Salvia divinorum drug profile

Salvia divinorum drug profile

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 structure of salvinorum a

Molecular formula: C23H28O8
Molecular weight: 432.47 g/mol

top of page

Physical form

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.

top of page


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.

top of page


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.

top of page

Mode of use

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.

top of page

Other names

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.

top of page


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.

Salvinorin A and the other diterpenoids of the plant are not detected by conventional drug screening methods.

top of page

Control status

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.

top of page

Medical use

There is no approved medicinal use for Salvia divinorum or salvinorin A. However, there is intensive research to explore the therapeutic potential of structurally related KOR agonists or antagonists.

top of page


Albertson, D. N., and Grubbs, L. E. (2009), ‘Subjective effects of Salvia divinorum: LSD- or marijuana-like?’, Journal of Psychoactive Drugs, Volume 41, pp. 213–217.

Appel, J., and Kim-Appel, D. (2007), ‘The rise of a new psychoactive agent: Salvia divinorum’, International Journal of Mental Health and Addiction, Volume 5, pp. 248–253.

Baggott, M. J., Erowid, E. Erowid, F., and Mendelson, J. E. (2004), ‘Use of Salvia divinorum, an unscheduled hallucinogenic plant: a web-based survey of 500 users’, Clinical Pharmacology and Therapeutics, Volume 75, p. 72.

Bertea, C. M., Luciano, P., Bossi, S. et al. (2006), ‘PCR and PCR–RFLP of the 5S-rRNA-NTS region and salvinorin A analyses for the rapid and unequivocal determination of Salvia divinorum’, Phytochemistry, Volume 67, pp. 371–378.

Beerepoot, P., Lam, V., Luu, A., Tsoi, B., Siebert, D., and Szechtman, H. (2008), ‘Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole’, Neuroscience Letters, Volume 446, pp. 101–104.

Biglete, S. A., Lai, E. P., Lee, D. Y., Nyi, P. P., Torrecer, G. I., and Anderson, I. B. (2009), ‘Influence of age on Salvia divinorum abuse: results of an Internet survey’, Clinical Toxicology, Volume 47, p. 712.

Braida, D., Capurro, V., Zani, A. et al. (2009), ‘Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents’, British Journal of Pharmacology, Volume 157, pp. 844–853.

Braida, D., Limonta, V., Capurro, V. et al. (2008), ‘Involvement of κ-opioid and endocannabinoid system on salvinorin A-induced reward’, Biological Psychiatry, Volume 63, pp. 286–292.

Capasso, R., Borrelli, F., Cascio, M. G., Aviello, G., Huben, K. et al. (2008), ‘Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between κ-opioid and cannabinoid CB1 receptors’, British Journal of Pharmacology, Volume 155, pp. 681–689.

Carlezon, W. A., Jr., Béguin, C., Knoll, A. T., and Cohen, B. M. (2009), ‘Kappa-opioid ligands in the study and treatment of mood disorders’, Pharmacology and Therapeutics, Volume 123, pp. 334–342.

Chavkin, C., Sud, S., Jin, W. et al. (2004), ‘Salvinorin A, an active component of the hallucinogenic sage Salvia divinorum is a highly efficacious κ-opioid receptor agonist: structural and functional considerations’, The Journal of Pharmacology and Experimental Therapeutics, Volume 308, pp. 1197–1203.

Epling, C., and Játiva-M, C. D. (1962), ‘A new species of Salvia from Mexico’, Botanical Museum Leaflets, Harvard University, Volume 20, pp. 75–76.

Giroud, C., Felber, F., Augsburger, M., Horisberger, B., Rivier, L., and Mangin, P. (2000), ‘Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland’, Forensic Science International, Volume 112, pp. 143–150.

González, D., Riba, J., Bouso, J. C., Gómez-Jarabo, G., and Barbanoj, M. J. (2006), ‘Pattern of use and subjective effects of Salvia divinorum among recreational users’, Drug and Alcohol Dependence, Volume 85, pp. 157–162.

Gruber, J. W., Siebert, D. J., Der Marderosian, A. H., and Hock, R. S. (1999), ‘High performance liquid chromatographic quantification of salvinorin A from tissues of Salvia divinorum Epling & Játiva-M.’, Phytochemical Analysis, Volume 10, pp. 22–25.

Grundmann, O., Phipps, S. M., Zadezensky, I., and Butterweck, V. (2007), ‘Salvia divinorum and salvinorin A: An update on pharmacology and analytical methodology’, Planta Medica, Volume 73, pp. 1039–1046.

Hanes, K. R. (2001), ‘Antidepressant effects of the herb Salvia divinorum: a case report’, Journal of Clinical Psychopharmacology, Volume 21, pp. 634–635.

Harding, W. W., Tidgewell, K., Byrd, N. et al. (2005), ‘Neoclerodane diterpenes as a novel scaffold for μ opioid receptor ligands’, Journal of Medicinal Chemistry, Volume 48, pp. 4765–4771.

Hofmann, A. (1979), LSD — Mein Sorgenkind. Die Entdeckung einer ‘Wunderdroge’, J. G. Cotta’sche Buchhandlung Nachfolger GmbH, Stuttgart, ISBN: 3-12-923601-5 (original edition).

Hooker, J. M., Xu, Y., Schiffer, W., Shea, C., Carter, P., and Fowler, J. S. (2008), ‘Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans’, NeuroImage, Volume 41, pp. 1044–1050.

Imanshahidi, M., and Hosseinzadeh, H. (2006), ‘The pharmacological effects of Salvia species on the central nervous system’, Phytotherapy Research, Volume 20, pp. 427–437.

Jermain, J. D., and Evans, H. K. (2009), ‘Analyzing Salvia divinorum and its active ingredient salvinorin A utilizing thin layer chromatography and gas chromatography/mass spectrometry’, Journal of Forensic Sciences, Volume 54, pp. 612–616.

Khey, D. N., Miller, B. L., and Griffin, O. H. (2008), ‘Salvia divinorum use among a college student sample’, Journal of Drug Education, Volume 38, pp. 297–306.

Lange, J. E., Daniel, J., Homer, K., Reed, M. B., and Clapp, J. D. (2010), ‘Salvia divinorum: Effects and use among YouTube users‘ Drug and Alcohol Dependence 108, pp. 138–140.

Li, Y., Husbands, S. M., Mahon, M. F., Traynor, J. R., and Rowan, M. G. (2007), ‘Isolation and chemical modification of clerodane diterpenoids from Salvia species as potential agonists at the κ-opioid receptor’, Chemistry and Biodiversity, Volume 4, pp. 1586–1593.

McDonough, P. C., Holler, J. M., Vorce, S. P., Bosy, T. Z., Magluilo, J., Jr., and Past, M. R. (2008), ‘The detection and quantitative analysis of the psychoactive component of Salvia divinorum, salvinorin A, in human biological fluids using liquid chromatography–mass spectrometry’, Journal of Analytical Toxicology, Volume 32, pp. 417–421.

Medana, C., Massolino, C., Pazzi, M., and Baiocchi, C. (2006), ‘Determination of salvinorins and divinatorins in Salvia divinorum leaves by liquid chromatography/multistage mass spectrometry’, Rapid Communications in Mass Spectrometry, Volume 20, pp. 131–136.

Mowry, M., Mosher, M., and Briner, W. (2003), ‘Acute physiologic and chronic histologic changes in rats and mice exposed to the unique hallucinogen salvinorin A’, Journal of Psychoactive Drugs, Volume 35, pp. 379–382.

National Institute on Drug Abuse (2009), ‘NIDA InfoFacts: Salvia’.

Nozawa, M., Suka, Y., Hoshi, T., Suzuki, T., and Hagiwara, H. (2008), ‘Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A’, Organic Letters, Volume 10, pp. 1365–1368.

Ortega, A., Blount, J. F., and Manchand, P. S. (1982), ‘Salvinorin, a new trans-neoclerodane diterpene from Salvia divinorum (Labiatae)’, Journal of the Chemical Society, Perkin Transactions 1, pp. 2505–2508.

Paulzen, M., and Gründer, G. (2008), ‘Toxic psychosis after intake of the hallucinogen salvinorin A’, Journal of Clinical Psychiatry, Volume 69, pp. 1501–1502.

Pfeiffer, A., Brantl, V., Herz, A., and Emrich, H. M. (1986), ‘Psychotomimesis mediated by κ opiate receptors’, Science, Volume 233, pp. 774–776.

Pichini, S., Abanades, S., Farré, M. et al (2005), ‘Quantification of the plant-derived hallucinogen Salvinorin A in conventional and non-conventional biological fluids by gas chromatography/mass spectrometry after Salvia divinorum smoking’, Rapid Communications in Mass Spectrometry, Volume 19, pp. 1649–1656.

Prisinzano, T. E. (2009), ‘Natural products as tools for neuroscience: discovery and development of novel agents to treat drug abuse’, Journal of Natural Products, Volume 72, pp. 581–587.

Przekop, P., and Lee, T. (2009), ‘Persistent psychosis associated with Salvia divinorum use’, American Journal of Psychiatry, Volume 166, p. 832.

Roth, B. L., Baner, K., Westkaemper, R. et al. (2002), ‘Salvinorin A: A potent naturally occurring nonnitrogenous κ opioid selective agonist’, Proceedings of the National Academy of Sciences, US, Volume 99, pp. 11934–11939.

Scheerer, J. R., Lawrence, J. F., Wang, G. C., and Evans, D. A. (2007), ‘Asymmetric synthesis of salvinorin A, a potent κ-opioid receptor agonist’, Journal of the American Chemical Society, Volume 129, pp. 8968–8969.

Schmidt, M. D., Schmidt, M. S., Butelman, E. R. et al. (2005), ‘Pharmacokinetics of the plant-derived κ-opioid hallucinogen Salvinorin A in nonhuman primates’, Synapse, Volume 58, pp. 208–210.

Seeman, P., Guan, H.-C., and Hirbec, H. (2009), ‘Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil’, Synapse, Volume 63, pp. 698–704.

Siebert, D. (2004), ‘Localization of salvinorin A and related compounds in glandular trichomes of the psychoactive sage, Salvia divinorum’, Annals of Botany, Volume 93, pp. 763–771.

Siebert, D. J. (1994), 'Salvia divinorum and Salvinorin A: new pharmacological findings', Journal of Ethnnopharmacology, Volume 43,pp. 53–56.

Siemann, H., Specka, M., Schifano, F., Deluca, P., and Scherbaum, N. (2006), ‘Salvia divinorum – Präsenz einer neuen Droge im Internet’, Gesundheitswesen, Volume 68, pp. 323–327.

Substance Abuse and Mental Health Services, Office of Applied Studies (2008), ‘The NSDUH Report: Use of Specific Hallucinogens: 2006’, Rockville, MD.

‘Teen marijuana use tilts up, while some drugs decline in use’, 14 December 2009.

Tsujikawa, K., Kuwayama, K., Miyaguchi, H., Kanamori, T., Iwata, Y. T., and Inoue, H. (2009), ‘In vitro stability and metabolism of salvinorin A in rat plasma’, Xenobiotica, Volume 39, pp. 391–398.

Valdés, L. J., III, Butler, W. M., Hatfield, G. M., Paul, A. G., and Koreeda, M. (1984), ‘Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint Salvia divinorum’, Journal of Organic Chemistry, Volume 49, pp. 4716–4720.

Valdés, L. J., III, Hatfield, G. M., Koreeda, M., and Paul, A. G. (1987), ‘Studies of Salvia divinorum (Lamiaceae), an hallucinogenic mint from the Sierra Mazateca in Oaxaca, Central Mexico’, Economic Botany, Volume 41, pp. 283–291.

Vohra, R., Seefeld, A., Cantrell, F. L., and Clark, R. F. (2009), ‘Salvia divinorum: exposures reported to a statewide poison control system over 10 years’, The Journal of Emergency Medicine.

Vortherms, T. A., and Roth, B. L. (2006), ‘Salvinorin A. From natural product to human therapeutics’, Molecular Interventions, Volume 6, pp. 259–267.

Wolowich, W. R., Perkins, A. M., and Cienki, J. J. (2006), ‘Analysis of the psychoactive terpenoid salvinorin A content in five Salvia divinorum herbal products’, Pharmacotherapy, Volume 26, pp. 1268–1272.

Zhang, Y., Butelman, E. R., Schlussman, S. D., Ho, A., and Kreek, M. J. (2005), ‘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’, Psychopharmacology, Volume 179, pp. 551–558.

top of page