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Sassafras

Scientific Name(s): Laurus albidus Nutt., Sassafras albidum (Nutt.) Nees var. molle (Raf.) Fernald
Common Name(s): Ague tree, Asari Radix et Rhizoma, Cinnamon wood, Saloop, Sassafras, Saxifras, Winauk

Medically reviewed by Drugs.com. Last updated on Mar 22, 2022.

Clinical Overview

Use

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, and sassafras is not considered safe for use. Safrole, the main constituent of sassafras root bark and oil, has been banned by the US Food and Drug Administration (FDA), including for use as a flavoring or fragrance, and should not be used internally or externally, as it is potentially carcinogenic. Safrole has been used in the illegal production of 3,4-methylene-dioxymethamphetamine (MDMA), also known by the street names "ecstasy" or "Molly," and the sale of safrole and sassafras oil is monitored by the US Drug Enforcement Administration (DEA).

Dosing

Clinical trials are lacking. External or internal use should be avoided; sassafras oil and the main constituent safrole are potentially carcinogenic. Sassafras oil is toxic in doses as low as 5 mL in adults.

Contraindications

Not considered safe for use.

Pregnancy/Lactation

Avoid use. Emmenagogue and abortifacient effects have been documented. Information regarding use during breastfeeding is lacking.

Interactions

None well documented.

Adverse Reactions

Diaphoresis, hot flashes, and dermatitis have been reported.

Toxicology

Sassafras oil and safrole have demonstrated carcinogenic and hepatotoxic potential in animal studies. Symptoms of sassafras oil poisoning in humans include vomiting, stupor, lowering of body temperature, exhaustion, tachycardia, spasms, hallucinations, and paralysis; effects may be fatal.

Scientific Family

  • Lauraceae (laurel)

Botany

There are 3 recognized species of sassafras trees, 2 native to Asia (Sassafras tzuma, Sassafras randaiense) and 1 native to eastern North America (S. albidum). Fossils show that sassafras was once widespread in Europe, North America, and Greenland. The trees can grow up to 30 m in height and 2 m in diameter, although they are usually smaller. Sassafras bears small, light-yellow flowers and leaves that are 10 to 15 cm in length and oval shaped (on older branches) or mitten shaped or 3-lobed (on younger shoots and twigs). All parts of the tree are strongly aromatic. The drug is derived from the peeled root of the plant (root bark).Bisset 1994, Khan 2010

Synonyms include Laurus sassafras L.; Sassafras officinale Nees & Eberm.; Sassafras sassafras (L.) Karst., nom. inval.; and Sassafras variifolium (Salisb.) Kuntze.USDA 2020 The plant should not be confused with the evergreen Doryphora sassafras.

History

The FDA has banned the use of sassafras as a drug or food product due to potential carcinogenicity; however, its use and sale persist throughout the United States. Safrole-free sassafras is permitted for use.FDA 2019, Khan 2010

American Indians used sassafras for centuries for a variety of illnesses. Early settlers later exported sassafras to Europe.Winter 1984 Discovery, identification, and descriptions of sassafras bark during the late 16th century by explorers and physicians have been described.Estes 1995

The oil obtained from the roots and wood has been used as a scent in perfumes and soaps. The leaves and pith, when dried and powdered, have been used as a thickener in soups. The roots have often been dried and steeped for tea. The oil has been used as a topical antiseptic, pediculicide, and carminative, and applied externally for the relief of insect bites and stings. Other external uses have included treatment of rheumatism, gout, sprains, swelling, and cutaneous eruptions.Duke 2002, Newall 1996

Sassafras has been used as a sweat-inducing agent, a flavoring for dentifrices, root beers, and tobaccos, and as a treatment for eye inflammation.Duke 2002, Khan 2010 Sassafras has also anecdotally been thought to be a CNS stimulant.Duke 2002

Chemistry

Sassafras oil makes up approximately 2% of the roots and 6% to 9% of the root bark. The main constituent of the oil is safrole, which chemically is p-allyl-methylenedioxybenzene; safrole comprises up to 80% of the oil. In addition, the volatile oil contains anethole, pinene apiole, camphor, eugenol, and myristicin.Duke 1992, Newall 1996

The plant contains less than 0.2% total alkaloids (primarily boldine, isoboldine, norboldine, cinnamolaurine, norcinnamolaurine, and reticuline), along with tannins, resins, mucilage, and wax.Barnes 2007, Duke 1992, Newall 1996 A wide variety of mineral elements is found in the leaves and stem of the plant.Duke 1992

An analysis performed on sassafras teas using supercritical fluid extraction with gas chromatographic-mass spectrometric methods commonly reported safrole levels of 1%.Heikes 1994

Uses and Pharmacology

Use of sassafras as a drug or food product has been banned by the FDA due to potential carcinogenicity.FDA 2019, Khan 2010 Safrole is used as the base material for piperonyl methyl ketone, a precursor to illicit MDMA synthesis.Schäffer 2013 Inhibition and induction of various hepatic microsomal enzymes has been recorded.Barnes 2007

Antifungal activity

In vitro data

Antifungal activity of the essential oil of laurel plants, including sassafras, has been investigated in vitro.Simić 2004

Anti-inflammatory activity

Animal and in vitro data

In an investigation in mice comparing anti-inflammatory activity of safrole with indomethacin, potency of safrole compounds was less than that of indomethacin for inhibiting carrageenan-induced hindpaw edema.Pereira 1989 Sassarandianol extracted from the related S. randaiense plant exhibited anti-inflammatory activity in vitro.Hou 2015

Cancer

Sassafras has been shown to be potentially carcinogenic due to safrole content and is not considered safe for use in humans.FDA 2019, Khan 2010, Yu 2012 Studies have suggested an association of oral squamous cell carcinoma among chewers of safrole-containing betel quid.Dietz 2011 In addition, epidemiological evidence indicates that individuals who chew betel nut or areca quid, which contain high levels of safrole, have an increased risk of esophageal cancer and hepatocellular carcinoma. This observation appears to be related to the formation of safrole-DNA adducts.Bode 2015

The International Agency for Research on Cancer (IARC) has classified safrole as a possible Group 2B carcinogen.Martins 2018 According to IARC Working Group monographs on the evaluation of carcinogenic risks to humans, there is sufficient evidence demonstrating carcinogenicity with safrole in animals, but inadequate evidence in humans.Pflaum 2016

In vivo and in vitro data

Botanical o-quinones can be formed by O-dealkylation of methylenedioxy rings, resulting in catechols that are further oxidized to o-quinones. Safrole-derived o-quinones have a variety of biological targets in vivo, resulting in various biological effects ranging from chemoprevention to toxicity.Bolton 2018 For example, hydroxychavicol, a CYP-450 oxidized derivative of safrole, significantly inhibited growth and proliferation through reactive oxygen species (ROS) formation in human prostate cancer cells using PC-3 cell lines.Gundala 2014

In vitro studies have demonstrated apoptotic-inducing activity of safrole on human tongue squamous cancer cells.Heikes 1994, Yu 2012 One report suggested that safrole-free extracts induced malignant mesenchymal tumors in more than 50% of black rats treated.Benedetti 1977

Safrole-related cytotoxicity, DNA damage, and apoptosis in macrophages is believed to be caused by generation of ROS and inhibition of antioxidative enzymes, possibly via Akt phosphorylation.Chien 2018 In addition, one study proposed that betel quid containing safrole induces tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolic activation, resulting in higher NNK-induced genotoxicity; this study provided insight into the synergistic mechanisms of cigarette smoking– and betel quid–induced oral cancer.Tsou 2019

Cardiovascular effects

Animal data

An N-acylhydrazone extract of sassafras oil showed vasodilatory and hypotensive activity in rats.Zapata-Sudo 2010

Dosing

Clinical trials are lacking. External or internal use should be avoided; sassafras oil and the main constituent safrole are potentially carcinogenic. Sassafras oil is toxic in doses as low as 5 mL in adults.Duke 2002, FDA 2019, Khan 2010

Pregnancy / Lactation

Avoid use in pregnancy, due to documented emmenagogue and abortifacient effects.Ernst 2002, Newall 1996 Information regarding use during breastfeeding is lacking.

Interactions

None well documented. Because safrole is a potent inhibitor of CYP-450 enzymes, specifically CYP1A2, 2A6, and 2E1 and to a lesser extent CYP2D6 and 3A4, interactions may be expected.Khan 2010, Segelman 1976, Ueng 2005

Adverse Reactions

Diaphoresis, hot flashes,Haines 1991 and contact dermatitis have been reported.Duke 2002

Aqueous and alcoholic extracts are reported to have caused ataxia, hypersensitivity to the touch, CNS depression, and hypothermia in mice.Segelman 1976

Toxicology

Toxicity of sassafras may be increased in conjunction with CYP1A2 inducers.Hu 2019

The induction of CYP-448 activity has been associated with mutagenic and carcinogenic activity of the inducing agent, namely safrole.Iwasaki 1986 Safrole and its metabolite 1′-hydroxysafrole is genotoxic and hepatotoxic, and has caused hepatic tumors in animal studies.Chiang 2011, Dietz 2011, Khan 2010, Ueng 2005 Sassafras oil and safrole have thus been banned for use as flavors and food additives by the FDA because of their carcinogenic and hepatotoxic potential.Duke 2002, Newall 1996

Based on animal data and a margin of safety factor of 100, safrole 0.66 mg/kg body weight is considered hazardous for humans; the amount obtained from sassafras tea may be as high as 200 mg (3 mg/kg).Bisset 1994, Segelman 1976

Sassafras oil is toxic in doses as low as 5 mL in adults.Duke 2002, Grande 1987, Spoerke 1980

Symptoms of sassafras oil poisoning in humans include vomiting, stupor, lowering of body temperature, exhaustion, tachycardia, spasm, hallucinations, and paralysis; effects may be fatal.Duke 2002, Newall 1996

The IARC has classified safrole as a possible Group 2B carcinogen.Martins 2018 According to IARC Working Group monographs on the evaluation of carcinogenic risks to humans, there is sufficient evidence demonstrating carcinogenicity with safrole in animals, but inadequate evidence in humans.Pflaum 2016

Index Terms

  • Laurus albidus Nutt.
  • Laurus sassafras L.
  • Sassafras albidum (Nutt.) Nees var. molle (Raf.) Fernald
  • Sassafras officinale Nees & Eberm.
  • Sassafras randaiense
  • Sassafras sassafras (L.) Karst., nom. inval.
  • Sassafras tzuma
  • Sassafras variifolium (Salisb.) Kuntze

References

Disclaimer

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.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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