Artemisia absinthium

Abstract and key points

Artemisia absinthium, also known as wormwood, is a plant from the Asteraceae/Compositae family which has been used medicinally since Roman times. It has been used orally and topically and small quantities are found in some foods and alcoholic drinks. Traditional use is based on wormwood as a bitter tonic for digestive disorders and loss of appetite.

Wormwood has been claimed to have anti-cancer effects but there is no evidence from clinical trials with cancer patients to support this claim.

Few cases of adverse effects have been reported but there are safety concerns for extracts that contain thujone which is reported to cause a wide range of toxic effects. 

NB: Not to be confused with Artemisia annua (sweet wormwood).

Citation

Karen Pilkington, CAM Cancer Consortium. Artemisia absinthium [online document], August 22, 2022.

Document history

Revised by Karen Pilkington in August 2022.
Assessed as up to date in August 2020 by Barbara Wider.
Assessed as up to date in January 2019 by Barbara Wider.
Assessed as up to date in February 2017 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
First published in May 2014 authored by Karen Pilkington.

What is it?

Description and background

Artemisia absinthium of the Asteriaceae or Compositae family, other names: Absinth(e), Wormwood, Common wormwood, Absinthii herba. Not to be confused with Artemisia annua (Sweet wormwood).  

Artemisia abinthium is a perennial plant, which grows as a small bush with feathery leaves and pale yellow flowers.  The applicable parts are those that are above ground. (NMD 2022) The plant is native from Europe to Siberia and Western Himalaya but is now found in other countries including Australia and India (POWO 2022) and across the northern United States and in Canada (US Forestry Service). The medical use of the wormwood plant dates back to at least Roman times and it was used as an anthelmintic (for removal of intestinal worms) and purgative, gradually becoming a general remedy for various diseases (Lachenmeier 2010). Use as a ‘cure-all’ continued through to the 19th century. The adoption of wormwood-flavoured alcoholic extracts and distillates as aperitifs as well as patent medicine led to large scale production and mass use. Chronic use was linked with a syndrome known as absinthism consisting of addiction, hyperexcitability, epileptic fits and hallucination (although this has since been disputed) and this led to a decline in use (Lachenmeier 2010). Interest in the plant was renewed due to research in conditions such as Crohn’s disease (Krebs 2010) and stroke (Bora 2010). These have not, however, been replicated.

No data are available on the prevalence of use in cancer patients.

Ingredient and quality issues

Wormwood’s aerial parts contain bitter principles (absinthin and anabsinthin), resins and organic acids. A volatile oil is present the composition of which has been found to vary with the largest part formed by monoterpenes. In some cases, the oil contains between 10% and 90% of thujone (a monoterpene ketone) which has been linked to adverse and toxic effects (Lachenmeier 2010; Judpentiene 2004). High concentrations of other monoterpenes including myrcene, and trans-sabinyl acetate have also been identified.

Alleged indications

Traditional use is based on wormwood as a bitter tonic for digestive disorders and loss of appetite. It is promoted as a sedative and anti-inflammatory and for external use for wounds, ulcers, skin blotches and insect bites. The European Medicines Agency Committee on Herbal Medicinal Products (HMPC) concluded that, on the basis of its long-standing use, wormwood herb preparations can be used for temporary loss of appetite or for mild heartburn and stomach/gut disorders (HMPC 2017, 2020).

In the context of cancer, A. absinthium has been investigated in in vitro studies for its potential cytotoxic effects.

Mechanisms of action

Wormwood has bactericidal, insecticidal and vermicidal activity mainly due to the thujone oils (Blagojevic 2006; Lopes-Lutz 2008). The thujone constituent is also a central nervous system stimulant which acts by modulating gamma-aminobutyric acid (GABA) type A receptors. However, this effect is more closely linked with observed toxic effects of wormwood (Lachenmeier 2010). Wormwood has been reported to reduce levels of tumour necrosis factor α (TNF-α), and may have a beneficial effect in a range of conditions influenced by pro-inflammatory cytokines such this (Krebs 2009; Krebs 2010).

In vitro studies in breast cancer and leukaemia cell lines indicate anti-proliferative activity together with promotion of apoptosis (programmed cell death) (Shafi 2012; Wegiera 2012). Crude extracts of the above ground parts of the plant have been reported to have induced anti-proliferative effects on human breast cancer cells which could possibly trigger apoptosis (Shafi 2012). A pilot study in leukaemia cell lines found that various plants from the Asteraceae family induced cell death by apoptosis but the correlation between polyphenol content and activity was inconsistent (Wegiera 2012). Subsequent in vitro studies have reported various anticancer effects in breast cancer cells including apoptosis and suppression of proliferation (Mughees 2020), and reduced migration and viability (Moacă 2019). Effects on apoptosis have also been observed in human colorectal cancer cells (Nazeri 2020) and liver cancer cells (Wei 2019). Migration and viability of melanoma cells were reduced (Moacă 2019) but proliferation of colorectal cancer cells appeared unaffected (Sultan 2020) by Artemisia absinthe extracts.

Application and dosage

There is no documented safe or effective dose for the use in treatment of cancer. Traditionally, wormwood has been used orally and topically. Based on traditional use, in temporary loss of appetite and mild dyspeptic/gastrointestinal disorders, a tea or tincture has been used containing the equivalent of 2-3g of the herb divided into 2 or 3 doses orally for not more than 2 weeks (HMPC 2020). Typical doses for other therapeutic uses are not available but the European Medicines Agency has advised that, due to potential for neurotoxicity, chemotypes with low content of thujone are preferred and the intake of thujone should not exceed 6 mg/day (HMPC 2020). Wormwood above ground parts have been used in flavouring alcoholic drinks including absinthe but use was banned in many countries due to toxicity related to thujone. Many countries now regulate absinthe and either specify maximum content of thujone or that absinthe should be thujone free.

Legal issues and cost

Wormwood was classified as an unsafe drug and banned in many countries including the USA although "thujone-free" wormwood extract has been approved by the US Food and Drug Administration (FDA) for use in foods and as a flavouring in alcoholic drinks (Bora 2010). In Europe, Artemisia absinthium L. has been recognised by the European Medicines Agency as a herb for which use is based on traditional use (HMPC 2020).

Wormwood products are available on the internet and the thujone content varies depending on the method of preparation. Based on suggested doses, the cost of one month’s treatment would be between 7 and 36 Euros.

Does it work?

Clinical trials, case studies

No clinical trials or case studies of wormwood in humans with cancer have been published.

Is it safe?

Adverse events

Wormwood oil has been reported to cause nausea, vomiting and muscle aches (NMD 2022). There have been very few anecdotal reports of the toxicity of Artemisia (Lachenmeier 2010). Chronic ingestion of absinthe, an alcoholic drink containing wormwood, has been reported to be linked to a syndrome known as absinthism. This is said to consist of gastro-intestinal symptoms, insomnia and hallucinations (NMD 2022). More severe adverse effects such as addiction, paralysis, epilepsy, brain damage, and psychiatric disorders and suicide have also been reported. However, the possible contribution of chronic alcohol intake has been also highlighted and the existence of a separate syndrome questioned (Lachenmeier 2015). There has also been a suggestion that some symptoms may be due to adulteration with metals or toxic plants (NMD 2022). One case of rhabdomyolysis leading to acute renal failure has been reported following accidental ingestion of 10ml of wormwood oil purchased on the internet (Weisbord 1997). Artemisia absinthia is a member of the Asteraceae/Compositae (daisy, sunflower etc.) family and may cause allergic reactions in people who are allergic to other plants in this group (HMPC 2020).

Contraindications

Wormwood has been assessed as likely unsafe for use in pregnancy if amounts larger than those found in food stuffs are ingested (NMD 2022). Insufficient information is available to assess its safety in lactation or when used topically in pregnancy. Thujone containing extracts have potentially toxic effects and therefore pose a particular risk with equivocal evidence on carcinogenicity from animal studies (Pelkonen 2013).

Wormwood is contraindicated in obstruction of the bile duct, cholangitis and liver disease (HMPC 2020) and in seizure disorders (NMD 2022).

Interactions

Thujone is metabolised via the cytochrome P450 enzyme system with involvement of the specific enzymes CYP2A6, CYP3A4 and CYP2B6 (Pelkonen 2012). Therefore, there is a theoretical risk of interactions with drugs and other herbs metabolised via this system. There is also a risk if used with other thujone-containing herbs such as Salvia spp. (sage) or Thuja spp.

Due to its potential effects on the central nervous system, there is a potential for interaction with anti-convulsant (anti-epilepsy) drugs (NMD 2022) and with drugs that act via GABA receptors (HMPC 2020).

One case has been reported of a probable interaction between warfarin and Artemisia absinthium leading to gastrointestinal bleeding (Açıkgöz 2013).

Warnings

These are described under Adverse events (above) and relate particularly to thujone-containing extracts. The European Medicines Agency recommends caution in people with gall-bladder disease or other biliary disorders and that driving and operating machinery is avoided during treatment (HMPC 2020). Most forms of tinctures contain alcohol.

References

Açıkgöz SK, Açıkgöz E. Gastrointestinal bleeding secondary to interaction of Artemisia absinthium with warfarin. Drug Metabol Drug Interact. 2013;28(3):187-9. doi: 10.1515/dmdi-2013-0021.

Blagojevic P , Radulovic N , Palic R , Stojanovic G . Chemical composition of the essential oils of Serbian wild-growing Artemisia absinthium and Artemisia vulgaris. J Agric Food Chem. 2006;54(13); 4780-4789

Bora KS, Sharma A. Neuroprotective effect of Artemisia absinthium L. on focal ischemia and reperfusion-induced cerebral injury. J Ethnopharmacol. 2010 Jun 16;129(3):403-9. doi: 10.1016/j.jep.2010.04.030.

HMPC, Committee on Herbal Medicinal Products. European Union herbal monograph on Artemisia absinthium L., herba. EMA/HMPC/751490/2016 Corr., 4th March 2020.  [new version]

Judþentienë A, Mockutë D. Chemical composition of essential oils of Artemisia absinthium L. (wormwood) growing wild in Vilnius. CHEMIJA. 2004;15(4): 64–68.

Krebs S, Omer B, Omer TN, Fliser D. Wormwood (Artemisia absinthium) for poorly responsive early-stage IgA nephropathy: a pilot uncontrolled trial. Am J Kidney Dis. 2010 Dec;56(6):1095-9. doi: 10.1053/j.ajkd.2010.06.025.

Krebs S, Omer TN, Omer B. Wormwood (Artemisia absinthium) suppresses tumour necrosis factor alpha and accelerates healing in patients with Crohn's disease - A controlled clinical trial. Phytomedicine. 2010 Apr;17(5):305-9. doi: 10.1016/j.phymed.2009.10.013.

Lachenmeier DW, Walch SG, Padosch SA, Kröner LU. Absinthe--a review. Crit Rev Food Sci Nutr. 2006;46(5):365-77.

Lachenmeier DW. Wormwood (Artemisia absinthium L.)--a curious plant with both neurotoxic and neuroprotective properties? J Ethnopharmacol. 2010 Aug 19;131(1):224-7.

Lopes-Lutz D, Alviano DS, Alviano CS, Kolodziejczyk PP. Screening of chemical composition, antimicrobial and antioxidant activities of Artemisia essential oils. Phytochemistry. 2008 May;69(8):1732-8.

Moacă EA, Pavel IZ, Danciu C, Crăiniceanu Z, Minda D, Ardelean F, et al. Romanian Wormwood (Artemisia absinthium L.): Physicochemical and Nutraceutical Screening. Molecules (Basel, Switzerland). 2019;24(17).

Mughees M, Wajid S, Samim M. Cytotoxic potential of Artemisia absinthium extract loaded polymeric nanoparticles against breast cancer cells: Insight into the protein targets. Int J Pharm. 2020 Aug 30;586:119583. doi: 10.1016/j.ijpharm.2020.119583. Epub 2020 Jun 27. PMID: 32603837.

Nazeri M, Mirzaie-Asl A, Saidijam M, Moradi M. Methanolic extract of Artemisia absinthium prompts apoptosis, enhancing expression of Bax/Bcl-2 ratio, cell cycle arrest, caspase-3 activation and mitochondrial membrane potential destruction in human colorectal cancer HCT-116 cells. Mol Biol Rep. 2020 Nov;47(11):8831-8840.

NMD, Natural Medicines Comprehensive Database. Wormwood. Available at: https://naturalmedicines.therapeuticresearch.com/ [requires subscription], accessed on 28th July 2022.

Pelkonen O, Abass K, Wiesner J. Thujone and thujone-containing herbal medicinal and botanical products: toxicological assessment. Regul Toxicol Pharmacol. 2013 Feb;65(1):100-7. doi: 10.1016/j.yrtph.2012.11.002.

POWO, Plants of the World Online. Artemisia absinthium L, Royal Botanic Gardens Kew, 2022, accessed on 22 August 2022.

Shafi G, Hasan TN, Syed NA, Al-Hazzani AA, Alshatwi AA, Jyothi A, Munshi A. Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer. Mol Biol Rep. 2012 Jul;39(7):7373-9.

Sultan MH, Zuwaiel AA, Moni SS, Alshahrani S, Alqahtani SS, Madkhali O, Elmobark ME. Bioactive Principles and Potentiality of Hot Methanolic Extract of the Leaves from Artemisia absinthium L "in vitro Cytotoxicity Against Human MCF-7 Breast Cancer Cells, Antibacterial Study and Wound Healing Activity". Curr Pharm Biotechnol. 2020;21(15):1711-1721.

Wegiera M, Smolarz HD, Jedruch M, Korczak M, Koproń K. Cytotoxic effect of some medicinal plants from Asteraceae family on J-45.01 leukemic cell line--pilot study. Acta Pol Pharm. 2012 Mar-Apr;69(2):263-8.

Wei X, Xia L, Ziyayiding D, Chen Q, Liu R, Xu X, et al. The Extracts of Artemisia absinthium L. Suppress the Growth of Hepatocellular Carcinoma Cells through Induction of Apoptosis via Endoplasmic Reticulum Stress and Mitochondrial-Dependent Pathway. Molecules (Basel, Switzerland). 2019;24(5). 

Weisbord, M.D., Jeremy B. Soule, M.D., and Paul L. Kimmel, M.D. Poison on Line — Acute Renal Failure Caused by Oil of Wormwood Purchased through the Internet. N Engl J Med 1997; 337:825-827

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