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Available on Amazon
also on all local Amazon sites, just change .com for the local version (.co.uk, .jp, .nl, .de, .fr etc.)



Category: Natural chemicals



Introduction and description

paintings by Arthur Rackham

Safrole is a colourless or slightly yellow oily liquid.

It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil or synthesized from other related chemicals.

It is also the principal component of brown camphor oil.  It is water insoluble and has according to Wikipedia a "sweet shop aroma".


It is found in small amounts in a wide variety of plants, where it functions as a natural pesticide.  The table below shows some [not all]  of the main sources.

Plant Sources

  • Acorus calamus and gramineus  - from the rhizones; also contain asarone and eugenol
  • Atherosperma moschatum – the southern or Tasmanian Sassafras
  • Cananga odorata – not the flowers which are used in perfumery but probably the bark or root [Rasch] .  Commonly called Ylang-ylang
  • Cinnamonum camphora – camphor tree leaves and roots
  • Doryphora longifolia and sassafras   - commonly known as Sassafras, Yellow-, Canary- or Golden sassafras, or Golden Deal, is a species of evergreen tree native to New South Wales and Queensland, Australia.
  • Illicium verum - commonly called Star anise, star aniseed, or Chinese star anise
  • Magnolia virginiana – the swamp sassafras
  • Monodora myristica - commonly known as calabash nutmeg, ehuru, Jamaican nutmeg, nuscade de Calabash, ariwo, airama, African nutmeg and African orchid nutmeg
  • Myristica fragrans – the nutmeg; some safrole, but mostly myristicin
  • Ocotea cymbarum/odorifera and pretiosa  - commonly known as Brazilian sassafras or American cinnamon
  • Piper amalago, auritum, [betel], sanctum, hispidinervum, callosum spp – gold pepper, amalgo pepper; in smoking blends sometimes called ‘herbal ecstasy’[although great care is needed here as this name can cover a whole raft of unrelated sustances].  These forest shrubs contain high concentrations of safrole in their leaves
  • Sassafras albidum – the Sassafras tree
  • Syzygium aromaticum – cloves, also contains eugenol
  • Tasmannia glaucifolia -  fragrant pepperbush, is a shrub endemic to New South Wales,  Australia
  • Umbellularia californica – the California laurel, Californis bay, Oregon myrtle, pepperwood, headache [cure] tree, california sassafras [leaves not bark]

The roots of the North American species Sassafras albidum is a primary source of ‘true’ sassafras oil.  Ocotea cymbarum oil made from Ocotea pretiosa  is the other main natural sources along with sassafras oil from Ocotea odorifera/cymbarum

Chinese sassafras oil uses Cinnamomum camphora and commercial production is now centred on Brazil and China.

Why are some people so interested in safrole?

Piperadine;  the Phenylpropenes - Isosafrole, Safrole and MyristicinPiperine  (chavicine) and  Piperazine are all compounds which while technically not phenethylamine derivatives, still have some structural and pharmacological similarities to the ethylenedioxyphenethylamines.

And  phenethylamines are "a class of psychoactive drugs".  Drs Alexander and Ann Shulgin wrote an entire book about phenelthylamines called PIHKAL – Phenethylamines I Have Known and Loved.

Safrole is also a precursor in the synthesis of the recreational drug MDMA ("Ecstasy.").  There are even people who imply that the body somehow turns safrole into MDMA. 

It doesn’t.

Further interest has been sparked because of the way it is treated by governments.  Due to its role in the manufacture of MDMA, safrole and isosafrole as well as piperonal are Category I precursors under regulation No 273/2004 of the European Community. In the US, safrole is currently a List I chemical.  Safrole is also listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

Now this has really roused people’s interest.  Instead of saying – it is a precursor, in the same way that crude oil is a precursor to plastics – these people think the effects of  MDMA and safrole will be the same.


Safrole is not toxic at low doses.  It was used at one time to make root beer and provided the main flavouring.  In some countries root beer is still available using safrole.


The smell and flavour of safrole gives soft drinks and baked goods a characteristic "sweet-shop" aroma.  It is also used as a fragrance and added to soaps and toiletries.

Commercial safrole is the raw material for the flavouring and fragrance ‘heliotropin’, which has a floral odour commonly described as being similar to that of vanilla or cherry. It is used as flavouring and in perfume. It is also a minor natural component of the extract of vanilla. It is a common additive in inexpensive synthetic vanilla flavour and sweets [‘candy’ as the Americans call it]

We can also see from the plant list above that safrole occurs in nutmeg, mace, cloves and star anise.  It also occurs in very very small amounts in other spices -  cumin, black pepper and ginger.  In the majority of the plants we eat or the flavourings we consume the amounts of safrole are tiny.  The amount of safrole in root beer, for example, was only 20ppm.  Consume any of these food stuffs in the ‘normal’ way – that is infrequently and in the normal recipe amounts - and no harm can come to you - and we will see below that there may even be some good.  A sprinkle of nutmeg on your egg custard, a lovely Chinese meal with a hint of star anise will do you no harm.


At one time sassafras tea was available in the USA.  Meyler’s Side Effects of Drugs cites the case of a 72 year old woman who developed diaphoresis [excessive sweating] and hot flashes after the daily ingestion of 10 cups of sassafras tea a day! but all the symptoms resolved themselves after she stopped drinking the tea.  The safrole content in teas brewed from the root bark of the sassafras tree is highly variable with one analysis of six samples ranging from 0.09 to 4.66mg per cup.   So that is quite a lot of safrole.

And  it is also present in the Betel quids chewed  by huge numbers of people in the far East giving their mouths that familiar red stain [Source; Wang and Hwang – Phenolic compounds of betel quid chewing juice Food Science 1993; 20].  It is worth adding that the properties of betel are not derived from the safrole.

As you up the dose, safrole becomes a poison – in other words a drug capable of giving you delirium and thus euphemistically called a delerient  when it is actually poisoning you.

Safrole taken at the sorts of doses needed to produce delirium is a potential carcinogen.  The study that identified the possible carcinogenic properties of safrole is the following one – extracted and summarised here. 

Extract from l'-Hydroxysafrole, a Proximate Carcinogenic Metabolite of Safrole in the Rat and Mouse - Peter Borchert, James A. Miller, Elizabeth C. Miller, and Thomas K. Shires - McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wisconsin 53706


When fed as 0.5% of the diet for 8 to 10 months:

  • 1'-hydroxysafrole induced a high incidence of hepatocellular carcinomas in male rats.  A few isolated papillomas of the forestomach were observed
  • safrole induced only a low incidence under these conditions [ie 8 to 10 months].  Of the adult male mice fed 0.4 or 0.5% of safrole for 13 months and killed at 16 months, 30% had liver tumors
  • the incidence was 11% in the controls

 l'-Acetoxysafrole, because of its toxicity, was fed to rats at only 0.6 the molar level of the above compounds. These rats did not develop hepatic tumors, but all of those that survived at least 6 months developed multiple papillomas of the forestomach; squamous cell carcinomas were found in the forestomachs of two of these rats.


  • Eighty-four and 82%, respectively, of male mice given injections of l'-hydroxy- or 1'-acetoxysafrole at 1 to 21 days of age and killed at 12 to 14 months of age had liver tumors;
  • the incidences were 40% for male mice given injections of safrole
  • and 8% for the controls.

The evidence is actually a bit weak. The study is of rats and mice, not human beings, and they are fed the stuff every day for 10 months. The team also injected their rats, which seems somewhat unnecessary, since the normal route is ingestion.

But the evidence is there.  Safrole, as you can see, is less of a problem than 1'-hydroxysafrole, but there are isoenzymes in human liver cells – CYP2C9, CYP2A6, CYP2D6 and CYP2E1 and the cytochrome P450 that can transform safrole into the carcinogen 1’-hydroxysafrole.  So safrole is a potentially toxic product and the main damage is clearly to the liver. 

At the sort of high doses needed to produce a deleriant effect, the same risk of liver damage is there.

At low doses no problems are normally experienced, but at high doses real damage can occur and nothing much may happen, because many of these plants are not hallucinogens they just cause delirium through poisoning – which may give you hallucinations – or not as the case may be.

Toxicity and Essential oils


In some people’s minds an essential oil somehow equates to the essence of a plant. 

It isn’t. 

The extraction process not only concentrates the chemicals in the plants but also removes chemicals in the process.  Those that smell and taste tend to remain, but there can be any number of chemicals that are removed in the process.  Unfortunately, there are a number of people who seem to believe that ingestion of essential oils containing safrole will make you ‘high’ .  Essential oils need to be used at the best of times with great care and their main use has been in aromatherapy, which requires no ingestion.  Ingest an essential oil therefore and you could be really ill, really ill.

Sassafras oil in the USA is now devoid of any safrole as a result of concerns about health.  A law was passed by the  FDA in 1960.  Some essential oils have safrole levels so high that some aromatherapists even discourage their use externally! Brazilian and Chinese oils contain about 80% safrole.  A commercial sample of essential oil from Sassafras albidum contained 82%.  Brown camphor essential oil also has about 80% safrole. White camphor essential oil can have up to 13 percent safrole. Nutmeg essential oil in contrast contains 2 percent safrole, while cinnamon leaf essential oil has under 1 percent.

If you take the essential oil you are at risk from not just delerium but liver damage, it constitutes a massive over-dose …

Of particular concern is the uncontrolled availability of sassafras oil because of its use in so called aromatherapy.  Internal use of this oil in recommended doses up to 12 drops per day can lead to a daily intake up to 0.2 grams of safrole” [Meyer’s Side effects of drugs].

Medicinal use

We will now turn to the ever reliable Dr Duke's phytochemical database to find the activity of safrole in its entirety.

Dr Duke’s list of Biological Activities of SAFROLE

The effects of safrole depend entirely on the amount consumed at low low doses – the sorts of amount found in plants and in a meal made with these plants, the effects seem principally to be related to the parasympathetic nervous system.  At overdose levels – which is when poisoning occurs, the effects are very clearly all linked to the sympathetic nervous system.  Whatever ‘psychoactive’ effects are being experienced are from the delirium induced by being poisoned, assuming you don’t die from liver failure first

Normal low doses


Anesthetic; JE26:79;

Antiaggregant; IC50=110 uM; JE29:184;

Antibacterial; JE26:79;

Anticonvulsant; JBH;

Antiseptic; M11;

Cancer-Preventive; 525;

CNS-Depressant; JBH;

Hepatoregenerative; CRC;

Carminative; JE26:80;



CNS-Stimulant; HHB;

Calcium-Antagonist; IC50=57 uM gpg; K17576 K27796;

Calcium-Antagonist; IC50=58 uM; LAB58;

Carcinogenic; M11;

Hepatocarcinogenic; CAN;

Hepatotoxic; M29;

Psychoactive; RJH;

Irritant; RIN;

Mutagenic; AHP152;

Neurotoxic; RJH;

Tremorigenic; AFR27:212 [producing tremours]

 Used externally, safrole has a role in controlling lice.  It is a “Pediculicide” but is also a general pesticide as mentioned above.  It is also a Nematicide; MLC=1 mg/ml; SZ44:183.  A nematicide is a type of chemical pesticide used to kill plant-parasitic nematodes.


References and further reading

  •  Meyler’s Side Effects of Drugs – Elsevier publishing
  •  A Modern Herbal – Mrs M Grieve
  •  Medical Toxicology of Natural Substances – Foods, Fungi, Medicinal Herbs, Plants and Venomous Animals pub. Wiley

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