Thujone: A Visit from the Green Fairy

Published in the March 2026 issue of Clinical & Forensic Toxicology News

Introduction

Thujone is a monoterpene ketone consisting of 2 isomers, α- and β-thujone. It is most associated with the spirit absinthe, an herbal liqueur that was very popular in Europe during the late 19th century. The botanical components of absinthe include fennel, green anise, hyssop, lemon balm, and wormwood (Artemisia absinthium) – the source of thujone found in the beverage. Thujone is also found in many other plant species throughout the world, such as sage, oregano, tansy, and juniper species. The term “green fairy” became associated with absinthe because of its emerald-green color and anecdotes of absinthe consumption leading to hallucinogenic experiences, which were purported to expand the consumer’s consciousness and inspire creativity.

Historical and cultural context

The origins of wormwood consumption by humans are documented as far back as 1552 B.C. in Egyptian papyrus, and it is also mentioned in the Old Testament and Shakespeare. Its described usage is quite varied, from treatment of menstrual cramps to exploiting its bitter taste to wean babies from breastfeeding. But, its namesake comes from anthelmintic properties recognized by the Egyptians, and it was used to treat parasitic afflictions. The creation of classical absinthe containing wormwood is attributed to French physician Pierre Ordinaire, ca. 1789, and commercial production is associated with Henri-Louis Pernod around 1797. The high-proof spirit (45 – 75% ABV) began to gain popularity at the turn of the 19th century and outpaced production of red wine in France (1). It was a drink that transcended all social classes, was present in numerous bars and cafes, and became associated with creative professions like artists, poets, writers, and intellectuals.

Legal status and regulation

As consumption of absinthe increased, violent crimes were attributed to the potent spirit, and the temperance movement had placed absinthe in its focus (1). Notably, wine producers were among those backing the temperance movement against absinthe, seemingly lobbying against their own interests as producers of alcohol, but the apparent intent was to slander absinthe due to its displacement of wine as the beverage of choice. What followed were anecdotes and speculation about the evils of absinthe and its role in eliciting unruly and criminal behavior; however, little attention was paid to the fact that excessive consumption of alcohol from any source (including wine) can be dangerous both physically and socially (2). Belgium became the first country to ban absinthe in 1905, followed by Switzerland in 1908, then the United States in 1912, Italy in 1913, France in 1915, and then Germany in 1923. Since then, absinthe has been reinstated in the marketplace after legalization was enacted through European Union legislation passed in 1988, and bans were lifted in the United States and France in 2007 and 2011, respectively.

The European Union has placed limits on the amount of thujone from 0.5 mg/kg to 35 mg/kg depending on the type of food/drink being prepared. The United States Food and Drug Administration (FDA) has ruled that “thujone-free” is less than 10 mg/kg and is applied specifically to distilled spirits labelled as absinthe. Notably, the regulation of thujone is limited only to its usage in food and beverages, as wormwood oils containing 30-50% thujone are readily available for purchase online. In the US, there are no regulations specific to thujone regarding products made with sage or sage oil, which can contain anywhere from 20 – 50% thujone and are listed as Generally Recognized as Safe (GRAS) by the FDA.

Pharmacology and toxicology

Mechanism of action

In addition to its antiparasitic properties, thujone is recognized as a convulsant, and chronic users of absinthe were said to suffer from seizures, sleep disorders, mental collapse, and hallucinations. This constellation of symptoms was historically referred to as absinthism. Research has shown thujone’s mechanism of action is through inhibitory modulation of the γ-aminobutyric acid type A receptor (GABA_A) (3). Activation of the GABA_A receptor generally results in anxiolytic, anticonvulsant, sedative, hypnotic, and euphoric presentations; thus, a known convulsant like thujone is a likely candidate for a GABA_A antagonist. Measurements of GABA-induced chloride currents measured in whole neurons were suppressed when exposed to a-thujone and were restored when thujone was removed, indicating its modulation is reversible. When compared with the classical GABA_A receptor antagonist, picrotoxin, many similarities exist, such as the protective effect provided by other agonists of GABA_A, like diazepam and phenobarbital. The LD50 of α-thujone in mice is reported as 45 mg/kg, with those receiving 60 mg/kg doses reaching 100% mortality within one minute.

Metabolism and biotransformation

Investigations into a metabolic profile have indicated that primary detoxification occurs via the cytochrome P450 system and produces two major metabolites, 7- and 4-OH-thujone, along with the minor metabolite 2-OH-thujone (3–5). Evidence suggests that thujone undergoes phase II metabolism via conjugation with glucuronide and/or sulphate (4, 6). Interestingly, one study indicated the detection of glutathione and cysteine conjugates, but did not detect glucuronide or sulphate conjugates (5).

Human case reports and analytical detection

Since amounts of thujone in foodstuffs are regulated in many parts of the world, instances of adverse events related to the much-maligned terpene are relatively few. In 1997, the New England Journal of Medicine reported a case of a man who had ingested 10 mL of oil of wormwood ordered on the internet, thinking it was absinthe (7). He had a series of seizures when found by paramedics, and it was unknown how many subsequent convulsant events he sustained. At the hospital, he developed acute renal failure attributed to rhabdomyolysis induced by the seizures. He was hospitalized for 8 days. A 7-month-old child was given homeopathic oil of the thuja plant (Arborvitae) for the purpose of inducing calm during an immunization series. The child had a series of eight seizures that resolved after discontinuation of thuja administration and treatment with phenobarbital (8). A 49-year-old man was admitted to the hospital in a manic state resulting from his 3-year daily habit of consuming a liter of an infusion made from the mugwort plant (Artemisia vulgaris), a close relative of wormwood. The laboratory developed a method using HPLC and fluorescence to detect total thujone in serum after a liquid-liquid extraction and applied the same approach to urine. Testing revealed the presence of thujone in the patient’s serum at 27.7 and 24.1 µg/mL on Day 0 and Day 1, respectively. Analysis of the patient’s urine was negative for parent thujone (9).

The analysis was repeated with a previously published method utilizing GC-FID for detection in human serum (10). Unlike the LC assay, the GC method was able to distinguish between α- and β-thujone, but agreement for total thujone was observed between the two methods, 27.7 µg/mL via HPLC and 22.3 µg/mL via GC (α = 18.9 µg/mL and β = 3.4 µg/mL). Another study developed a sensitive LC-MS/MS method with extracted urine to detect thujone metabolites 2-OH-thujone, 4-OH-thujone, and 7-OH-thujone (6). Human subjects were given a sage infusion to drink and submitted urine samples for analysis. In all samples, the authors detected both 4- and 7-OH-thujone, along with α-thujone; 2-OH-thujone was not detected in any sample.

Conclusion

While the toxicity of thujone is real, its relevance in modern culture is largely relegated to its mythology and the malignment of absinthe during the late 19th century. Although regulations exist regarding its usage/occurrence in foodstuffs, the same protections do not extend to non-food products such as “essential” oils and tinctures made from thujone-containing plant species. While examples of documented thujone toxicity are sparse, products containing high concentrations of thujone do exist in the marketplace, and misuse could result in a medical emergency for the unsuspecting user.

References

1. Padosch SA, Lachenmeier DW, Kröner LU. Absinthism: a fictitious 19th century syndrome with present impact. Subst Abuse Treat Prev Policy 2006;1:14.
2. Adams J. Hideous Absinthe: A History of the Devil in a Bottle. University of Wisconsin Press; 2004.
3. Höld KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE. α-Thujone (the active component of absinthe): γ-Aminobutyric acid type A receptor modulation and metabolic detoxification. Proc Natl Acad Sci USA 2000;97:3826- 31.
4. Höld KM, Sirisoma NS, Casida JE. Detoxification of alpha- and beta-Thujones (the active ingredients of absinthe): site specificity and species differences in cytochrome P450 oxidation in vitro and in vivo. Chem Res Toxicol 2001;14:589- 95.
5. Abass K, Reponen P, Mattila S, Pelkonen O. Metabolism of a-thujone in human hepatic preparations in vitro. Xenobiotica 2011;41:101-11.
6. Thamm I, Tiefenbacher K, Rychlik M. Quantification of a-thujone and its metabolites in human urine after consumption of a sage infusion using stable isotope dilution assays. Toxins 2018;10:511.
7. Weisbord SD, Soule JB, Kimmel PL. Poison on line—acute renal failure caused by oil of wormwood purchased through the internet. N Engl J Med 1997;337:825-7.
8. Stafstrom CE. Seizures in a 7-month-old child after exposure to the essential plant oil Thuja. Pediatr Neurol 2007;37:446-8.
9. Di Lorenzo C, Ferretti F, Moro E, et al. Identification and quantification of thujone in a case of poisoning due to repeated ingestion of an infusion of artemisia vulgaris L. J Food Sci 2018;83:2257-64.
10. Dybowski MP, Dawidowicz AL. The determination of α-and β-thujone  in human serum – simple analysis of absinthe congener substance. Forensic Sci Int 2016;259:188-92.

Mike Tanner, PhD, DABCC(TC), NRCC (TC) is the director of science and technology at DRUGSCAN in Horsham, Penn.

The author has nothing to disclose.