# Thujone

**Thujone** is a bicyclic monoterpene ketone (molecular formula C₁₀H₁₆O, CAS 546-80-5) that occurs as two epimers, α-thujone and β-thujone, in the essential oils of plants such as wormwood (*Artemisia absinthium*), garden sage (*Salvia officinalis*), tansy (*[Tanacetum vulgare](https://www.edgepedia.org/tansy)*), and white cedar (*Thuja occidentalis*).<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Thujone)</sup><sup> • </sup><sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> It is best known as the toxic constituent of wormwood oil and of the historical liqueur absinthe, and it acts on the nervous system as a blocker of the GABA-gated chloride channel.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup>

| Key fact | Detail |
|---|---|
| Identity | Monoterpene ketone, C₁₀H₁₆O, molecular weight 152.23 g/mol, boiling point 200–201 °C at 760 mm Hg<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Thujone)</sup> |
| Stereochemistry | Three chiral centers; α- and β-thujone are the two known natural epimers, each naturally occurring as a single enantiomer<sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8955314/)</sup> |
| Mechanism | α-Thujone is a noncompetitive blocker of the GABA-gated chloride channel (GABA<sub>A</sub> receptor), causing excitation and convulsions in a dose-dependent manner<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup><sup> • </sup><sup>[5](https://www.sciencedirect.com/science/article/pii/S0273230012002218)</sup> |
| Main metabolite | 7-hydroxy-α-thujone, formed rapidly by cytochrome P450 in liver microsomes, together with five minor metabolites<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup> |
| EU food limits | 10 mg/kg in alcoholic beverages (35 mg/kg for those produced from *Artemisia* species); 0.5 mg/kg in non-alcoholic *Artemisia* beverages; thujone may not be added as such to food<sup>[6](https://eur-lex.europa.eu/legal-content/en/ALL/?uri=CELEX%3A32008R1334)</sup> |
| US rule | *Artemisia* (wormwood) and *Thuja occidentalis* flavor materials must yield finished food that is thujone free<sup>[7](https://www.govinfo.gov/content/pkg/CFR-2022-title21-vol3/pdf/CFR-2022-title21-vol3-chapI-subchapB.pdf)</sup> |
| Historical dose | Total thujone in analyzed pre-ban absinthe ranged from 0.5 to 48.3 mg/L, far below the long-cited 260 mg/L estimate<sup>[8](https://pubmed.ncbi.nlm.nih.gov/18419128/)</sup> |

## Chemistry and stereochemistry

Thujone is a ketone built on the thujane skeleton, a bicyclo[3.1.0]hexane ring system bearing a methyl group and an isopropyl group; the IUPAC name of the natural enantiomer is (1S,4R,5R)-4-methyl-1-(propan-2-yl)bicyclo[3.1.0]hexan-3-one.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Thujone)</sup><sup> • </sup><sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> The molecule has three chiral centers, and the two natural epimers differ in configuration at one of them: α-thujone (3-thujone) and β-thujone (3-isothujone).<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup><sup> • </sup><sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8955314/)</sup> [Biosynthesis](https://www.edgepedia.org/biosynthesis) produces only one enantiomer of each epimer, although more stereoisomers are possible in the laboratory; the naturally occurring forms are (−)-α-thujone and (+)-β-thujone, and the mirror-image forms (+)-α-thujone and (−)-β-thujone are also known.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup><sup> • </sup><sup>[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8955314/)</sup>

The biosynthetic route starts from the general monoterpene precursor geranyl diphosphate (GPP) and proceeds through a four-step pathway whose first committed product is sabinene, formed by the enzyme sabinene-synthase.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> [Sabinene](https://www.edgepedia.org/sabinene) has been demonstrated to be the precursor of thujone in wormwood, tansy, and sage.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> The pathway has been studied in detail mainly in two species, *Salvia officinalis* and *Thuja plicata*, both of which accumulate mainly α-thujone.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup>

## Occurrence in plants

Thujone occurs in nature as a mixture of the α- and β-isomers, and its content varies widely with species, chemotype, plant organ, and developmental stage.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC1062158/)</sup><sup> • </sup><sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> In *Thuja occidentalis* (arbor vitae, white cedar), thujone is characteristically the dominant component of the essential oil, which makes up 1.4–4% of the dried herb; thujone accounts for 0.76–2.4% of that oil, 85% of it α-thujone, and dried twigs were determined to contain 7.6 mg/g of thujone.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC1062158/)</sup>

**Sage and wormwood** show much larger intraspecific variability. In wormwood, the proportions of α- and β-thujone in the oil reached their highest values (66.8% and 25.4%, respectively) at the floral budding stage and decreased after flowering, and different populations range from α-thujone-dominant to β-thujone-dominant chemotypes.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> In sage, total thujone content of the oil has been classified into high (39–44%), medium (22–28%), and low (about 9%) groups, with α/β ratios ranging from 10:1 to 1:10.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup> Tansy shows more than 40 chemotypes, many of them without thujones at all.<sup>[2](https://doi.org/10.1007/s11101-020-09671-y)</sup>

## Mechanism of toxicity

α-Thujone is a rapidly acting convulsant. A 2000 study by K. M. Höld and colleagues at the [University of California](https://www.edgepedia.org/university-of-california), Berkeley established four lines of evidence that it modulates the γ-aminobutyric acid type A (GABA<sub>A</sub>) receptor, the principal inhibitory chloride channel of the mammalian brain: its poisoning signs in mice resemble those of the classical antagonist picrotoxinin and are alleviated by diazepam and phenobarbital; a *Drosophila* strain resistant to chloride-channel blockers is also tolerant to α-thujone; it competitively inhibits binding of [<sup>3</sup>H]ethynylbicycloorthobenzoate to mouse brain membranes; and it reversibly suppresses GABA-induced currents in rat dorsal root ganglion neurons.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup> In other words, thujone blocks inhibitory signaling, which explains the excitation and convulsions seen at toxic doses.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup><sup> • </sup><sup>[5](https://www.sciencedirect.com/science/article/pii/S0273230012002218)</sup>

The two isomers differ in potency. β-Thujone is less toxic than α-thujone to mice and *Drosophila* and is 2.3-fold less potent in the binding assay.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup> Later work on recombinant receptors showed that α-thujone inhibits several GABA<sub>A</sub> receptor subtypes by a similar mechanism, with the strongest effect on α1β2δ receptors, suggesting that tonic GABAergic inhibition is more sensitive to the compound than phasic inhibition.<sup>[10](https://pubmed.ncbi.nlm.nih.gov/23376563/)</sup>

## Metabolism

Thujone is metabolized quickly. In mouse liver microsomes with NADPH, the cytochrome P450 system converts α-thujone mainly to 7-hydroxy-α-thujone, plus five minor products (4-hydroxy-α-thujone, 4-hydroxy-β-thujone, two other hydroxythujones, and 7,8-dehydro-α-thujone).<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup> All metabolites assayed are detoxification products: α-thujone is 56-fold more potent than its 7-hydroxy metabolite in the binding assay and much more toxic to mice and houseflies.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup> Human liver microsomes produce 7-hydroxy- and 4-hydroxythujone as major metabolites.<sup>[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC6315428/)</sup>

Human in vivo data come from a sage-tea study in which volunteers drank 900 mL of an infusion containing 0.64 mg/L α-thujone, individual doses of 4.6–14.3 µg/kg body weight. α-Thujone and its hydroxylated metabolites were excreted in urine within 8 hours by almost all volunteers; over 24 hours only 3.3–7.1% of the dose was recovered as the parent compound plus hydroxy metabolites, with 4-hydroxythujone the major excreted isomer for most volunteers.<sup>[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC6315428/)</sup> The authors concluded that fast metabolism keeps the potentially toxic parent compound in the body only briefly.<sup>[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC6315428/)</sup>

## Absinthe and the absinthism question

Absinthe, a wormwood-flavored liqueur popular in the 19th and early 20th centuries, was long believed to cause a distinct syndrome, "absinthism", marked by hallucinations, seizures, and sleep disorder, and α-thujone was identified as its toxic agent.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)</sup><sup> • </sup><sup>[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC1475830/)</sup> The scientific background to the anti-absinthe campaign rested largely on the experimental work of the French physician Valentin Magnan in the 1870s, which modern knowledge of thujone content has called into question.<sup>[13](https://pubmed.ncbi.nlm.nih.gov/19831287/)</sup>

Chemical analysis of surviving bottles revised the historical record. Thirteen authentic pre-ban (before 1915) absinthes contained total thujone between 0.5 and 48.3 mg/L, with an average of 25.4 ± 20.3 mg/L and a median of 33.3 mg/L, and the authors concluded that the thujone concentration of pre-ban absinthe was generally overestimated in the past.<sup>[8](https://pubmed.ncbi.nlm.nih.gov/18419128/)</sup> The long-cited figure of about 260 mg/L cannot be confirmed by these analyses.<sup>[8](https://pubmed.ncbi.nlm.nih.gov/18419128/)</sup> Absinthes produced according to historic recipes contained only low concentrations (mean 1.3 ± 1.6 mg/L, range 0–4.3 mg/L), 50 to 100 times below the no-observed-effect level for convulsions determined in animal experiments, and nothing besides ethanol was found in the analyzed absinthes that could explain the syndrome.<sup>[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC1475830/)</sup><sup> • </sup><sup>[8](https://pubmed.ncbi.nlm.nih.gov/18419128/)</sup> Consistent with this, in a pilot drinking study two subjects consumed 110 mL of absinthe containing 3.85 mg thujone; blood alcohol exceeded 1 g/L while no thujone was detectable in blood (detection limit 0.34 ng/mL), and the subjects showed only typical signs of alcohol effects.<sup>[14](https://www.ema.europa.eu/en/documents/scientific-guideline/public-statement-use-herbal-medicinal-products-containing-thujone-revision-1_en.pdf)</sup>

## Regulation

Because thujone is potentially toxic, its presence in food and beverages is regulated in several countries.<sup>[15](https://www.fda.gov/media/165441/download)</sup> In the European Union, Regulation (EC) No 1334/2008 lists thujone (alpha and beta) among substances that shall not be added as such to food, while setting maximum levels for thujone naturally present in flavoring ingredients: 10 mg/kg in alcoholic beverages except those produced from *Artemisia* species, 35 mg/kg in *Artemisia* alcoholic beverages, and 0.5 mg/kg in non-alcoholic *Artemisia* beverages.<sup>[6](https://eur-lex.europa.eu/legal-content/en/ALL/?uri=CELEX%3A32008R1334)</sup> In the United States, thujone is not authorized as a flavoring substance, and 21 CFR 172.510 requires that foods flavored with *Artemisia* (wormwood) or white cedar (*Thuja occidentalis*) be finished-food thujone free.<sup>[7](https://www.govinfo.gov/content/pkg/CFR-2022-title21-vol3/pdf/CFR-2022-title21-vol3-chapI-subchapB.pdf)</sup><sup> • </sup><sup>[16](https://www.govinfo.gov/content/pkg/CFR-2020-title21-vol3/pdf/CFR-2020-title21-vol3-part172-subpartF.pdf)</sup>

The Joint FAO/WHO Expert Committee on Food Additives evaluated thujone in 1981, allocated no ADI, and recommended that amounts of thujone isomers in foods and beverages from thujone-containing flavoring agents such as sage be reduced to the lowest practicable level.<sup>[17](https://inchem.org/documents/jecfa/jecmono/v16je25.htm)</sup> The Council of Europe derived a tolerable daily intake of 10 µg/kg body weight per day from a no-observed-effect level of 5 mg/kg body weight for convulsions in the female rat, dosed 6 days per week for 14 weeks, with a 500-fold safety factor.<sup>[5](https://www.sciencedirect.com/science/article/pii/S0273230012002218)</sup> For herbal medicinal products, the [European Medicines Agency](https://www.edgepedia.org/european-medicines-agency)'s Committee on Herbal Medicinal Products adopted a public statement (EMA/HMPC/732886/2010 Rev.1, first published 2012) that describes the chemical, toxicological, pharmacological, and pharmacokinetic properties of thujone and recommends maximum daily intakes from such products.<sup>[14](https://www.ema.europa.eu/en/documents/scientific-guideline/public-statement-use-herbal-medicinal-products-containing-thujone-revision-1_en.pdf)</sup> The International Fragrance Association also restricts thujone as a fragrance ingredient, with neurotoxicity identified as the intrinsic property driving the restriction.<sup>[1](https://pubchem.ncbi.nlm.nih.gov/compound/Thujone)</sup>

## References

1. [Thujone, C10H16O, CID 261491, PubChem](https://pubchem.ncbi.nlm.nih.gov/compound/Thujone)
2. [Németh & Balogh (2020). Thujone, a widely debated volatile compound: What do we know about it? Phytochemistry Reviews](https://doi.org/10.1007/s11101-020-09671-y)
3. [Höld et al. (2000). α-Thujone (the active component of absinthe): GABA type A receptor modulation and metabolic detoxification. PNAS](https://pmc.ncbi.nlm.nih.gov/articles/PMC18101/)
4. [Fundamental Chemistry of Essential Oils and Volatile Organic Compounds, Methods of Analysis and Authentication (2022)](https://pmc.ncbi.nlm.nih.gov/articles/PMC8955314/)
5. [Thujone and thujone-containing herbal medicinal and botanical products: Toxicological assessment (2012)](https://www.sciencedirect.com/science/article/pii/S0273230012002218)
6. [Regulation (EC) No 1334/2008 on flavourings, EUR-Lex](https://eur-lex.europa.eu/legal-content/en/ALL/?uri=CELEX%3A32008R1334)
7. [21 CFR 172.510, Flavoring substances and adjuvants (2022 edition), GovInfo](https://www.govinfo.gov/content/pkg/CFR-2022-title21-vol3/pdf/CFR-2022-title21-vol3-chapI-subchapB.pdf)
8. [Lachenmeier et al. (2008). Chemical composition of vintage preban absinthe. J. Agric. Food Chem.](https://pubmed.ncbi.nlm.nih.gov/18419128/)
9. [Thuja occidentalis (Arbor vitae): A Review of its Pharmaceutical, Pharmacological and Clinical Properties](https://pmc.ncbi.nlm.nih.gov/articles/PMC1062158/)
10. [Czyzewska & Mozrzymas (2013). Monoterpene α-thujone exerts a differential inhibitory action on GABA(A) receptors. Eur. J. Pharmacol.](https://pubmed.ncbi.nlm.nih.gov/23376563/)
11. [Quantification of α-Thujone and Its Metabolites in Human Urine after Consumption of a Sage Infusion (2019)](https://pmc.ncbi.nlm.nih.gov/articles/PMC6315428/)
12. [Lachenmeier et al. (2006). Absinthism: a fictitious 19th century syndrome with present impact](https://pmc.ncbi.nlm.nih.gov/articles/PMC1475830/)
13. [Absinthe, epileptic seizures and Valentin Magnan (2009)](https://pubmed.ncbi.nlm.nih.gov/19831287/)
14. [EMA/HMPC Public statement on the use of herbal medicinal products containing thujone, Revision 1 (2012)](https://www.ema.europa.eu/en/documents/scientific-guideline/public-statement-use-herbal-medicinal-products-containing-thujone-revision-1_en.pdf)
15. [FDA document on thujone regulation in food and beverages](https://www.fda.gov/media/165441/download)
16. [21 CFR Part 172 Subpart F (2020 edition), GovInfo](https://www.govinfo.gov/content/pkg/CFR-2020-title21-vol3/pdf/CFR-2020-title21-vol3-part172-subpartF.pdf)
17. [JECFA 519. Thujone, WHO Food Additives Series 16 (1981)](https://inchem.org/documents/jecfa/jecmono/v16je25.htm)

---
*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Carbonyl and carboxyl chemistry › Aldehydes and ketones › Ketones › Natural-product, fragrance, and flavor ketones*

*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 15, 2026 · Edited: Oct 15, 2026 · Last review: Oct 15, 2026*

*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*

License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license