Visiting the 'green fairy': Absinthe-tourism - A potential challenge for travel medicine?

Increasingly, travellers are looking for novel and unusual tourism experiences. Local produce, such as wine and food, has long been a strong visitor magnet. The search for pleasurable experiences has extended to substances that may be illegal at home, or to those surrounded by mystery. Travel medicine needs to be aware of new trends in tourism, especially if they involve substances with potential health risks, so that appropriate travel health advice can be given including the consideration of potential adverse reactions with current medications or pre-existing conditions. This article introduces a relatively new trend, 'absinthe-tourism', the mysterious drink itself, its flamboyant history and the escalating health issues in the 19th century that finally led to its ban in many countries. Absinthe is now freely available from reputable distilleries. Today, medical concern lies rather with unscrupulous suppliers on the internet, high alcohol content and adulterations. Until evidence suggests otherwise, there may be no concern for healthy travellers on the 'fairy-trail'.

A new chemical tool for absinthe producers, quantification of α/ß-thujone and the bitter components in Artemisia absinthium.

The concentrations of α/ß-thujone and the bitter components of Artemisia absinthium were quantified from alcoholic wormwood extracts during four phenological stages of their harvest period. A solid-phase micro-extraction method coupled to gas chromatography-mass spectrometry was used to determine the concentration of the two isomeric forms of thujone. In parallel, the combination of ultra-high pressure liquid chromatography and high resolution mass spectrometry allowed to quantify the compounds absinthin, artemisetin and dihydro-epi-deoxyarteannuin B. This present study aimed at helping absinthe producers to determine the best harvesting period.

The determination of α- and ß-thujone in human serum - Simple analysis of absinthe congener substance.

Absinthe is a strong spirit beverage, mostly green in color, containing besides ethyl alcohol (main component), alcoholic macerate of wormwood and other plants such as star anise and fennel seed. Due to the potential risks associated with the presence of α- and ß-thujone many countries have implemented strict rules limiting the content of these congeners in alcohol products. The presented paper describes a simple and sensitive method for the determination of α- and ß-thujone in human serum using Solid Phase Extraction as a sample preparation method combined with GC/MS analysis. The procedure involves the protein precipitation process, which generally degrades the protein-analyte complex, and SPE isolation of thujone from the examined materials. The described method is characterized by a low LOD and a very high recovery of the analytes. The present method for the estimation of α- and ß-thujone concentration in human fluids after the consumption of alcoholic beverages and other foods containing the substance is applicable in forensic and clinical toxicology because of its simplicity and rapidness with high sensitivity.

[Trait-aggression and suicide of Vincent van Gogh]. / Vincent van Gogh vonás-agressziója és öngyilkossága.

Although in recent decades the literature has paid special attention to Vincent van Gogh's life, work and illness, there has still not been an examination of the connections between his trait aggression and his suicide. The present study traces, in the light of this trait aggression, the predictive factors that can be observed on the path leading to the artist's suicide. Biographical documents, case history data, as well as letters and the findings of earlier research have been used in the course of the analysis. Among the distal suicide risk factors we find a positive family anamnesis, childhood traumas (emotional deprivation, identity problems associated with the name Vincent), a vagrant, homeless way of life, failures in relationships with women, and psychotic episodes appearing in rushes. The proximal factors include the tragic friendship with Gauguin (frustrated love), his brother Theo's marriage (experienced as a loss), and a tendency to self-destruction. Both factor groups on the one hand determined the course of development of the trait aggression and on the other can also be regarded as a manifestation of that trait aggression. It can be said that the trait aggression played an important role in Van Gogh's suicide.

Drugs on the Internet, Part V: absinthe, return of the emerald mask.

Absinthe, a famous liquor of the 19th century, has become immensely popular with its return to legality and mass marketing and drug culture enhancement of its purported unique effects. The electronic world of the Internet has greatly expedited the extent and depth of societal knowledge about the allure of the green fairy, absinthe. An extensive number of websites exists, representing 22 categories of topics about or using the word absinthe. Recent research has dispelled many myths about absinthe and its effects, yet beliefs about its magical powers persist, thus maintaining its reputation as an extraordinary experience within a bohemian lifestyle.

[Absinthe rehabilitated]. / L'absinthe réhabilitée.

Absinthe (Artemisia absinthium) has been known for its medicinal properties since Antiquity. The Egyptians in 1600 BC, then Hippocrates, Galien, The Salerne School in 1649, and 18th-century physicians all recommended it for a variety of maladies. In 1780-1790 in Switzerland (Val de Travers), a traditional healer and, probably, a itinerant physician by the name of Docteur Ordinaire, transformed this purgative elixir into an aperitif liqueur, a move followed by two centuries of unexpected success. Absinthe was manufactured in France, at Pontarlier, for tax reasons. In 1900, the town counted 25 distilleries. Its production then extended to other French provinces. La fée verte ("green fairy") was particularly popular with the military, literary and artistic circles, and, finally the general public. In 1902, following a parliamentary vote, the Minister of the Interior asked the National Academy of Medicine to issue an opinion on "The indication of aperitif liqueurs, including absinthe". The Commission on Alcoholism, chaired by J.V. Laborde, examined the composition of absinthe liqueurs, the physiological and toxic action of their essences, the risks associated with "bitter" aperitifs, and the composition of essence-based liqueurs that were not used as aperitifs. The Commission compiled a list of the most dangerous aperitifs and liqueurs placing absinthe at the top, and recommended that the authorities prohibit the manufacture, circulation, advertisement and sale of all such drinks, including absinthe. However, because these drinks, and especially absinthe, represented an important source of tax revenue, this recommendation was only acted upon 13 years later, with a law adopted in March 1915. Despite subsequent prohibition of the production of absinthe liqueur, manufacturers in the Val de Travers region and a distillery in Pontarlier continued to work in secret until the prohibition was finally lifted in the year 2000. This decision was based on scientific analyses showing that thuyone was only toxic when ingested in very large amounts incompatible with normal consumption. In addition, it was found that the high alcohol content, often including adulterated alcohol, was particularly detrimental. A handful of manufacturers are now authorized, with strict limits placed on the alcohol content and thuyone concentration. Does this mean that the Academy of Medicine was wrong? While the report can be criticized, the fight against alcoholism was a worthy and necessary cause at the time, and remains so today.

Modulation of GABAergic synaptic currents and current responses by α-thujone and dihydroumbellulone.

α-Thujone (1a), a constituent of wormwood, has been suspected to cause adverse psychoactive reactions in addicted drinkers of absinthe. While the content of 1a in absinthe is too low for such effects, at higher doses it can indeed induce seizures and inhibit GABA(A) receptors (GABA(A)Rs). The effect of 1a on GABAergic synaptic currents and the mechanisms by which it modulates GABA(A)Rs remain unknown. To address these issues, cultured hippocampal neurons were used to investigate the action of 1a on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and on responses to exogenous GABA applications. Since lipophilic compounds often show nonspecific actions related to their hydrophobicity, the action of 1a was compared to that of dihydroumbellulone (2), a configurationally pseudoenantiomeric constitutional isomer. α-Thujone (1a) reduced mIPSC frequency and amplitude and also moderately affected their kinetics, indicating both pre- and postsynaptic mechanisms. Analysis of current responses to exogenous GABA revealed that 1a reduced their amplitude, affecting their onset, desensitization, and deactivation, suggesting an effect on receptor gating. In contrast, 2 caused only a weak or negligible effect on GABAergic currents, supporting the effects of 1a on GABAergic inhibition as being due to specific interactions with GABA(A)Rs.

Risk assessment of thujone in foods and medicines containing sage and wormwood--evidence for a need of regulatory changes?

Thujone is a natural substance found in plants commonly used in foods and beverages, such as wormwood and sage, as well as in herbal medicines. The current limits for thujone in food products are based on short-term animal studies from the 1960s, which provided evidence for a threshold-based mechanism, yet only allowed for the derivation of preliminary values for acceptable daily intakes (ADI) based on the no-observed effect level (NOEL). While the 2008 European Union Regulation on flavourings deregulated the food use of thujone, the European Medicines Agency introduced limits for the substance in 2009. The present study re-evaluates the available evidence using the benchmark dose (BMD) approach instead of NOEL, and for the first time includes data from a long-term chronic toxicity study of the National Toxicology Program (NTP). The NTP data provide similar results to the previous short-term studies. Using dose-response modelling, a BMD lower confidence limit for a benchmark response of 10% (BMDL10) was calculated as being 11 mg/kg bw/day for clonic seizures in male rats. Based on this, we propose an ADI of 0.11 mg/kg bw/day, which would not be reachable even for consumers of high-levels of thujone-containing foods (including absinthe). While fewer data are available concerning thujone exposure from medicines, we estimate that between 2 and 20 cups of wormwood or sage tea would be required to reach this ADI, and view that the short-term medicinal use of these herbs can also be regarded as safe. In conclusion, the evidence does not point to any need for changes in regulations but confirms the current limits as sufficiently protective for consumers.

Wormwood (Artemisia absinthium L.)--a curious plant with both neurotoxic and neuroprotective properties?

The medical use of the wormwood plant Artemisia absinthium L. dates back to at least Roman times, while during the last century this tradition was seemingly on the decline due to fears of absinthism, a syndrome allegedly caused by the wormwood-flavoured spirit absinthe and more specifically as a result of thujone, a monoterpene ketone often present in the essential oil of wormwood. If threshold concentrations are exceeded, thujone does in fact exhibit neurotoxic properties leading to dose-dependent tonic-clonic seizures in animals, likely caused by GABA type A receptor modulation. Research has shown that the concentrations of thujone present in absinthe were not sufficient to exceed these thresholds, and the marketing of wormwood-flavoured alcoholic beverages has ultimately been reinstated. The declining fears of absinthism may have led to a revival of the medical uses of wormwood, evidenced by several experimental reports, e.g. on the treatment of Crohn's disease. Most recently in this journal, neuroprotective properties of wormwood were detected in rats, and the plant was suggested to be possibly beneficial in the treatment of strokes. While these results sound promising and worthwhile for further investigation, the well-defined profile of adverse properties of wormwood demands a more cautious interpretation of these results. It remained unclear in the studies, for example, if the threshold dose for thujone (e.g. as set by the European Medicines Agency) would be exceeded during therapeutic usage. Due to the colourful history of wormwood, its application in humans should be preceded by a thorough and careful risk-benefit analysis.

Absinthe, epileptic seizures and Valentin Magnan.

Absinthe is an alcoholic liquor containing extracts from the wormwood plant. It was widely consumed in France in the late nineteenth century. Its production was banned in 1915, partly because it was thought to cause neurological disturbances, including mental changes and epileptic seizures. Modern knowledge of an acceptable content of the convulsant alpha-thujone in absinthe has allowed the lifting of the production bans, and called into question the experimental work of Valentin Magnan in the 1870s, which formed the scientific background to the campaign against absinthe. An examination of Magnan's published investigations suggests that his science was very adequate by the standards of his time, and that he had shown that an alcohol-soluble component of wormwood did produce lapses of consciousness, myoclonic jerks and tonic-clonic convulsions in animals. Whether that component, presumably thujone, was present at convulsant concentrations in some of the available absinthes of Magnan's time cannot now be known.

Long-term stability of thujone, fenchone, and pinocamphone in vintage preban absinthe.

Research was conducted to ascertain whether analyses of vintage absinthe samples represent their original composition in the early 1900s. Absinthe stored in traditional green glass bottles and irradiated with ultraviolet light for up to 200 h exhibited unchanged composition. Samples stored in clear glass exhibited an 18% reduction in beta-thujone content and a concurrent decoloration. These experiments indicate the stability of thujone in vintage absinthes, as these were stored in green glass bottles. The preserved color of the preban absinthes subjected to analysis indicates that no significant light exposure occurred throughout the duration of storage, and therefore provides indirect proof that no loss of terpenes occurred. The stability of absinthe was further demonstrated through the reanalysis of samples from 2001-2005, which exhibited no changes in thujone content as of 2008. A previous evaluation of preban absinthe was therefore valid and not confounded by significant thujone deterioration over time.

Multivariate curve resolution of spectrophotometric data for the determination of artificial food colors.

In the analysis of food additives, past emphasis was put on the development of chromatographic techniques to separate target components from a complex matrix. Especially in the case of artificial food colors, direct spectrophotometric measurement was seen to lack in specificity due to a high spectral overlap between different components. Multivariate curve resolution (MCR) may be used to overcome this limitation. MCR is able to (i) extract from a complex spectral feature the number of involved components, (ii) attribute the resulting spectra to chemical compounds, and (iii) quantify the individual spectral contributions with or without a priori knowledge. We have evaluated MCR for the routine analysis of yellow and blue food colors in absinthe spirits. Using calibration standards, we were able to show that MCR equally performs as compared to partial least-squares regression but with much improved chemical information contained in the predicted spectra. MCR was then applied to an authentic collective of different absinthes. As confirmed by reference analytics, the food colors were correctly assigned with a sensitivity of 0.93 and a specificity of 0.85. Besides the artificial colors, the algorithm detected a further component in some samples that could be assigned to natural coloring from chlorophyll.

Chemical composition of vintage preban absinthe with special reference to thujone, fenchone, pinocamphone, methanol, copper, and antimony concentrations.

Thirteen samples of authentic absinthe dating from the preban era (i.e., prior to 1915) were analyzed for parameters that were hypothesized as contributing to the toxicity of the spirit, including naturally occurring herbal essences (thujone, pinocamphone, fenchone), methanol, higher alcohols, copper, and antimony. The total thujone content of preban absinthe was found to range between 0.5 and 48.3 mg/L, with an average concentration of 25.4 +/- 20.3 mg/L and a median concentration of 33.3 mg/L. The authors conclude that the thujone concentration of preban absinthe was generally overestimated in the past. The analysis of postban (1915-1988) and modern commercial absinthes (2003-2006) showed that the encompassed thujone ranges of all absinthes are quite similar, disproving the supposition that a fundamental difference exists between preban and modern absinthes manufactured according to historical recipes. Analyses of pinocamphone, fenchone, base spirits, copper, and antimony were inconspicuous. All things considered, nothing besides ethanol was found in the absinthes that was able to explain the syndrome "absinthism".

[Thujone-attributable effects of absinthe are only an urban legend--toxicology uncovers alcohol as real cause of absinthism]. / Thujon-Wirkungen von Absinth sind nur eine Legende. Toxikologie entlarvt Alkohol als eigentliche Absinthismus-Ursache.

In the discussion about thujone as possible toxic constituent of the wormwood-containing alcoholic beverage absinthe, the dose-response-relationship is frequently ignored. The effects of absinthe are very often attributed only to thujone, an association that is not scientifically proven. Especially the alleged psychotropic effects of thujone are scientifically unproven. However, the question about thujone effects in absinthe is irrelevant, because thujone is contained in both modern commercial absinthes and historic pre-ban products in such low amounts that a pharmacological effect can be excluded per se. The effects of the spirit that are summarized under the term absinthism observed in late 19th century's France, can be explained by chronic alcohol misuse and dependence alone according to today's standards of knowledge. Especially from the perspective of youth and public health protection, an ambiguous and biased reporting about absinthe should be avoided. For example, the alleged antagonistic effects of thujone on the action of ethanol might lead to a trivialization of alcohol-related harms. Scientifically unproven speculations about the influence of certain drinking rituals of absinthe on its toxicity must be rebutted. A return to more evidence and less conjecture in the reporting about absinthe would be desirable.

Absinthe--is its history relevant for current public health?

This paper briefly addresses the history of the social experience with absinthe in France during the 19th century and the beginning of the 20th. We draw on some important parallels of this history with that of smoking to demonstrate that public health threats in the form of (ill-)health related behaviour recur in different disguises, while the social causes if these threats are left to endure. Probably the most important of the parallels between absinthe and smoking is their association with social disadvantage. Nevertheless, it appears that it is not yet fully realized that tackling these threats requires an equity approach.