The psychoactive plant Salvia divinorum, or the ‘diviner’s sage’, is a rare member of the mint family (Lamiaceae; formerly Labiatae), characterised in the mid-twentieth century. The plant is endemic to a limited area of the highlands of the Mexican Oaxaca state, where the Mazatec Indians ingest its fresh leaves or leaf preparations for divinatory rituals, healing ceremonies and medical purposes. Since the late 1990s, the use of the plant as a ‘legal’ herbal hallucinogen has been increasing, partly due to its availability. Smoking the dried and crushed leaves provides short-lived but intense hallucinations. The effective dose of salvinorin A, the active ingredient of the plant, is comparable to that of the synthetic hallucinogens LSD or DOB. The toxicity of Salvia divinorum is currently poorly understood.
The chemical identification of the psychoactive principle of Salvia divinorum was completed simultaneously by Ortega and Valdés in the early 1980s. The main ingredient responsible for the psychoactive effect of the plant is a neoclerodane diterpene called salvinorin A. The IUPAC systematic name is (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester (CAS number: 83729-01-5). Unlike classical natural or synthetic hallucinogens, salvinorin A does not contain a nitrogen atom — it is not an alkaloid.
The dried leaves, leaf extracts and pure salvinorin A are stable at ambient temperature in the absence of light or air, although there is no systematic study on this. Salvinorin A is unstable in basic solutions and is soluble in conventional organic solvents, including acetone, acetonitrile, chloroform, dimethyl sulfoxide and methanol, but is essentially insoluble in hexane and water.
Molecular structure of salvinorum A
Molecular formula: C23H28O8
Molecular weight: 432.47 g/mol
Salvia divinorum is a 0.5 to 1.5 metre high perennial shrublike herb. It can be easily recognised from its square-shaped and hollow stem and opposite pairs of ovate-lanceolate, jagged-edged leaves, which are usually velvety or hairy. The characteristic flower of the plant has a white corolla surrounded by a violet blue calyx. Salvia divinorum hardly ever sets seeds, and even when produced, they are rarely viable. The propagation of the plant is thus exclusively vegetative and most of the Salvia divinorum plants now cultivated worldwide are clones of a few early Oaxaca collections.
Dried and crushed leaves fortified with extracts from other leaves are dark green, brownish or even blackish green, due to concentrated pigments.
Pure salvinorin A forms colourless crystals with a melting point of 242–244 oC.
Salvinorin A has a unique mode of action and pharmacology. The potent and selective full agonist activity at κ-opioid receptor (KOR) subtypes is primarily responsible for the hallucinogenic effect of the drug. Whereas, ‘classical’ hallucinogens such as psilocybin, LSD or DOB, all alkaloidal in nature, interact with specific serotonin receptor subtypes. Salvinorin A shows no significant binding to over 50 other (psycho)pharmacologically important receptors, transporter proteins and ion channels.
In humans, salvinorin A induces short-lived, profound hallucinations. Inhalation of doses equivalent to 200–500 micrograms of salvinorin A leads to loss of control over physical movements (incapacitation); uncontrollable laughter; vivid, colourful and often bizarre, dream- or film-like hallucinations. Temporal boundaries among past, present and future disappear and the user is transported to alternative time and places (‘spatiotemporal dislocation’) with perceptions of being in several locations simultaneously. The ‘trip’, especially at higher doses, can be frightening and can cause serious psychotic disturbances. It has been reported that this can last for hours after the hallucinations have disappeared. Common after-effects include tiredness, dizziness and amnesia. Emergency reports have described lasting psychosis in vulnerable individuals.
Although preliminary experiments by Mowry et al. (2003) indicated that salvinorin A has relatively low toxicity to rodents, no other study has examined the acute or chronic physiological toxic effect of Salvia divinorum leaves or of the various extracts.
Because Salvia divinorum seeds are difficult to obtain, the plant is propagated from cuttings. Seedlings as well as dried leaves are readily available either from Internet suppliers or specialised shops in countries where no regulatory restrictions exist. Home cultivation of plants is possible and instructions describing optimal growing conditions, the use of fertilisers and pest control chemicals are available on the Internet in several languages.
Salvinorin A is found in the resin secreted by special, hairy epidermal cells (trichomes), which are especially abundant on the leaves. Preparations of one leaf fortified by extracts of 4 to 49 other leaves (the respective products then labelled as 5X to 50X extracts) are also available online and in specialised shops. However, the actual salvinorin A concentration of Salvia divinorum products is generally unknown. Pure, crystalline salvinorin A does not appear to be offered on markets (neither online or in smartshops) but illustrated procedures for its isolation are available on the Internet.
Chemical total syntheses of salvinorin A have recently been completed but they are too complex to be used for the production of the substance.
To date, salvinorin A has not been found in any other Salvia species analysed.
Traditionally, the Mazatec Indians roll the fresh leaves of the plant into a cigar-like ‘quid’, which is then sucked or chewed while retaining the juice in the mouth to increase absorption of the active ingredient.
Alternatively, the fresh foliage is crushed by hand or ground on a milling stone which can be used for making a drinkable infusion. At least six fresh leaves are needed to achieve noticeable effects, which manifest after about 10 minutes and lasts for 45 minutes or longer.
For recreational use, the most common way of administration is smoking the crushed dried leaves from a pipe or water bong, providing short-lasting (15–20 minute) hallucinations within a minute. Typically, 0.25–0.75 gram leaf material is smoked.
Chewing the bitter leaves as a quid gives a longer lasting effect and the typical dosages to produce mild to medium effects are 10–30 grams of fresh leaves or 2–5 grams of dried leaves.
Sublingual application of aqueous ethanol tinctures made from leaves results in an onset taking 5–10 minutes and lasting up to 2 hours.
Drinking tea made by steeping the leaves in hot water is relatively ineffective because salvinorin A is readily degraded in the gastrointestinal tract. Vaporisation of the dried leaves or extracts without burning requires special devices and rather high temperatures (>200 oC) and is not a typical method of use.
Health risks of inhaling the vapours of pure salvinorin A are high because the inhaled amount cannot be controlled. This can lead to an ‘overdose’, in the form of psychotic disturbances.
In Mexico, the plant is called in Spanish ‘hojas de la pastora’ or ‘ska María pastora’. Common names in English are: Diviner’s Sage, Lady Salvia, Magic Mint, Purple Sticky, Sally D, Sage of the Seers or simply and most widely Salvia. Names in other European languages include: French — sauge des devins, sauge divinatoire; German — Wahrsagersalbei.
The salvinorin A content of botanical samples can be analysed by thin layer chromatography or high performance liquid chromatography with UV detection. The detection and quantitation of salvinorin A in blood, urine and saliva at nanogram/ml level requires more sensitive methods such as gas chromatography or high performance liquid chromatography, both coupled with a mass spectrometer. The mass spectrum obtained by electron ionisation of salvinorin A shows significant fragments at m/z 94, 55, 121, 107, 273, 166, 220, 252, 234, 359, 318, 404 and 432 (in decreasing abundance).
The UV spectrum of the methanolic solution of salvinorin A shows a maximum at 211 nm. The characteristic absorption bands in the infra-red spectrum of salvinorin A in KBr pellet are at 3 220, 1 745, 1 735, 1 240, and 875 cm-1. For the unequivocal identification of powdered plant material, DNA fingerprinting methods can be used.
The chemical composition of Salvia divinorum leaves depends on the developmental stage of the plant and/or type of preparation. Systematic studies of plants obtained from various collections show that the salvinorin A concentration of mature plants ranges from 0.89–3.7 mg/g dried leaves (corresponding to an average of 0.245 %).
Results of recent analyses of Salvia divinorum, five product samples obtained via the Internet or from ‘head shops’ in the US indicated wide variations in salvinorin A concentrations. In dried leaves (nominal ‘1X enrichment’, where the ‘X’ refers to the number of times the extract is stronger than the leaf) the concentration of the psychoactive ingredient was 0.408 mg/g, while in the 5X (two samples), 10X and 20X enriched extracts, the salvinorin A concentrations were 0.126/1.137, 0.951 and 0.461 mg/g, respectively. This suggests that labelling did not correspond to actual content.
The study of the samples also revealed that some contained Vitamin E and caffeine as adulterants.
A recent analysis of samples sold in Japan showed salvinorin A concentrations in the range of 3.2–5.0 mg/g for the dried leaves, and, 4.1–38.9 mg/g for the 2X to 25X enriched preparations.
Neither Salvia divinorum nor salvinorin A are listed in any of the Schedules of the United Nations Drug Conventions.
However, in recent years both Salvia divinorum and its active principle salvinorin A have become controlled under drugs legislation in Belgium, Denmark, Italy, Latvia, Lithuania, Romania and Sweden, in Australia and Japan as well as in a number of states of the US.
Croatia, Germany, Poland and Spain only regulate the plant. In Estonia, Finland and Norway, Salvia divinorum falls under medicines legislation. Lastly, in Canada it is illegal to sell Salvia without authorisation under the Natural Health Products Regulation.
There is limited information on the extent of use of Salvia divinorum and its preparations in European countries.
In Romania, a 2008 survey amongst Bucharest-based young people aged 15 to 34 who attend recreational settings, showed that 0.3 % had tried Salvia divinorum at least once in their life.
In an online survey of UK club-goers carried-out late 2009, 3.2 % of respondents admit to a last month consumption of Salvia divinorum, making it the fifteenth most commonly used drug with this frequency. Lifetime prevalence reaches 29.2 %. These findings cannot, however, be considered as representative of the wider population of club-goers, due to the methodological limitations of online surveys.
In the US, the annual National Survey on Drug Use and Health conducted in 2006 indicates that the last 12 month use of Salvia divinorum was 0.3 % among persons aged 12 or older; overall, about 1.8 million persons admit to using the drug in their lifetime.
According to the more recent ‘Monitoring the Future’ report of the National Institute on Drug Abuse, last year prevalence of Salvia divinorum in 2009 was 6.0 % among high school seniors (this percentage is higher than the previous year prevalence for ecstasy). It appears that the use is restricted and experimental, rather than as a social or party drug.
According to a 2006 study conducted by Khey et al. among students in a US college (average age 19.8 years), the lifetime, last year and last month prevalences were 6.7, 3.0 and 0.5 % respectively, with half of the sample expressing no desire to use the drug again: this suggests that Salvia divinorum use may have a low continuation rate.
Prices vary between countries and depend on the type and amount of product concerned. In early 2011, an ‘EMCDDA snapshot’ of online shops found that the European market prices for Salvia divinorum dried leaves ranged from EUR 0.27 (1 kilogram package) to EUR 1.5 per gram (one-gram package).
A ‘2011 EMCDDA snapshot’ also showed that ‘Salvia 5X’ extracts are sold in small amounts such as ½ gram for around EUR 11–12. ‘Salvia 40X’ costs around EUR 30 for ½ gram.
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