Salvinorin A

Effects

Overview

Salvinorin A is the main active psychoactive molecule within Salvia Divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans. It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psilocin and mescaline) because it contains no nitrogen atoms, making it a terpenoid and not an alkaloid as is the norm. This means it cannot be rendered as a salt. PW

Salvinorin A is a κ-opioid receptor agonist and hallucinogen and is the main active constituent in Salvia divinorum (also known as diviner's sage, ska maría pastora, or simply salvia). It is usually taken via inhalation such as smoking or via oral administration.[1–4] WP

The drug is structurally distinct from other naturally occurring hallucinogens (such as dimethyltryptamine (DMT), psilocybin, ergine (LSA), and mescaline), for instance containing no nitrogen atoms; hence, it is not an alkaloid (and cannot be rendered as a salt), but rather is a terpenoid. It also differs in subjective experience, compared to other hallucinogens, and has been described as having strong dissociative-esque effects.[3][4] WP

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 route of administration.[5] WP

Salvinorin A is found with several other structurally related salvinorins. Salvinorin is a trans-neoclerodane diterpenoid. It is the first known compound acting as a κ-opioid receptor agonist that is not an alkaloid.[5] WP

History

History

Salvia divinorum has been used as an entheogen by the Mazatec people of Mexico for hundreds of years. The American anthropologist Jean Bassett Johnson made expeditions to Mexico in the mid-to-late 1930s, observed the entheogenic use of Salvia divinorum by the Mazatecs there, and was the first to describe the existence of the plant in 1939. Subsequently, other researchers, including Blas Pablo Reko and Robert J. Weitlaner, also described the plant and its use in the 1940s and 1950s. Arturo Gómez-Pompa classified the plant as belonging to the genus Salvia in 1957, but was unable to completely identify it at the time due to absence of flowering material. Finally, Robert Gordon Wasson and Albert Hofmann collected flowering specimens of the plant in the early 1960s and sent them to Carl Epling, the leading expert on the Salvia genus of the time, who defined the plant as a new species named Salvia divinorum in 1962.[1][6–12] WP

Salvinorin A was isolated from Salvia divinorum and identified by Alfredo Ortega and colleagues in 1982. 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 doctoral research, published in 1983. Valdés named the chemical divinorin, and also isolated an analogue that he named divinorin B. The naming was subsequently changed to salvinorin A and salvinorin B after the work was published in 1984. Valdés later isolated salvinorin C as well. Daniel Siebert identified salvinorin A as the active constituent of Salvia divinorum via self-experimentation in 1993 and published these findings in 1994. Jonathan Ott published a paper on use of salvinorin A by various means and its effects in 1995. D. M. Turner published his book Salvinorin: The Psychedelic Essence of Salvia Divinorum, further describing salvinorin A's hallucinogenic effects in humans, in 1996.[1][6][13–19] WP⚠ A word may be missing here. It reads this way in the source too.

Salvinorin A was identified as a highly selective and potent κ-opioid receptor (KOR) agonist by Bryan L. Roth and colleagues in 2002. Dennis McKenna has shared that he identified salvinorin A as an extremely high-affinity KOR ligand while working at Shaman Pharmaceuticals in the early 1990s, but did not publish his findings as he could not believe how potent it was and thought that his results were erroneous. Roland Griffiths and colleagues and other researchers characterized the effects of salvinorin A in humans in formal clinical studies in the 2010s. Griffiths and colleagues further showed that salvinorin A's hallucinogenic and other effects in humans were blocked by the KOR antagonist naltrexone in 2016.[1][4][5][6][20–28] WP⚠ A word may be missing here. It reads this way in the source too.

Legal status

• Australia: Salvinorin A is illegal to possess and sell in Australia. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Austria: Salvinorin A is illegal to possess, produce and sell under the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich). PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Belgium: Salvinorin A is illegal to possess and sell in Belgium. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Croatia: Salvinorin A is illegal to possess and sell in Croatia. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Czech Republic: Salvinorin A is illegal to possess and sell in Czech Republic. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Canada: Salvia divinorum and its preparations and derivatives (including Salvinorin A) are schedule IV in Canada.[29] PW
• Denmark: Salvinorin A is a Class B drug in Denmark. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Germany: Salvinorin A is not controlled in Germany, however Salvia Divinorum was added to BtMG Anlage I, making it illegal to grow, import, possess, sell, or transfer it as of March 1, 2008[30] PW
• Ireland: Salvinorin A is illegal to possess and sell in Ireland. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Italy: Salvinorin A is illegal to possess and sell in Italy. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Latvia: Salvinorin A is illegal to possess and sell in Latvia. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Lithuania: Salvinorin A is illegal to possess and sell in Lithuania. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• New Zealand: Salvinorin A is illegal to possess and sell in New Zealand. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Poland: Salvinorin A is illegal to possess and sell in Poland. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Romania: Salvinorin A is illegal to possess and sell in Romania. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Spain: Salvinorin A is illegal to possess and sell in Spain. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Sweden: Salvinorin A is illegal to possess and sell in Sweden. PW⚠ PsychonautWiki itself has flagged this text: citation needed.
• Switzerland: Salvia divinorum as well as Salvinorin A are controlled substances specifically named under Verzeichnis D.[31] PW
• United Kingdom: Salvia is legal to produce, supply, or import if sold not for human consumption under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[32][33] PW
• United States: Salvinorin A is illegal in certain states. PW⚠ PsychonautWiki itself has flagged this text: citation needed.

Legal status

Salvinorin A is sometimes regulated together with its host, Salvia divinorum, due to its psychoactive and analgesic effects. WP

United states

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 Analogue Act.[34][35] WP

Florida

"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."[36] WP

Australia

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.[37] WP

Sweden

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 April 1, 2006, in their regulation SFS 2006:167 listed as "salvinorin A", making it illegal to sell or possess.[38] WP

Salvinorin A has been screened for its possible use as a structural "scaffold" in medicinal chemistry in developing new drugs for treating psychiatric diseases such as cocaine dependence.[3][39][40] WP

Pharmacology

Pharmacodynamics

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 shows atypical properties as an agonist of the KOR relative to other KOR agonists. In addition to its KOR agonism, salvinorin A has been found to act as a dopamine D₂ receptor partial agonist, with an affinity of 5–10 nM, an intrinsic activity of 40–60%, and an EC₅₀ of 48 nM. As such, the dopamine D₂ receptor might also play a role in its effects.[41–44] WP

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. Salvinorin A has also been shown to have effect on cannabinoid CB1 receptors. It significantly increases prolactin and inconsistently increases cortisol. It causes dysphoria by stopping release of dopamine in the striatum. Salvinorin A increases activity of DAT while decreasing activity of SERT.[5][45–48] WP

Salvinorin A is capable of inhibiting excess intestinal motility (e.g. diarrhea), through its potent κ-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.[49][50] WP

Pharmacokinetics

Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of administration must be used for better absorption. It is absorbed by oral mucosa. It has a half-life of around 8 minutes in non-human primates.[17][51] WP

Chemistry

Formula

C23H28O8 PC

CAS number

83729-01-5 PC

Molar mass (g/mol)

432.5 PC

IUPAC name (computed by PubChem)

methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate PC

SMILES

CC(=O)O[C@H]1C[C@H]([C@@]2(CC[C@H]3C(=O)O[C@@H](C[C@@]3([C@H]2C1=O)C)C4=COC=C4)C)C(=O)OC PC

InChIKey

OBSYBRPAKCASQB-AGQYDFLVSA-N PC

PubChem CID

128563

Pop culture

No references added yet.

References

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2. Journal / agency Doss MK, May DG, Johnson, MW. The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain. Scientific Reports. 2020. doi:10.1038/s41598-020-73216-8 · PMID 33009457 · PMC7532139
3. Journal / agency Butelman ER, Kreek MJ. Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders. Frontiers in Pharmacology. 2015. doi:10.3389/fphar.2015.00190 · PMID 26441647 · PMC4561799
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5. Journal / agency Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB. Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences of the United States of America. September 2002. doi:10.1073/pnas.182234399 · PMID 12192085 · PMC129372
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29. Other Branch, L. S. Consolidated federal laws of Canada, Controlled Drugs and Substances Act. 2022
30. Other 21. BtMÄndV Einundzwanzigste Betäubungsmittelrechts-Änderungsverordnung
31. Other Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien
32. Other Psychoactive Substances Act 2016
33. Wikipedia Legal status of Salvia divinorum. 2022
34. Other 21 CFR — Schedules of Controlled Substances §1308.11 Schedule I
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36. Other Statutes & Constitution:View Statutes: Online Sunshine
37. Other Poisons Standard. October 2015
38. Other Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor. 2006
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