Wormwood: Recommendations On Safety
1. Do not use in pregnancy.
2. Do not use in porphyria.
3. The volatile oil should not be taken internally.
A man of 31 drank 10 mL of essential oil of wormwood, thinking it was absinthe. He became agitated and incoherent with tonic and clonic seizures, and developed acute renal failure resulting from rhabdomyolysis (myoglobin release due to muscle injury). He recovered after 8 days of hospital treatment and had normal serum electrolyte, creatine kinase and creatinine concentration after 17 days.
The possible association between ingestion of ketones and convulsions has received much attention. Two cases of convulsions have occurred in association with use of volatile oil of sage Salvia officinalis, which contains ketones. Convulsions have been induced in rats by injected oil of hyssop, which mainly contains pinocamphone. Thujone was first isolated in 1845 and it is argued that thujone is the convulsant constituent in wormwood. Intraperitoneal injection of thujone was convulsant in mice and the action was blocked by earlier intraperitoneal administration of diazepam or phenobarbital. Hold et al (2000) showed that alpha-thujone acts at the noncompetitive blocker site of the γ-aminobutyric acid (GABA) type A receptor and blocks ion-flow through the channel, which is activated by GABA. These receptors are the primary mediators of inhibitory neurotransmission so this is an antiinhibitory action that could lower the threshold for seizures as this action is found with other convulsants. Another team argue that alpha-thujone inhibits 5-HT3 receptors by channel blockade which enhances the channel-blocking potency of serotonin (5-HT) and thus elevates mood. The animal studies on ketone-containing oils are discussed in the posts on hyssop. Their relevance to the internal usage of the herb or tincture is tenuous, but, taken together, the studies discussed here support the advice against internal use of the volatile oil.
4. Use caution with the dose of the tincture which should be used at the lowest effective dose but the cautions based on toxicity associated with the use of absinthe have been exaggerated.
There are two issues of interest: could a tincture or tea be dangerous because of the content of thujone and related ketone components such as camphor and thujyl acetate and, if so, would it be possible to take an excessive dose in a tincture or a tea? This discussion will be on use of the whole plant not the oil. Whilst some wormwood contains no thujone, this ketone could contribute to, for example, the nervine and antibacterial actions of wormwood. This has been suggested by Juteau et al (2003), who found that non-thujone containing samples of volatile oil showed no antibacterial action (three bacteria) and only moderate inhibition of two yeasts. Antibacterial action was also associated with a higher concentration of thujone in the two oils tested (five bacteria, including Pseudomonas aeruginosa) but other constituents were also active.
A shadow has been cast over wormwood because of the debate on the safety of the alcoholic drink Absinthe, which is distilled using wormwood. Absinthe is distilled from a macerate of Artemisia pontica and Artemisia absinthium and other herbs, often aniseed and fennel and sometimes hyssop. It was developed in Switzerland and commercial production began in 1797 and increased such that the annual production in Pontarlier, France was estimated at 10 million litres in 1905 where the main manufacturer was Pernod Fils. It was banned in many countries by 1915 but is now available again. There is substantial variation in quality and production methods, and quality assurance of Absinthe has been extensively reviewed by Lachenmeier et al (2006a).
Absinthe was considered to be associated with symptoms of ‘absinthism’ such as convulsions, hallucinations and sleeplessness. However, consumption of alcohol was very high in France. Strang (1999) argues that the role of ethanol poisoning in alcoholism was underestimated and this was the cause of symptoms thought to be due to Absinthe. The evidence for an association between psychiatric problems and Absinthe was hotly debated in the latter part of the 19th century by French physiologists. Absinthe was banned after a determined campaign by the temperance movement in France, who sought to decrease consumption of alcohol, and claims that Absinthe exacerbated epilepsy were used to support this campaign. These claims were based on the clinical experience of the main protagonist Dr Valentin Magnan and on his subsequent use of crude animal experiments in public demonstrations. Dyes were also claimed to be the cause of symptoms associated with absinthe and Lachenmeier (2007) notes that some samples in his analysis of 23 present-day samples of Absinthe contained dyes not included on the label.
The connection with convulsions has excited added interest as it has been argued that the mental health problems of the artist Vincent Van Gogh (1853-1890) were associated with his excessive consumption of Absinthe, resulting in mood swings linked with exacerbation of temporal lobe epilepsy in the presence of an early limbic lesion. It has also been argued that the symptoms of Van Gogh could be explained by attacks of porphyria associated with excessive consumption of Absinthe and thus camphor. The porphyrogenic action of terpenes, in particular camphor, was shown to be dose dependent in vitro and it was argued that consumption of 500 mL of Absinthe in a day could lead to a dangerous concentration of thujone. The diagnosis of temporal lobe epilepsy for Van Gogh, on admission to hospital in Aries in 1888, tends to support the first of these two hypotheses.
The debate on the safety of Absinthe is controversial and colored by different views on the reintroduction of the sale of Absinthe in Europe. Since the early 1990s Absinthe has been available again in Europe with a legal maximum of 35 mg thujone/kg of Absinthe (EEC 1988) in bitters and 10 mg/kg in alcoholic beverages with more than 25% volume of alcohol. Research to show whether different products comply with this ruling has revealed great variation in thujone concentration. In a sample of 23 current products, concentration of thujone was 0-70 mg/L. A review of 147 Absinthe products analyzed by four different centres found that 55% of samples contained under 2 mg thujone/kg Absinthe and 5% contained more than the legal limit of 35 mg/kg.
The concentration of thujone has been linked with the safety of Absinthe and therefore the concentration has been investigated in a range of samples. Results depend on the recipe, extraction of thujone and concentration of thujone in the source material. A study of 13 samples of vintage Absinthes found 0.5-48 mg thujone/L with a median concentration of 33.3 mg/L. Interestingly, the highest concentrations were found in four samples of Pernod Fils Absinthe which had been manufactured before the ban in 1915 and were found to still contain 42-48 mg thujone/L. In another study, three different sources of wormwood were used to manufacture Absinthe according to three recipes. In the resulting nine samples of absinthe, the concentration of thujone was 0-4.3 mg/L and it has been argued that the concentration of thujone in pre-ban absinthes may have been low. Lachenmeier & Kuballa (2007) argue that some figures given are based on overestimates of thujone concentration due to use of theoretical figures or because of confusion of similar results for thujone and linalool in chromatography. Hyssop is also used in the manufacture of Absinthe and pinocamphone was found in 23 out of 32 samples but at concentrations considered safe.
The sources above show that the oil and absinthe vary significantly in composition and thujone concentration but Lachenmeier et al (2006b) assert that consumption of absinthe does not produce a dangerous thujone intake. Padosch et al (2006) review the literature on safety and question whether the excitatory action of thujone was the cause of absinthism. Lachenmeier (2007b) summarizes the argument and suggests that absinthe should be appreciated for its taste, not for its purported thujone content.
The references given above include detailed discussion of the safety of Absinthe, but how might the concentration of thujone in herbal medicines be estimated? The possible dose of thujone in a prescription of a tincture depends on variables such as the original concentration of volatile oil in the sample, which is likely to be highest in fresh plant material but will vary widely depending on the source. The extraction of thujone depends on the concentration of ethanol in the tincture and the time period of maceration. Gambelunghe & Melai (2002) prepared two tinctures of leaves from the same source: a maceration in 20% ethanol for 1 month yielded 0.2 mg/L beta-thujone, whereas a maceration in 95% ethanol for 6 months yielded 62 mg/L of beta-thujone. The amount and source of the wormwood is not given. A study comparing distillation and percolation found that no thujone was extracted during percolation in 30% ethanol. We found no studies on extraction from fresh samples, but this could support the recommendation made by Cullen for a short maceration. To estimate the amount of thujone in a 1:5 tincture containing 200 g of herb in 1000 mL tincture, we used the values given in a summary of 29 reports where the mean concentration of volatile oil was found to be 0.5% (maximum 1.6%) and mean thujone was 18% (range 0-70.6%). Taking the mean of 18% thujone in 0.5% volatile oil, and complete extraction of the volatile oil (which is unlikely), a daily dose of 3 mL per day would give a mean daily dose of 0.56 mg of thujone, which Lachenmeier et al (2006) argue is far below the level where adverse pharmacological effects would occur. The studies on Absinthe and thujone have been summarized very briefly in this discussion, but include substantial experimental data and discussion of the results. The conclusion is that the dose of thujone in a tincture may be low, and use of wormwood tincture can be recommended without concern.
