Artemisia – Wormwood (Absinthii herba)
|Latin name of the genus:||Artemisia|
|Latin name of herbal substance:||Absinthii herba|
|Botanical name of plant:||Artemisia absinthium l.|
|English common name of herbal substance:||Wormwood|
Latin name of the genus: Artemisia
Latin name of herbal substance: Absinthii herba
Botanical name of plant: Artemisia absinthium L.
English common name of herbal substance: Wormwood
- I.REGULATORY STATUS OVERVIEW1
- II.ASSESSMENT REPORT
- BASED ON ARTICLE 10A OF DIRECTIVE 2001/83/EC AS AMENDED
- (WELL-ESTABLISHED USE)
- BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE 2001/83/EC AS
- (TRADITIONAL USE)
- II.1 I
- II.1.1 Description of the herbal substance(s), herbal preparation(s) or combinations thereof
- II.1.2 Information on period of medicinal use in the Community regarding the specified indication
- II.2.1 Pharmacology
- II.2.1.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- II.2.1.2 Assessor’s overall conclusions on pharmacology
- II.2.2 Pharmacokinetics
- II.2.2.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- II.2.2.2 Assessor’s overall conclusions on pharmacokinetics
- II.2.3 Toxicology
- II.2.3.1 Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- II.2.3.2 Assessor’s overall conclusions on toxicology
- II.3.1 Clinical Pharmacology
- II.3.1.1 Pharmacodynamics
- II.18.104.22.168 Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity.
- II.22.214.171.124 Assessor’s overall conclusions on pharmacodynamics
- II.3.1.2 Pharmacokinetics
- II.126.96.36.199 Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity.
- II.188.8.131.52 Assessor’s overall conclusions on pharmacokinetics
- II.3.2 Clinical Efficacy6
- II.3.2.1 Dose response studies
- II.3.2.2 Clinical studies (case studies and clinical trials)
- II.3.2.3 Clinical studies in special populations (e.g. elderly and children)
- II.3.2.4 Traditional use
- II.3.2.5 Assessor’s overall conclusions on clinical efficacy
- II.3.3 Clinical Safety/Pharmacovigilance
- II.3.3.1 Patient exposure
- II.3.3.2 Adverse events
- II.3.3.3 Serious adverse events and deaths
- II.3.3.4 Laboratory findings
- II.3.3.5 Safety in special populations and situations
- II.184.108.40.206 Intrinsic (including elderly and children) /extrinsic factors
- II.220.127.116.11 Drug interactions
- II.18.104.22.168 Use in pregnancy and lactation
- II.22.214.171.124 Overdose
- II.126.96.36.199 Drug abuse
- II.188.8.131.52 Withdrawal and rebound
- II.184.108.40.206 Effects on ability to drive or operate machinery or impairment of mental ability
- II.3.3.6 Assessor’s overall conclusions on clinical safety
I.REGULATORY STATUS OVERVIEW1
MA: Marketing Authorisation;
TRAD: Traditional Use Registration;
Other TRAD: Other national Traditional systems of registration;
Other: If known, it should be specified or otherwise add ’Not Known’
1This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
2Not mandatory field
BASED ON ARTICLE 10A OF DIRECTIVE 2001/83/EC AS AMENDED
BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE 2001/83/EC AS
II.1.1 Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Herbal substance(s) 3:
Absinthii herba [European Pharmacopoeia]
Basal leaves or slightly leafy, flowering tops, or mixture of these dried, whole or cut organs of Artemisia absinthium L. Content: minimum 2 ml/kg of essential oil (dried drug); bitterness value: minimum 10,000
Synonyms: German- Magenkraut, Wermutkraut; Engl- Wormwood; French- Absinthe, Armoise amère; Polish- Ziele piolunu; Romanian- Iarbă de pelin.
Artemisia absinthium is a species of wormwood, native to temperate regions of Europe, Asia and northern Africa. It grows naturally on uncultivated, arid ground, on rocky slopes and wastelands; it can also be cultivated in dry soil.
The time of harvesting is important for the quality and the composition of the constituents. Metabolism processes change over the flowering period and ripenening of the fruit, e.g. during the flowering period the concentration of bitter constituents increases. [HÄNSEL & STICHER 2007].
Absinthii herba is used medically with a very long tradition, but it is also used as an ingredient in the liquor absinthe. In the beginning of the 19th century many countries banned the use of absinthe. Since 1988 the European Union permits a maximum thujone level of 5 mg/kg in alcoholic beverages with less than 25% volume of alcohol, 10 mg/kg in alcoholic beverages with more than 25% volume of alcohol, and 35 mg/kg in alcohol labelled as bitters. The use and sale of absinthe in the member states is permitted within this framework [88/388/EEC 1988].
Constituents: [HAGERROM 2006, WICHTL 2002, HÄNSEL & STICHER 2007] Volatile oil:
Further volatile oil components are sequiterpenes like
3According to the ‘Procedure for the preparation of Community monographs for traditional herbal medicinal products’ (EMEA/HMPC/182320/2005 Rev.2) and the ‘Procedure for the preparation of Community monographs for herbal medicinal products with
Other constituents: flavonoids (such as quercetin, rutin), caffeic acids, chlorogenic acid, syringic acid, salicylic acid, vanillic acid, carotenoids, coumarins,
The extraction method modifies the content of thujone in the preparation as much as the variable amount of thujone in the starting material. TEGTMEIER & HARNISCHFEGER  examined the thujone content of different preparations of A. absinthium.
Table 1:Influence of the extraction procedure on the thujone concentration in the extracts of A. absinthium [essential oil content: 0.5% (m/v); thujone content in the essential oil: 4.8% (m/v)]; thujone yield in % [thujone content in extract/actual thujone content]
(mean ± SD; n=6) [TEGTMEIER & HARNISCHFEGER 1994]
GAMBELUNGHE & MELAI  examined two ethanolic preparations. The first preparation (macerating A. absinthium for 30 days with ethanol 20%) contained 0.2 mg/l
NIESEL  examined the extraction rates for different herbal substances referring to their contents of essential oil (tea preparation with boiling water). For peppermint leaves it was shown that
i)comminuted herbal substance
ii)expressed juice from fresh Absinthii herba
iii)tincture (1:5); extraction solvent: ethanol 70% (v/v)
Combinations of herbal substance(s) and/or herbal preparation(s)4:
Absinthii herba is used in combinations with many other herbal substances / herbal preparations. The main combination substances such as Gentianae radix, Angelicae radix, Curcuma rhizoma, Millefolii herba, Taraxaci radix, Menthae piperitae herba, Levistici herba, Liquiritiae radix and Foeniculus fructus exhibit bitter and/or aromatic properties and are usually used for dyspeptic or choleretic complaints.
This monograph refers exclusively to Absinthii herba.
Vitamin(s)5: not applicable
Mineral(s): not applicable
II.1.2 Information on period of medicinal use in the Community regarding the specified indication
The following herbal substances and herbal preparations have been on the European market for a period of 30 years and were proposed for the monograph on traditional use.
i)comminuted herbal substance
iii)tincture (1:5) extraction solvent: ethanol 70% (v/v)
Posology and indications of the traditional herbal substance and preparations of Absinthii herba:
comminuted herbal substance in tablets
comminuted herbal substance for tea preparation
4According to the ‘Guideline on the clinical assessment of fixed combinations of herbal substances/herbal preparations’ (EMEA/HMPC/166326/2005)
5Only applicable to traditional use
tincture (1:5); extraction solvent: ethanol 70% (v/v)
II.2.1.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Herbal substance/Herbal preparations:
in vitro studies:
Also Ramos et al. showed a DPPH reduction caused by a hydroalcoholic extract (A. absinthium from Cuba) with an IC50 of 121 µg/ml [RAMOS et al. 2003].
To evaluate human CNS cholinergic receptor binding activity, investigations with an ethanolic extract (80% EtOH) of leaves from A. absinthium were carried out. Human cerebral cortical cell membranes were used to prove the activity of the ethanolic extract to displace
For the evaluation of
An aqueous crude extract of A. absinthium was used to analyze effects on the osmotic stability of human erythrocytes. The extract protected human erythrocytes against hypotonic shock. It was discussed that the flavonoids might be responsible for this effect which might lead to an exacerbation of the van der Waals contacts inside the lipid layer of the membrane [DE FREITAS et al. 2008].
In a growth inhibitory assay, aqueous and ethanolic extracts of A. absinthium were tested for their effect against Naegleria fowleri. Both extracts inhibited strongly the growth of N. fowleri. A sesquiterpene lactone fraction was prepared from the ethanolic extracts. For this fraction a LD50 value of 31.9 µg/ml was obtained in the test system. For artemisin (from A. annua) the IC50 was reported with 5 g/ml. Therefore it was postulated, that the sesquiterpene lactone fraction of A. absinthium may contain artemisin or a compound with similar activity [MENDIOLA et al. 1999].
Hernandez et al. prepared an aqueous extract as well as a sesquiterpene lactone fraction from A. absinthium and tested them in a growth inhibition test against Plasmodium falciparum. In the aqueous extract the maximum percentage of inhibition of growth (89.9%) was observed at the dilution 1:35. The LD50 value of the sesquiterpene lactone fraction was 31.4 µg/ml [HERNANDEZ et al. 1990].
in vivo studies:
The ulcerated rats were given the fractions orally at a dose of 5 mg/kg 3 h prior and 3 h after treatment with acetylsalicylic acid (200 mg/kg) for three days. On the fourth day the rats were operated (pylorus ligation) and gastric juice was collected for a period of 4 h. Thereafter the animals were killed and the stomach was removed. The average numbers of ulcers per stomach were recorded and the inhibition of ulcer formation calculated in percent. Acid output, peptic activity and mucin activity were also determined.
Phytochemical analysis of the fractions showed the absence of alkaloids and anthraquinones but indicated the presence of glycosidic sugars and saponins.
Significant antiulcer effects have been observed. Fractions I and II reduced the ulcer index by 65% and 44%, respectively. The other fractions decreased it by 33%, 11% and 27%. Also fractions I and II showed a decrease (40% and 33%, respectively). Fractions I, II and III also decreased significantly the volumes of gastric juice (~1/3). Furthermore, for fraction II a decrease in peptic activity was observed. After treatment
with acetylsalicylic acid a decrease in total hexoses in the gastric juice was recorded in the controls. In fractions I and II (together with acetylsalicylic acid) the amount of total hexoses within the carbohydrates corresponded to the controls but the amount of fucose increased. Also, the amount of total protein in the gastric juice increased after treatment with fractions I and II. Fraction I caused a significant change in the performance of rats in the swimming test (increased duration of swimming). During all studies, injurious or toxic effects were not observed and no lethal effects occurred with dosages up to 10 mg/kg. Subsequently no LD50 could be determined [SHAFI et al. 2004].
An i.v. injection of decoctions of Absinthii herba (equal to 5 g herbal substance) caused a threefold increase of bile secretion in dogs [KREITMAIR 1951].
Dried aerial parts of A. absinthium were extracted with methanol (80% MeOH) and tested for their hepatoprotective activity. The dry extract was administered in various experiments to mice or rats with a concentration of 500 mg/kg. Based on the yield of the dry extract (8%) this is equivalent to 6.25 g herbal substance/kg.
A. absinthium leaves (fresh, stored frozen after collection) were extracted with organic solvents of different polarities and tested as repellents against
An ethanolic extract (90% EtOH) from dried aerial parts of A. absinthium was fractionated into hexane- soluble and
For the screening of antimalarial effects leaves of A. absinthium were dried and extracted with ethanol (95% EtOH). The extract was dried, dissolved in deionised water, filtered and the filtrate was concentrated to dryness. Swiss albino mice were infected with 1x 107 parasitized (Plasmodium berghei) blood cells from a donor mouse. The ethanolic extract was given orally, subcutaneously or
Freshly extracted essential oil from
P. aeroginosa. No activity was observed against S. thyphi, E. coli, C. albicans, C. utilis or A. niger [KAUL et al.1976].
The essential oil of French A. absinthium showed antimicrobial activity against C. albicans and S. cerevisiae var. chevaleri (growth inhibitor concentration for 50% of the microorganisms: 0.1 and 0.05 mg/ml, respectively), while no activity could be found against E. coli, S. aureus and E. hirae [JUTEAU et al. 2003]. The essential oil of a
Dried plant samples of A. absinthium were extracted with CHCl3 and tested for their antifungal (hyphal growth inhibition) and antibacterial (disk diffusion method) activity. The dose of 20 µl essential oil was found to be fungicide against the tested 34 agricultural pathogenic fungal species. The essential oil showed only a weak antibacterial activity against 13 of the 64 tested strains from plant, food and clinical origin (600, 900 and 1200 µg/disk) [KORDALI et al. 2005].
The freshly extracted essential oil from air dried leaves of A. absinthium was tested for its insecticidal activity. The essential oil was toxic to house flies in concentrations of 10% (mortality rate 3.3%), 15% (mortality rate 6.6%) and 20% (mortality rate 20%) [KAUL et al. 1978].
The essential oil of A. absinthium (hydrodestillation method) was found to be toxic to adults of Sitophilus granarius (Coleoptera). The concentration of 9 µl oil/l air caused a mortality rate of 86.7% after 48 h (53.3% and 73.3% after 12 and 24 h, respectively). Chamazulene (17.8%), nuciferol butanoate (8.2%), nuciferol propionate (5.1%) and caryophyllen oxide (4.3%) were the main constituents of the essential oil. The compounds
Essential oils of A. absinthium were extracted by three methods (microwave assisted process, distillation in water and direct steam distillation) and tested for their relative toxicity as contact ascaricides to the two spotted spider mite, Tetranychus urticae. The LC50 from the oil obtained by direct steam distillation was significantly lower (0.04 mg/cm2) than that of the microwave assisted process and distillation in water (both 0.13 mg/cm2). Chromatographic analysis indicated that a sesquiterpene (C15H24) present in the direct steam distillation oil (absent in the two other oils) might enhance the toxicity [CHIASSON et al. 2001].
The structure of a
It was reported that in the
Following the suggestion that thujone binds to the cannabinoid receptor it was demonstrated that thujone exhibits only a weak affinity for cannabinoid receptors (CB1 and CB2) and fails to elicit typical cannabinoid
The mechanisms of
The effect appears to be due to the parent compound, while metabolism leads to detoxification [HÖLD et al. 2000a].
Orally administered absinthin increased the amount of gastric juice and free HCL while this was not observed after gavage administration [KREITMAIR 1951].
II.2.1.2 Assessor’s overall conclusions on pharmacology
It is long known that the bitter constituents stimulate the gustatory nerves in the mouth and increase the secretion of gastric juice and bile, thereby promoting appetite and digestion. Additionally, more recent studies show that taste receptors (bitter taste) could not only be found in the lingual epithelium but also in the gastrointestinal tract of animals [Rozengurt 2006].
These new findings support literature data which describe the use of Absinthii herba – not only in form of the herbal tea or hydroalcoholic preparations, but also in form of the powdered herbal drug – for the relief of mild dyspeptic/gastrointestinal disorders/complaints. The indication ‘lack of appetite’ should be restricted to fluid preparations only. For this indication, both the tradition of use (more than 30 years) and the plausibility are proven.
Other possible pharmacodynamic actions such as antimicrobial, anthelmintic, antipyretic, analgesic and hepatoprotective properties are also described.
II.2.2.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Herbal substance/Herbal Preparations: No data available.
After oral administration of a mixture of α- and
Site specificity and species differences in metabolism of the thujone
II.2.2.2 Assessor’s overall conclusions on pharmacokinetics
Limited data are available on pharmacokinetics. For the herbal substance or the herbal preparation no data are available; therefore no conclusion can be drawn. For thujone and even absinthin more data exist, but these are not transferable to the herbal substance or herbal preparations.
Experimental data from animals indicate that the metabolism of thujone differs strongly in dependence of the animal species. The CYP system (Cytochrome P450) seems to be involved in the metabolic detoxification of thujone.
II.2.3.1 Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
Herbal substance/Herbal preparations:
single dose toxicity:
The LD50 of an extract of A. absinthium (not specified) was given with 1 mg/kg in rats (i.p.) [HAGERROM 2006].
repeat dose toxicity:
All rats survived the end of the study, and no changes in body weight, haematological parameters and histopathological examinations were observed. In serum biochemical examinations, levels of total protein, albumin, blood urea nitrogen, Na und Cl were slightly but significantly increased in males of the 2% group. Because there were no other changes in other related parameters, these changes were considered to be of no toxicological significance. Relative liver weights were significantly increased in both sexes of the 2% group. However, since there were no increases in their absolute weights and no histopathological treatment related changes were observed in the liver, these changes were not interpreted as toxicological effects. Other effects were not seen [Muto et al. 2003].
Chronic administration of an essence of Absinthii herba (not specified) caused epilepsy with consecutively stupor in dogs [Kreitmair 1951].
reproductive and developmental studies:
Antifertility studies were carried out in Wistar albino rats of proven fertility. Antifertility activity of an ethanolic dry extract (50% EtOH) of leaves of A. absinthium was assessed in terms of
No effects on ovulation (no influence of the
There are no data available on reproductive and developmental studies for aqueous preparations of
No studies using herbal preparations of Absinthii herba were located.
single dose toxicity:
The oral LD50 of the essential oil of A. absinthium was 0.96 g/kg in rats [Opdyke 1975]. The minimal dosage which caused spasms in cats was
The undiluted essential oil was not irritating on the back of hairless mice and slightly irritating to intact or abraded rabbit skin for 24 h under occlusion [Opdyke 1975].
A 2% preparation in petrolatum produced no sensitization reaction in 25 volunteers (maximization test) [Opdyke 1975].
No phototoxic effects were reported for undiluted essential oil on hairless mice and swine [Opdyke 1975].
single dose toxicity:
The oral LD50 of a mixture from α- and
repeated dose toxicity:
Thujone was administered to rats by gavage at doses of 12.5, 25 or 50 mg/kg/day on five days per week for 13 weeks. There was an increased lethality of 60% in females and 37% in males at the top dose level. The NOEL for convulsions in the males was 12.5 mg/kg but no NOEL could be established in females in this study [Surber 1962].
In a further study, thujone was administered to rats by gavage at doses of 0, 5, 10 or 20 mg/kg/day 6 times per week for 14 weeks. There were 3 deaths in females and 1 in males associated with
convulsions at the top dose level. The NOEL for convulsions was reported to be 10 mg/kg in males and 5 mg/kg in females; no changes were reported in haematologic or
Negative results have been reported from in vitro mutagenicity tests in Salmonella typhimurium with
Thujone was tested at 1.5 and 3% in DMSO for its effect on the mutagenicity of aflatoxin B1 in the Salmonella typhimurium strain TA100. The plates treated with thujone showed evidence of colony damage which indicates some mutagenic activity on the part of thujone (Kim et al. 1992).
special studies on mechanisms of toxicity
Several studies on the mechanism of neurotoxicity of
other biological effects
Studies on primary cultures of chick embryo liver cells indicate that thujone is porphyrogenic, leading to accumulation of copro- and protoporphyrins. It induces
II.2.3.2 Assessor’s overall conclusions on toxicology
There are only limited preclinical safety data for Absinthii herba or preparations thereof.
Also for the essential oil the data are unsatisfactory. The limited toxicological data on thujone and the quality of the available studies, mainly published in the 1960s, were considered to be insufficient to set an maximum daily intake (MDI).
The results of the single dose toxicity studies show that the
Thujone has a neurotoxic potential and produces convulsions in animals by acting on the central nervous system. There are several anecdotal and case study reports on the acute effects of
Thujone has been evaluated by the Council of Europe which allocated a temporary maximum daily intake (TMDI) of 10 µg/kg/d based on a NOEL for convulsions of 5 mg/kg in the female rat, dosed by gavage on 6 days per week for 14 weeks, to which a safety factor of 500 was applied [Council of Europe 2007]. The “temporary acceptable daily intake” is in this context a value for the acceptable daily intake proposed for guidance when data are sufficient to conclude that use of the substance is safe over the relatively short period of time required to generate and evaluate further safety data, but are insufficient to conclude that the use of the substance is safe over a lifetime. A
According to the Directive 88/388/EEC 1988 a maximum thujone level of 5 mg/kg in alcoholic beverages with not more than 25% volume of alcohol and of 35 mg/kg in alcohol labelled as bitters (40% volume of alcohol and more) are allowed. Taking into consideration a daily intake of
The maximum daily intake (acceptable daily intake for food) is a measure of the amount of a specific substance that can be ingested (orally) over a lifetime without an appreciable health risk. For a
Dettling et al.  had shown that ~15 mg thujone/person (60 kg) lead to changes in attention performances, while for the intake of ~1.5 mg thujone/person no such changes were described even though expected. The authors proposed for safety reasons a limit of 1.5 mg/person in a single dose, were effects could barely be seen.
At the time of this assessment a daily intake of 3.0 mg/person is considered acceptable for a maximum duration of use of 2 weeks. This is due to the fact, that this daily dose is supposed to be taken divided into three single doses. Therefore the single dose (1 mg thujone) is only 2/3 of the amount which was for safety concerns postulated as the lowest described limit of thujone action. The content of thujone must be shown for every batch.
The data from reproductive studies suggest that Absinthii herba might influence gravidity. Moreover it was proven that thujone stimulates the uterus [BIELENBERG 2002]. Therefore ethanolic preparations of Absinthii herba with high content of thujone should be contraindicated during pregnancy and lactation while aqueous preparations or preparations with a low content of thujone are not recommended during pregnancy and lactation.
Due to the lack of data on mutagenicity, carcinogenicity and reproductive and developmental toxicity, a list entry for Absinthii herba can not be recommended.
II.3.1 Clinical Pharmacology
II.220.127.116.11 Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity.
Four healthy test persons (female, age
In a clinical study, a dry ethanolic preparation of A. absinthium (not specified) was administered to 15 patients with hepatic disorders via a duodenal tube. First, the basal secretion was measured for 10 min before sample administration. In this way also the basis secretion of 22 healthy volunteers was measured for comparison. The following parameters were measured: volume of duodenal secretion, amount of bilirubin, cholesterol, lipase and
All parameters were significantly increased when the preparation was given. The stimulation of secretion of lipase
In a further clinical study, 2.5 mg of a dry ethanolic preparation of A. absinthium (not specified) and
All parameters were increased
according to Jagusch 1988. The following parameters were measured: volume and amount of bilirubin, total cholesterol,
The parameters volume, bilirubin, total cholesterol and
II.18.104.22.168 Assessor’s overall conclusions on pharmacodynamics
Ethanolic preparations from A. absinthium are able to stimulate gastric, intestinal and biliary secretion probably due to the content of bitter substances and essential oil. The essential oil acts antispasmodic in small amounts. In high dosages or after
Earlier hypotheses claimed that bitter tasting substances evoke secretory reflexes of the gastrointestinal tract via taste receptors in the lingual epithelium. The current notion is that additionally taste receptors are expressed in the gastrointestinal mucosa. It is postulated that activation of bitter taste receptors generate integrated responses as secretion, motility or absorption [STERNINI 2007].
In the studies of Jagusch 1988 and Kistler 1988 a dosage (0.02 g herbal substance) was used which is a hundred times below the dosage described for medicinal use. This might explain why the observed moderate effects were not significant.
II.22.214.171.124 Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity.
Within a drinking test two subjects (65 kg body weight) consumed 110 ml absinth with 3.85 mg thujone (content of absinth 35 mg/l) within 15 min. Blood samples were drawn 15, 30, 60, 90, and 120 min after drinking. The determination of the blood alcohol level was applied via
Blood alcohol concentrations >1 g/l were determined, whereas thujone could not be detected in blood samples (detection limit 0.34 ng/ml). Conjugates of thujone were not determined. The two subjects showed typical signs of alcoholisation (e.g. staggering, chattiness) while hallucinogenic effects were not described by the two subjects [Kröner et al. 2005].
II.126.96.36.199 Assessor’s overall conclusions on pharmacokinetics
According to the study by Kroener at al. (2005) in both subjects no free thujone could be detected in the blood samples. First measurements were taken 15 and 30 min after beginning of the drinking. It was not clear if other time frames could have shown other results. It remains unclear whether the measurement of unmetabolized thujone in blood is possible at all, because no data are known with regard to the
Due to lack of comprehensive data no conclusions can be drawn.
II.3.2 Clinical Efficacy6
II.3.2.1 Dose response studies
II.3.2.2 Clinical studies (case studies and clinical trials)
The capsules contained powdered A. absinthium herb and powdered
The patients were
Response to treatment was defined as a decrease in the CDAI score of at least 70 points from the qualifying score, or a decrease in 30% of CDAI score from the baseline score. For the HAMD total score, the primary outcome measure was the absolute decrease of the Hamilton total depression score between baseline and the following treatment weeks. Response was defined as a decrease in total score of >50% from baseline and remission as a score <10 points.
After week 2 in the placebo group 16 patients (80%) showed CD exacerbation due to reduction in steroid dose, whereas there were only two (10%) such patients in the group receiving A. absinthium. The exacerbation of CD symptoms necessitated the
At week 10 13 patients (65%) of the verum group were almost free of CD symptoms and there was no need to restart the steroid treatment in the
Nine patients of the placebo group tolerated the reduction of the steroids (unchanged CDAI score). After 6 weeks the number of patients who showed clinical improvement were significantly higher in the verum group as compared to the placebo group. This significant difference continued beyond week 10.
There was almost no change in the subjective feelings of illness in
6 In case of traditional use the
treatment phase (week 10) 70% of the patients of the A. absinthium group and none in the placebo group showed remission of depressive symptoms. The authors assumed that the efficacy might be due to the
Tahir et al. tested A. absinthium (powdered) in 20 patients against amoebiasis. All patients had symptoms and signs of amoebiasis i.e., abdominal pain and tenderness, loose motion mucous in stool often mixed with blood and tenesmus and Entamoeba histolytica was diagnosed in stool under the microscope. Patients suffering from other gastrointestinal, cardiovascular, respiratory, endocrinal, nervous system and sexually transmitted diseases were excluded from the study.
The powdered herbal substance was administered in the form of a capsule (500 mg). Three capsules every six hours were given to the patients for a period of fifteen days. The efficacy was assessed weekly in terms of improvement, in termination of the symptoms and signs of disease without the aid of any other drug for the management of this condition. The patients were between
After treatment with 6 g A. absinthium/day for 15 days the following results were achieved:
All the patients had abdominal pain and loose motions at the beginning of the treatment. Regarding abdominal pain the relief in symptoms was recorded as complete in 13 patients and partial in 6 patients, while the relief in loose motions was noted in 14 (total) and 4 (partly) patients. Seventeen patients had abdominal tenderness before treatment and relief was noted in 11 (total) and 4 (partly) patients. Blood stained stool was present in 7 patients before treatment and relief was seen in 6 patients (total), while mucous stained stool was present in 10 patients before treatment and relief was seen in 8 (total) and 1 (partly) patients. Blood with mucous stained stool was present in 3 patients and in 2 patients a total relief was achieved. Tenesmus was seen in 13 patients at the beginning and a relief was recorded for 8 (total) and 2 (partly) patients). The average relief in all symptoms was noted in 84.66% of the cases, while 15.34% of the cases showed negligible or no relief. This reflects the fact that amoeba in stool disappeared in 70% of cases after 15 days treatment.
The authors report that the amoebicidal,
II.3.2.3 Clinical studies in special populations (e.g. elderly and children)
II.3.2.4 Traditional use
Artemisia absinthium has a
Already the Egyptians used A. absinthium (or a closely related species) as an antiseptic, a stimulant and tonic, and as a remedy for fevers and menstrual pains (Ebers Papyrus). Hippocrates recommended Absinthii herba as a cure for jaundice. Pliny’s “Historica Naturalis” describes the extract of Absinthii herba as having a
During the last decades A. absinthium is used as “amarum aromaticum” to promote the appetite in cases of gastritis, hypoacidity, and dyspepsia. The plant is also described as a choleretic [BHP 83, HAGERROM 2006, MARTINDALE 1989]. An ethnopharmacobotanical study
in Pakistan showed that A. absinthium is used against liver diseases, hepatitis, blood purification, jaundice, diabetes, skin diseases, allergy, scabies, tetanus and as brain tonic [QURESHI et al. 2002]. In Russia, Lithuania, Poland and America Absinthii herba was used in folk medicine against dyspeptic complaints [MADAUS 1976].
The dried comminuted herbal substance has been described in Pharmacopoeias and Pharmacognosy handbooks for decades, while the tincture was described in various German Pharmacopoeias [GERMAN PHARMACOPOEIA 1872,
The use for more than 30 years could be proven for
–comminuted herbal substance in tablets 3 times daily 760 mg herbal substance (2.28 g herbal substance daily) for the treatment of dyspeptic complaints such as minor gastrointestinal spasms, repletion and flatulence
–comminuted herbal substance for tea preparation
–tincture (1:5); extraction solvent ethanol 70% (v/v) 3 times daily, each single dosage equivalent to 1 g herbal substance to improve appetite and stimulate a digestion in cases of hypoacidity and chronic gastritis [SCHULZE & HÄNSEL 2004; SCHMID & SCHULTZ 1979].
II.3.2.5 Assessor’s overall conclusions on clinical efficacy
Although A. absinthium has been used to treat loss of appetite, indigestion, biliary disorders, and other gastrointestinal problems, clinical data supporting these uses are lacking. Also for the described use as an antiparasitic and anthelmintic agent, there are no published studies evaluating the efficacy for these indications in humans.
The pharmacodynamic properties (clinical data) support the use of A. absinthium for the treatment of loss of appetite and for the symptomatic treatment of dyspepsia and mild spasmodic disorders of the gastrointestinal tract. This is also confirmed by results of another typical bitter drug (Gentiana lutea). G. lutea was tested as a dry extract in isolated rat stomach cells and in a multicentre uncontrolled study (205 patients). A concentration dependent rise in gastric acid production was observed in rat cells, while in patients a rapid and dramatic relief of symptoms (constipation, flatulence, appetite loss, vomiting, heartburn, abdominal pain, nausea) was achieved [GEBHARDT 1997, WEGENER 1998]. Such findings could explain why bitters, also when encapsulated, show therapeutic effects; suggesting that the reflex effect via lingual taste receptors is not the only mechanism of action.
Based on the pharmacological and clinical data and the
a)Traditional herbal medicinal product used in temporary loss of appetite
b)Traditional herbal medicinal product used for mild dyspeptic/gastrointestinal disorders
According to the discussion concerning the safety of preparations of A. absinthium with respect to their content of thujone, following preparations and related posologies were agreed on:
a)comminuted herbal substance for tea preparation:
to be taken 30 min before meals
b)comminuted herbal substance in tablets: 2.28 g herbal substance daily comminuted herbal substance for tea preparation:
tincture (1:5); extraction solvent: ethanol 70% (v/v): approx.
The intake of thujone should not exceed 3.0 mg/day and the duration of intake is restricted to a maximum of 2 weeks. Chemotypes of A. absinthium with low content of thujone should be preferred.
The published study on the possible reduction in steroid dosages in Crohn’s disease after A. absinthium intake is well conducted. However,
II.3.3 Clinical Safety/Pharmacovigilance
II.3.3.1 Patient exposure
II.3.3.2 Adverse events
Undesirable effects for aqueous preparations from the herbal substance are not reported. In the literature it is described, that contact with the flowers can provoke a
II.3.3.3 Serious adverse events and deaths
II.3.3.4 Laboratory findings
No data available.
II.3.3.5 Safety in special populations and situations
Dettling et al.  investigated if the impact of thujone (absinthe) on attention performance and mood differs from the one experienced with beverages that contain only alcohol. 22 healthy subjects were tested using an attention performance test, which was developed for aptitude diagnostics in the area of
performance and which is applied in the diagnostics of alcohol and
The calculated total amount of thujone consumed was 0.28 mg/kg and 0.028 mg/kg for men and 0.24 mg/kg and 0.024 mg/kg for women. The alcohol content was adjusted to 16 g/l in all beverages. The amount of liquid to be consumed depended on the weight of the subject. It was tried to attain a maximum blood alcohol concentration of 0.05% (= 0.5‰) for each subject. Before drinking every subject received a small standard meal; the beverage had to be drunk then within 10 min. All tests were performed before drinking (T0) and 30 (T1) and 90 min (T2) after drinking.
The results between
While within the treatment groups the mood state changed either from
II.188.8.131.52 Intrinsic (including elderly and children) /extrinsic factors
No data available. Use in children and adolescents under 18 years of age is not recommended because data are not sufficient and medical advice should be sought.
II.184.108.40.206 Drug interactions
No data available.
The action of thujone is explained in the literature by its binding to the GABA receptor. The intake of Absinthii herba preparations might therefore influence the effect of medicinal products acting via the GABA receptor, even if such effects were not seen clinically.
II.220.127.116.11 Use in pregnancy and lactation
No data available. Most sources recommend contraindication in pregnancy and lactation due to the uterus stimulating effects of thujone.
Tests on reproductive toxicity have only been performed with a dry ethanolic extract of A. absinthium orally administered to pregnant rats. Results showed significantly reduced sites of implantations and a reduction in the numbers of born pups per rat.
Safety during pregnancy and lactation has not been established. Because of the amounts of thujone in the preparations covered by the assessment report, the proposed contraindication was changed into the sentence “The use should be avoided during pregnancy and lactation.” after discussion in MLWP and HMPC.
Limited data are available for Absinthii herba. After intake of a concentrated infusion of Absinthii herba a male developed dizziness, atony, tremor of the legs, lasting uresiaesthesia and burning in the glans penis [LEWIN 1929] and it is stated that excessive doses of Absinthii herba preparations may cause vomiting, severe diarrhea, retention of urine or dazed feelings [ROTH ET AL. 1994]. On the other hand it is stated that after excessive or long lasting intake of Absinthii herba preparations aversions against the intake may develop. Therefore, acute or chronic intoxications due to Absinthii herba preparations are not suspected [HÄNSEL & STICHER 2007].
Overdosage of alcoholic Absinthii herba preparations or the use of the essential oil may cause CNS disturbances which can lead to convulsions and ultimately to unconsciousness and death [GESSNER 1974; ROTH ET AL. 1994].
Cases with severe intoxications in humans have been reported after consumption of essential oil rich in thujone [CENTINI & LAURINI 1987, MILETT ET AL. 1981]. Convulsions resembling epilepsy have been reported after the ingestion of isolated thujone [COBB 1922].
There are no cases of overdose reported concerning herbal tea preparations.
II.18.104.22.168 Drug abuse
No data available.
II.22.214.171.124 Withdrawal and rebound
No data available.
II.126.96.36.199 Effects on ability to drive or operate machinery or impairment of mental ability
No data available.
Attention performance [DETTLING ET AL. 2004] was changed under the influence of high thujone concentrations. For safety reasons affected patients should not drive or operate machinery after intake of Absinthii herba preparations.
II.3.3.6 Assessor’s overall conclusions on clinical safety
Limited data are available. From the study of Dettling et al.  it can be assumed that at least a concentration of
The use in children and adolescents is not recommended. The use of Absinthii herba during pregnancy or lactation should be avoided. Absinthii herba should not be used in cases of obstruction of the bile duct, cholangitis, or liver disease. Medical advice is needed in cases of gall stones or other biliary disorders. The intake of Absinthii herba preparations might influence the effect of medicinal products acting via the GABA receptor. After intake of preparations from Absinthii herba, patients should not drive or operate machinery for safety reasons. Duration of use should be limited to a maximum of 2 weeks.
Absinthii herba is well known and derived traditional herbal medicinal products have been used for centuries in European countries. Sufficient data are available to develop a Community monograph on the traditional use of Artemisia absinthium L., herba – provided the indications are suitable for self- medication. The proposed indications are:
a)Traditional herbal medicinal product use in temporary loss of appetite
b)Traditional herbal medicinal product used for mild dyspeptic/gastrointestinal disorders
The pharmacological studies in vitro and in vivo showed stimulating effects on the gastric, intestinal and biliary secretion.
The intake of thujone should not exceed 3.0 mg/day and the duration of use should be limited to 2 weeks. Chemotypes of A. absinthium with low content of thujone should be preferred.
Use of Absinthii herba should be avoided during pregnancy and lactation and Absinthii herba should not be taken in children and adolescent under 18 years of age and in patients with obstruction of the bile duct, cholangitis or liver disease. The intake of Absinthii herba preparations might influence the effect of medicinal products acting via the GABA receptor. For safety reasons, patients should not drive or operate machinery after intake of preparations from Absinthii herba.
Because the minimum required data on mutagenicity (Ames test) are not available for herbal preparations of Absinthii herba, an inclusion to the Community list of traditional herbal substances and preparations is not recommended.