Artemisia Absinthium

Introduction Overview

Generic Name

Artemisia absinthium

Brand Name

Wormwood

Dosage Form

Essential oil, capsule, tablet, tincture, aqueous extract

Drug Class

Herbal remedy, traditional anthelmintic, anti-inflammatory, antimicrobial agent

Pharmacokinetics

Absorption:
Wormwood's pharmacokinetics have not been extensively studied in humans in a traditional pharmacokinetic context due to its status as a herbal preparation rather than a conventional pharmaceutical agent. When administered orally, compounds such as essential oils (containing thujone, chamazulene, and other terpenoids), flavonoids, and bitter glucosides are absorbed in the gastrointestinal tract. The absorption profile is influenced by the formulation (oil, capsules, tinctures) and the presence of lipophilic essential oils facilitating absorption. Traditional use as an infusion suggests that bioactive compounds can be absorbed in sufficient quantities when taken orally; however, detailed human absorption data are lacking.

Distribution:
Once absorbed, components of wormwood such as thujone demonstrate wide distribution given their lipophilic nature. Thujone readily crosses the blood-brain barrier, which accounts for its neurotoxic and CNS stimulant effects. Essential oils and flavonoids may distribute into various tissues including the liver, kidneys, and CNS. However, the exact plasma protein binding and volume of distribution parameters have not been fully elucidated. Animal studies indicate a potential affinity of constituents for lipid-rich tissues, supporting the development of central neurotoxicity with prolonged exposure.

Metabolism:
Wormwood's bioactive compounds undergo hepatic metabolism predominantly through the cytochrome P450 enzyme system. Thujone and related monoterpenes are metabolized by phase I enzymes, including hydroxylation and oxidation reactions, reducing and transforming to more polar metabolites for excretion. Some flavonoid components may also undergo conjugation via phase II processes such as glucuronidation and sulfation. Metabolic pathways can be influenced by concomitant medications that induce or inhibit cytochrome enzymes, potentially altering the toxicity profile and efficacy.

Elimination:
Metabolites of wormwood constituents are primarily eliminated renally, with small amounts possibly excreted via bile into feces. The elimination half-life of thujone and other volatile oils is not well defined but animal toxicology studies suggest relatively rapid clearance when administered acutely. Repeated ingestion or high doses may lead to accumulation, consistent with observed chronic toxicity syndromes. Clinical data regarding exact pharmacokinetic parameters such as clearance, half-life, and bioavailability remain insufficient and require further investigation.

Dosage Forms

Available Dosage Forms:
- Essential oil preparations (approximate 1-2% volatile oil by weight containing thujone, chamazulene, etc.)
- Capsules (powdered wormwood herb, commonly 250 mg per capsule in clinical trials such as SedaCrohn)
- Tablets (standardized powdered herb or extract-based)
- Tinctures (alcoholic extract solutions)
- Aqueous extracts (decoctions or infusions used traditionally)

Dosages for Adults and Adolescents:
- Traditional herbal infusion doses commonly range from 2 to 3 grams daily of dried herb
- Clinical studies for Crohn's disease have used wormwood powder capsules containing 250 mg wormwood taken three capsules twice daily (approximately 1.5 g daily total)
- For antiprotozoal effects (intestinal amoebiasis), 500 mg capsules three times daily for 15 weeks have been reported
- No formal dosage recommendations exist due to limited clinical data and safety concerns

Specific Patient Populations:
- Use is contraindicated during pregnancy and lactation due to abortifacient and emmenagogue properties
- Caution and avoidance advised in patients with hepatic heme synthesis defects (e.g., porphyria) due to porphyrogenic thujone
- Elderly or patients with neurological disorders should avoid wormwood due to neurotoxicity risk
- Children under 2 years are not studied and use is not recommended

Clinical Guidelines:
- Clinical use and dosing should be under medical supervision given potential toxicity
- Because of the variability in thujone content, preparations standardized to be thujone-free or with minimal thujone content are preferred
- Due to lack of regulatory quality control, only reputable standardized products should be used if clinically indicated

Mechanism Of Action

Wormwood (Artemisia absinthium) exhibits a complex multifaceted mechanism of action mediated primarily by its essential oils, bitter glucosides, flavonoids, and lactones. The principal molecular mechanism relates to the bioactive constituents absinthin, anabsinthin, and monoterpenoid thujone derivatives that interact with multiple cellular targets.

The anthelmintic activity is believed to arise from compounds such as lactones related to santonin and the neurotoxic effects of thujone, which can stun intestinal parasites like roundworms. This allows normal peristalsis to expel the worms effectively. At the cellular level, thujone acts as a potent GABA_A receptor antagonist, leading to increased neuronal excitability, convulsions, and death of susceptible parasites. Additionally, wormwood exhibits antimicrobial actions by disrupting bacterial cell membranes and inhibiting microbial growth, likely through interference with enzyme systems and redox processes.

Anti-inflammatory and antioxidant properties stem largely from flavonoid compounds such as 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (p7F), which inhibit nuclear factor kappa B (NF-κB) activation — a key regulator of proinflammatory gene expression. This reduces production of nitric oxide, prostaglandin E2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α), thereby attenuating inflammatory responses in conditions like Crohn disease and immunoglobulin A nephropathy.

The neuropharmacological effects include affinity of wormwood constituents for nicotinic and muscarinic cholinergic receptors which may underlie purported cognitive enhancement effects. However, the neurotoxicity of thujone through GABA_A receptor antagonism presents a narrow therapeutic window. Compared with similar herbal agents, wormwood's unique combination of bitter lactones, essential oils, and flavonoids provides a spectrum of activities from anthelmintic to immunomodulatory effects. Clinical studies support these mechanisms, particularly the anti-inflammatory and immunosuppressive effects in Crohn disease and IgA nephropathy, mediated by suppression of TNF-α and NF-κB pathways.

Pharmacological Actions

Anthelmintic activity primarily through lactones and thujone-mediated neurotoxicity to parasites
Antimicrobial action against bacteria, fungi, and protozoa via essential oil constituents
Anti-inflammatory effects mediated by inhibition of NF-κB and reduction of proinflammatory mediators such as TNF-alpha, COX-2, and iNOS
Antioxidant activity through free radical scavenging by flavonoid constituents
Antiprotozoal efficacy demonstrated in clinical studies against Entamoeba histolytica
Hepatoprotective effects via inhibition of hepatic microsomal enzymes and antioxidative mechanisms
CNS activity including cognitive enhancement potential via cholinergic receptor interactions
Immunomodulatory effects reducing symptoms in inflammatory bowel diseases such as Crohn's disease
Antipyretic properties documented in animal studies
Antifungal activity effective against Candida albicans and Aspergillus species
Emmenagogue and abortifacient actions related to uterine stimulation
Flavouring agent properties due to aromatic volatile oils
Bitter tonic effects increasing gastric, biliary, and intestinal secretions
Neurotoxic potential via GABA_A receptor antagonism by thujone, leading to excitability and convulsions

Therapeutic Or Clinical Uses

Traditional use as an intestinal anthelmintic to treat parasitic worm infections
Adjunctive therapy in Crohn disease for steroid-sparing and symptom remission
Treatment of intestinal amoebiasis caused by Entamoeba histolytica
Potential use in immunoglobulin A nephropathy to reduce proteinuria and TNF-alpha activity
Relief of dyspepsia and chronic gastric discomfort
Anti-inflammatory treatment in autoimmune and inflammatory disorders
Use as an antimicrobial agent against bacterial and fungal infections
Potential hepatoprotective agent in toxic liver damage models
Traditional use as diaphoretic and febrifuge for chronic fevers
Emmenagogue and abortifacient in traditional medicine (pregnancy contraindicated)
Flavoring agent in alcoholic beverages such as vermouth and historically in absinthe
Topical use in traditional medicine for tendon inflammation
Use as a bitter tonic to stimulate appetite and digestive secretions
Potential cognitive enhancer in neurodegenerative diseases based on cholinergic receptor activity
Herbal supplementation for gastrointestinal and immune support

Side Or Adverse Effects

Neurotoxicity due to thujone content, manifesting as excitability, convulsions, and seizures
Absinthism syndrome characterized by digestive disorders, thirst, restlessness, vertigo, limb tremors, numbness, delirium, paralysis, and potential death
Gastrointestinal cramps, vomiting, and nausea with high or prolonged doses
Dermatitis and allergic reactions reported with essential oil exposure
Renal failure in cases of toxic ingestion of essential oil preparations
Headache, dizziness, and CNS disturbances following excessive use
Potential for drug-induced liver injury as evidenced by herb-related hepatotoxicity cases
Increased bleeding risk when combined with anticoagulants like warfarin
Abortifacient effects causing miscarriage or uterine contractions in pregnancy
Interaction-induced lowered seizure threshold and reduced efficacy of anticonvulsants such as phenobarbital
Restlessness and insomnia related to CNS stimulant properties
Hypersensitivity reactions particularly in individuals allergic to Artemisia species
Potential worsening of peptic ulcers and hyperacidity due to irritant effects on GI mucosa
Possible interactions reducing efficacy of antacids, H2 blockers, proton pump inhibitors, and sucralfate
Severe intoxication may lead to multi-organ failure including congestive heart failure

Precautions

Avoid use in pregnancy and lactation due to abortifacient and emmenagogue effects
Caution in patients with hepatic porphyrias or heme synthesis defects because of porphyrogenic thujone
Avoid in individuals with known hypersensitivity to wormwood or its components
Use under medical supervision in patients with neurological disorders due to neurotoxicity risks
Monitor coagulation status if used concomitantly with warfarin or other anticoagulants
Avoid use concurrent with anticonvulsant therapy due to risk of lowering seizure threshold
Discontinue use if gastrointestinal irritation or adverse reactions occur
Not recommended for children under 2 years old due to lack of safety data
Avoid use in patients with peptic ulcer disease or hyperacidity
Exercise caution when using in elderly patients due to increased susceptibility to CNS effects
Beware of potential interactions with gastrointestinal medications affecting gastric acidity or motility
Ensure use of standardized, thujone-free preparations to minimize toxicity
Avoid excessive use or prolonged treatment courses to prevent cumulative toxicity
Inform healthcare providers of wormwood use prior to surgery or invasive procedures
Use only products from reputable sources with quality control to avoid adulteration

Warnings

Classified as an unsafe herb by FDA due to neurotoxic potential of thujone and derivatives
Can cause convulsions and CNS toxicity, with fatal outcomes at high doses
Long-term repeated ingestion may cause severe neurological damage (absinthism)
Potentially fatal interactions with warfarin leading to enhanced anticoagulant effects
Contraindicated in pregnancy and breastfeeding due to risk of miscarriage and infant harm
Use may precipitate acute attacks in patients with porphyrias due to porphyrogenic compounds
Essential oil misuse can cause rhabdomyolysis, renal failure, and congestive heart failure
Avoid use in patients with known hypersensitivity to prevent severe allergic reactions
Do not exceed recommended doses due to narrow therapeutic window and toxicity risks
Products adulterated with heavy metals (e.g., copper, antimony) historically contributed to toxicity
No safety data established for pediatric population below 2 years of age
May worsen hyperacidity and peptic ulcers if used without appropriate medical oversight
Not approved or regulated by FDA for safety or efficacy assessment
Abrupt withdrawal after long-term use may require medical monitoring due to CNS effects
Ensure differentiation from absinthe liquor, which contains wormwood but is associated with higher toxicity

Contraindication

Pregnancy and lactation due to abortifacient and emmenagogue effects
Known hypersensitivity or allergy to wormwood or any of its constituents
Underlying defects in hepatic heme synthesis such as porphyrias
History of seizures or epilepsy due to proconvulsant thujone content
Severe hepatic or renal impairment due to risk of accumulation and toxicity
Peptic ulcer disease and active gastrointestinal inflammation
Concurrent use with phenobarbital or other anticonvulsants without close monitoring
Patients taking warfarin or other anticoagulants without monitoring for enhanced anticoagulation
Children under the age of 2 due to unknown safety profile
Use of unstandardized or high-thujone content preparations
Individuals with severe psychiatric illness given risk of neurotoxicity and delirium
Avoid essential oil ingestion due to high toxicity risk
Patients with low seizure threshold or taking other neurotoxic drugs
Use in surgical settings without prior disclosure to medical team
Use in individuals with glutamate or GABA neurotransmitter imbalance disorders

Drug Interactions

May potentiate anticoagulant effects of warfarin, increasing risk of bleeding; monitor INR closely
Possible interactions reducing efficacy of anticonvulsants like phenobarbital by lowering seizure threshold
May affect absorption or efficacy of gastrointestinal agents such as antacids, H2 blockers, proton pump inhibitors, and sucralfate
Potential additive neurotoxic effects when combined with other CNS stimulants or neurotoxic agents
Possible interference with cytochrome P450 enzymes can alter metabolism of concomitant drugs
Co-administration with other herbal supplements containing terpenoids may increase neurotoxicity risk
May interact with drugs metabolized via hepatic microsomal enzymes affecting plasma levels
Use with caution alongside other drugs that modulate TNF-alpha or immune function
Potential pharmacodynamic interactions with drugs affecting blood pressure due to hypotensive effects
Limited data suggest possible interactions with CNS-active agents affecting cholinergic or cannabinoid receptors
No well-documented interactions with commonly used antibiotics but caution advised with antimicrobials
Concomitant use with sedatives may alter CNS excitation balance
Potential to alter metabolism or response to steroid medications when used for inflammatory conditions
Interactions with drugs affecting electrolyte balance should be monitored due to possible GI effects
Use cautiously with other neurotoxic herbs or supplements to avoid additive toxicity

Preparations Of The Drug

Essential oil extracts standardized for volatile oils containing thujone, chamazulene, phellandrene, and caryophyllene oxide
Powdered herb encapsulated in doses typically around 250 mg per capsule used in clinical studies
Tablets formulated from dried wormwood herb or standardized extracts
Alcoholic tinctures prepared from aerial parts for oral administration or topical use
Aqueous extracts and infusions used traditionally as bitters and digestive tonics
Thujone-free standardized extracts developed for safer use such as SedaLeukin and SedaCrohn formulations
Commercial formulations for Crohn’s disease containing combination of wormwood with rose, cardamom, and mastic resin
Flavored alcoholic preparations such as vermouth containing thujone-free wormwood extract
Powdered dried leaf or stems used in traditional herbal medicine and folk preparations
Topical poultices made from fresh or dried aerial parts for musculoskeletal inflammation
Essential oil capsules with controlled thujone levels to minimize neurotoxicity
Botanical supplements available in various herbal mixtures targeting digestive, inflammatory, or antiparasitic uses
Standardized wormwood extracts with defined absinthin content for quality assurance
Liquid extracts with defined dry herb equivalence and concentration of bitter principles
Herbal tea blends incorporating wormwood for medicinal and flavoring purposes