Pulegone: The Minty Terpene With a Toxicity Story

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Pulegone smells like pennyroyal mint — sweet and faintly camphorous — and it is the rare terpene with a genuine toxicology file: a poisoning literature going back to the 1800s, a federal two-year cancer bioassay, and a 2018 removal of its synthetic form from the US food-additive list. The other half of its story is perfume and mint flavoring. The difference between the halves is dose.

What Pulegone Is

Pulegone is a monoterpene ketone (C₁₀H₁₆O) whose naturally dominant form is the (R)-(+) enantiomer. Its home plant is pennyroyal: oil from European pennyroyal (Mentha pulegium) typically runs 75–85% pulegone, and oil from American pennyroyal around 30%.^[1] Catnip, peppermint, spearmint and rosemary carry smaller amounts, and it serves the mint family as a working insecticide.^[2] It boils at about 224°C at atmospheric pressure — stated with the pressure, as our guide to terpene boiling points insists. Our terpene education hub has the wider map.

Pulegone in Cannabis

Pulegone has not been established as a routine cannabis constituent; where reported, it appears to occur only in trace amounts. The Mudge metabolomics survey of 33 chemovars kept pulegone among its twenty reference standards — and it never turned up among the terpenes defining any chemotype.^[3] We found no published evidence establishing pulegone as a routinely detected component of cannabis terpene profiles. Strain lore still attaches it to OG Kush and Headband and calls it sedative — vendor copy, not lab data. Cultivar names are a poor guide to chemistry, a lesson our look at the terroir of cannabis covers in detail.

The behavioral evidence is stranger than the marketing: the one mouse study usually compressed into “calming” reported effects its own authors framed as aversive, anxiolytic-like, and psychostimulant, with motor incoordination at high doses.^[4] The claim that pulegone “counteracts THC’s effect on short-term memory” rests on even less: an in vitro screen of mint- and daisy-family plants for acetylcholinesterase inhibition.^[5] No cannabis, no inhaled doses, no human memory. For a minor cannabis terpene with a genuinely deeper research file, nerolidol is the better story.

The Toxicity Story

Pulegone’s distinctive chapter begins with pennyroyal oil, long used in folk medicine — sometimes fatally. A 1996 Annals of Internal Medicine case review counted poisonings back to 1869: moderate-to-severe toxicity — liver injury, seizures, coma — generally followed ingestion of at least 10 mL of the oil, with deaths reported at larger amounts.^[1] The same year, pediatricians reported two infants poisoned by mint tea brewed with pennyroyal; one died of liver failure.^[6] The mechanism is well mapped: liver cytochrome P450 enzymes oxidize pulegone to menthofuran, whose reactive products bind liver proteins and deplete glutathione — the acetaminophen-overdose playbook, run on a monoterpene.^[7]

The National Toxicology Program then fed pulegone to rats and mice by gavage for two years, and concluded in 2011: clear evidence of carcinogenic activity in female rats (urinary bladder tumors) and mice of both sexes (liver tumors), no evidence in male rats.^[8] These were high experimental exposures — 18.75 to 150 mg/kg, administered five days per week — but animal doses cannot be converted into human equivalents through simple body-weight multiplication. The experiment establishes a carcinogenic hazard; exposure data determine how relevant that hazard is to ordinary use.

In October 2018 the FDA removed synthetic pulegone and five other synthetic flavorings from the food-additive list, because the Delaney Clause forbids approving any additive shown to cause cancer in animals at any dose. Revocation was required, in the FDA’s own words, “as a matter of law” — even as its exposure assessment found the substances “do not pose a risk to public health under the conditions of their intended use.” Naturally occurring pulegone in mint flavors remains legal.^[9] Europe separates food limits from herbal-medicine guidance: a food TDI of 0.1 mg/kg per day has been used for pulegone and menthofuran combined, while the EMA’s revised assessment proposed 0.75 mg/kg per day as acceptable lifelong exposure from herbal medicinal products. The agency found no certain cases of liver injury caused by peppermint or mint oil, although it acknowledged that adverse effects may be underreported.^[10]

The newest wrinkle is inhaled. A 2019 risk analysis using published measurements from five mint- or menthol-flavored e-liquids and one smokeless-tobacco product calculated margins of exposure below the threshold regulators commonly use for carcinogens.^[11] Inhalation toxicology remains poorly characterized, and cannabis vapes were not tested — but the result raises a relevant question for any inhaled product deliberately flavored with pulegone-containing mint oils.

Isopulegol: The Quieter Twin

Isopulegol (C₁₀H₁₈O) is a closely related monoterpene alcohol — though not merely pulegone with its ketone changed to a hydroxyl group: its double bond is arranged differently as well. It turns up in lemongrass, eucalyptus and, in trace amounts, cannabis. Its biggest job is industrial: synthetic routes to (−)-menthol cyclize citronellal to isopulegol and hydrogenate it — a major industrial route to the menthol used in many products. Its research record is small and preclinical: in mice, acute isopulegol produced depressant- and anxiolytic-like effects,^[12] and a follow-up study reported protection against induced gastric ulcers.^[13] No human study has evaluated isopulegol for any condition that we could find — and unlike its twin, it has not accumulated a toxicity file, though it also has far less research of every kind.

What Labs Can Measure

Expanded commercial terpene methods can include both pulegone and isopulegol; one GC/MS method, for example, measures them as part of a 40-analyte panel.^[14] On a COA, “ND” beside a listed analyte generally means it was not detected above the laboratory’s stated limit. A dash is less informative — it can mean non-detect, not reported, or not tested, depending on the laboratory’s legend.

Is Pulegone Safe?

At the very low exposures associated with intended food uses, the FDA found no public-health risk even while the law required delisting synthetic pulegone. Cannabis exposure is less well characterized, although the available evidence does not establish pulegone as a routine cannabis constituent. Concentrated pennyroyal oil is another world: approximately 10 mL has caused severe poisoning, while quantities above 15 mL — around one tablespoon — have been fatal, and it has no safe role in home medicine. Rodent carcinogenicity at high chronic doses is real, but it does not establish a comparable cancer risk from mint candy or cannabis flower.

Is Pulegone in Weed?

Pulegone has not been established as a routinely occurring cannabis constituent. It was included among the reference standards in one 33-chemovar study but did not help define any resulting chemotype.^[3] Claims that OG Kush, Headband, or other cultivars are rich in pulegone should be treated as unsupported unless a batch-specific COA actually reports it.

What Is the Difference Between Pulegone and Isopulegol?

Pulegone is a ketone, isopulegol an alcohol — closely related minty skeletons that also differ in where the double bond sits, with completely different biographies: pulegone carries the toxicity literature, while isopulegol’s small file points toward mouse studies of calming and stomach-protective effects and a working life as menthol’s final synthetic precursor.

References

1. Anderson IB, Mullen WH, Meeker JE, et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med. 1996;124:726-734. doi:10.7326/0003-4819-124-8-199604150-00004
2. Kumar P, Mishra S, Malik A, Satya S. Insecticidal properties of Mentha species: a review. Ind Crops Prod. 2011;34(1):802-817. doi:10.1016/j.indcrop.2011.02.019
3. Mudge E, et al. The terroir of cannabis: terpene metabolomics as a tool to understand Cannabis sativa selections. Planta Med. 2019;85:781-796. doi:10.1055/a-0915-2550
4. Silveira NS, Oliveira-Silva GL, Lamanes BF, Prado LCS, Bispo-da-Silva LB. The aversive, anxiolytic-like, and verapamil-sensitive psychostimulant effects of pulegone. Biol Pharm Bull. 2014;37(5):771-778. doi:10.1248/bpb.b13-00832
5. Orhan I, et al. Acetylcholinesterase inhibitory and antioxidant properties of Cyclotrichium niveum, Thymus praecox subsp. caucasicus var. caucasicus, Echinacea purpurea and E. pallida. Food Chem Toxicol. 2009;47(6):1304-1310. doi:10.1016/j.fct.2009.03.004
6. Bakerink JA, et al. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics. 1996;98(5):944-947.
7. Gordon WP, et al. Hepatotoxicity and pulmonary toxicity of pennyroyal oil and its constituent terpenes in the mouse. Toxicol Appl Pharmacol. 1982;65(3):413-424. doi:10.1016/0041-008X(82)90387-8
8. National Toxicology Program. Toxicology and carcinogenesis studies of pulegone (CAS No. 89-82-7) in F344/N rats and B6C3F1 mice (gavage studies). NTP Technical Report 563. 2011. https://ntp.niehs.nih.gov/go/tr563
9. US Food and Drug Administration. Food additive regulations; synthetic flavoring agents and adjuvants. Federal Register. 2018;83:50490. October 9, 2018.
10. European Medicines Agency, Committee on Herbal Medicinal Products. Public statement on the use of herbal medicinal products containing pulegone and menthofuran (revision 1). 2016.
11. Jabba SV, Jordt SE. Risk analysis for the carcinogen pulegone in mint- and menthol-flavored e-cigarettes and smokeless tobacco products. JAMA Intern Med. 2019;179(12):1721-1723. doi:10.1001/jamainternmed.2019.3649
12. Silva MI, de Aquino Neto MR, Teixeira Neto PF, et al. Central nervous system activity of acute administration of isopulegol in mice. Pharmacol Biochem Behav. 2007;88(2):141-147.
13. Silva MI, Moura BA, Neto MR, et al. Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action. Naunyn Schmiedebergs Arch Pharmacol. 2009;380(3):233-245.
14. Agilent Technologies. Analysis of terpenes in cannabis using the Agilent Intuvo 9000/5977B GC/MSD. Application note 5994-2032EN. PDF

Editor’s note: This article was originally published on May 13, 2019, by Petar Petrov. In October 2026, the editors rebuilt and expanded it on the same page, and it now incorporates material from two earlier Terpenes and Testing articles that redirect here: “Terpene Spotlight: Pulegone” by Cara Wietstock (2017) and “Isopulegol & Pulegone” by Caleb Summeril (2018). The toxicity, regulatory and isopulegol sections are new; the behavioral and memory research the original summarized is now presented in the cited studies’ own, more cautious terms.

Last updated October 2026 · Originally published May 13, 2019.

Photo: EmirDzaferovic, CC0, via Wikimedia Commons