Sassafras

Generic name: Laurus Albidus Nutt., Sassafras Albidum (Nutt.) Nees Var. Molle (Raf.) Fernald
Brand names: Ague Tree, Asari Radix Et Rhizoma, Cinnamon Wood, Saloop, Sassafras, Saxifras, Winauk

Usage of Sassafras

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

Sassafras side effects

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

Before taking Sassafras

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

How to use Sassafras

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

Warnings

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

What other drugs will affect Sassafras

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

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