|Systematic (IUPAC) name|
|Molar mass||432.46362 g/mol|
|Specific rotation||-45.3 °C at 22 deg C/D (c = 8.530 CHCl3); -41 °C at 25°C/D (c = 1 in CHCl3)|
|Melting point||238 to 240 °C (460 to 464 °F) (also reported 242–244 °C)|
|Boiling point||760.2 °C (1,400.4 °F)|
|Solubility in water||25.07 mg/L at 25 °C (water, est) mg/mL (20 °C)|
|(what is this?)|
Salvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans. Salvinorin A is considered a dissociative exhibiting atypically psychedelic effects.
It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psilocybin, and mescaline) because it contains no nitrogen atoms; hence, it is not an alkaloid (and cannot be rendered as a salt) but a terpenoid. It also differs in subjective experience, compared to other hallucinogens, and has been described as dissociative.
Salvinorin A can produce psychoactive experiences in humans with a typical duration of action being several minutes to an hour or so, depending on the method of ingestion.
Salvinorin A is found with several other structurally related salvinorins. Salvinorin is a trans-neoclerodane diterpenoid. It acts as a kappa opioid receptor agonist and is the first known compound acting on this receptor that is not an alkaloid.
- 1 History
- 2 Pharmacology
- 3 Associated compounds
- 4 Synthesis
- 5 Other salvinorins
- 6 Semi-synthetic analogues
- 7 Pharmaceutical action
- 8 Legal status
- 9 See also
- 10 References
- 11 Further reading
- 12 External links
Salvinorin A was first described and named in 1982 by Alfredo Ortega and colleagues in Mexico. They used a combination of spectroscopy and x-ray crystallography to determine the chemical structure of the compound, which was shown to have a bicyclic diterpene structure. Around the same time, Leander Julián Valdés III independently isolated the molecule as part of his PhD research, published in 1983. Valdés named the chemical divinorum, and also isolated an analog that he named divinorum B. The naming was subsequently corrected to salvinorin A and B after the work was published in 1984. Valdés later isolated salvinorin C.
Salvinorin A is a trans-neoclerodane diterpenoid with the chemical formula C23H28O8. Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid as it does not contain a basic nitrogen atom. Salvinorin A has no action at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of 'classical' psychedelics such as LSD and mescaline.
Potency and selectivity
Salvinorin A is active at doses as low as 200 µg. Synthetic chemicals, such as LSD (active at 20–30 µg doses), can be more potent. Research has shown that salvinorin A is a potent κ-opioid receptor (KOR) agonist (Ki = 2.4 nM, EC50 = 1.8 nM). It has a high affinity for the receptor, indicated by the low dissociation constant of 1.0 nanomolar (nM). It has been reported that the effects of salvinorin A in mice are blocked by κ-opioid receptor antagonists. In addition, salvinorin A has recently been found to act as a D2 receptor partial agonist, with an affinity of 5–10 nM, an intrinsic activity of 40–60%, and an EC50 of 48 nM. This suggests that the D2 receptor may also play an important role in its effects.
Salvinorin A is unique in that it is the only naturally occurring substance known to induce a visionary state via this mode of action; there are synthetic KOR agonists, (e.g. enadoline, ketazocine, pentazocine and relatives), which show similar hallucinatory and dissociative effects.
Salvinorin A's potency should not be confused with toxicity. Mice chronically given dosages "many times that of what humans are exposed to" did not show signs of organ damage. However, "further studies should be done on blood pressure effects" and "Pulse pressure did appear to increase with salvinorin A exposure twenty and forty minutes after exposure, however, this increase was not statistically significant" (note that the data shows an increase in pulse pressure that was roughly 1.5–2 times the control group's).
Interestingly, salvinorin A shows atypical properties as an agonist of the KOR relative to other KOR agonists. For instance, it is 40-fold less potent in promoting internalization (that is, receptor downregulation) of the human KOR relative to the prototypical KOR agonist U-50488, and it shows minimal antipruritic effects and no analgesic effects in mice, though conflicting reports exist in regards to antinociception. Like most other KOR agonists, salvinorin A does produce effects such as sedation, psychotomimesis, dysphoria/aversion, and anhedonia/depression however. The drug has been found not to produce diuresis in mice, possibly due to its short duration.
Effect on intestinal motility
Salvinorin A is capable of inhibiting excess intestinal motility (e.g. diarrhea), through its potent k-opioid-activating effects. The mechanism of action for salvinorin A on ileal tissue has been described as 'prejunctional', as it was able to modify electrically induced contractions, but not those of exogenous acetylcholine. A pharmacologically important aspect of the contraction-reducing properties of ingested salvinorin A on gut tissue is that it is only pharmacologically active on inflamed and not normal tissue, thus reducing possible side-effects.
Salvinorin A is soluble in organic solvents such as ethanol and acetone, but not especially so in water. It is possible Salvinorin A may also be soluble in lipids as are some related terpenoids such as cannabinoids and curcuminoids.
Detection in urine
Humans who smoked 580 μg of the pure drug had urine salvinorin A concentrations of 2.4–10.9 µg/L during the first hour, but the levels fell below the detection limit by 1.5 hours after smoking. Analytical measurements may be performed using gas or liquid chromatography-mass spectrometry.
Many other terpenoids have been isolated from Salvia divinorum, including other salvinorins and related compounds named divinatorins and salvinicins. None of these compounds have shown significant (sub-micromolar) affinity at the kappa-opioid receptor, and there is no evidence that they contribute to the plant's psychoactivity.
The biogenic origin of salvinorin A synthesis has been elucidated using nuclear magnetic resonance and ESI-MS analysis of incorporated precursors labeled with stable isotopes of carbon (Carbon-13 13C) and hydrogen (Deuterium 2H). It "is biosynthesized via the 1-deoxy-d-xylulose-5-phosphate pathway," rather than the classic mevalonate pathway typical for plant terpenoids.
Terpenoids are biosynthesized from two C5 precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The NMR and MS study by Zjawiony suggested that the biosynthesis of salvinorin A proceeds via the 1-deoxy-d-xylulose-5-phosphate pathway. In the deoxyxylulose phosphate pathway, D-glyceraldehyde 3-phosphate and pyruvate, the intermediates of the glycolysis, are converted into 1-deoxy-D-xylulose 5-phosphate via decarboxylation. Subsequent reduction with NADPH generates 2C-methyl-D-erythritol 2,4-cyclodiphosphate, via the intermediates 4-diphosphocytidyl-2-C-methyl-D-erythritol and 4-diphosphocytidyl-2c-methyl-d-erythritol-2-phosphate, which then lead to IPP and DMAPP.
The allylic cation generated by the ionization of DMAPP yields geranyl diphosphate (GPP), a monoterpene diphosphate with the newly formed double bond in trans. Subsequent addition of IPP generates a diterpene, geranylgeranyl diphosphate (GGPP). Cyclization via electrophilic addition of the GGPP affords Iabdanyl cation. Upon the further rearrangements of the methyl groups and hydrides, clerodane pyrophosphate was generated. Additional oxidation and cyclization clerodane pyrophosphate concludes the biosynthesis of salvinorin A.
A total asymmetric synthesis of salvinorin A, which relies on a transannular Michael reaction cascade to construct the ring system, was achieved in 2007 by Evans and co-workers in 4.5% overall yield over 30 steps. More recently, a synthesis was published by a Japanese group, requiring 24 steps to yield salvinorin A in 0.15% yield.
An attempt at the synthesis of salvinorin A has also been published by a group at RMIT University, adopting a convergent synthesis of a functionalized cyclohexanone with a α,β-unsaturated lactone.
Salvinorin A is one of several structurally related salvinorins found in the Salvia divinorum plant. Salvinorin A can be synthesized from the inactive salvinorin B by acetylation. The de-acetylated analog salvinorin B is devoid of human activity. It was speculated that salvinorin C might be even more potent than salvinorin A, but human tests and receptor binding assays could not confirm this. Salvinorin A seems to be the only active naturally occurring salvinorin.
Research on salvinorin derivatives has produced a number of semi-synthetic compounds, several of which can be conveniently made from salvinorin B. Most derivatives are selective kappa opioid agonists as with salvinorin A, although some are even more potent, with the most potent compound 2-ethoxymethyl salvinorin B being 10x stronger than salvinorin A. A few derivatives such as herkinorin have reduced kappa opioid action and instead act as mu opioid agonists.
Salvinorin A has only been administered to humans in a few studies. One such study found that its effects peak at about 2 minutes, that its subjective effects overlap with those of serotonergic psychedelics, and that it temporarily impairs recall and recognition memory.
Results from a small study by an assistant professor at the University of Iowa indicate that it may have potential as an analgesic and as a therapeutic tool for treating drug addictions. κ-opioid agonists have very marked effects on all types of addiction including alcohol, cocaine, and opiate abuse.
Salvinorin A is sometimes regulated together with its host, Salvia divinorum, due to its psychoactive and analgesic effects.
Salvinorin A is not scheduled at the federal level in the United States. Its molecular structure is unlike any Schedule I or II drug, so possession or sales is unlikely to be prosecuted under the Federal Analog Act.
Salvinorin A is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.
"Salvinorin A" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida. There is an exception however for "any drug product approved by the United States Food and Drug Administration which contains Salvinorin A or its isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, if the existence of such isomers, esters, ethers, and salts is possible within the specific chemical designation."
Sveriges riksdags health ministry Statens folkhälsoinstitut classified Salvinorin A (and Salvia divinorum) as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Apr 1, 2006, in their regulation SFS 2006:167 listed as "salvinorin A", making it illegal to sell or possess.
- salvinorin A, PubChem, retrieved 2012-11-23
- MacLean, Katherine; Johnson, Matthew; Reissig, Chad; Prisinzano, Thomas; Griffiths, Roland (8 November 2012). "Dose-related Effects of Salvinorin A in Humans: Dissociative, Hallucinogenic, and Memory Effects". National Center for Biotechnology Information. Retrieved 4 September 2014.
- "Salvia Chemistry". Retrieved 4 September 2014.
Unique in its structure, salvinorin A is considered a diterpenoid and not an alkaloid (opiates fall into this category), due to its lack of nitrogen atoms.
- Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB (2002). "Salvinorin A: a potent naturally occurring nonnitrogenous κ opioid selective agonist". Proceedings of the National Academy of Sciences U.S.A. 99 (18): 11934–9. doi:10.1073/pnas.182234399. PMC 129372. PMID 12192085.
- Ortega A, Blount JF, Manchard PD. (1982). "Salvinorin, a new trans-neoclerodane diterpene from Salvia divinorum (Labiatae)". Journal of the Chemical Society, Perkins Transactions I: 2505–8. doi:10.1039/P19820002505.
- Valdés LJJ III (1983). The pharmacognosy of Salvia divinorum (Epling and Jativa-M): An Investigation of Ska Maria Pastora (Mexico) (PhD thesis). University of Michigan.
- Valdés III LJJ, Butler WM, Hatfield GM, Paul AG, Koreeda M. (1984). "Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint Salvia divinorum". Journal of Organic Chemistry 49 (24): 4716–20. doi:10.1021/jo00198a026.
- Valdés III LJJ, Chang HM, Visger DC, Koreeda M. (2001). "Salvinorin C, a new neoclerodane diterpene from a bioactive fraction of the hallucinogenic Mexican mint Salvia divinorum". Organic Letters 3 (24): 3935–7. doi:10.1021/ol016820d. PMID 11720573.
- Prisinzano TE (2005). "Psychopharmacology of the hallucinogenic sage Salvia divinorum". Life Sciences 78 (5): 527–31. doi:10.1016/j.lfs.2005.09.008. PMID 16213533.
- Harding WW, Schmidt M, Tidgewell K, Kannan P, Holden KG, Gilmour B, Navarro H, Rothman RB, Prisinzano TE (2006). "Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A". Journal of Natural Products 69 (1): 107–12. doi:10.1021/np050398i. PMC 2544632. PMID 16441078.
- Imanshahidi M, Hosseinzadeh H (2006). "The pharmacological effects of Salvia species on the central nervous system". Phytotherapy Research 20 (6): 427–37. doi:10.1002/ptr.1898. PMID 16619340.
However, when smoked (in a manner similar to free base cocaine), the compound is effective in doses of 200–500 μg and produces visions that last from 30 minutes to an hour or two, while doses over 2 mg are effective for much longer. At doses greater than 500 μg the subject is often no longer aware of their surroundings and may enter an uncontrollable delirium. This compound is the most potent naturally occurring hallucinogen thus far isolated.
- Marushia, Robin (2002). "Salvia divinorum: The Botany, Ethnobotany, Biochemistry and Future of a Mexican Mint" (PDF). Ethnobotany. Archived from the original (PDF) on October 7, 2007. Retrieved 2006-12-23.
- Greiner T, Burch NR, Edelberg R (1958). "Psychopathology and psychophysiology of minimal LSD-25 dosage; a preliminary dosage-response spectrum". AMA Archives of Neurology and Psychiatry 79 (2): 208–10. doi:10.1001/archneurpsyc.1958.02340020088016. PMID 13497365.
- Lee D, Ma Z, Liu-Chen L, Wang Y, Chen Y, Carlezon W, Cohen B. (2005). "New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human K opioid receptors". Bioorganic and Medicinal Chemistry 13 (19): 5635–9. doi:10.1016/j.bmc.2005.05.054. PMID 16084728.
- Zhang Y, Butelman ER, Schlussman SD, Ho A, Kreek MJ (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 (Berl.) 179 (3): 551–8. doi:10.1007/s00213-004-2087-0. PMID 15682306.
- Seeman P, Guan HC, Hirbec H (2009). "Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil". Synapse 63 (8): 698–704. doi:10.1002/syn.20647. PMID 19391150.
- Note: the Mowry et al. study used the following data: 1600 μg/kg (0.0016 mg/g) daily injections for 14 days on "Swiss-Webster mice, aged 4–6 months" of unknown weight (when purchasing mice, an estimated maximum mass is 25 g). Given that the average weight for males in the United States is 190.9 lbs (according to Wikipedia), or 86,590.7834 g, and that a single gram mixture of plain leaf contains roughly 3 mg/g of Salvinorin A (according to Daniel Siebert), this translates to the mice receiving an effective dose of roughly 6,494,309 times more than a human (human doses range from minimal, 200 μg, to upwards of 24 mg, and body weights for both humans and mice vary tremendously).
- Mowry M, Mosher M, Briner W (2003). "Acute physiologic and chronic histologic changes in rats and mice exposed to the unique hallucinogen salvinorin A" (PDF). Journal of Psychoactive Drugs 35 (3): 379–82. doi:10.1080/02791072.2003.10400021. PMID 14621136.
- Linda P. Dwoskin (29 January 2014). Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Elsevier Science. pp. 483–. ISBN 978-0-12-420177-4.
- Rao S. Rapaka; Wolfgang Sadée (19 June 2008). Drug Addiction: From Basic Research to Therapy. Springer Science & Business Media. pp. 236–. ISBN 978-0-387-76678-2.
- Parker L. Mott (2 December 2011). A Literature Review on the Status and Effects of Salvia Divinorum on Cognitive, Affective, and Behavioral Functioning. Universal-Publishers. pp. 27–. ISBN 978-1-61233-777-7.
- José Biller (2008). The Interface of Neurology & Internal Medicine. Lippincott Williams & Wilkins. pp. 681–. ISBN 978-0-7817-7906-7.
- Inan S, Lee DY, Liu-Chen LY, Cowan A (2009). "Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A". Naunyn Schmiedebergs Arch. Pharmacol. 379 (3): 263–70. doi:10.1007/s00210-008-0358-8. PMID 18925386.
- Capasso R, Borrelli F, Capasso F, Siebert DJ, Stewart DJ, Zjawiony JK, Izzo AA (2006). "The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A inhibit enteric cholinergic transmission in the guinea-pig ileum". Neurogastroenterology and Motility 18 (1): 69–75. doi:10.1111/j.1365-2982.2005.00725.x. PMID 16371085.
- Capasso R, Borrelli F, Zjawiony J, Kutrzeba L, Aviello G, Sarnelli G, Capasso F, Izzo AA (2007). "The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A reduce inflammation-induced hypermotility in mice". Neurogastroenterology and Motility 20 (2): 142–8. doi:10.1111/j.1365-2982.2007.00994.x. PMID 17931335.
- "Salvia divinorum". European Monitoring Centre for Drugs and Drug Addiction. Retrieved 4 September 2014.
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.
- Pichini S, Abanades S, Farré M, Pellegrini M, Marchei E, Pacifici R, Torre Rde L, Zuccaro P (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 19 (12): 1649–1656. doi:10.1002/rcm.1970. ISSN 1097-0231. PMID 15915477.
Salvinorin A was not detected in urine samples collected from 1.5–9.5 h after smoking, probably because of a dilution effect, which yielded concentrations below the LOD obtainable with this methodology.
- Bigham AK, Munro TA, Rizzacasa MA, Robins-Browne RM (2003). "Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage Salvia divinorum". Journal of Natural Produects 66 (9): 1242–4. doi:10.1021/np030313i. PMID 14510607.
- Munro TA, Rizzacasa MA (2003). "Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A". Journal of Naturla Products 66 (5): 703–5. doi:10.1021/np0205699. PMID 12762813.
- Kutrzeba L, Dayan FE, Howell J, Feng J, Giner JL, Zjawiony JK (2007). "Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway". Phytochemistry 68 (14): 1872–81. doi:10.1016/j.phytochem.2007.04.034. PMC 2065853. PMID 17574635.
- Siebert DJ (2004). "Localization of salvinorin A and related compounds in glandular trichomes of the psychoactive sage, Salvia divinorum". Annals of Botany 93 (6): 763–71. doi:10.1093/aob/mch089. PMID 15087301. "A peltate glandular trichome on the abaxial leaf surface", and "The fact that most of the salvinorin content of fresh leaves can be extracted into chloroform without the solvent penetrating the epidermis indicates that these compounds are secreted externally to the epidermis."
- Kunkle D (2007). "Leaf glandular trichome (Salvia divinorum)". Dennis Kunkel Microscopy, Inc. Retrieved 2011-10-14.
- Scheerer JR, Lawrence JF, Wang GC, Evans DA (2007). "Asymmetric synthesis of salvinorin A, a potent kappa opioid receptor agonist". Journal of the American Chemical Society 129 (29): 8968–9. doi:10.1021/ja073590a. PMID 17602636.
- Nozawa M, Suka Y, Hoshi T, Suzuki T, Hagiwara H (2008). "Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A". Organic Letters 10 (7): 1365–8. doi:10.1021/ol800101v. PMID 18311991.
- Burns AC, Forsyth CJ. (2008). "Intramolecular Diels−Alder/Tsuji allylation assembly of the functionalized trans-decalin of salvinorin A". Organic Letters 10 (1): 97–100. doi:10.1021/ol7024058. PMID 18062692.
- Lingham AR, Hügel HM, Rook TJ (2006). "Studies towards the synthesis of salvinorin A". Australian Journal of Chemistry 59 (5): 340–8. doi:10.1071/CH05338.
- White K, Robinson JE, Zhu H, et al. (2014). "The G-protein biased k-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo". J. Pharmacol. Exp. Ther. 352 (1): 98–109. doi:10.1124/jpet.114.216820. PMID 25320048.
- Kutrzeba L, Ferreira Z (2009). "Salvinorins J from Salvia divinorum: mutarotation in the neoclerodane system". Journal of Natural Products 72 (7): 1361–3. doi:10.1021/np900181q. PMID 19473009.
- Lee DY, Karnati VV, He M, Liu-Chen LY, Kondaveti L, Ma Z, Wang Y, Chen Y, Beguin C, Carlezon WA, Cohen B (2005). "Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues". Bioorganic & Medicinal Chemistry Letters 15 (16): 3744–7. doi:10.1016/j.bmcl.2005.05.048. PMID 15993589.
- Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, Cohen BM, Béguin C (2008). "Standard protecting groups create potent and selective κ opioids: salvinorin B alkoxymethyl ethers". Bioorganic & Medicinal Chemistry 16 (3): 1279–86. doi:10.1016/j.bmc.2007.10.067. PMC 2568987. PMID 17981041.
- Harding WW, Tidgewell K, Byrd N, Cobb H, Dersch CM, Butelman ER, Rothman RB, Prisinzano TE (2005). "Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands". Journal of Medicinal Chemistry 48 (15): 4765–71. doi:10.1021/jm048963m. PMID 16033256.
- Tidgewell K, Harding WW, Lozama A, Cobb H, Shah K, Kannan P, Dersch CM, Parrish D, Deschamps JR, Rothman RB, Prisinzano TE (2006). "Synthesis of salvinorin A analogues as opioid receptor probes". Journal of Natural Products 69 (6): 914–8. doi:10.1021/np060094b. PMID 16792410.
- Holden KG, Tidgewell K, Marquam A, Rothman RB, Navarro H, Prisinzano TE (2007). "Synthetic studies of neoclerodane diterpenes from Salvia divinorum: exploration of the 1-position". Bioorganic and Medicinal Chemistry Letters 17 (22): 6111–5. doi:10.1016/j.bmcl.2007.09.050. PMC 2111044. PMID 17904842.
- Lee DY, He M, Liu-Chen LY, Wang Y, Li JG, Xu W, Ma Z, Carlezon WA, Cohen B (2006). "Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A analogues". Bioorganic & Medicinal Chemistry Letters 16 (21): 5498–502. doi:10.1016/j.bmcl.2006.08.051. PMID 16945525.
- Béguin C, Richards MR, Li JG, Wang Y, Xu W, Liu-Chen LY, Carlezon WA, Cohen BM (2006). "Synthesis and in vitro evaluation of salvinorin A analogues: effect of configuration at C(2) and substitution at C(18)". Bioorganic & Medicinal Chemistry Letters 16 (17): 4679–85. doi:10.1016/j.bmcl.2006.05.093. PMID 16777411.
- A1 US 2007/0213394 A1, Beguin C, Carlezon WA, Cohen BM, He M, Lee D Y-W, Richards MR, Liu-Chen L-Y, "Salvinorin derivatives and uses thereof", published 2007-09-13, assigned to Temple University
- MacLean, K. A.; Johnson, M. W.; Reissig, C. J.; Prisinzano, T. E.; Griffiths, R. R. (2012). "Dose-related effects of salvinorin a in humans: Dissociative, hallucinogenic, and memory effects". Psychopharmacology 226 (2): 381–392. doi:10.1007/s00213-012-2912-9.
- Masis, Julie (2007-02-28). "Mexican drug gains U.S. following". Reuters. Archived from the original on 2007-05-28. Retrieved 2007-08-22.
- Prisinzano, Thomas; Kevin Tidgewell; Wayne W. Harding (2005). "k Opioids as potential treatments for stimulant dependence". The AAPS Journal (Springer New York) 7 (3): E592–E599. doi:10.1208/aapsj070361. ISSN 1550-7416. PMC 2751263. PMID 16353938.
- Xuei X, Dick D, Flury-Wetherill L, Tian HJ, Agrawal A, Bierut L, Goate A, Bucholz K, Schuckit M, Nurnberger J Jr, Tischfield J, Kuperman S, Porjesz B, Begleiter H, Foroud T, Edenberg HJ (November 2006). "Association of the kappa-opioid system with alcohol dependence". Molecular Psychiatry 11 (11): 1016–24. doi:10.1038/sj.mp.4001882. PMID 16924269.
- 21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I.
- Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534
- Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL
- Chavkin, Charles; Sud, Sumit; Jin, Wenzhen; Stewart, Jeremy; Zjawiony, Jordan K.; Siebert, Daniel J.; Toth, Beth Ann; Hufeisen, Sandra J.; Roth, Bryan L. (2004). "Salvinorin A, an active component of the hallucinogenic sage Salvia divinorum is a highly efficacious κ-opioid receptor agonist: structural and functional considerations". Journal of Pharmacology and Experimental Therapeutics 308 (3): 1197–203. doi:10.1124/jpet.103.059394. PMID 14718611. Retrieved 2007-03-24.
- Munro, Thomas A.; Rizzacasa, Mark A.; Roth, Bryan L.; Toth, Beth A.; Yan, Feng (January 2005). "Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist". Journal of Medicinal Chemistry 48 (2): 345–8. doi:10.1021/jm049438q. PMC 2777653. PMID 15658846.[dead link]
- Baselt, Randall C. (2008). "Disposition of Toxic Drugs and Chemicals in Man" (8th ed.). Foster City, CA: Biomedical Publications: 1405–6. ISBN 978-0- 9626523-7-0.
- Salvia divinorum (2007) – EMCDDA drugs profile
- The Salvia divinorum – Research and Information Center (Daniel Siebert)
- Salvia divinorum – Erowid vault
- Lycaeum Salvinorin A
- Tryptamind Salvinorin A Downloadable salvinorin extraction photos.