Wormwood

Scientific Name(s): Artemisia absinthium L. Family: Asteraceae (daisies)

Common Name(s): Wormwood , absinthium , armoise , wermut , absinthe , absinthites , ajenjo , pelin otu , aci pelin , ak pelin , buyuk pelin , vilayati afsanteen 1 , 2 , 3 , 4

Uses

Wormwood was traditionally used to treat worm infestations, although there is no clinical data supporting this use. Anti-inflammatory, antipyretic, and chemotherapeutic activity is documented in nonhuman studies. Information regarding the plant's use in Crohn disease 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 dosage forms. However, there is no recent clinical evidence to support dose recommendations for wormwood. Traditional use for treating dyspepsia was dosed at 3 to 5 g daily as an infusion or 2 to 3 g daily as the herb.

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 with hepatic heme synthesis (thujone is a porphyrogenic terpenoid).

Pregnancy/Lactation

Documented abortifacient and emmenagogue effects. Avoid use.

Interactions

None well documented.

Adverse Reactions

Thujone produces a state of excitement and is a powerful convulsant. 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 Food and Drug Administration (FDA) because of the neurotoxic potential of thujone and its derivatives. The safety of wormwood is poorly documented despite its long history as a food additive. Convulsions, dermatitis, and renal failure have been documented.

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 in height. Its small flowers, which bloom July through August, are green to yellow and arranged in large, spike-like panicles. The deeply lobed leaves are grayish-green in color. Leaves and stems no thicker than 4 mm are used medicinally. 1 , 2 , 5 , 6

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 documents the plant's use as an abortifacient, as a blood depurative, and in treating stomach aches. It has also been used as an appetizer. 7 Caribbean folk medicine documents the use of wormwood for menstrual pain, vaginitis, and other unspecified female complaints. 8 Extracts of the plant are used as a bitter seasoning for food and added to drinks such as beer, tea, or coffee. In western European traditional herbal medicine, wormwood was recommended for gastric pain, cardiac stimulation, and to restore declining mental function. French and Spanish New Mexicans used the plant species along with other plants as an emmenagogue. 8 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. 4 , 9 , 10 , 11

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 known for its aphrodisiac and healing properties and also was 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, with toxic consequences. Thujone-free wormwood extract is currently used as a flavoring, primarily in alcoholic beverages such as vermouth. 2 , 12 , 13

Chemistry

The medicinal or active components in wormwood are the essential oils, anabsinthin, absinthin, resins, and organic acids. The bitter taste of wormwood is caused by the glucosides absinthin and anabsinthin, and several related compounds. 2 , 14

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). 15

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 )-thujone 2 , 3 ; 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. 12 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 , 6 , 12 , 16

Wormwood contains trace amounts of thymol and carvacrol, as well as other phenolic compounds with potent antioxidant and free radical-scavenging activity. 3

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 , 12

Animal data

A similar study of plants in central Italy reported some 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 considered 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 double-blind, placebo-controlled trial examined the efficacy of administering an herbal blend (3 × 500 mg per day) containing wormwood versus placebo over 10 weeks in 40 patients suffering from Crohn disease. Twenty patients received the treatment, while the remaining patients received placebo. All patients achieved good control of their symptoms through use of steroids and other medications. Outcome measures included the effect of wormwood on steroid dependence and psychological measures, such as decline in symptoms of depression often associated with Crohn disease. Physical and psychological symptoms worsened for patients taking placebo. However, those receiving wormwood showed gradual improvement of symptoms, with 13 patients nearly free of physical and psychological symptoms and less dependent on steroids. Patients suffered no serious adverse reactions. 6

Inflammation
In vitro

pF7, a flavonoid isolated from A. absinthium , has antioxidant activity and has inhibited nuclear factor-kappa B (NF-kappa B activation). The regulatory functions of pF7 were examined on the production of nitric oxide (NO), prostaglandin (E2 and PGE2), tumor necrosis factor (TNF-alpha), and expression of 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-kappa B. 15

Other pharmacological activity
Antihemolytic effect

In vitro, the plant species protected human erythrocytes against hypotonic shock. 21

GI ulcer

In rats, extracts of the plant species reduced the volume of gastric juice, acid output, and peptic activity in ulcerated rats. 22

CNS

A. absinthium has been studied for cognitive enhancement because of its nicotinic and muscarinic cholinergic receptor activity (concentration that inhibits 50% [IC 50 ] of less than 1 mg/mL) in homogenates of human cerebral cortical membranes. 23 The intoxicating effects of thujone were believed to activate receptors responsible for marijuana intoxication; however, thujone exhibited low affinity for rat cannabinoid receptors. 24 Methanol extracts of A. absinthium enhanced neurite outgrowth induced by nerve growth factor and PC12D cells. 25

Dosage

Wormwood is commercially available as an essential oil, as well as in capsule, tablet, tincture, and aqueous extract dosage forms. However, there is no recent clinical evidence to support dose recommendations for wormwood. Its classical use for treating dyspepsia was at a dose of 3 to 5 g daily as an infusion or 2 to 3 g daily as the herb.

Pregnancy/Lactation

Avoid use because of documented abortifacient and emmenagogue effects. 26 , 27

Interactions

Acetaminophen

Wormwood has a hepatoprotective action against acetaminophen and carbon tetrachloride-induced liver toxicity in rats and mice. The mechanism of action may be associated with inhibition of hepatic microsomal drug metabolizing enzymes, antioxidant activity, and/or blocking calcium channels. 4

GI medications

Theoretically, the plant may affect the efficacy of antacids, histamine-receptor antagonists, proton pump inhibitors, and sucralfate. 28

Phenobarbital

The thujones in wormwood may reduce the clinical efficacy of phenobarbital by lowering the seizure threshold. 29

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 , 26

Toxicology

Avoid use with hypersensitivity to any of the components of wormwood, particularly the essential oil composition. Theoretically, wormwood may be contraindicated in patients with an underlying defect with hepatic heme synthesis because thujone is a porphyrogenic terpenoid. 28 , 30

Wormwood is classified as an unsafe herb by the FDA because of the neurotoxic potential of thujone and its derivatives. Few studies document the safety of wormwood despite its long history of use as a food additive. Thujone bears a superficial structural resemblance to camphor, pinene, anethole, and citral. 31

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. 32 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. 13 , 17 , 33

Dermatitis

Wormwood oil is used as an ingredient in rubefacient preparations; the flowers may induce topical eruptions in sensitized persons. 5 , 34

Renal failure

A 31-year-old man suffered convulsions after drinking 10 mL of essential oil from wormwood or A. absinthium . The patient mistakenly assumed the essential oil was actually absinthe liquor and consumed the 10 mL full strength. The seizure was believed to be caused by the essential oil of wormwood, which also led to rhabdomyolysis, renal failure, and congestive heart failure. The patient recovered and laboratory parameters returned to normal after 17 days. 35

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