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Wormwood

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

Clinical Overview

Use

Wormwood was traditionally used to treat worm infestations, although no clinical data support this use. Anti-inflammatory, antipyretic, and chemotherapeutic activity are documented in nonhuman studies. Initial studies suggest that wormwood may improve Crohn disease symptoms, but information regarding the plant's use in immunoglobulin A (IgA) nephropathy is limited. In Germany, woodworm is used to treat loss of appetite, dyspepsia, and biliary dyskinesia. 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 dosage forms. However, no recent clinical evidence supports dosing recommendations. Traditional use of the herb for treating dyspepsia was dosed as an infusion of 2 to 3 g daily.

Contraindications

Avoid use 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. Documented abortifacient and emmenagogue effects.

Interactions

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

Adverse Reactions

The volatile oil thujone 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; 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.

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 about 1.2 m tall. 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.1, 2, 3, 4

History

The name "wormwood" is derived from ancient use of the plant and its extracts as an intestinal anthelmintic. In Pakistan's indigenous medicinal systems, the leaves and flowering tops are used as an anthelmintic, antiseptic, febrifuge, and stomachic, and to alleviate chronic fever, dyspepsia, and hepatobiliary ailments. An ethobotanical study in Turkey documented the plant's use as an abortifacient, as a blood depurative, and in treating stomachaches. Caribbean folk medicine documents wormwood use for menstrual pain, vaginitis, and other unspecified female complaints.5 Extracts of the plant are used as a bitter seasoning for food and added to drinks such as beer, tea, or coffee, and it has also been used as an appetizer.6 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 the plant species along with other plants as an emmenagogue.5 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.7, 8, 9, 10

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, but in the 19th century, absinthe-based liquor was believed to have aphrodisiac and healing properties and was also reputed to stimulate creativity. The emerald-green color of absinthe liquor came from chlorophyll; however, copper and antimony salts were reportedly added as colorants to inferior batches, resulting in toxic consequences. Thujone-free wormwood extract is used as a flavoring, primarily in alcoholic beverages such as vermouth.2, 11, 12

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.2, 13

Lactones include arabsin, artabin, ketopelenolide, and others related to santonin.1 An important isolated flavonoid is 5,6,3′,5′-tetramethoxy 7,4′-hydroxyflavone (p7F).14

Essential oils

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)-thujone2, 15; however, the thujone content varies widely.16

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 (about 1% to 2% by weight), as well as phellandrene, pinene, azulene, and more than 6 other minor components.11 Flowers may contain oil composed of up to 35% thujones. cis- and trans-epoxycymenes account for up to 57% of the volatile oil derived from Italian absinthium. The herb is standardized based on absinthin.1, 4, 11, 16

Wormwood contains trace amounts of thymol and carvacrol, as well as other phenolic compounds with potent antioxidant and free radical-scavenging activity.15

Uses and Pharmacology

Scientific literature contains mostly phytochemical, ethnopharmacological, and ethnobotanical investigations, with little clinical investigation of wormwood.

Anthelmintic activity

The anthelmintic activity of the plant is thought to be caused by 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.1, 11

Animal data

A study of plants in central Italy reported veterinary use of the plant as an anthelmintic for cows.17

Clinical data

An ethnobotanical and ethnopharmacological study documented the use of wormwood for treating intestinal worms in Dominica, West Indies.18

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.19

Antimicrobial activity

Thujone oils are recognized as the active constituents affecting microbial growth.16

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.16

Animal data

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.20

Crohn disease

Clinical data

In Germany, a multicenter, double-blind, placebo-controlled trial examined the efficacy of SedaCrohn, an herbal supplement containing A. absinthium, 500 mg 3 times per day in 40 patients with Crohn disease.4 The study had 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 stable patients treated with corticosteroids. Treatment with 5-aminosalicylates, azathioprine, and methotrexate was allowed, but the study excluded patients treated with a tumor necrosis factor (TNF)-alpha inhibitor.21 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 the CDAI and Hamilton Depression scale (HAM-D). 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 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 in this study. The study did not report adverse effect data.

A second German, multicenter, open-label trial randomized 20 patients with Crohn disease to receive SedaCrohn 750 mg 3 times per day or placebo for 6 weeks. The study included stable patients treated with a 5-aminosalicylate, azathioprine, or methotrexate, but excluded patients treated with 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 the 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). The mean CDAI score dropped 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). The CDAI score dropped below 150 in 6 patients treated with wormwood. The 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.

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).41

IgA nephropathy

Clinical data

In an uncontrolled pilot study, 10 patients with biopsy-proven IgA nephropathy were given SedaLeukin, a thujone-free wormwood preparation, 1.8 g/day for 6 months.22 Wormwood was evaluated because it may reduce TNF-alpha activity. 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. 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 dropped 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 dropped out of the study due to adverse effects.

Inflammation

In vitro

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.14

Other uses

Antihemolytic effect

In vitro, an extract of the plant protected human erythrocytes against hypotonic shock.23

GI ulcer

Extracts of the plant reduced the volume of gastric juice, acid output, and peptic activity in ulcerated rats.24

CNS

A. absinthium has been studied for cognitive enhancement because of its nicotinic and muscarinic cholinergic receptor activity (concentration that inhibits 50% of less than 1 mg/mL) in homogenates of human cerebral cortical membranes.25 The intoxicating effects of thujone were believed to activate receptors responsible for marijuana intoxication; however, thujone exhibited low affinity for rat cannabinoid receptors.26 Methanol extracts of A. absinthium enhanced neurite outgrowth induced by nerve growth factor and pheochromocytoma 12D cells.27

Dosing

Wormwood is commercially available as an essential oil, as well as in capsule, tablet, tincture, and aqueous extract dosage forms. However, no clinical evidence supports dosing recommendations. Traditional use of the herb for treating dyspepsia was dosed as an infusion of 2 to 3 g daily.28

Pregnancy / Lactation

Avoid use because of documented abortifacient and emmenagogue effects.29, 30

Interactions

Acetaminophen

Wormwood has hepatoprotective action 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 calcium channels.7

GI medications

Theoretically, the plant may affect the efficacy of antacids, histamine-receptor antagonists, proton pump inhibitors, and sucralfate.31

Phenobarbital

The thujones in wormwood may reduce the clinical efficacy of phenobarbital by lowering the seizure threshold.32

Warfarin

A case report describes a probable interaction between wormwood and warfarin.33 An 82-year-old woman treated with warfarin for atrial fibrillation was hospitalized with GI bleeding and an extremely high INR after consumption of wormwood. The Naranjo adverse reaction probability scale score was 6, suggesting a probable relationship between ingestion of wormwood and a high INR with warfarin.

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.2, 29

Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, wormwood was among the 22% (116) of the single-ingredient products.42

Toxicology

Avoid use with hypersensitivity to any of the components of wormwood, particularly the essential oil. Wormwood may be contraindicated in patients with an underlying defect with hepatic heme synthesis because thujone is a porphyrogenic terpenoid.31, 34

Wormwood is classified as an unsafe herb by the FDA because of the neurotoxic potential of thujone and its derivatives; it is generally regarded as safe if it is thujone free.35 Few studies document the safety of wormwood despite its long history of use as a food additive.36

Convulsions

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.37 Other studies document a dose of 120 mg/kg as fatal, including a subcutaneous median lethal dose of thujone in mice as 134 mg/kg.12, 17, 38 A 31-year-old man suffered convulsions after drinking 10 mL of wormwood essential oil.39

Dermatitis

Wormwood oil is used as an ingredient in rubefacient preparations; the flowers may induce topical eruptions in sensitized individuals.3, 40

Rhabdomyolysis and renal failure

A 31-year-old man suffered convulsions after drinking 10 mL of wormwood essential oil. The patient mistook the essential oil as absinthe liquor and consumed the 10 mL full strength. The seizure was believed to be caused by the 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.39

References

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10. Muto T, Watanabe T, Okamura M, Moto M, Kashida Y, Mitsumori K. Thirteen-week repeated dose toxicity study of wormwood (Artemisia absinthium) extract in rats. J Toxicol Sci. 2003;28(5):471-478.14746350
11. Arnold WN. Absinthe. Sci Am. 1989;260(6):112-117.2658044
12. Lachenmeier DW, Emmert J, Kuballa T, Sartor G. Thujone—cause of absinthism? Forensic Sci Int. 2006;158(1):1-8.15896935
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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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