comprehensive body of research describing the traditional Mazatec use of the plant, however, the modern ethnobotanical use of this plant is not well documented. There are a limited number of botanical investigations into this plant and there are still several aspects of the botany of Salvia divinorum which need further investigation. One study has investigated the phylogenetic relationship of Salvia divinorum to other species in the genus. To date the main focus of chemistry research on Salvia divinorum has been salvinorin A, the main active compound in Salvia divinorum , and other related diterpenoids. Finally, the effects of salvinorin A, a KOR agonist, have primarily been investigated using animal models. Conclusions As Salvia divinorum use increases worldwide, the emerging cultural use patterns will warrant more research. More botanical information is also needed to better understand this species, including germination, pollination vector and a better understanding of the endemic environment of Salvia divinorum . As well there is a gap in the genetic knowledge of this species and very little is known about its intra-species genetics. The terpenes in Salvia divinorum are very well documented, however, other classes of constituents in this species warrant further investigation and identification. To date, the majority of the pharmacology research on Salvia divinorum has focused on the effects of salvinorin A using animal models. Published human studies have not reported any harmful effects when salvinorin A is administered within the dose range of 0.375–21 µg/kg but what are the implications when applied to a larger population? More data on the toxicology and safety of Salvia divinorum are needed before larger scale clinical trials of the potential therapeutic effects of Salvia divinorum and salvinorin A are undertaken.

Ethnopharmacological relevance Consumer use of botanicals has increased despite, in many instances, the paucity of research demonstrating efficacy or identifying liabilities. This research employed the place preference/aversion paradigm to characterize the psychoactive properties of Salvia divinorum extract (10, 30, 100 mg/kg), salvinorin A (0.1, 0.3, 1.0 mg/kg), Mitragyna speciosa MeOH extract (50, 100, 300 mg/kg), Mitragyna speciosa alkaloid-enriched fraction (12.5, 25, 75 mg/kg) and mitragynine (5, 10, 30 mg/kg) in rats. Material and methods Following apparatus habituation and baseline preference scores, male Sprague-Dawley rats were given eight counter-balanced drug versus vehicle conditioning trials followed by a preference test conducted under drug-free states. S ( + )-amphetamine (1 mg/kg) served as the positive control (in Exp. 2) and haloperidol (0.8, 1.0 mg/kg) served as the negative control in both studies. Results Rats displayed place aversion to both Salvia divinorum and salvinorin A that exceeded that of haloperidol. Rats showed place preference to mitragynine that was similar to that of S ( + ) - amphetamine. This CPP effect was much less pronounced with the Mitragyna speciosa extract and its fraction. Conclusions These findings suggest that both botanicals possess liabilities, albeit somewhat different, that warrant caution in their use.

In recent years, various herbal products adulterated with synthetic cannabinoids have been distributed worldwide via the Internet. These herbal products are mostly sold as incense, and advertised as not for human consumption. Although their labels indicate that they contain mixtures of several potentially psychoactive plants, and numerous studies have reported that they contain a variety of synthetic cannabinoids, their exact botanical contents are not always clear. In this study, we investigated the origins of botanical materials in 62 Spice-like herbal products distributed on the illegal drug market in Japan, by DNA sequence analyses and BLAST searches. The nucleotide sequences of four regions were analyzed to identify the origins of each plant species in the herbal mixtures. The sequences of "Damiana" (Turnera diffusa) and Lamiaceae herbs (Mellissa, Mentha and Thymus) were frequently detected in a number of products. However, the sequences of other plant species indicated on the packaging labels were not detected. In a few products, DNA fragments of potent psychotropic plants were found, including marijuana (Cannabis sativa), "Diviner's Sage" (Salvia divinorum) and "Kratom" (Mitragyna speciosa). Their active constituents were also confirmed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), although these plant names were never indicated on the labels. Most plant species identified in the products were different from the plants indicated on the labels. The plant materials would be used mainly as diluents for the psychoactive synthetic compounds, because no reliable psychoactive effects have been reported for most of the identified plants, with the exception of the psychotropic plants named above.

Background Salvia divinorum is a potent, naturally occurring hallucinogen gaining popularity as a recreational drug in North America. To date, detailed epidemiologic information about the use of this substance among adolescents living outside the United States has been limited. This study provides information on the prevalence and correlates of Salvia divinorum use among adolesecents in Canada using a nationally representative sample. Methods Data were obtained from a representative sample of 42,179 Canadian adolescents aged 12–17 years living across all 10 provinces who completed the Youth Smoking Survey in 2008–09. Results Overall, 3.8% of adolescents reported using Salvia in the past year and 6.2% had used the substance in their lifetime. A conservative estimate suggests 23.2% of youth were repeat users. Salvia use was highest among youth in British Columbia and Quebec. Comparatively, the prevalence of 12-month Salvia use was higher than 12-month cocaine and amphetamine use but lower than 12-month ecstasy, cannabis, and other hallucinogen use. Correlates of Salvia use included older age, male gender, high available spending money, binge drinking, illicit drug use and smoking in fully adjusted models. Findings suggest low self-esteem may be an important correlate specific to the use of this substance among youth. Conclusions Salvia divinorum use is prevalent among Canadian adolescents. Salvia may be a significant public health issue in Canada given it is readily available, under limited regulation, and little is known about the abuse liability of the substance, interactions with other substances, and potential complications from use.

Background Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)—a highly selective agonist at the κ opiate receptor—is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. Methods In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. Results SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects. Conclusions SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with κ opiate receptor agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved, and to explore the basis for individual variability in its effects.

Background A plant with dissociative and psychoactive properties began to attract the attention of the media and United States policymakers following a well-publicized suicide in 2006 and reports that the plant served as a ‘legal high' and substitute for cannabis. As a result, Salvia divinorum and its active ingredient, salvinorin A, were classified as Schedule I substances by the Florida Legislature on July 1, 2008. As of yet, no research has explored the efficacy of this policy or similar policies in other jurisdictions. Methods Three self-report studies collected from young adults both prior to and following the policy's implementation are employed to investigate the potential relationship between the policy and usage rates. In addition, law enforcement personnel from the state's most populated areas were interviewed to determine the extent to which they were encountering salvia in their work. Results It was indicated that less than two-thirds of those surveyed were aware of the drug's legal status. Lifetime prevalence of salvia use was largely unchanged. However, the rates of self-reported past year and past month use in Florida were significantly lower following the scheduling. Though use of Salvia divinorum appears to have decreased, perceptions of peer use increased markedly. Law enforcement officers and laboratories reported rarely, if ever, dealing with cases of salvia possession. Conclusions Data suggests the classification of Salvia divinorum as a Schedule I drug was followed by a substantial reduction in recreational use. We caution that other factors may have influenced use, that the efficacy of scheduling novel substances is likely to vary by drug type, that such a reduction in reported use may only exist transiently until a sophisticated illicit market develops to replace the legitimate one, and that a state's success in regulating salvia may be related to their regulation of and enforcement of other drug prohibitions.

Salvia divinorum, a hallucinogenic herb, has in recent years become popular among teenagers and young adults. Salvia is presently marketed as a "legal" alternative to other drugs of abuse, but little is known about the clinical toxicity of this substance.The purpose of this study is to describe the clinical and demographic features of this emerging substance of recreational abuse using data obtained from the records of a poison control center.We performed retrospective review of exposures to the herbal hallucinogen Salvia divinorum as reported to the California Poison Control System (CPCS) over the last 10 years. Demographic and clinical data were collected and compiled from the computerized records of the CPCS for the search terms "salvia" and "sage."There were 37 exposures to S. divinorum and 96 exposures to non-hallucinogenic Salvia species. Eighteen (49%) of the exposures were to S. divinorum alone. Intentional Salvia exposures resulted in a variety of neurologic, cardiovascular, and gastrointestinal effects. Notably, the use of concomitant substances of abuse was associated with a high rate of complications and psychomotor disturbances.Intentional use of S. divinorum, whether alone or in combination with alcoholic beverages and other drugs, causes neurologic, cardiovascular, and gastrointestinal effects. This poison-center-based review helps to characterize the clinical toxicity of S. divinorum, but more clinical and pharmacologic research is warranted for this rapidly emerging substance of abuse.

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. Salvia divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 minutes for 60 minutes after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 minutes (first time point) and definite subjective effects were no longer present at approximately 20 minutes after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects.

Salvia divinorum is a new recreational drug where few studies have been conducted on its prevalence and predictors of use. Using a sample of undergraduate students, this study investigated these issues. While a small number reported experimenting with salvia, logistic regression models showed that demographics, marijuana use, and self-control are statistically significant predictors. The effect of gender on use was explained by low self-control; but the effect of marijuana use remained. Results also showed that White males who frequently smoke marijuana and have extremely low self-control are most likely to use salvia. Limitations and future research are discussed.

A 26-year-old male came to hospital around midnight complaining about muscle pain of the extremities as well as the tongue and slightly raised temperature. He reported the intake of an unknown amount of sinicuichi tea he had fermented over 24 h by adding yeast and sugar. The patient was treated with Vomex A (dimenhydrinate) and released from hospital the following afternoon. A blood sample taken shortly after submission and a small amount of the used plant material were available for analysis. Herbal drugs are widely used as stimulants as a legal alternative to illegal psychoactive drugs or in traditional context. Among many others like Sassafras officinalis, Salvia divinorum or Ephedra, Heimia salicifolia ("sinicuichi"), a species of the lythraceae family, is available via several online shops. Brewed up or fermented and consumed, the so-called sinicuichi tea may cause exhilarating feelings and an alteration of awareness accompanied by bradycardia, relaxation of the muscles and a pleasant faintness. Therefore Sinicuichi brew and heimia leaves are widely used for medication by the natives of Central and South America. After liquid extraction with acetone five different alkaloids were detected in the plant material by LC-MS/MS operated in the Q1 scan mode applying a TurboIonSpray source. Subsequently, Product Ion Spectra were recorded and after confirming the molecular formula by determining the accurate masses, possible structures of H. salicifolia alkaloids were assigned. The information of the Product Ion Spectra was then used to set up a sensitive multiple reaction monitoring (MRM) method. Applying the MRM method to the patient's serum sample after alkaline liquid-liquid extraction all of the five heimia alkaloids detected in the plant material were also detected qualitatively in the serum extract, confirming the ingestion.

Salvia divinorum (salvia) is a plant that appears to be enjoying increased popularity as a legal hallucinogen in many U.S. jurisdictions. While the popular press has claimed that its use has become widespread, there have been no epidemiological studies published documenting this within the U.S.A sample of college students was randomly drawn from a large public university in the southwestern U.S. and invited to participate in an online survey that included salvia use among a set of other drug use items.From the sample of 1516 college student respondents, a pattern of use emerged that indicates that salvia is indeed becoming a significant member of the list of drugs used, with 4.4% of students reporting using salvia at least once within the past 12 months. Subpopulations that are typically most at risk for drug use within college students (Whites, males, fraternity members, heavy episodic drinkers) also were most likely to use salvia.The results indicate that more research is needed to determine the generalizability of these findings, and identify whether there are any negative consequences experienced either by the user or the community associated with this drug.

Data from clinical and preclinical studies converge implicating the plant-derived hallucinogen salvinorin A as an important pharmacologic tool; this psychoactive compound may expand scientific understandings on mammalian kappa-opioid receptor systems. Human salvinorin A effects, consistent with kappa-opioid receptor agonism, include antinociception, sedation, dysphoria and distorted perceptions. The experiments reported here measured salvinorin A (1-3mg/kg, i.p.) discriminative stimulus properties in male Sprague-Dawley rats conditioned to recognize the discriminative stimulus cue generated by the well characterized kappa-opioid agonist U-69593 (0.56 mg/kg, i.p.). At three distinct active doses, salvinorin A fully substituted for U-69593 without altering response rates. The lever choice pattern in U-69593 trained animals reverted to vehicle lever responding when a kappa selective antagonist compound, nor-BNI (4.5 nM, i.c.v.) was administered 1h prior to salvinorin A, yet nor-BNI alone failed to impact the rate or pattern of subject responses. These findings confirm and extend results published after similar drug discrimination tests were performed in rhesus monkeys. The discussion section of this article highlights public concern over salvinorin A misuse and emphasizes several potential pharmacotherapeutic applications for salvinorin A or analogue compounds.

Salvia divinorum Epling & Jativa-M. is a perennial herb belonging to the Lamiaceae family; its active ingredient, the neoclerodane diterpene salvinorin A, is a psychotropic molecule that produces hallucinations. A comparative evaluation of S. divinorum fresh and dried leaves, S. officinalis fresh leaves, and dried powdered leaves claimed to be S. divinorum was done. HPLC-MS data confirmed the presence of salvinorin A in both S. divinorun leaf extracts and the powdered leaves, whereas no salvinorin A was found in S. officinalis. The non-transcribed spacer (NTS) in the 5S-rRNA gene of all leaf samples and the dried powdered leaves was amplified by PCR using a pair of primers located at the 3' and 5' ends of the coding sequence of 5S-rRNA gene. The resulting PCR products (about 500bp for S. divinorum and 300bp for S. officinalis) were gel purified, subcloned into pGEM-T Easy vector and sequenced. By aligning the isolated nucleotide sequences, great diversities were found in the spacer region of the two species. Specific S. divinorum primers were designed on the sequence of the 5S-rRNA gene spacer region. In addition, a PCR-restriction fragment length polymorphism (PCR-RFLP) method was applied using NdeI and TaqI restriction enzymes. An NdeI site, absent in S. officinalis, was found in S. divinorum NTS region at 428-433bp. For TaqI, multiple sites (161-164, 170-173, and 217-220bp) were found in S. officinalis, whereas a unique site was found in S. divinorum (235-238bp). The results of this work show that the combined use of analytical chemical (HPLC-MS) and molecular (DNA fingerprinting) methods lead to the precise and unequivocal identification of S. divinorum.

At present, the Mexican mint Salvia divinorum is an unregulated hallucinogen. This has resulted in various on-line botanical companies advertising and selling S. divinorum as a legal alternative to other regulated plant hallucinogens. It is predictable that its misuse will increase rapidly. The active ingredient in S. divinorum is the neoclerodane diterpene, salvinorin A (1a), which has been shown to be a kappa agonist both in vitro and in vivo. This review will cover the current state of research into the psychopharmacology of S. divinorum.

Patterns of recreational drug use undergo constant change. Health care providers must remain vigilant and informed regarding emerging drugs of abuse to care better for their patients. There is also a role for improved surveillance and characterization of novel drugs. This report reviews the clinical manifestations and toxicity of several new drugs of abuse, including dextromethorphan, hallucinogenic tryptamines (including "Foxy Methoxy"), hallucinogenic amphetamines (including 2C-B and 2C-T-7), as well as the herbal hallucinogen, Salvia divinorum .

Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ, δ, and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki = 2 nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki = 21, 36 and 39 nM).

Salvinorin A is a novel hallucinogen isolated from the widely available leaves of Salvia divinorum. Based on its mechanism of action, salvinorin A has shown potential as a stimulant abuse therapeutic. However, there are no methods for the detection of salvinorin A or its metabolites in biological fluids. In order to begin developing salvinorin A as a potential therapeutic, an understanding of its metabolism is needed. Here, a straightforward synthesis of a deuterium labeled analog of salvinorin A and its utility as an internal standard for the detection of salvinorin A and its metabolites in biological fluids by LC-MS is described.

Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at the "receptorome" (that portion of the proteome encoding receptors). An overview of the receptorome is given and various in silico, public-domain resources are described. Newly developed tools for the in silico mining of data derived from the National Institute of Mental Health Psychoactive Drug Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail. Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies.

Smoking of Salvia divinorum leaves is the most common method for its psychotropic effects. Eleven thermal degradation products, including a new neoclerodane diterpene derivative, were isolated from the smoke of S. divinorum leaves, and their structures were identified by spectroscopic methods. The isolated compounds were evaluated for their binding affinities at the opioid receptors, and salvinorin A is still the most potent kappa opioid receptor agonist.

Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

Health care and legal officials in the USA have growing concern over the use of a legal shamanist drug. Salvia divinorum, commonly known as ska Maria Pastora or diviner's sage, is a potent hallucinogenic herb that is currently legal in the USA. The plant is native to Mexico and was imported into the USA in the early 1960s. Scientists identified Salvinorum A as the active chemical that causes the hallucinogens. But neurologist Ethan Russo (MT, USA) warns that ‘we don't know how [Salvia] works. It doesn't work on serotonin, dopamine or any of the known neurotransmitters.’ Users claim the drug is non-addictive, but its long-term effects are not known. (Deutsche Presse-Agentur 9 July 2001) TS