Wormwood

Scientific Name(s): Artemisia absinthium L.
Common Name(s): Absinthe, Absinthites, Absinthium, Aci pelin, Ajenjo, Ak pelin, Armoise, Büyük pelin, Pelin otu, Vilayati afsanteen, Wermut, Wormwood

Medically reviewed by Drugs.com. Last updated on Jun 21, 2023.

Clinical Overview

Use

Wormwood has traditionally been used as an intestinal anthelmintic and to treat dyspepsia, although no clinical data support these uses. Antimicrobial, antifungal, and antipyretic activity are documented in nonclinical studies. Initial clinical studies suggest that wormwood may have antiulcer, antiprotozoal, or anti-inflammatory (ie, in Crohn disease and immunoglobulin A [IgA] nephropathy) effects, but information regarding use is limited. Wormwood is also used as a flavoring agent.

Dosing

Wormwood is commercially available as an essential oil, as well as in capsule, tablet, tincture, and aqueous extract doseforms. However, clinical evidence is lacking to support dosing recommendations.

Contraindications

Avoid use in individuals with hypersensitivity to any of the components of wormwood, particularly the essential oil. It may be contraindicated in patients with an underlying defect of hepatic heme synthesis, because thujone is a porphyrogenic terpenoid.

Pregnancy/Lactation

Avoid use. Abortifacient and emmenagogue effects have been documented.

Interactions

A single case report suggests that wormwood coadministered with warfarin may increase the international normalized ratio (INR).

Adverse Reactions

Thujone, the volatile oil in wormwood, produces a state of excitement and is a powerful convulsant. Repeated ingestion of wormwood may result in absinthism, a syndrome characterized by digestive disorders, thirst, restlessness, vertigo, trembling of the limbs, numbness of the extremities, loss of intellect, delirium, paralysis, and death.

Toxicology

Wormwood is classified as an unsafe herb by the US Food and Drug Administration (FDA) because of the neurotoxic potential of thujone and its derivatives; when used in foods, it is generally regarded as safe if it is thujone free. The safety of wormwood is poorly documented despite its long history as a food additive. Convulsions, dermatitis, and renal failure have been reported.

Scientific Family

• Asteraceae (daisy)

Botany

Wormwood is an odorous, perennial shrub native to Europe and naturalized in the northeastern, central, and northwestern United States. Its aromatic leaves have a strong sage odor and bitter taste, and its multibranched stems are covered with fine, silky hairs. The plant has a fibrous root system and grows to approximately 1.2 m in height. Its small flowers, which bloom July through August, are green to yellow and arranged in large, spikelike panicles. The deeply lobed leaves are grayish-green in color. Leaves and small stems no thicker than 4 mm are used medicinally.(Gambelunghe 2002, Leung 1980, Omer 2007, Watson 2002)

History

The name "wormwood" is derived from ancient use of the plant and its extracts as an intestinal anthelmintic. In traditional medicinal systems, the aerial parts have been used for anthelmintic, antiseptic, febrifuge, and stomachic purposes, and to alleviate chronic fever, dyspepsia, and hepatobiliary ailments.(Batiha 2020, Khattak 1985, Krebs 2010) An ethnobotanical study in Turkey documented the plant's use as an abortifacient, an appetite stimulant, and a blood depurative, as well as a treatment for stomachache.(Kültür 2007) Caribbean folk medicine documents wormwood use for menstrual pain, vaginitis, and other unspecified female complaints.(Lans 2007) Various parts of the plant (aerial parts, leaves, inflorescences) have been used as a bitter seasoning to flavor food and added to alcoholic and nonalcoholic beverages.(Shikov 2017) In western European traditional herbal medicine, wormwood was recommended for gastric pain and cardiac stimulation and to restore declining mental function. French and Spanish New Mexicans used A. absinthium together with other plant species for emmenagogic purposes.(Lans 2007) In traditional Chinese medicine, practitioners treated acute bacillary dysentery by applying fresh and dried absinthium. A poultice of the plant has been used medicinally for tendon inflammation, and wormwood tea was used traditionally as a diaphoretic.(Gilani 1995, Guarrera 2005, Muto 2003, Zhang 2005)

Wormwood extract is the main ingredient in absinthe, a toxic liquor that induces absinthism, a syndrome characterized by addiction, GI problems, auditory and visual hallucinations, epilepsy, brain damage, and increased risk of psychiatric illness and suicide; the drink has been banned in several countries. In the 19th century, absinthe-based liquor was believed to have aphrodisiac and healing properties and was reputed to stimulate creativity. The emerald-green color of absinthe liquor was due to chlorophyll; however, copper and antimony salts were reportedly added as colorants to inferior batches and thought to have contributed to toxicity. Thujone-free wormwood extract is used as a flavoring, primarily in alcoholic beverages such as vermouth.(Arnold 1989, Gambelunghe 2002, Lachenmeier 2006)

Chemistry

The medicinal or active components in wormwood are the essential oils, anabsinthin, absinthin, resins, and organic acids. The bitter taste is caused by the glucosides absinthin and anabsinthin and several related compounds.(Gambelunghe 2002, Tyler 1987)

Lactones include arabsin, artabin, ketopelenolide, and others related to santonin.(Leung 1980) An important isolated flavonoid is 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (p7F).(Lee 2004)

Many Artemisia species contain monoterpenoid thujone derivatives with toxic CNS effects. Wormwood typically contains small amounts of thujone derivatives, including 0.2% (Z)-thujone and 0.5% (E)-thujone(Gambelunghe 2002, Kordali 2005); however, thujone content varies widely.(Blagojević 2006)

The major components of wormwood oil include chamazulene (18%), nuciferol butanoate (8%), nuciferol propionate (5%), and caryophyllene oxide (4%). The essential oils also contain a large amount of aromatic compounds (41%) and a low level of oxygenated monoterpenes (24%). The plant contains a pleasant smelling volatile oil (approximately 1% to 2% by weight), as well as phellandrene, pinene, azulene, and more than 6 other minor components.(Arnold 1989) Flowers may contain oil composed of up to 35% thujones. Several chemotypes have been detected, including cis- and trans-epoxy-ocimenes, which account for up to 57% of the volatile oil derived from Italian absinthium. The herb is standardized based on absinthin.(Arnold 1989, Blagojević 2006, Leung 1980, Omer 2007)

Wormwood contains trace amounts of thymol and carvacrol, as well as other phenolic compounds with potent antioxidant and free radical–scavenging activity.(Kordali 2005)

Uses and Pharmacology

Scientific literature regarding wormwood consists mostly of phytochemical, ethnopharmacological, and ethnobotanical investigations; limited clinical investigation has been conducted.

Anthelmintic activity

The anthelmintic activity of the plant is thought to be due to lactones related to santonin, which is found in wormseed and other species of Artemisia. In addition, thujone can stun roundworms, which can then be expelled by normal intestinal peristalsis.(Arnold 1989, Leung 1980)

Animal data

A study of plants in central Italy reported veterinary use of the plant as an anthelmintic for cows.(Guarrera 1999)

Clinical data

An ethnobotanical and ethnopharmacological study of herbal treatments of intestinal worms documented the use of wormwood for treating intestinal worms in Dominica, West Indies, according to resident interviews.(Quinlan 2002)

Antifungal activity

In vitro data

The essential oils distilled from the aerial parts of A. absinthium inhibited the growth of Candida albicans and Saccharomyces cerevisiae var. chevalieri.(Juteau 2003)

Anti-Inflammatory/Antioxidant activity

In vitro data

pF7, a flavonoid isolated from A. absinthium, had antioxidant activity and inhibited nuclear factor kappa B (NF-KB) activation. The regulatory functions of pF7 were examined on the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), and TNF-alpha, and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and collagen-induced arthritis. The production of COX-2, PGE₂, iNOS, and NO in lipopolysaccharide-stimulated RAW 264.7 cells was inhibited by pF7. pF7 also suppressed TNF-alpha activity and inhibited NF-KB.(Lee 2004)

Antimicrobial activity

Thujone oils are recognized as the active constituents affecting microbial growth.(Blagojević 2006)

Animal and in vitro data

The essential oils of wormwood have antimicrobial activity against Escherichia coli, Salmonella enteritidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, C. albicans, and Aspergillus niger. The activity was comparable with that of erythromycin.(Blagojević 2006) Hexane-, chloroform-, and water-soluble extracts of A. absinthium exhibited antipyretic activity against subcutaneous yeast injections in rabbits. No toxic effects were documented for the plant extract at doses up to 1.6 g/kg.(Khattak 1985)

Antiprotozoal effects

Clinical data

Clinical studies have also evaluated the effects of A. absinthium on amoebiasis caused by Entamoeba histolytica (amoeba that causes dysentery). Patients with intestinal amoebiasis (N=25) were given a 500 mg capsule containing powdered A. absinthium herb 3 times a day for 15 weeks. Patients at various stages of the disease experienced relief, with complete eradication achieved in 70%.(Szopa 2020)

CNS activity

Animal and in vitro data

A. absinthium has been studied for cognitive enhancement effects because of its nicotinic and muscarinic cholinergic receptor activities (concentration that inhibits 50% of less than 1 mg/mL) in homogenates of human cerebral cortical membranes.(Wake 2000) In a study in rats, it was hypothesized that activation of cannabinoid receptors was responsible for the intoxicating effects of thujone; however, study results showed that thujone exhibited low affinity for rat cannabinoid receptors.(Meschler 1999) In a study evaluating effects of medicinal plants on nerve growth factor–potentiating activities, methanol extracts of A. absinthium enhanced neurite outgrowth induced by nerve growth factor and pheochromocytoma 12D cells.(Li 2004)

Crohn disease

Clinical data

In Germany, a multicenter, double-blind, placebo-controlled trial in patients with Crohn disease (N=40) examined the efficacy of the herbal supplement SedaCrohn; each SedaCrohn 400 mg capsule contains primarily wormwood powder (250 mg), in addition to rose (100 mg), cardamom (40 mg), and mastic resin (10 mg). Three capsules containing either wormwood powder or placebo were taken twice daily. The study consisted of 2 phases: a 10-week double-blind phase during which wormwood was administered and corticosteroid doses were tapered, and a 10-week observational phase after discontinuation of wormwood, in which corticosteroids were restarted as needed. The study enrolled patients receiving stable daily doses of corticosteroids; treatment with 5-aminosalicylates, azathioprine, and methotrexate was allowed, but patients treated with a tumor necrosis factor alpha (TNF-alpha) inhibitor were excluded. The study enrolled patients with a score of 170 or more on the Crohn Disease Activity Index (CDAI). Outcomes of the study included clinical improvement on CDAI and Hamilton Depression (HAM-D) scale. In the first phase of the study, 90% of patients treated with wormwood had an improvement in CDAI scores despite corticosteroid tapering, while CDAI scores increased in placebo-treated patients. At week 10, almost complete remission of Crohn disease symptoms was reported in 65% of patients treated with wormwood, compared with 0% with placebo. In the second phase of the study, it was necessary to restart corticosteroids in 10% of patients treated with wormwood, compared with 80% of patients treated with placebo. At week 10, HAM-D scores decreased by 9.8±5.8 points with wormwood and by 3.4±6.6 points with placebo. A HAM-D score less than 10 was achieved by 70% of patients treated with wormwood, compared with 0% treated with placebo. No patients discontinued treatment early; the study did not report adverse effect data.(Omer 2007)

A second multicenter, open-label trial in Germany randomized 20 patients with Crohn disease to receive SedaCrohn 750 mg 3 times per day or placebo for 6 weeks. The study included patients treated with a stable dose of 5-aminosalicylate, azathioprine, or methotrexate, but excluded patients receiving a TNF-alpha inhibitor. Enrolled patients had a CDAI score of 200 or more. Outcomes included changes in TNF-alpha levels and clinical improvement on CDAI and HAM-D. TNF-alpha levels decreased substantially in patients receiving wormwood (24.5±3.5 pg/mL at baseline vs 8±2.5 pg/mL at week 6) but did not appreciably change in patients receiving placebo (25.7±4.6 pg/mL at baseline vs 21.1±3.2 pg/mL at week 6). Mean CDAI score decreased in patients receiving wormwood (275±15 at baseline vs 175±12 at week 6) but did not decrease substantially in patients receiving placebo (282±11 at baseline vs 260±14 at week 6). CDAI score dropped below 150 in 6 patients treated with wormwood. Mean HAM-D score decreased by 9.8±5.8 points with wormwood compared with 3.4±6.6 points with placebo. No patients discontinued treatment early in this study and no "out of the line" adverse effects were attributed to wormwood.(Krebs 2010)

A meta-analysis identified 7 placebo-controlled clinical trials that evaluated the efficacy and tolerability of herbal medicines in inflammatory bowel disease. Based on 2 studies (n=60) evaluating A. absinthium in patients with Crohn disease, a significant result was identified for induction of clinical remission (relative risk, 27 [95% CI, 3.23 to 260.81]).(Rahimi 2013)

GI ulcer

Animal data

Extracts of A. absinthium plant reduced the volume of gastric juice, acid output, and peptic activity in ulcerated rats.(Shafi 2004)

Clinical data

Clinical studies reported that ethanolic A. absinthium extracts can increase gastric, biliary, and intestinal secretion after oral administration; this effect may be due to the essential oil and bitter substances content.(Batiha 2020)

Hepatoprotective effects

Animal data

Wormwood demonstrated hepatoprotective activity against acetaminophen- and carbon tetrachloride–induced liver toxicity in rats and mice. The mechanism of action was associated with inhibition of hepatic microsomal drug metabolizing enzymes, antioxidant activity, and/or blocking of calcium channels.(Gilani 1995)

IgA nephropathy

Clinical data

A noncontrolled pilot study evaluating wormwood's potential to reduce TNF-alpha activity included 10 patients with biopsy-proven IgA nephropathy. Patients had normal renal function and protein excretion between 500 and 3,500 mg/day, despite treatment with ramipril and valsartan. Renal function and blood pressure were compared with baseline values following treatment with SedaLeukin (a thujone-free wormwood preparation) 1.8 g/day for 6 months. The urine protein-creatinine ratio decreased significantly from 2,340±530 mg/g to 315±200 mg/g (P<0.001). Estimated glomerular filtration rate and endogenous creatinine clearance did not change during the study. Mean blood pressure decreased from 120.5±8.6/83±4.8 mm Hg at baseline to 108±9/71±7.7 mm Hg (P<0.002). Wormwood was well tolerated; no patients discontinued the study due to adverse effects.(Krebs 2010)

Dosing

Wormwood is commercially available as an essential oil, as well as in capsule, tablet, tincture, and aqueous extract doseforms. However, clinical evidence is lacking to support dosing recommendations. Traditional dosing of the herb as an infusion has ranged from 2 to 3 g daily for various uses.(Heilpflanzen-Welt Bibliothek 2021)

Pregnancy / Lactation

Avoid use. Abortifacient and emmenagogue effects have been documented.(Brinker 1998, Ernst 2002)

Interactions

Theoretically, the plant may affect the efficacy of antacids, histamine receptor antagonists, proton pump inhibitors, and sucralfate.(Skyles 2004)

The thujones in wormwood may reduce the clinical efficacy of phenobarbital by lowering the seizure threshold.(Miller 1998)

Warfarin: Wormwood may enhance the anticoagulant effect of warfarin. Monitor therapy.(Açιkgöz 2013)

Adverse Reactions

Thujone produces a state of excitement and is a powerful convulsant. Ingestion of wormwood may lead to absinthism, a syndrome characterized by digestive disorders, thirst, restlessness, vertigo, trembling of the limbs, numbness of the extremities, loss of intellect, delirium, paralysis, and death.(Brinker 1998, Gambelunghe 2002)

Data collected between 2004 and 2013 from 8 US centers in the Drug-Induced Liver Injury Network revealed that 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements. Of the 217 supplement products implicated in liver injury, 175 had identifiable ingredients, of which wormwood was among the 32 (18%) single-ingredient products.(Navarro 2014)

Toxicology

Avoid use in individuals with hypersensitivity to any of the components of wormwood, particularly the essential oil. Wormwood may be contraindicated in patients with an underlying defect of hepatic heme synthesis because thujone is a porphyrogenic terpenoid.(Bonkovsky 1992, Skyles 2004)

Wormwood is classified as an unsafe herb by the FDA because of the neurotoxic potential of thujone and its derivatives; when used in foods, it is generally regarded as safe if it is thujone free.(FDA 2020) Few studies document the safety of wormwood despite its long history of use as a food additive.(Weisbord 1997) Previous reports document neurotoxic effects with long-term use of A. absinthium due to the presence of thujone and its analogues. Administration of high doses of A. absinthium can cause CNS disorders, intestinal cramps, vomiting, dizziness, and headache. A. absinthium essential oil is contraindicated during pregnancy or breastfeeding, and in individuals with allergy, hyperacidity, and peptic ulcer.(Batiha 2020)

In a 13-week dose toxicity study, convulsions were observed in rats given thujone in concentrations as low as 25 mg/kg/day. An increase in mortality was shown in rats given 50 mg/kg/day.(Logarto 2001) Other studies report a dose of 120 mg/kg as fatal, including a subcutaneous median lethal thujone dose of 134 mg/kg in mice.(Guarrera 1999, Lachenmeier 2006, Windholz 1983)

A case report describes a 31-year-old man who experienced convulsions after drinking 10 mL of wormwood essential oil, which the patient mistook for absinthe liquor. The seizure was believed to be caused by wormwood essential oil, which also led to rhabdomyolysis, renal failure, and congestive heart failure. The patient recovered, and laboratory parameters returned to normal after 17 days.(Weisbord 1997)

References

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