Salvinorin A
methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-dodecahydro-2H-naphtho[2,1-c]pyran-7-carboxylate
Overview
Salvinorin A belongs to Psychedelics.
Effects
- A brief, extremely intense and disorienting hallucinogenic state: often strongly dissociative: depersonalisation, a sense of merging with or becoming objects, contact with entities, and revisiting places or memories, with frequent loss of awareness of the real environment.
- The character is usually described as alien and unsettling rather than pleasurable. Dysphoria, fear, confusion and uncontrollable movement or laughter are common, and recall/recognition memory is temporarily impaired.
- When smoked, onset is almost immediate (<30 s), effects peak at ≈1–2 minutes and largely resolve within ≈20–30 minutes. The buccal/sublingual route is slower (onset 10–15 min) and lasts about an hour.
- Physical effects can include incoordination, dizziness, sweating and a heavy, sedated body feeling.
Dosing & duration
Smoked / vaporised, Buccal / sublingual (quid). Not a recommendation. Salvinorin A is one of the most potent naturally occurring psychoactives and is dosed in micrograms: the figures below are for pure, smoked salvinorin A and are extremely sensitive to small changes. It is orally inactive (destroyed in the gut), so it is smoked/vaporised or held in the mouth. The buccal route needs substantially more. Plant leaf and '×5/×10/×20' standardised extracts vary enormously in potency and are far harder to gauge.
Dose ranges
≈100–200 µg (smoked)
≈200–750 µg (smoked pure)
≈0.75–2 mg (smoked)
Duration
<30 s (smoked), 10–15 min (buccal)
≈1–2 min (smoked)
≈20–30 min (smoked), ≈1 h (buccal)
Chemical & Physical Properties
| Formula | C23H28O8 |
| Molar mass | 432.46 g/mol |
| State | Solid |
| Melting point | 238–240 °C, also reported as 242–244 °C |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | Not reported |
| LogP | 2.5 (predicted, XLogP3) |
| Solubility | Soluble in ethanol and acetone. Poorly soluble in water (~25 mg/L) |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 83729-01-5 |
| CAS (enantiomer) | |
| PubChem CID | 128563 |
| InChIKey | OBSYBRPAKCASQB-AGQYDFLVSA-N |
| InChI | InChI=1S/C23H28O8/c1-12(24)30-16-9-15(20(26)28-4)22(2)7-5-14-21(27)31-17(13-6-8-29-11-13)10-23(14,3)19(22)18(16)25/h6,8,11,14-17,19H,5,7,9-10H2,1-4H3/t14-,15-,16-,17-,19-,22-,23-/m0/s1 |
| 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 |
Synonyms
- Salvinorin A
- Active principle of Salvia divinorum
- Sally-D
Pharmacodynamics & Biochemistry
Salvinorin A is the main active constituent of the sage Salvia divinorum and is pharmacologically unique: a highly potent, highly selective full agonist at the κ-opioid receptor (KOR, Kᵢ ≈2.4 nM, EC50 ≈1.8 nM). It is the first known KOR agonist that is not an alkaloid: a trans-neoclerodane diterpenoid containing no nitrogen atom, so it cannot form a salt. Crucially, it has no activity at the 5-HT2A receptor, the target of 'classical' serotonergic psychedelics such as LSD, psilocin and mescaline, so its hallucinogenic effect is mechanistically distinct. Its effects in humans are blocked by the opioid antagonist naltrexone but not by the 5-HT2A antagonist ketanserin, confirming the KOR mechanism. It is additionally a dopamine D2 partial agonist (affinity ~5–10 nM, ~40–60% intrinsic activity) and has some cannabinoid CB1 activity, and it modulates the dopamine and serotonin transporters. KOR-driven suppression of striatal dopamine release underlies its characteristic dysphoria.
Biological targets
- KOR
- D2
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| κ receptor | Ki 2.4 nM | Human |
| D2 | Ki 5.0 nM | Human |
Pharmacokinetics
| Bioavailability | Orally inactive (degraded in the GI tract), absorbed via oral mucosa or lungs. Plasma protein binding ≈83% |
| Tmax | Smoked: onset <30 s, peak ≈1–2 min, buccal: onset 10–15 min |
| Half-life | ≈50 min (human plasma, ≈8 min in non-human primates): subjective effects much shorter |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Ester hydrolysis (esterases/CYP450) to inactive salvinorin B. Delactonation. Glucuronidation (UGT2B7) to salvinorin A glucuronide |
| Excretion | Urine and bile |
Toxicology & Safety
Not reported
Salvinorin A is extraordinarily potent (active from ~200 µg smoked) and produces brief but overwhelming, disorienting effects, a hallmark being complete loss of awareness of one's real surroundings, so the dominant hazard is behavioural: falls, burns (from the smoking implement) and injury during the peak. Unlike serotonergic psychedelics the experience is frequently dysphoric, frightening or unpleasant rather than euphoric, reflecting its κ-opioid pharmacology (sedation, dysphoria, anhedonia, psychotomimesis). Physiological toxicity appears low and no lethal dose is established, but a sober sitter and a safe, hazard-free setting are essential. Limited human data must never be read as evidence of safety.[3][5]
Legal Status
US: Not federally scheduled. UK: Controlled (PSA 2016). DE: Not scheduled (plant listed)
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- Traditional entheogenic and healing use of Salvia divinorum leaves by the Mazatec people of Oaxaca, Mexico: chewed as a quid or drunk as a crushed-leaf infusion.
- Modern recreational and psychonautic use, usually of dried leaf or standardised extracts smoked for the short, intense effect. Deterred for many by its dysphoric character.
- A significant research tool as the prototypical non-alkaloid, highly selective κ-opioid agonist, used to probe KOR pharmacology and dissociation.
Sources & Evidence
- PubChem: Salvinorin A (CID 128563) — identifiers & experimental properties
- IUPHAR/BPS Guide to PHARMACOLOGY: salvinorin A (ligand 1666) — κ-opioid full agonist CC BY-SA 4.0
- Wikipedia: Salvinorin A — pharmacology, effects, dosing, pharmacokinetics & legal status CC BY-SA 4.0
- Roth BL, Baner K, Westkaemper R, et al. (2002). Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc Natl Acad Sci U S A 99:11934-9.
PMID 12192085 · doi:10.1073/pnas.182234399
- Cunningham CW, Rothman RB, Prisinzano TE (2011). Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacol Rev 63:316-47.
PMID 21444610 · doi:10.1124/pr.110.003244
- EMCDDA: Salvia divinorum drug profile (legal status & effects)
- GOV.UK: Psychoactive Substances Act 2016 (UK control of salvia/salvinorin A) OGL v3.0
- Béguin C, Richards MR, Wang Y, et al. (2005). Synthesis and in vitro pharmacological evaluation of salvinorin A analogues modified at C(2). Bioorg Med Chem Lett 15:2761-5.
PMID 15869877 · doi:10.1016/j.bmcl.2005.03.113