Sassafras (Sassafras albidum): A Comprehensive Reference
1. Identity: Botanical Classification, Names, and Natural Source
Sassafras albidum (Nutt.) Nees (synonyms: Sassafras officinale Nees et Eberm.; Sassafras variifolium (Salisb.) Kuntze) belongs to the family Lauraceae. An older accepted botanical synonym is Laurus albidus Nutt. Vernacular names include sassafras, saxifrax, ague tree, cinnamon wood, and saloop (English); Fenchelholz (German); and Bois de Sassafras (French).
Sassafras is native to North America and China. Three recognized species of sassafras trees exist: two are native to Asia (Sassafras tzuma and Sassafras randaiense) and one is native to eastern North America (S. albidum). The North American species is native to the entire eastern United States and Canada, as well as Mexico, and is commonly found in fields, open woods, or along fences.
Sassafras is a deciduous tree native to eastern North America, recognizable by its aromatic bark and its unusual leaves, which may be oval, mitten-shaped, or three-lobed on the same tree. It is a shrubby tree that can grow 20 to 40 feet tall. The stems bear alternate, mitten-shaped, fuzzy leaves three to six inches long. Small yellow/green flowers develop in March and April, producing succulent oval dark blue drupes supported by red peduncles in August.
Because of their sassafras-like odor, which is presumably due to the content of safrole, several other plants are also called "sassafras": Atherosperma moschatum Labill. (Australian sassafras), Mespilodaphne sassafras Meister (Brazilian sassafras), and Doryphora sassafras Endl. (New Caledonian sassafras). Ocotea pretiosa, which grows in Brazil, and Sassafras albidum, which grows in eastern North America, are the main natural sources of safrole.
Common Preparations and Forms
- The root with or without bark and the volatile oil are used medicinally.
- All parts of the plant have been used historically. The young leaves are dried and powdered to make filé, a thickening agent for soups and stews. The flowers may be used in salads or dried and used for tea. The root was used to make root beer.
- The bark, especially the root bark, is the primary part of the plant used medicinally.
- Commercially, herbal products include sassafras root bark powders and tinctures.
- Currently, only safrole-free products derived from sassafras are permitted for sale in the United States, although the potential presence of other carcinogens remains a concern.
2. Traditional and Historical Use
Indigenous North American Use
Long before European arrival, Indigenous peoples across what is now the United States recognized the plant by its distinctive aroma and incorporated it into systems of medicine. Sassafras was used extensively for food and medicine by Native Americans long before European colonizers arrived. It was used by the Cherokee as a blood thinner to purify blood, to treat skin diseases, and rheumatism, among other ailments. Native American peoples used it for many different conditions including as a de-worming agent, an anti-diarrheal agent, for colds and rheumatic conditions, and as a wash and poultice for skin eruptions and rashes. Native Americans used infusions made from the root bark as a remedy to treat fevers, diarrhea, and rheumatism.
Colonial and Early American Use
One of the first exports of the Jamestown Colony, sassafras was employed by the Native Americans in the 16th century to ward off evil spirits and illness. Sassafras "was perhaps the first Native American herb to be exported to Europe." Later, it became part of colonial and early American herbal practice, where it was promoted as a cleansing spring tonic, warming circulatory herb, aromatic tea plant, and aid for discomforts ranging from stomach upset to rheumatic pain.
The early Eclectic physician Wooster Beach listed sassafras in his mid-19th-century materia medica as an alterative and stimulant for rheumatic conditions and eruptive diseases. It is a diaphoretic, helping the body to produce a fever to fight infection, then producing perspiration to rid the body of wastes, and as such was used for colds, influenza, and rheumatic conditions.
In Europe, sassafras was used to "cure" syphilis, although this was later determined to be ineffective. In the southern United States, the roots were boiled, then combined with molasses, and allowed to ferment into the first root beer. A cup of sassafras root tea has been a traditional spring tonic in the South for hundreds of years.
African American and Creole Traditions
Enslaved Africans, drawing on both inherited African healing traditions and knowledge shared by Indigenous peoples, incorporated sassafras into their own systems of herbal medicine. In these contexts, sassafras bark tea was valued as a "blood purifier" and general restorative. The blending of these traditions solidified the plant's role as a central element in African American herbalism and, eventually, in Creole cuisine, where it became an essential thickening agent (filé) in Louisiana gumbo.
Culinary Use: Filé Powder and Root Beer
In the American South, dried and ground sassafras leaves became filé powder, an important thickener and seasoning in gumbo and related dishes. Until 1960, the beverage root beer contained approximately 30 ppm safrole, being made from the root of Sassafras albidum, which contains about 85% safrole in the essential oil from its root bark.
Traditional Use as Eyewash
Sassafras has been used as a sudorific and flavoring agent and for the treatment of eye inflammation. The pith is also a demulcent and has been used as an eyewash for inflammatory eye conditions such as conjunctivitis.
3. Key Constituents and Active Compounds
Essential Oil and Safrole
The volatile oil of sassafras is believed to be the major active constituent of the plant. This oil contains up to 85% of the terpenoid known as safrole. Sassafras albidum root contains 1–2% of volatile oil, which in turn consists largely of safrole. The essential oils of Sassafras albidum, obtained by hydrodistillation of the root bark and root wood, have been analyzed by GC and GC/MS. The main component of the root bark and root wood oils is safrole (61.29–88.80%).
Safrole is an organic compound with the formula CH₂O₂C₆H₃CH₂CH=CH₂. It is a colorless oily liquid, although impure samples can appear yellow. A member of the phenylpropanoid family of natural products, it is found in sassafras plants, among others. Small amounts are found in a wide variety of plants, where it functions as a natural antifeedant.
Other Constituents
S. albidum has three major root bark components: methyleugenol, safrole, and camphor. Other components found in sassafras root bark include tannins, flavonoids, and essential oils, which contribute to its medicinal properties. The root bark also contains camphor, eugenol, sesquiterpenes, and tannins, which contribute antimicrobial, anti-inflammatory, and astringent properties.
Safrole, methyleugenol, and/or estragole are constituents of other plants including nutmeg (Myristica fragrans), star anise (Illicium verum), and cinnamon (Cinnamomum). Myristicin occurs in nutmeg, elemicin occurs in nutmeg and parsley, all of which are members of the alkenylbenzene class of compounds.
Alkaloids
Aporphine and tetrahydrobenzylisoquinoline alkaloids have been identified in Sassafras albidum.
4. Mechanisms of Action
Safrole: Hepatotoxic and Carcinogenic Mechanism
Safrole itself is not the direct problem. The danger comes from what the liver does with it. When safrole is consumed, the body metabolizes it into a compound called 1′-hydroxysafrole, which is then converted into a highly reactive molecule (1′-sulfooxysafrole) that binds to DNA in liver cells. The major DNA adduct isolated is formed from a reactive sulphate ester.
The allyl group directly contributes to mutagenicity, while the methylenedioxy group is associated with changes in the cytochrome P450 system and epigenetic aspects of carcinogenicity. In rats, safrole and related compounds produced both benign and malignant tumors after oral intake. Changes in the liver are also observed through the enlargement of liver cells and cell death.
Cytochrome P450 Inhibition
Safrole, described in the scientific literature as a hepatotoxin and a methylenedioxy phenyl compound found in sassafras oil and certain other essential oils, was studied using recombinant cytochrome P450 (CYP) and human liver microsomes to investigate its selective inhibitory effects on human P450 enzymes. Safrole was demonstrated to be a non-selective inhibitor of CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP3A4. Safrole strongly inhibited CYP1A2, CYP2A6, and CYP2E1 activities with IC₅₀ values less than 20 μM.
Anti-Inflammatory and Other Proposed Mechanisms
Safrole is a member of the phenylpropene class of compounds and has been studied for its antimicrobial and anti-inflammatory properties. The eugenol content of sassafras provides broad-spectrum antimicrobial and anti-inflammatory properties similar to those documented for clove and basil, which contain eugenol as a primary active compound. The tannin content provides astringent effects relevant for digestive and skin applications. Camphor contributes mild analgesic and circulatory-stimulating properties.
5. Scientific Evidence by Area of Use
Overview of Clinical Evidence
Human studies are lacking to verify the efficacy of sassafras for any condition. Animal and in vitro studies have investigated the potential antifungal, anti-inflammatory, and cardiovascular effects of sassafras and its components. However, clinical trials are lacking. All evidence for therapeutic applications of sassafras is either preclinical (animal models) or in vitro. The following sub-sections describe the available experimental evidence.
5.1 Anti-Inflammatory Activity
Evidence level: In vitro and animal studies only; no human clinical trials.
In vitro studies have demonstrated that safrole, one of the primary compounds in sassafras, exhibits anti-inflammatory properties. Research using synthetic safrole derivatives also provided indirect mechanistic evidence: the anti-inflammatory activities of compounds synthesized from safrole — the principal chemical constituent of sassafras oil — were determined in mice. These indenyl-acetic and indenyl-propionic acids exhibited potencies 4- to 10-fold less than indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. These studies concern synthetic derivatives, not sassafras preparations used directly, and no human clinical data exist.
5.2 Antifungal Activity
Evidence level: In vitro laboratory studies only; no human clinical trials.
The antifungal activity of Sassafras albidum essential oil (alongside other Lauraceae species) was investigated against 17 micromycetes, including food poisoning and spoilage fungi and plant and animal pathogens. Fungistatic and fungicidal concentrations (MIC and MFC) were determined using macrodilution and microdilution tests. In sassafras essential oil, safrole was the major component, and the essential oil of cinnamon showed the strongest antifungal activity — suggesting that sassafras performed less potently than other tested Lauraceae oils. There is experimental support for antimicrobial and antifungal potential, as sassafras essential oil has shown activity against a variety of organisms in laboratory settings. However, there is a major difference between antimicrobial action in vitro and safe internal use in people. The first is a research finding; the second is a clinical recommendation, and sassafras does not bridge that gap convincingly.
Twenty-one phenylpropanoids (including eugenol and safrole) and synthetic analogues were evaluated for antifungal properties against a panel of human opportunistic pathogenic fungi, including clinical isolates of Candida albicans and non-albicans Candida spp., Cryptococcus neoformans, and dermatophytes. This study further confirmed antifungal activity for the phenylpropanoid class but involved isolated compounds and in vitro models only.
5.3 Anticancer / Cytotoxic Properties (Paradoxical Findings)
Evidence level: In vitro cell studies only; paradoxically, in vivo data demonstrate carcinogenicity. No clinical trials.
In vitro studies have paradoxically identified cytotoxic properties in safrole against cancer cell lines. However, the overwhelmingly dominant and well-replicated in vivo finding is that safrole is itself carcinogenic. Despite potential apoptotic and cytotoxic effects found in cell studies, data indicates that safrole is "reasonably anticipated to be a human carcinogen." Sassafras contains safrole, which causes liver cancer in animal models and is classified as a carcinogenic substance. Some studies point to cytotoxic or cell-signaling effects from safrole and other constituents. These effects are sometimes framed as potentially useful because compounds that influence cell survival or stress pathways may attract pharmacological interest. But a compound showing cytotoxic or anticancer-like effects in cell experiments does not mean consuming sassafras is protective.
5.4 Antimicrobial Activity
Evidence level: In vitro only; no human clinical trials.
Research suggests that sassafras could offer a potential treatment for leishmaniasis, a parasitic disease. A study investigating the effects of an extract from Sassafras albidum bark on leishmaniasis parasites found that the extract effectively killed the parasites without harming surrounding healthy cells. This remains preliminary in vitro data. No human trials have been conducted.
5.5 Diaphoretic and Febrifuge Properties
Evidence level: Historically documented anecdotal and case reports only; no controlled clinical trials.
Diaphoresis and hot flashes have been reported from sassafras use. These effects were historically interpreted as therapeutically desirable ("sweating out" fever), and individual case reports support the diaphoretic effect; however, no controlled clinical trials have evaluated sassafras as a treatment for fever or infection in humans.
6. Body Systems and Health Areas Associated with Sassafras
Hepatic (Liver) System
Sassafras albidum root contains volatile oil consisting largely of safrole, a weakly hepatocarcinogenic agent in laboratory animals. Some metabolites of safrole have mutagenic activity in bacteria and weak hepatocarcinogenic effects in rodents. Sassafras oil is very toxic. If damage to the liver or kidneys occurs, it may take several months to heal. Sassafras oil can also cause cancer if someone uses it for a long time.
Musculoskeletal System
Traditionally, sassafras oil was used to treat various ailments including arthritis. Some proponents within the complementary and alternative medicine community cite its anti-inflammatory and pain-relieving properties, particularly for conditions like arthritis and gout. This is based on traditional use and in vitro findings only — no clinical trials support these uses.
Gastrointestinal System
Sassafras oil was historically used to treat digestive issues. It was classified as an alterative, assisting the body's elimination processes whether through stimulating the digestive system, the renal system, or the sweat glands. No human studies confirm gastrointestinal efficacy.
Dermatological System
The tea was used externally as a wash for skin eruptions and rashes. Contact dermatitis has also been reported from sassafras use.
Ophthalmic Use
The pith, being a demulcent, was used as an eyewash for inflammatory eye conditions such as conjunctivitis. No clinical trial data support this use.
Urinary System
Sassafras was historically used to treat urinary tract infections. These uses are based solely on traditional practice with no human clinical trial verification.
7. Dosage Forms and Dosages Reported in Studies
Tea samples, prepared as recommended in commonly used herbal medicine information sources or on product labels, contain between 0.09 mg and 4.66 mg of safrole per cup. One product, containing 2.5 g of sassafras bark per tea bag, was estimated to provide up to a 200-mg dose of safrole. The actual amount of safrole ingested depends on the safrole content, the duration of the infusion, and the amount of tea consumed.
Safrole contents of 0.09–4.66 mg/cup were found for brewed teas prepared from sassafras root bark powders and tinctures.
Sassafras oil is toxic in doses as low as 5 mL in adults. Consuming just 5 mL of sassafras oil can kill an adult.
Dietary administration of safrole at up to 5000 mg/kg body weight to mice and rats caused increases in the incidences of hepatocellular carcinoma or cholangiocarcinoma in the animal carcinogenicity studies. These were experimental doses administered in animal studies and are not translatable to human use recommendations.
8. Safety Considerations and Regulatory Status
Carcinogenicity
Safrole is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. Safrole caused liver tumors in two rodent species and by two different routes of exposure. Dietary administration of safrole caused liver cancer (hepatocellular carcinoma) in male mice and benign or malignant liver tumors (hepatocellular carcinoma or adenoma or cholangiocarcinoma) in rats of both sexes.
The National Toxicology Program (NTP), in its 15th Report on Carcinogens (2021), classifies safrole as "reasonably anticipated to be a human carcinogen" based on sufficient evidence of carcinogenicity from studies in experimental animals. Safrole caused liver tumors in two rodent species and by two different routes of exposure. Safrole is also classified as a Group 2B possible human carcinogen by IARC.
According to a 1977 study of the metabolites of safrole in both rats and humans, two carcinogenic metabolites of safrole found in the urine of rats, 1′-hydroxysafrole and 3′-hydroxyisosafrole, were not found in human urine. The human relevance of animal carcinogenicity findings at low dietary exposure levels is genuinely contested in the scientific literature, but the regulatory response to the animal carcinogenicity data has been consistent across US and European food safety authorities.
FDA Regulatory Action
In the United States, safrole was once widely used as a food additive in root beer, sassafras tea, and other common goods, but was banned for human consumption by the FDA after studies in the 1960s suggested that safrole was carcinogenic, causing permanent liver damage in rats. In 1960, the FDA officially banned the use of safrole as a direct food additive and as a component of flavoring agents. This ban effectively prohibited the use of sassafras oil, which contains a significant amount of safrole, in commercially produced food and beverages.
Safrole, the main constituent of sassafras root bark and oil, has been banned by the U.S. Food and Drug Administration (FDA), including for use as a flavoring or fragrance. Based on these data, the FDA continues to classify safrole as a Substance Generally Prohibited From Direct Addition or Use as Human Food.
Even "safrole-free" sassafras used in medicinal amounts has been linked with tumors.
Acute Toxicity
Symptoms of sassafras oil poisoning in humans include vomiting, stupor, lowering of body temperature, exhaustion, tachycardia, spasms, hallucinations, and paralysis; effects may be fatal. Short-term effects from safrole-rich herbal drinks include nausea, dizziness, vomiting, and confusion; chronic exposure can result in liver damage from hepatotoxic metabolites.
Drug Interactions via Cytochrome P450 Inhibition
Because safrole is a potent inhibitor of CYP-450 enzymes, particularly CYP1A2, 2A6, and 2E1, and to a lesser extent CYP2D6 and 3A4, interactions are expected. In vitro, safrole inhibited human CYP1A2, CYP2A6, and CYP2E1. The inhibition of these enzymes could theoretically alter the metabolism of drugs that are substrates for these isoforms, though this has not been studied in human clinical pharmacokinetic trials.
Pregnancy and Breastfeeding
Emmenagogue and abortifacient effects have been documented. Information regarding use during breastfeeding is lacking. Safrole and its toxic metabolites cross the placenta and enter breast milk in laboratory animals.
Safrole as a Precursor to Controlled Substances
Safrole continues to be the prevalently used starting material for the synthesis of piperonylmethylketone (PMK), the most important precursor for the clandestine manufacturing of MDMA. MDMA can also be synthesized directly from safrole. Due to its unambiguous role as a precursor for illicit drug manufacturing, safrole as well as its isomerization product cis-/trans-isosafrole are subjected to precursor monitoring legislation in Germany. Safrole is a List I Chemical in the United States. The sale of safrole and sassafras oil is monitored by the US Drug Enforcement Administration (DEA).
Dermatological Reactions
Diaphoresis, hot flashes, and dermatitis have been reported from exposure to sassafras.
9. Summary of Evidence Strength
The table below characterizes the state of evidence for each investigated area of use:
- Carcinogenicity (hepatic): Safrole is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals, having caused liver tumors in two rodent species and by two different routes of exposure. Evidence is strong at the preclinical (animal) level; no direct human epidemiological confirmation but consistent with mechanistic data.
- Anti-inflammatory: In vitro and animal data only; no clinical trials. Evidence is preliminary and weak for human relevance.
- Antifungal: In vitro data only; no clinical trials. Evidence is preliminary.
- Antimicrobial (including anti-parasitic): In vitro data only; no clinical trials. Evidence is preliminary.
- Diaphoretic/sudorific: Anecdotal and case report evidence only; no controlled clinical data.
- Analgesic: Based on synthetic safrole derivatives in animal models; no clinical trials.
- Blood purification/tonic: Traditional use only; no scientific evidence.
- Syphilis treatment: Used in Europe to "cure" syphilis, although this was later determined to be ineffective.
References
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