Cubeb Pepper (Piper cubeba)

Piper cubeba L.f.
Evidence Level
Preliminary
3 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

Cubeb, also called tailed pepper or Java pepper, is the dried berry of Piper cubeba, a climbing vine in the pepper family native to Java and Borneo. The dried berry keeps a short stalk, the tail, which helps tell it apart from black pepper (Piper nigrum) and long pepper (Piper longum). Cubeb is used as a spice, to flavor gin and other drinks, and in traditional medicine, mainly for digestive and breathing complaints. The berries contain lignans such as cubebin, hinokinin and yatein, and an aromatic essential oil whose makeup varies widely between samples. Cubeb has far less piperine than black or long pepper, so piperine research does not carry over. No human trial has tested cubeb on its own; what is known about its effects comes from cell and animal studies. In the US it is listed as a natural flavoring substance under 21 CFR 172.510.

Studied Dose No human dose has been tested for cubeb on its own. Animal studies gave fruit extract by mouth at 200 mg/kg (mice) and 250 to 500 mg/kg (rats), and powdered fruit at 810 to 1,220 mg/kg (rats); these amounts do not convert directly into a human dose.
Active Compound Lignans (cubebin, hinokinin, yatein, dihydrocubebin) and essential oil compounds such as eugenol, methyl eugenol and cubebenes; piperine is present only at about 0.1%.

Benefits

Lignans and aromatic oil compounds in the dried berries

The berries contain lignans such as cubebin, hinokinin and yatein, plus an essential oil behind their spicy, warming aroma. The oil varies by sample: one analysis was led by methyl eugenol and eugenol, another by Z-isoeugenol, dihydroeugenol and β-pinene. Piperine is only about 0.1%, versus 2 to 9% in black pepper.

Traditional use as a culinary spice and in herbal medicine

Cubeb is used as a cooking spice, to flavor gin and other drinks, and in Unani and other traditional systems, mostly for digestive and breathing complaints and in urinary formulas. These are records of traditional practice, not research findings, and no human trial has tested cubeb alone for any of these uses.

Inflammation and allergy responses in mice (animal study)

In mice, a cubeb fruit extract given by mouth at 200 mg/kg reduced swelling in several induced inflammation tests, and a week of dosing reduced a delayed skin allergy reaction. The paper reported pain relief only for a rose extract tested alongside it. These are animal results that no human study has checked.

Liver enzymes and oxidative markers in rats (animal study)

Rats given a cubeb ethanol extract by mouth (250 or 500 mg/kg) for 7 days before a chemical liver challenge had smaller rises in liver enzymes, less lipid peroxidation and lower TNF-alpha and IL-6 gene activity than untreated rats, with larger effects at the higher dose. This is a rat injury model, not evidence in people.

Kidney blood markers in rats given gentamicin (animal study)

In rats given the antibiotic gentamicin, which strains the kidneys, cubeb powder by mouth at 810 or 1,220 mg/kg, given before or after the drug, lowered serum urea and creatinine and showed less tissue damage than in untreated rats. The doses are very large by body weight, and no human study has tested this.

Mechanism of action

1

Lignans block the drug-clearing enzyme CYP3A4 in lab tests

Five lignans isolated from cubeb, including hinokinin, yatein and dihydrocubebin, inactivated the liver enzyme CYP3A4 in test-tube work in a time-dependent way, and a cubeb extract fraction blocked 75% of its activity. Whether food or supplement amounts do this in people has not been tested.

2

Hormone pathway activity in cell studies

An ethanol extract of cubeb inhibited the aromatase enzyme, bound human estrogen receptors alpha and beta, and blocked estradiol-driven growth of a breast cell line; the same group earlier reported anti-androgen activity. These are cell and enzyme findings only.

3

Antioxidant and inflammatory signaling in lab and animal work

In rats, cubeb extract restored liver antioxidant measures (catalase and non-protein thiols), lowered TNF-alpha and IL-6 gene activity and raised IL-10. In cell work, an extract inhibited COX-1, COX-2 and 5-LOX and reduced IL-6 release from stimulated immune cells. None of this has been measured in people.

Clinical trials

1
Cubeb Extract in Mouse Inflammation and Allergy Models (animal study)
PubMed

Animal study, not a human trial: oral extracts of Piper cubeba fruit, Physalis angulata flower and Rosa hybrida flower tested in mouse models of paw and ear swelling, formaldehyde-induced arthritis, contact hypersensitivity and hot plate pain. (Choi et al. 2003, J Ethnopharmacol)

Mice; no human participants. Extracts were given by mouth at 200 mg/kg.

The extracts, cubeb included, reduced acute and subacute swelling, and a week of dosing significantly inhibited the type IV allergic reaction (P<0.05). The abstract reports a pain-relief effect only for the rose extract. Mouse results and doses do not translate directly to people.

2
Cubeb Extract Before a Chemical Liver Injury in Rats (animal study)
PubMed

Animal study, not a human trial: an acute oral toxicity check, then 7 days of a 70% ethanol extract of cubeb fruit (250 or 500 mg/kg by mouth) or the comparison silymarin before a carbon tetrachloride liver challenge. (AlSaid et al. 2015, Biomed Res Int)

Male Wistar rats, 6 per group; no human participants.

Single oral doses up to 1,000 mg/kg caused no deaths or behavior changes. Pretreatment dose-dependently reduced the rise in liver enzymes (SGOT, SGPT, GGT, ALP) and lipid peroxidation, restored antioxidant markers, lowered TNF-alpha and IL-6 gene expression and raised IL-10, with less tissue damage at 500 mg/kg. A rat model only.

3
Cubeb Extract and Drug-Clearing Liver Enzymes (lab study)
PubMed

Test-tube study, not a human trial: screening of 30 Indonesian medicinal plant samples for inhibition of the human drug-metabolizing enzymes CYP3A4 and CYP2D6 with a radiometric assay. (Usia et al. 2006, Phytomedicine)

No participants; enzyme assays with plant extract fractions.

An ethyl acetate fraction of cubeb blocked 75.0% of CYP3A4 activity, while strong CYP2D6 blocking was seen only with black pepper fruit and leaf. The authors flag possible herb and drug interactions. Test-tube results do not show what a food or supplement amount does in the body.

Side effects and drug interactions

Common Potential side effects

No human safety study of cubeb exists. In rats, single oral extract doses up to 1,000 mg/kg caused no deaths or behavior changes, and a review reports no signs of toxicity at 2,000 mg/kg of a methanol extract. Long-term effects in people are unknown.
A 2025 review notes that excessive doses of the berries may cause burning pain, nausea, griping, vomiting and purging, and describes cubeb as having oxytocic (uterus-stimulating) effects that make it harmful in pregnancy. Stay with ordinary food amounts if you are pregnant.
Some cubeb oils are rich in methyl eugenol (about 41% in one analysis). In 2018 the FDA stopped allowing synthetic methyl eugenol as an added flavoring because it caused cancer in laboratory animals, while finding no clinical or epidemiological evidence linking typical intake of spices and herbs that naturally contain it to cancer. Swallowing concentrated cubeb oil has not been studied.
In cell studies a cubeb extract bound estrogen receptors and blocked aromatase. People with hormone-sensitive conditions should ask a doctor before using concentrated cubeb products.

Important Drug interactions

Medicines cleared by CYP3A4: in test-tube work, cubeb lignans inactivated this enzyme and an extract fraction blocked 75% of its activity. This has not been measured in people, but anyone taking prescription drugs cleared by CYP3A4 should check with a pharmacist before using concentrated cubeb.
Hormone therapies (estrogen products or aromatase inhibitors): cell studies show anti-estrogen and aromatase-blocking activity of unknown clinical relevance; ask the prescriber first.
The drug interactions reported for black pepper's piperine come from studies of isolated piperine. Cubeb contains about 0.1% piperine against 2 to 9% in black pepper, so those findings cannot be assumed to apply to cubeb in either direction.

Frequently asked questions about Cubeb Pepper (Piper cubeba)

How is cubeb different from black pepper and long pepper?

All three are dried berries of Piper vines, but they are different species: cubeb is Piper cubeba, black pepper is Piper nigrum and long pepper is Piper longum. Cubeb berries keep a short stalk, the tail. Cubeb has about 0.1% piperine, against about 2 to 9% in black pepper and 3 to 5% in long pepper, so the piperine absorption research behind black pepper extract does not apply to it. Its aroma comes mainly from essential oil compounds such as eugenol and methyl eugenol.

Has cubeb been tested in people?

Not on its own. Searches of PubMed and ClinicalTrials.gov found no controlled human trial of cubeb by itself. It appears only as one of several herbs in multi-herb formulas, where its own effect cannot be separated. The findings summarized on this page come from cell, enzyme and rodent studies.

Is cubeb allowed as a food flavoring in the US?

Yes. Cubeb (Piper cubeba) is listed among the natural flavoring substances in 21 CFR 172.510, to be used in the minimum amount needed. It does not appear in the separate GRAS lists of spices (21 CFR 182.10) or essential oils (21 CFR 182.20). A flavoring listing covers small food uses and does not establish safety at supplement doses.

What is in cubeb essential oil?

It depends on the sample. One analysis found mostly methyl eugenol (41%), eugenol (34%) and the cubebenes; another found Z-isoeugenol, dihydroeugenol, β-pinene, E-caryophyllene and 1,8-cineole as the main compounds. The FDA no longer allows synthetic methyl eugenol as an added flavoring because of cancer findings in lab animals, though it found no clinical or epidemiological evidence linking typical intake of foods that naturally contain it to cancer. Cubeb oil has not been studied for safety when swallowed.

Should cubeb be avoided during pregnancy?

Stick to ordinary food amounts. A 2025 review describes cubeb as having uterus-stimulating (oxytocic) effects that make it harmful in pregnancy, and no safety studies exist in pregnant or breastfeeding women. Ask a doctor or midwife before using any concentrated cubeb product.

What is Cubeb Pepper?

Cubeb, also called tailed pepper or Java pepper, is the dried berry of Piper cubeba, a climbing vine in the pepper family native to Java and Borneo. The dried berry keeps a short stalk, the tail, which helps tell it apart from black pepper (Piper nigrum) and long pepper (Piper longum).

What is Cubeb Pepper used for?

NutraSmarts does not list Cubeb Pepper under a health category. What the research covers: The berries contain lignans such as cubebin, hinokinin and yatein, plus an essential oil behind their spicy, warming aroma.

What is the recommended dosage of Cubeb Pepper?

No human dose has been tested for cubeb on its own. Animal studies gave fruit extract by mouth at 200 mg/kg (mice) and 250 to 500 mg/kg (rats), and powdered fruit at 810 to 1,220 mg/kg (rats); these amounts do not convert directly into a human dose. Always follow the product label and check with a healthcare provider for personal advice.

Is Cubeb Pepper safe, and does it have side effects?

Side effects and cautions reported for Cubeb Pepper include: No human safety study of cubeb exists. In rats, single oral extract doses up to 1,000 mg/kg caused no deaths or behavior changes, and a review reports no signs of toxicity at 2,000 mg/kg of a methanol extract. Long-term effects in people are unknown. It may also interact with some medications. Cubeb Pepper is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Cubeb Pepper interact with any medications?

Possible interactions include: Medicines cleared by CYP3A4: in test-tube work, cubeb lignans inactivated this enzyme and an extract fraction blocked 75% of its activity. This has not been measured in people, but anyone taking prescription drugs cleared by CYP3A4 should check with a pharmacist before using conc… If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Cubeb Pepper?

NutraSmarts rates the evidence for Cubeb Pepper as Preliminary (1 out of 5). It is backed by 3 study summaries and 12 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(12 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Drissi B, Mahdi I, Yassir M, Ben Bakrim W, Bouissane L, Sobeh M. Cubeb (Piper cubeba L.f.): A comprehensive review of its botany, phytochemistry, traditional uses, and pharmacological properties. Front Nutr. 2022;9:1048520. doi: 10.3389/fnut.2022.1048520.PubMedUsed to support: Review of cubeb botany, chemistry, traditional use and lab and animal pharmacology. It reports that the plant is native to Java and Borneo, is used to flavor drinks such as gin, and is used traditionally mainly for digestive and breathing complaints. It lists 28 lignans (including cubebin, hinokinin and yatein) and one essential oil analysis led by methyl eugenol (41.31%) and eugenol (33.95%). It reports no toxicity signs in rats at 2,000 mg/kg of a methanol extract and states that no systematic pharmacokinetic or clinical data exist.
  2. Drissi BE, Mahdi I, Ortaakarsu AB, Abdelfattah MAO, Bakrim WB, Khatib S, Mahmoud MF, Bouissane L, Sobeh M. Cubeb (Piper cubeba L.): nutritional value, phytochemical profiling and dermacosmeceutical properties. Front Nutr. 2024;11:1352548. doi: 10.3389/fnut.2024.1352548.PubMedUsed to support: Lab analysis of cubeb berries: 43 compounds (organic acids, phenolic acids, flavonoids) in a water extract and 36 volatile compounds in the essential oil, with Z-isoeugenol, dihydroeugenol, β-pinene, E-caryophyllene and 1,8-cineole as the major ones. The berries were rich in sodium and iron. Test-tube antioxidant, antibacterial and enzyme work only; no human or animal testing.
  3. Díaz-Guerrero P, Panzani S, Sanmartin C, Muntoni C, Taglieri I, Venturi F. "Pepper": Different Spices, One Name-Analysis of Sensory and Biological Aspects. Molecules. 2025;30(9):1891. doi: 10.3390/molecules30091891.PubMedUsed to support: Review comparing six spices called pepper, including black pepper (Piper nigrum), cubeb (Piper cubeba) and long pepper (Piper longum). It gives piperine content as about 2 to 9% in black pepper, about 0.1% in cubeb and 3 to 5% in long pepper, describes the tail that gives cubeb the name tailed pepper, and lists cubebin at 1 to 3%. Citing older sources, it notes that excessive doses of the berries may cause burning pain, nausea, griping, vomiting and purging, and that cubeb has oxytocic effects that make it harmful in pregnancy.
  4. Ahmad R, Alaswad D, Alshehab AJ, Aldholmi M, Al Sulays A, Al-Sulais W, Alqathama A, Alghorab FT, Alibrahim HA. Ultrasonic-assisted green, eco-friendly, and economical aqueous extraction of Piperine from pepper species: an alternative to replace organic harmful solvents. Ultrason Sonochem. 2026;132:107986. doi: 10.1016/j.ultsonch.2026.107986.PubMedUsed to support: Lab method paper on extracting and measuring piperine. In its small real-sample test, white pepper (Piper nigrum) had the highest piperine content, followed by black, long and cubeb pepper, so cubeb ranked lowest. No human or animal testing.
  5. Choi EM, Hwang JK. Investigations of anti-inflammatory and antinociceptive activities of Piper cubeba, Physalis angulata and Rosa hybrida. J Ethnopharmacol. 2003;89(1):171-5. doi: 10.1016/s0378-8741(03)00280-0.PubMedUsed to support: Mouse study of three plant extracts given by mouth at 200 mg/kg, including cubeb fruit: the extracts reduced acute and subacute swelling in induced inflammation models, and a week of dosing inhibited a type IV contact allergy reaction (P<0.05). The abstract reports pain relief on the hot plate test only for the rose (Rosa hybrida) extract. Animal work only.
  6. AlSaid M, Mothana R, Raish M, Al-Sohaibani M, Al-Yahya M, Ahmad A, Al-Dosari M, Rafatullah S. Evaluation of the effectiveness of Piper cubeba extract in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Biomed Res Int. 2015;2015:359358. doi: 10.1155/2015/359358.PubMedUsed to support: Rat study: single oral doses of a cubeb fruit ethanol extract up to 1,000 mg/kg caused no deaths or behavior changes. Seven days of 250 or 500 mg/kg by mouth before a carbon tetrachloride liver challenge dose-dependently reduced rises in liver enzymes and lipid peroxidation, restored antioxidant markers, lowered TNF-alpha and IL-6 gene expression and raised IL-10. Animal work only.
  7. Usia T, Iwata H, Hiratsuka A, Watabe T, Kadota S, Tezuka Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. doi: 10.1016/j.phymed.2004.06.022.PubMedUsed to support: Test-tube screen of 30 Indonesian medicinal plant samples against human CYP3A4 and CYP2D6: an ethyl acetate fraction of cubeb inhibited CYP3A4 activity by 75.0%; strong CYP2D6 inhibition was seen only with black pepper fruit and leaf. The authors point to possible herb and drug interactions. Lab work only.
  8. Usia T, Watabe T, Kadota S, Tezuka Y. Metabolite-cytochrome P450 complex formation by methylenedioxyphenyl lignans of Piper cubeba: mechanism-based inhibition. Life Sci. 2005;76(20):2381-91. doi: 10.1016/j.lfs.2004.12.005.PubMedUsed to support: Test-tube study of five lignans isolated from cubeb (clusin, dihydroclusin, yatein, hinokinin and dihydrocubebin): all inhibited CYP3A4 in a time-, concentration- and NADPH-dependent way, which marks them as mechanism-based inactivators of the enzyme. Isolated constituents in lab assays, not cubeb taken by people.
  9. Ahmad QZ, Jahan N, Ahmad G, Tajuddin. Nephroprotective effect of Kabab chini (Piper cubeba) in gentamycin-induced nephrotoxicity. Saudi J Kidney Dis Transpl. 2012;23(4):773-81. doi: 10.4103/1319-2442.98159.PubMedUsed to support: Rat study: cubeb powder given by mouth at 810 or 1,220 mg/kg, before or after the kidney-straining antibiotic gentamicin, lowered serum urea and creatinine and showed less kidney damage on tissue examination than in untreated rats. Animal work at very high doses by body weight.
  10. Yam J, Schaab A, Kreuter M, Drewe J. Piper cubeba demonstrates anti-estrogenic and anti-inflammatory properties. Planta Med. 2008;74(2):142-6. doi: 10.1055/s-2008-1034290.PubMedUsed to support: Cell and enzyme study of an ethanol extract of cubeb (P9605): it inhibited estradiol-driven growth of MCF-7 breast cells, inhibited aromatase, bound human estrogen receptors alpha and beta, inhibited COX-1, COX-2 and 5-LOX, and reduced IL-6 release from stimulated immune cells. The authors mention earlier anti-androgenic findings. Lab work only.
  11. U.S. Food and Drug Administration. 21 CFR 172.510 Natural flavoring substances and natural substances used in conjunction with flavors. Code of Federal Regulations (eCFR). 2026;Title 21, Part 172, Subpart F, Section 172.510. Read on eCFR (version of 2026-10-01)..SourceUsed to support: Not PubMed-indexed; official US regulation, read on eCFR. Cubeb (Piper cubeba L. f.) is listed among natural flavoring substances that may be used in food in the minimum quantity needed for their effect, with no further limitation stated for cubeb. Cubeb does not appear in the GRAS lists of spices (21 CFR 182.10) or essential oils and extracts (21 CFR 182.20) as read on the same date. A flavoring listing does not establish safety at supplement doses.
  12. U.S. Food and Drug Administration. Food Additive Regulations; Synthetic Flavoring Agents and Adjuvants. Federal Register. 2018;83 FR 50490 (October 9, 2018). Document 2018-21807..SourceUsed to support: Not PubMed-indexed; FDA final rule, read on the Federal Register. FDA stopped authorizing six synthetic flavoring substances, including methyl eugenol, because they caused cancer in laboratory animals, while concluding they do not pose a public health risk at intended use levels. FDA noted that exposure to methyl eugenol from foods that naturally contain it, such as basil and other spices, is much higher than from the synthetic additive, and found no clinical or epidemiological evidence linking typical intake of those foods to cancer.