Cannabis & Cannabinoids · Terpenes · The citrus aroma molecule in orange peel, other plants and cannabis

Limonene

Q: What is limonene?

Limonene is a small citrus-smelling molecule made by many plants, including orange and lemon peel, some thyme types and cannabis. It is a monoterpene with the formula C10H16. d-Limonene is the form most studied.

Q: Which plants contain limonene?

Citrus peel oils are the best-known source: a review says d-limonene is more than 90% of orange peel oil. Cannabis, some thyme types and many other plants also make it. Amounts vary by plant and batch.

Q: Is limonene in cannabis the same as in oranges?

Both are called limonene and share the formula C10H16, but it comes in two mirror-image forms. Safety studies mostly used d-limonene. One study of a hemp variety found cannabis enzymes make (-)-limonene. Our lab data do not say which form was measured.

Q: Does limonene reduce anxiety?

Evidence is limited. One small trial in 20 healthy adults found a high vaporized dose lowered anxious and paranoid ratings after THC; alone it matched placebo. Orange scent lowered self-rated anxiety in small trials, but those used whole oil. Mouse results are mixed. It is not a treatment for anxiety.

Q: Does limonene make THC safer or change how cannabis feels?

Not shown. In the one trial, limonene did not change THC blood levels or THC's effects on thinking and movement; only anxious and paranoid ratings fell, at the highest dose. No study tested limonene inside cannabis flower. Do not drive or make risky choices after THC.

Q: Does a lemon or citrus strain name mean more limonene?

Not in the numbers we have. In Nevada medians, Super Lemon Haze was among the lowest and Lemon Cherry Gelato was much higher. The same strain name also varies a lot between samples. A name is marketing, not a measurement.

Q: Can limonene cause a skin allergy?

Yes, mainly when it has reacted with air. In dermatitis clinics, about 5% of patients tested positive to oxidised limonene (5.0 to 5.2% in large series). Cleaners, hand cleansers and scented products are common sources. If a product with limonene makes your skin itch or blister, stop using it and ask a clinician.

Q: Is limonene safe?

Reviews call d-limonene low in toxicity as a food and cosmetic ingredient; skin irritation and allergy are the main human concerns. Pure limonene is flammable and dangerous if swallowed and breathed into the lungs. Safety of long-term vaporizing is unknown, and a lab test found terpenes added to THC raised breakdown products in vape and dab aerosol.

Q: Is limonene a cancer treatment?

No. Rodent studies found fewer chemically induced mammary tumours. In people, a phase I trial in 42 patients found it tolerated up to a limit with one partial response, and a 43-woman pilot found a 22% fall in one tumour marker. There is no placebo-controlled trial. Do not use limonene instead of cancer treatment.

Q: Does limonene help heartburn or gallstones?

No trial of limonene for heartburn was found. For gallstones, doctors used a limonene solvent through a bile-duct drain in a hospital procedure that cleared stones in 48% of 200 people. That is not something to take by mouth or do at home.

(4R)-1-methyl-4-prop-1-en-2-ylcyclohexene (d-limonene), C10H16 · also called Limonene, d-limonene, (R)-(+)-limonene, (+)-limonene, carvene, p-mentha-1,8-diene (dipentene is the unspecified or mixed form)

Limonene is a small, citrus-smelling plant molecule (a monoterpene). Reviews say it makes up more than 90% of orange peel oil, and cannabis also makes it. Most research is in animals and cells. One small trial found a high vaporized dose lowered THC-related anxiety ratings; orange-scent trials are small. Limonene that has sat in air can cause skin allergy.

General information, not medical advice. Last substantive update October 25, 2026 · Not medically reviewed. A named clinician has not signed off on this page. How this page is made

About Limonene

Limonene is a common citrus-smelling molecule: reviews say it is more than 90% of orange peel oil, and cannabis makes it too. Almost all research is in animals and cells. The best human study is a 20-person vaporizer trial in which a high dose lowered THC-related anxious and paranoid ratings but changed nothing else. Orange-scent trials used whole oil. Oxidised limonene (limonene that has sat in air) is a common skin allergen, found in about 5% of people tested in dermatitis clinics. Reviews call limonene low in toxicity at food and cosmetic levels, and the FDA lists it among food flavourings generally recognised as safe. No source read shows that a "lemon" or "citrus" strain has more limonene, or that more limonene changes how cannabis feels.

What it is

Limonene is a monoterpene: a small molecule of ten carbon atoms with the formula C10H16 (PubChem compound 440917 for d-limonene). It comes in two mirror-image forms. d-Limonene is the (R)-(+) form that most food-safety and human studies used. The (S)-(-) form is a different molecule. In a study of one hemp variety, the cannabis enzymes made (-)-limonene.

Cannabis makes limonene in the resin glands of the female flower. In one analysis of 33 flower samples, d-limonene was 6.2% of total terpenes in CBD-dominant samples and 7.2% in THC-dominant ones. In a separate study of two strains, limonene was among the high-amount terpenes.

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Where you meet limonene

Citrus peel oil is the best-known source. A 1999 review says d-limonene is more than 90% of orange peel oil, and a 2007 review says it is a major part of orange, lemon, mandarin, lime and grapefruit oils. Limonene is also found in some thyme types (7.5% and 17.8% of the headspace volatiles in two samples of one thyme subspecies) and is added to many foods, cosmetics and cleaning products as a flavour or fragrance.

Because it is also an added flavour, a limonene figure on a label does not tell you whether it came from the plant. This website's pages on citrus essential oils give more on those oils, including a separate skin-and-sunlight issue with some of them.

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What the lab numbers show

Our data hold 257 limonene measurements for 195 named strains, including 23 of the 28 strains that have a profile page here. They come from several kinds of source, each in a different unit, so numbers in different units must not be compared. A Nevada regulator dataset gives, for 64 strains, one median per strain in percent by weight (the source does not label the unit per column); these medians run from 0.033% (Trainwreck, 30 samples) to 0.8703% (182 samples), and the middle strain's median is about 0.26%. Most of these medians rest on more than 100 samples. A study of one California dispensary (February 2015 to February 2016) gives means in mg/g for 26 strains, from 0.9 (Jack Herer, 9 samples) to 9.1 (Gelato, 5 samples), each from 5 to 19 samples with the spread (SD) printed. In that study the limonene peak may overlap with beta-phellandrene, a different terpene, so those values can include some of it. A hemp field trial reports mg/g (means of 3 replicate plots, 0.36 to 3.84 mg/g for 27 varieties) and ppm. A few papers report single batches in micrograms per gram or in a table headed percent dry weight, with much smaller numbers and an uncertain unit, and 15 strains have a value printed in percent with no sample count; we do not compare those with the other sets.

The same strain name varies a lot. Blue Dream appears as 0.0599% (Nevada median of 363 samples, 307 with a value), as 1.1 mg/g (mean of 19 samples, SD 0.8) and as 19 micrograms per gram (one batch), and these are not comparable with each other. Gorilla Glue #4 appears at 0.2151% (660 samples) under one name and at 0.11% (89 samples) under a variant name. In the California set, Chemdawg averaged 4.2 mg/g from 6 samples (SD 1.1), while its Nevada median was 0.15% from 18 samples. These numbers are measurements of flower content from regulator, lab and published datasets, not from our own testing. They say nothing about effects, and our data do not say whether d- or l-limonene was measured.

Examples within the same unit and source type (Nevada medians, percent by weight): among our profile strains, the highest were Ice Cream Cake (0.4213%, 626 samples), Wedding Cake (0.3539%, 953 samples) and Sour Diesel (0.3517%, 61 samples); the lowest were Trainwreck (0.033%, 30 samples), Super Lemon Haze (0.0523%, 184 samples) and Blue Dream (0.0599%, 363 samples). Sample counts differ a lot, so smaller groups are less certain.

The popular claims

"Citrus or lemon strains have more limonene." The numbers do not support a simple link. In the Nevada medians (percent by weight), Super Lemon Haze was 0.0523% (184 samples), the fourth lowest of 64 strains, while Lemon Cherry Gelato was 0.4254% (212 samples). A strain's name is a marketing label, not a measurement.

"Limonene makes cannabis uplifting." No source read supports this. A 2025 analysis of 140 German medicinal cannabis flowers found no link between terpene profiles and sativa, indica or hybrid labels or estimated effects. In the one trial that gave limonene with THC, limonene alone matched placebo.

"Limonene cures cancer." It does not. Rodent studies and two small human studies exist; none shows treatment or prevention in people.

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What the research shows

Human: in a double-blind trial of 20 healthy adults who use cannabis, vaporized d-limonene alone matched placebo, and the highest dose given with 30 mg THC significantly lowered "anxious/nervous" and "paranoid" ratings; other effects and THC blood levels were unchanged. Orange-oil scent lowered self-rated anxiety in small trials in dental offices (72 and 200 patients), before a stress test (40 men) and in labour (84 women). A 1995 report of 12 people with depression says citrus fragrance cut antidepressant needs, but gave no numbers. Mixtures that included limonene (a CBD plus eight-terpene mix, a menthol-limonene-gingerol supplement, a heel-pain solution) showed small gains but cannot be credited to limonene. In people with cancer, high oral doses were tolerated up to a limit, and a pilot in 43 women found limonene reached breast tissue and lowered one tumour marker.

Animals and cells: in mice, limonene lowered anxiety-like behaviour in three papers, but one older paper found none and a slight anxiety-raising pattern at higher doses, along with sedation and muscle relaxation. Limonene lowered inflammation signals in rats and mice, and rodent studies found fewer chemically induced mammary tumours. In human immune cells in a dish, it had no effect.

Gallstones: doctors used a limonene solvent through a bile-duct drain in a hospital procedure; it is not a home remedy. Heartburn: no trial found.

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Regulatory status

In the US, section 182.60 of the Code of Federal Regulations lists limonene (d-, l- and dl-) among flavouring substances generally recognised as safe for their intended use in food; section 182.20 lists lemon, lime, sweet orange and bitter orange oils the same way (read 2026-10-25). That is a food flavour status. It does not speak to vaping, heating or cannabis products.

Companies' notified hazard classes for pure d-limonene (aggregated by PubChem from European notifications) include flammable, skin irritant, skin sensitiser and aquatic toxicity; these are notifications, not a regulator's ruling. We did not read IARC, EFSA, JECFA or EU cosmetics documents on limonene, so we say nothing about them.

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At a glance

Traditional uses history, not proof

Flavouring and fragrance ingredient in food, drinks, cosmetics and cleaning products (reviews)
Cleaning and degreasing agent made from citrus juice by-products (according to a 1997 paper)
Solvent used by doctors in the 1970s to 1990s to dissolve retained gallstones through a bile-duct drain (hospital reports)
Orange and citrus scents used in aromatherapy (modern, small trials)

Studied for research

Anxiety and paranoia caused by THC, one 20-person trial, low
Anxiety and mood from orange scent, small trials of whole orange oil, low
Low mood and depression, a 12-person report plus mouse studies, very low
Anxiety-like behaviour in animals, mixed results, very low
Sedation and sleep, mouse studies and one mixture trial, very low
Cancer research, a phase I trial and a breast cancer pilot, very low
Inflammation, mostly mice and rats, very low
Heartburn: no trial found; gallstones: a hospital procedure; IBS and pain: mixtures only

Main compounds

d-Limonene (R)-(+), C10H16; l-limonene (S)-(-)
Oxidation products (hydroperoxides) that cause skin allergy
Metabolites: perillic acid, limonene-1,2-diol, limonene-8,9-diol
Related cannabis terpenes: myrcene, pinene, caryophyllene, ocimene, beta-phellandrene

Common forms

Natural part of cannabis flower and extracts
Citrus peel oils (orange, lemon, lime, grapefruit, mandarin)
Pure compound in lab trials: vaporized, oral capsules, bile-duct solvent
Ingredient in cleaners, cosmetics and scented products

Research links: PubChem: D-Limonene · US eCFR: 21 CFR 182.60 (flavouring substances) · US National Toxicology Program report (PubMed) · Vaporized d-limonene and THC anxiety trial (PubMed) · Research Library · Genes & Biomarkers Library

What it is and its history

Name: Limonene (d-limonene is the (R)-(+) mirror form)
Chemical name: (4R)-1-methyl-4-prop-1-en-2-ylcyclohexene (d-limonene)
Other names: D-Limonene; (+)-Limonene; (R)-(+)-Limonene; (+)-Dipentene; Carvene; p-Mentha-1,8-diene; 1-methyl-4-prop-1-en-2-ylcyclohexene (no mirror form specified)
Common names: Limonene (English); d-Limoneno (Spanish)
Formula: C10H16
Molecular weight: 136.23
CAS number: 5989-27-5
PubChem ID: 440917
Chemical class: Monoterpene: a small aromatic hydrocarbon built from ten carbon atoms, with one ring and no oxygen (formula C10H16)
How the plant makes it: Cannabis makes terpenes in the resin glands (trichomes) of the female flower. A study of the hemp variety Finola found nine terpene-making enzymes whose products make up most of its resin terpenes, including (-)-limonene. A review notes terpenes and cannabinoids share a precursor. Which mirror form (d or l) a given cannabis variety makes was not examined in the sources read.
Where it is found: Cannabis flower: in one analysis of 33 samples, d-limonene was 6.2% of total terpenes in CBD-dominant and 7.2% in THC-dominant samples.; Citrus peel oils: a review says d-limonene is more than 90% of orange peel oil, and another says it is a major part of orange, lemon, mandarin, lime and grapefruit oils.; Thyme: limonene was 7.5% and 17.8% of the headspace volatiles in two samples of one thyme subspecies in one study.; Everyday products: a flavour, fragrance and cleaning-product ingredient; reviews describe wide use in cosmetics, foods and household products.
Related or similar compounds: Name: Other cannabis monoterpenes; Note: Myrcene, alpha- and beta-pinene, ocimene and terpinolene are different molecules with different properties.; Name: Beta-phellandrene; Note: PubChem CID 11142, C10H16. Some lab methods cannot cleanly separate limonene from this molecule, which is why some of our lab numbers carry a warning.; Name: l-Limonene ((S)-(-)); Note: The mirror image of d-limonene. It is a different molecule from d-limonene, and most food-safety research was done on d-limonene.

Traditional use and history history, not clinical proof

Tradition or era	Documented use	Source
Food and fragrance additive	The FDA lists limonene (d-, l- and dl-) among flavouring substances generally recognised as safe for their intended use in food (read 2026-10-25).	21 CFR 182.60 via eCFR
Industrial cleaner	A 1997 paper says d-limonene, a by-product of the citrus juice industry, was introduced as a more environmentally friendly defatting and cleaning agent than traditional organic solvents.	Karlberg and Dooms-Goossens 1997 (PubMed 9165203)
Medical gallstone solvent (1970s to 1990s)	Doctors described flushing a d-limonene preparation through a bile-duct drain to dissolve retained cholesterol gallstones (1976 report of four cases; 1991 report of 200 people).	Igimi et al. 1976 and 1991 (PubMed 790944, 1988264)
Aromatherapy and citrus scent	Orange and citrus oils have been tested as calming scents in clinics since the 1990s (1995 depression report; 2000 and 2005 dental office trials). These show a use, not a long tradition.	Komori 1995; Lehrner 2000, 2005
Cannabis entourage idea	A 2011 review proposed that cannabis terpenoids including limonene could add to THC's effects. It was a proposal rather than a finding.	Russo 2011 (PubMed 21749363)
Origin of the name and first isolation	NOT verified. Statements about when limonene was first named or isolated were not found in any source read.	none

History shows how a substance was used or discovered. It does not show that a product works or is safe today.

What is inside, and how it may work

What it contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.

Main compounds

Compound	Family	Where it is concentrated	Activity studied	Level of evidence
d-Limonene ((R)-(+)-limonene) PubChem 440917	Monoterpene (cyclic hydrocarbon)	Citrus peel oils; cannabis resin; some thyme types; many other plants Varies by plant and batch; see "What the lab numbers show" on the Overview tab for measured cannabis values and their units.	Studied for anxiety-like behaviour, inflammation and cancer markers mostly in animals and cells; two small human studies of limonene (a vaporized trial with THC and an oral breast-cancer pilot). ^{40 29 8}	Mixed
l-Limonene ((S)-(-)-limonene) PubChem 439250	Monoterpene	Reported for the cannabis variety Finola in one study	Less studied than d-limonene; the same human liver enzymes oxidise both forms in the lab. ^{4 30}	Laboratory research
Limonene hydroperoxides (oxidation products)	Oxygen-containing limonene derivatives	Form when limonene is exposed to air Patch tests use 0.3% limonene hydroperoxides (UK audit) or 3% oxidised limonene containing 0.33% hydroperoxides (multicentre study).	Strong skin sensitisers; limonene-1-hydroperoxide was the most potent in one study. ^{7 2 5}	Observational
Perillic acid (breakdown product) PubChem 1256	Monoterpene acid	Made in the body from limonene	Main circulating metabolite after high oral doses; it did not concentrate in breast tissue. ^{47 29 34}	Human data
Perillyl alcohol (breakdown product) PubChem 10819	Monoterpene alcohol	Made in the body from limonene (small amounts)	A minor limonene metabolite in the 4-volunteer oral study (less than 0.1% of the dose in urine). ^{37 30}	Human data
Limonene-1,2-diol and limonene-8,9-diol (breakdown products) PubChem 94217	Monoterpene diols	Made in the body from limonene	Limonene-8,9-diol accounted for about 32% of an oral dose in urine in 4 volunteers; limonene-1,2-diol about 4.3%. CID 94217 is for the 1,2-diol. ^{37 34}	Human data
Limonene oxide (1,2-epoxide) PubChem 91496	Monoterpene epoxide	Minor metabolite in rats	In male rats, the minor metabolite d-limonene-1,2-oxide binds to the kidney protein alpha-2u-globulin, which a review links to the rat-specific kidney damage. ¹³	Animal research
Beta-phellandrene PubChem 11142	Monoterpene	Cannabis and other plants	Not studied here. Listed because some lab methods may not separate it cleanly from limonene.	Not studied

Mechanisms, receptors and pathways

Target or pathway	Gene or receptor	What was found	Level
Adenosine A2A receptor, dopamine and GABA in the striatum	ADORA2A	In mice, limonene's anti-anxiety-like effect and its GABA-release effect were blocked by an A2A receptor blocker; limonene raised striatal dopamine. ³⁹	Animal research
Benzodiazepine site of the GABA-A receptor	GABA-A receptor (benzodiazepine site)	Inhaled limonene's anxiolytic-like effect in mice was not blocked by flumazenil, suggesting the benzodiazepine site is not involved. ²⁶	Animal research
NF-kB, TLR4/AP-1 and Nrf2 inflammation signalling	NFKB1, TLR4, NFE2L2	In mice, oral limonene lowered TNF-alpha, IL-1beta and COX-2, suppressed TLR4/NF-kB/AP-1 (not IRF3) and activated Nrf2; in rat colitis and fibroblast cells it blocked NF-kB movement. ^{20 51}	Animal research
Cyclin D1 (cell cycle)	CCND1	Tumour cyclin D1 fell by 22% after oral limonene in women with early breast cancer (open-label pilot). ²⁹	Human data
Growth-protein modification (isoprenylation) and detox enzymes	Farnesyl transferase	A review says monoterpenes may act by inducing detox enzymes, causing cell death and blocking isoprenylation of growth proteins; the 1996 human metabolism paper calls limonene a farnesyl transferase inhibitor. Not shown in patients' tumours. ^{8 34}	Review
Alpha-2u-globulin kidney protein (male rat only)	Alpha-2u-globulin	In male rats, the metabolite limonene-1,2-oxide binds this protein, which piles up in kidney cells; reviewers say people do not have this protein in the needed form. ^{13 32}	Animal research
Liver enzymes that break limonene down	CYP2C9, CYP2C19 (also CYP2C8, 2C18, 3A4 in recombinant tests)	Human liver microsomes oxidise (+)- and (-)-limonene to carveols and perillyl alcohols, mainly through CYP2C9 and CYP2C19. ^{30 38}	Laboratory research
Human immune cells	None found	In human blood immune cells in culture, D-limonene had no effect on any of 21 measured responses (0.001 to 10 micromolar). ³	Laboratory research

Absorption, metabolism and elimination

Absorption: By inhalation, about 70% of the limonene breathed in was taken up in volunteers in an exposure chamber. By mouth, blood peaks were reached 1 to 2 hours after a small single dose in 4 volunteers; in cancer patients on high doses, peak d-limonene blood levels were about 11 to 21 micromolar. After vaporizing 1 to 15 mg, blood d-limonene rose with the dose.
Distribution: Limonene concentrated in breast tissue (mean 41.3 micrograms per gram after 2 g a day) and in tumours at higher levels than in blood in two patients. A long slow phase in blood after inhalation suggested build-up in body fat.
Metabolism: Rapid. Main blood metabolites in cancer patients: perillic acid, dihydroperillic acid, limonene-1,2-diol, limonene-8,9-diol, uroterpenol. In 4 healthy volunteers, about 32% of an oral dose appeared in urine as limonene-8,9-diol. In the lab, human liver enzymes CYP2C9 and CYP2C19 break it down.
Elimination: Metabolite half-lives were 0.7 to 2.5 hours after a small oral dose, with elimination complete within 24 hours. After inhalation, about 1% left unchanged in breath and 0.003% in urine. Urine contained glucuronide-linked metabolites.
Bioavailability: Not established for vaporized or cannabis-flower limonene. Vaporization in the lab trial did not change THC blood levels.

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12benefits and uses looked at

53studies and sources checked

Low certaintybest evidence rating found

12lab markers tracked in trials

2 low certainty8 very low certainty2 not enough evidence

What was looked at

The 12 benefits and uses checked for Limonene, each with how strong the evidence is. Tap one to open it.

Anxiety and paranoia caused by THCLow certainty
Calming scent: anxiety and mood in people (orange oil)Low certainty
Low mood and depressionVery low certainty
Anxiety-like behaviour in animals (results disagree)Very low certainty
Sedation and sleepVery low certainty
The "entourage effect" and strain claimsNot enough evidence
Cancer research (not a treatment)Very low certainty
Inflammation and immune signalsVery low certainty
Heartburn and refluxNot enough evidence
Gallstones (a hospital procedure, not a supplement)Very low certainty
Irritable bowel symptoms (three-ingredient supplement)Very low certainty
PainVery low certainty

Lab markers tracked in the studies

Self-rated anxiety (state anxiety)"Anxious/nervous" and "paranoid" ratings after THCElevated plus maze (open-arm time) in miceBarbiturate sleeping time in miceShare of the night in slow-wave plus REM sleepCyclin D1 in breast tumour tissueBlood IL-6 (inflammation signal)Gut inflammation score and blood TNF-alpha in ratsAirway cytokines and over-reactivity in asthma miceDisappearance of retained gallstonesIBS symptom score (7x7 questionnaire)Foot function index (heel pain)

What is Limonene good for?

The uses people ask about and how strong the evidence is for each. For limonene, almost all of it is from animals or cells, and the human studies are small or tested whole oils or mixtures.

Anxiety and paranoia caused by THCLow certaintyOne double-blind trial in 20 healthy adults found that vaporized d-limonene at the highest dose, given with THC, lowered ratings of feeling anxious and paranoid compared with THC alone. It changed no other effect of THC. d-Limonene alone matched placebo. Small, not repeated. Calming scent (orange oil)Low certaintySmall trials found orange oil scent lowered self-rated anxiety in dental waiting rooms, before a stress test and in labour. The oil is mostly limonene, but these trials used whole oil, so limonene is not shown to be the cause. Low mood and depressionVery low certaintyA 1995 report of 12 people says a citrus fragrance cut antidepressant needs; it gives no numbers. Orange oil and limonene had antidepressant-like effects in stressed mice. Never change a medicine because of this. Anxiety-like behaviour in animalsVery low certaintyIn mice, inhaled or injected limonene lowered anxiety-like behaviour in three papers, but an older paper found no such effect and a slight anxiety-raising pattern at higher doses. Animal research, mixed results. Sedation and sleepVery low certaintyIn mice, high doses relaxed muscle and lengthened barbiturate sleep. In people, a CBD plus eight-terpene mix (1 mg of limonene) gave a small gain in deep plus REM sleep on a wrist tracker. Limonene alone was not tested. The "entourage effect" and strain claimsNot enough evidenceOnly the small THC trial tests the idea directly. Terpene profiles of 140 German medicinal cannabis flowers did not match sativa, indica or hybrid labels or estimated effects. Cancer research (not a treatment)Very low certaintyRats: fewer chemically induced mammary tumours. People: a phase I trial of 42 patients found limonene tolerated up to a limit, with one partial response; a 43-woman pilot found a 22% fall in one tumour marker. No placebo-controlled trial. Inflammation and immune signalsVery low certaintyAnimals and cells show lower inflammation signals. A human cell test found no effect, and one uncontrolled human study of orange peel extract saw lower IL-6. Heartburn and refluxNot enough evidenceWe found no trial. The claim comes from one narrative review. Gallstones (hospital procedure only)Very low certaintyDoctors cleared retained gallstones in 48% of 200 people by flushing a limonene solvent through a bile-duct drain. This is not for use by mouth or at home. Irritable bowel symptomsVery low certaintyA 56-person trial of a menthol, limonene and gingerol supplement found lower symptom scores than placebo. It cannot be credited to limonene. PainVery low certaintyA heel-pain solution with 1% limonene as a skin-absorption helper, and orange oil in labour, reported less pain. No trial tested limonene alone.

Benefits, one by one

Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.

Anxiety and paranoia caused by THC

Low certainty

One small, careful trial in 20 healthy adults found that a high dose of vaporized d-limonene, given together with THC, lowered ratings of feeling anxious and paranoid compared with THC alone. d-Limonene alone did nothing, and it did not change the other effects of THC. It is one small study, not repeated.

4 studiesVaporized pure d-limonene and pure THC in a lab. This is not cannabis…

Studies, doses and limits

What the trials found

In a double-blind trial, 20 healthy adults who use cannabis now and then breathed in vaporized THC alone (15 or 30 mg), d-limonene alone (1 or 5 mg), both together, or placebo. A 12-person subset also had 30 mg THC with 15 mg d-limonene. d-Limonene alone looked like placebo. With the highest d-limonene dose, ratings of "anxious/nervous" and "paranoid" were significantly lower than with 30 mg THC alone. Other effects of THC, including thinking and movement tests, were unchanged, and THC blood levels did not change. A 2011 review proposed this kind of terpene and THC teamwork, but it was a hypothesis then.

Results

Significantly lower "anxious/nervous" and "paranoid" ratings with 30 mg THC plus 15 mg d-limonene than with 30 mg THC alone. No numbers are given in the abstract.

Effect sizes as reported

Not given in the abstract.

Why this rating

A properly blinded, randomised design, but only 20 healthy people, one site, one route (vaporizer), pure compounds, short-term, and the effect was seen only at the highest dose in a 12-person subset. Not yet repeated by others. Co-author Russo wrote the 2011 review proposing the idea.

Form and dose studied

Vaporized pure d-limonene and pure THC in a lab. This is not cannabis flower and not an oral product. The authors say oral products need their own testing.

Who was studied

20 healthy adults who use cannabis intermittently.

Limits

Small; healthy volunteers; the highest-dose combination was tested in only 12 people; self-rated outcomes; the authors say the finding should be tested with oral products. It does not show that limonene inside a cannabis flower does the same.

Why researchers looked

Some people feel anxious or paranoid after THC. Researchers asked whether other cannabis chemicals, such as limonene, change that. This is part of the "entourage effect" idea.

Proposed mechanism Animal research

In mice, limonene's anti-anxiety effect depended on the adenosine A2A receptor. Whether that happens in people, or explains the trial result, is not known.

A proposed mechanism does not show that the effect happens in people.

THC still impaired thinking and movement in this trial even with d-limonene. Do not read this as a reason to drive or make decisions after THC. See the Safety tab.

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Calming scent: anxiety and mood in people (orange oil)

Low certainty

Several small trials found that the smell of orange essential oil lowered self-rated anxiety in dental waiting rooms, before a stress test and during labour. Orange oil is mostly limonene, but these trials used the whole oil, so they cannot say limonene is the cause.

5 studiesOrange or sweet orange essential oil as an air scent or inhaled from …

Studies, doses and limits

What the trials found

In a dental office, 72 patients waiting for treatment were exposed to orange odour or no odour: women in the orange group had lower state anxiety, a better mood and more calmness. In a later trial of 200 dental patients, orange and lavender odours both lowered anxiety and improved mood compared with no odour. In 40 healthy men given sweet orange oil, two of the doses (2.5 and 10 drops) stopped self-rated anxiety rising during a stress test, but heart rate and muscle measures still changed. In a single-blind trial of 84 women in labour, sweet orange oil lowered reported pain and anxiety compared with water. The authors of that trial suggest limonene is the active part, but did not test it.

Results

Lower self-rated anxiety or better mood in these small trials. The labour trial reported p = 0.0411 for pain and p < 0.0001 for anxiety. Other trials give no numbers in the abstract.

Effect sizes as reported

Not given in most abstracts.

Why this rating

Several small trials point the same way, but results are self-rated, a smell cannot be hidden from the person, whole orange oil was used (not limonene alone), and some effects were seen in one sex or one dose only.

Form and dose studied

Orange or sweet orange essential oil as an air scent or inhaled from a pad. Not limonene alone, not cannabis.

Who was studied

Dental patients (72, then 200), 40 healthy men, 84 women in labour.

Limits

Small groups; no blinding possible for a smell; self-report; whole oil; short-term; limonene not isolated; one trial found the effect only in women.

Why researchers looked

Citrus oils are used in aromatherapy, and limonene is the main smelly molecule in orange oil. Researchers asked whether orange scent calms people.

Traditional use

Citrus aromas have long been used in aromatherapy. This is a modern, small-scale practice, not proof.

Proposed mechanism Animal research

Not established in people. In mice, inhaled limonene lowered anxiety-like behaviour without acting through the benzodiazepine site (flumazenil did not block it).

A proposed mechanism does not show that the effect happens in people.

Oils left open to the air oxidise, and oxidised limonene is a skin allergen. See the Safety tab. Essential oils should not be swallowed.

^{23 24 12 31 26}

Low mood and depression

Very low certainty

Very little. One 1995 report of 12 people with depression says a citrus fragrance let them use less antidepressant medicine, but it gives no numbers and does not name limonene. Mouse studies found antidepressant-like effects from orange oil and limonene.

2 studiesCitrus fragrance (human); inhaled orange oil and limonene (mice).

Studies, doses and limits

What the trials found

The 1995 controlled clinical trial applied citrus fragrance to 12 people with depression. The authors report that the antidepressant doses needed could be markedly cut and that hormone and immune measures normalised. The abstract does not show numbers, a clear control, or limonene as the active part. Please do not change any medicine because of this report.

Results

Authors' report only: lower antidepressant needs in 12 people. No numbers shown.

Effect sizes as reported

Not given.

Why this rating

Twelve people, 1995, no numbers, unclear control, whole citrus fragrance. The mouse work is animal evidence and does not show an effect in people.

Form and dose studied

Citrus fragrance (human); inhaled orange oil and limonene (mice).

Who was studied

12 people with depression; mice under chronic mild stress.

Limits

Tiny, old, poorly described; claims stronger than the data shown; no replication found.

Why researchers looked

Citrus scents are often described as uplifting, and limonene is their main component.

Proposed mechanism Animal research

In stressed mice, inhaled limonene calmed the stress-hormone axis and raised monoamine levels. This is animal work.

A proposed mechanism does not show that the effect happens in people.

Never stop or lower an antidepressant without your doctor.

^{22 50}

Anxiety-like behaviour in animals (results disagree)

Very low certainty

In mice, three papers found anti-anxiety-like effects from inhaled or injected limonene or orange oil. One older paper found no anti-anxiety effect and even a slight anxiety-raising effect at higher doses. This is animal research, and the results are mixed.

4 studiesInhaled vapour or injection in mice. Not comparable to human exposure.

Studies, doses and limits

Results

Mice: inhaled (+)-limonene at 0.5% and 1% changed all elevated-plus-maze measures toward lower anxiety (Lima 2013). Injected limonene increased open-arm time and dopamine (Song 2021). Inhaled 10% orange oil gave an anxiolytic-like and sedative effect (Wolffenbuttel 2018). By contrast, limonene injected into the abdomen at 5 mg/kg and above slightly lowered open-arm entries, a mild anxiety-raising pattern, and was sedating at higher doses (do Vale 2002).

Effect sizes as reported

Not given in the abstracts.

Why this rating

Mouse studies only, different routes and doses, and the results point in different directions.

Form and dose studied

Inhaled vapour or injection in mice. Not comparable to human exposure.

Who was studied

Mice.

Limits

Mice; injection doses far above aroma exposure; mixed results; mouse anxiety tests do not map neatly onto human anxiety.

Why researchers looked

Animal tests are used to see whether a chemical might calm anxiety before any human trial.

Proposed mechanism Animal research

One mouse study found the anti-anxiety effect was blocked by a drug that blocks the adenosine A2A receptor and linked it to dopamine and GABA signals in the striatum. Another found flumazenil did not block it, so the benzodiazepine site is probably not involved.

A proposed mechanism does not show that the effect happens in people.

Animal results are not advice for people.

^{26 39 49 53}

Sedation and sleep

Very low certainty

In mice, high doses of limonene lowered movement, relaxed muscle and lengthened barbiturate sleep. In people, no trial tested limonene alone for sleep. One trial of a CBD plus eight-terpene mixture, which included 1 mg of limonene, found a small gain in deep plus REM sleep on a wrist tracker.

3 studiesInjected limonene in mice; an oral CBD plus terpene mix in people.

Studies, doses and limits

What the trials found

A crossover trial of 125 adults with insomnia gave a THC-free oral mix of CBD (300 mg) and eight terpenes (1 mg each, including limonene) or placebo. The mix gave 1.3 percentage points more time in slow-wave plus REM sleep (95% CI 0.1 to 2.5; p = .03), with no effect on total sleep time and no reported adverse events. Because it was a mixture, this says nothing about limonene alone.

Results

Mixture: +1.3% of the night in slow-wave plus REM sleep (SE 0.60). Mice: lowered movement and muscle relaxation (50 to 200 mg/kg injected); barbiturate sleep about 2.6 times longer at 200 mg/kg.

Effect sizes as reported

Mixture trial: 1.3% (95% CI 0.1 to 2.5).

Why this rating

Animal sedation at very high doses plus one human trial of a nine-ingredient mixture measured with a wrist device.

Form and dose studied

Injected limonene in mice; an oral CBD plus terpene mix in people.

Who was studied

Mice; 125 adults with insomnia (mixture trial).

Limits

Limonene not tested alone for sleep; wrist-tracker sleep measure; very high animal doses; funding not stated in the abstract.

Why researchers looked

Some people say limonene makes cannabis uplifting and others say it is calming. The sleep question comes from animal sedation tests and from terpene mixtures.

Proposed mechanism Animal research

Not established. The mouse sedation was seen at high injected doses.

A proposed mechanism does not show that the effect happens in people.

Do not drive or use machinery if you feel drowsy. Combining anything sedating with alcohol or sleep medicines can be unsafe. See the Safety tab.

^{48 53 49}

The "entourage effect" and strain claims

Not enough evidence

The idea is that terpenes like limonene change how cannabis feels. The only direct human test is the small trial above. Another study found terpene profiles did not line up with sativa, indica or hybrid labels or with estimated effects, and limonene had no effect in human immune cells in a lab test.

5 studiesNot applicable.

Studies, doses and limits

What the trials found

Only one direct human test: 20 healthy adults, vaporized pure compounds (see above). A 2025 analysis of 140 medicinal cannabis flowers on the German market found no statistical link between terpene profiles and the genetic labels (sativa, indica, hybrid) and no relation to estimated effects. In human immune cells in a dish, limonene had no effect on any of 21 tested responses.

Results

One small positive trial for THC-related anxiety; terpene profiles did not match strain labels; no immune effect in a dish.

Why this rating

One small trial, one outcome. No study tested whether limonene in real cannabis flower changes how people feel.

Limits

Strain names are unreliable labels: the same name can have very different chemistry. The lab numbers section on the Overview tab shows how much one strain name varies.

Why researchers looked

Cannabis sellers often say that a "citrus" strain with more limonene is uplifting. People want to know whether that is true.

Proposed mechanism Narrative review

A 2011 review proposed that terpenes could alter the effects of THC. It was a hypothesis.

A proposed mechanism does not show that the effect happens in people.

A "lemon" or "citrus" label does not tell you how much limonene is in a product or how it will feel.

^{36 40 14 3 11}

Cancer research (not a treatment)

Very low certainty

In rats, d-limonene and orange oil prevented chemically induced mammary tumours. In people, a 1998 trial in 42 patients with advanced cancer found limonene was tolerated up to a limit, with one partial response; a 2013 pilot in 43 women with breast cancer found it reached breast tissue and lowered one tumour marker. No trial shows it treats or prevents cancer.

6 studiesOral pure d-limonene in grams per day in trials. Not comparable to ci…

Studies, doses and limits

What the trials found

Phase I (Vigushin 1998): 32 people with refractory solid tumours took oral d-limonene (0.5 to 12 g/m2 a day) in 21-day cycles; the maximum tolerated dose was 8 g/m2 a day, with nausea, vomiting and diarrhoea limiting higher doses. One breast cancer patient had a partial response lasting 11 months and three colorectal patients had prolonged stable disease; none of 10 more breast cancer patients responded. Pilot (Miller 2013): 43 women with operable breast cancer took 2 g a day for 2 to 6 weeks before surgery. Limonene reached 41.3 micrograms per gram of breast tissue and tumour cyclin D1 fell 22% (p = 0.002); Ki67 and caspase-3 changed little. There was no placebo group.

Results

Phase I: maximum tolerated dose 8 g/m2 per day; 1 partial response among about 42; 3 stable disease. Pilot: cyclin D1 -22%, small rise in IGF-I.

Effect sizes as reported

Cyclin D1 -22% (p = 0.002). No survival or tumour-size outcome.

Why this rating

Animal work plus a small dose-finding trial and an open-label marker study with no control group. No clinical outcome in a controlled trial.

Form and dose studied

Oral pure d-limonene in grams per day in trials. Not comparable to citrus fruit, orange scent or cannabis.

Who was studied

People with advanced cancer; women with early breast cancer; rats.

Limits

No control groups; huge doses; marker changes are not patient outcomes; the authors of the pilot call for placebo-controlled trials.

Why researchers looked

Limonene is the main part of citrus peel oil and has anti-cancer activity in rodents. Researchers wanted to know if it does anything in people.

Proposed mechanism Mixed

Reviews suggest several routes, including detox enzymes, cell death and blocking a growth-protein step (isoprenylation). In the 2013 pilot, tumour cyclin D1 fell by 22%. These mechanisms are unproven in patients.

A proposed mechanism does not show that the effect happens in people.

Do not use limonene or citrus oil in place of cancer treatment. High oral doses caused nausea, vomiting and diarrhoea.

^{47 34 29 27 8 43}

Inflammation and immune signals

Very low certainty

In mice and rats, limonene lowered inflammation signals in the gut, lungs and kidney. In an uncontrolled human part of one study, an orange peel extract was linked to lower blood IL-6 in older adults. In a lab test on human immune cells, limonene did nothing.

6 studiesPure limonene in animals; orange peel extract in people.

Studies, doses and limits

What the trials found

One observational study gave an orange peel extract containing d-limonene to healthy elderly people for 56 days and found blood inflammation markers, especially IL-6, fell. It had no control group described in the abstract. In human immune cells in a dish, limonene had no effect on any of 21 tested responses.

Results

Rats: lower gut inflammation scores and TNF-alpha at 10 mg/kg by mouth. Mice: lower airway cytokines (inhaled) and lower gut and kidney stress markers (100 and 200 mg/kg by mouth). Humans: IL-6 down (orange peel extract, observational). Human cells: no effect.

Effect sizes as reported

Not given in the abstracts.

Why this rating

Animals and cells, one uncontrolled human observation, and one null human cell test.

Form and dose studied

Pure limonene in animals; orange peel extract in people.

Who was studied

Mice, rats, human cells, healthy elderly volunteers.

Limits

Mouse doses are far above food exposure; extract not pure limonene; mixed results between a null cell test and positive animal tests.

Why researchers looked

Inflammation is behind many diseases, and limonene has anti-inflammatory activity in animals.

Proposed mechanism Animal research

In mice and cells, limonene reduced NF-kB, TLR4 and AP-1 signalling and cytokines, and activated Nrf2. In rat colitis, effects were similar to ibuprofen in one study.

A proposed mechanism does not show that the effect happens in people.

See the Safety tab. Oxidised limonene is an inflammatory skin allergen.

^{51 1 20 15 3 43}

Heartburn and reflux

Not enough evidence

Some supplement writers say d-limonene eases heartburn. We found no trial. The claim appears in one narrative review, which says d-limonene has a gastric acid neutralising effect, but the abstract gives no study.

1 studiesNot applicable.

Studies, doses and limits

Results

No trial results.

Why this rating

No trial found; only a review's statement.

Limits

Nothing to assess. Reflux can hide serious disease, so chest pain, trouble swallowing or weight loss need a doctor.

Why researchers looked

D-limonene is sold in some supplements for reflux.

Proposed mechanism Narrative review

A review says it neutralises stomach acid and supports normal movement of the gut. We found no study behind that statement.

A proposed mechanism does not show that the effect happens in people.

See a doctor for chest pain, black stools, vomiting blood, or trouble swallowing.

⁴³

Gallstones (a hospital procedure, not a supplement)

Very low certainty

In hospital reports from 1976 and 1991, doctors dissolved gallstones left in the bile duct after surgery by flushing a d-limonene preparation through a drain. In 200 people, stones disappeared completely in 48%. This is not something to take by mouth or do at home.

2 studiesA medical d-limonene solvent mixed with emulsifiers, given through a …

Studies, doses and limits

What the trials found

The 1976 paper describes four people (three successes, one partial). The 1991 paper reports 200 people: complete disappearance in 96 (48%), partial in 29 (14.5%), partial with a chelating agent in 16 (8%), ineffective in 59 (24.5%). The authors advise watching for side effects and frequent liver and pancreas tests during treatment.

Results

48% complete clearance in 200 people (uncontrolled).

Effect sizes as reported

96 of 200 complete; 29 partial.

Why this rating

Uncontrolled hospital series from decades ago, with no comparison group.

Form and dose studied

A medical d-limonene solvent mixed with emulsifiers, given through a tube into the bile system by doctors. Not a supplement.

Who was studied

Patients with retained gallstones after gallbladder surgery.

Limits

No control group; old; specialist procedure; the preparation is not the same as anything sold to consumers.

Why researchers looked

d-Limonene dissolves cholesterol, which is what many gallstones are made of.

Traditional use

A specialist medical procedure described in the 1970s and 1990s.

Proposed mechanism Lab chemistry

d-Limonene works as a solvent for cholesterol. This is chemistry, not a body effect.

A proposed mechanism does not show that the effect happens in people.

Never swallow or inject pure limonene or citrus oil for gallstones. The authors call for liver and pancreas tests during treatment.

^{16 17}

Irritable bowel symptoms (three-ingredient supplement)

Very low certainty

A 56-person trial of a supplement with menthol, limonene and gingerol found lower symptom scores than placebo after 30 days. Because it was a three-ingredient mix, it says nothing about limonene alone.

1 studiesFood supplement with standardised menthol, limonene and gingerol.

Studies, doses and limits

What the trials found

In a double-blind trial, 56 adults with IBS took the supplement or placebo on top of standard treatment for 30 days. The total symptom score was lower in the supplement group at the last visit (p = 0.009). Gut bacteria did not change significantly. The authors report no obvious side effects.

Results

Lower symptom score vs placebo, p = 0.009. No numbers in the abstract.

Effect sizes as reported

Not given.

Why this rating

A small trial of a three-ingredient mixture; funding not stated in the abstract.

Form and dose studied

Food supplement with standardised menthol, limonene and gingerol.

Who was studied

56 adults with IBS or IBS with functional dyspepsia.

Limits

Cannot attribute the effect to limonene; small; short.

Why researchers looked

Peppermint-type and ginger compounds are used for gut symptoms; limonene was added to the mix.

Traditional use

Mint and ginger have long-standing use for digestion. Limonene itself has none found in these sources.

Proposed mechanism Insufficient

Not established.

A proposed mechanism does not show that the effect happens in people.

Gut symptoms with bleeding, weight loss or night pain need a doctor.

¹⁸

Pain

Very low certainty

A trial of a plant-terpene skin solution for heel pain reported large pain drops, but limonene was only 1% of the mix, used to help the other ingredients through the skin. Orange oil scent lowered reported pain in labour. There is no trial of limonene alone for pain.

3 studiesA topical terpene mix; inhaled orange oil.

Studies, doses and limits

What the trials found

Plantar fasciitis (62 adults): a topical mix of camphor, menthol, eugenol, eucalyptol and vanillin in DMSO with 1% limonene and rosemary oil. 78.1% reported a drop of 85% or more in pain by day 10; the placebo had no effect. Labour (84 women): sweet orange oil inhaled lowered pain vs water (p = 0.0411).

Results

Topical mix: 78.1% with at least an 85% pain drop vs none on placebo. Orange oil in labour: p = 0.0411.

Effect sizes as reported

Not given beyond the above.

Why this rating

Mixtures and whole oil; limonene's own role not tested; DMSO active on skin.

Form and dose studied

A topical terpene mix; inhaled orange oil.

Who was studied

62 adults with heel pain; 84 women in labour.

Limits

Limonene not isolated; self-rated pain; small trials.

Why researchers looked

Cannabis terpenes, including limonene, are studied as possible contributors to pain relief.

Proposed mechanism Narrative review

A review says cannabis terpenes may contribute to pain and inflammation relief, mostly from preclinical work. In mice, limonene lowered inflammation signals.

A proposed mechanism does not show that the effect happens in people.

Skin products containing limonene that has been in the air can cause allergic rashes.

^{6 31 25}

Connections to the rest of health

How Limonene connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.

Explore every connection: goals, body systems, organs, symptoms, genes

Kind of connection Connected to Search

B. Body systems

Connected to	Kind of connection	Evidence status	Context	Studies
Nervous System	Biological association	Low certainty	Studied for: Anxiety and paranoia caused by THC Studied for: Calming scent: anxiety and mood in people (orange oil)	^{40 36 14 3 23 24 12 31 26 22 50 39 49 53 48 11 6 25}
Immune System	Biological association	Very low certainty	Studied for: Cancer research (not a treatment) Studied for: Inflammation and immune signals	^{47 34 29 27 8 43 51 1 20 15 3}
Digestive System	Biological association	Very low certainty	Studied for: Inflammation and immune signals Studied for: Heartburn and reflux	^{51 1 20 15 3 43 16 17 18}

C. Body parts and organs

Connected to	Kind of connection	Evidence status	Context	Studies
Skin	Adverse effect or risk	Moderate certainty	About 5% of dermatitis clinic patients tested positive in large patch-test series. Preparation or compound: Oxidised limonene (air-exposed) in products	^{5 2 42}
Kidney	Adverse effect or risk	Very low certainty	Kidney tumours in male rats only; reviewers say not relevant to people. Preparation or compound: d-Limonene by gavage in male rats	^{32 13}
Liver	Adverse effect or risk	Very low certainty	Liver-cell changes at high doses in male mice; no human liver injury found. Preparation or compound: d-Limonene by gavage in male mice	^{32 21}

I. Biomarkers

Connected to	Kind of connection	Evidence status	Context	Studies
Self-rated anxiety (state anxiety)	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	^{23 24 12 31}
"Anxious/nervous" and "paranoid" ratings after THC	Biological association	Low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	⁴⁰
Elevated plus maze (open-arm time) in mice	Biological association	Very low certainty	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{26 39 53}
Barbiturate sleeping time in mice	Biological association	Very low certainty	Measured in trials: raised. A lab change is not the same as a health benefit.	⁵³
Share of the night in slow-wave plus REM sleep	Biological association	Very low certainty	Measured in trials: raised. A lab change is not the same as a health benefit.	⁴⁸
Cyclin D1 in breast tumour tissue	Biological association	Very low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	²⁹
Blood IL-6 (inflammation signal)	Biological association	Very low certainty	Measured in trials: mixed. A lab change is not the same as a health benefit.	^{51 29}
Gut inflammation score and blood TNF-alpha in rats	Biological association	Very low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	⁵¹
Airway cytokines and over-reactivity in asthma mice	Biological association	Very low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	¹⁵
Disappearance of retained gallstones	Biological association	Very low certainty	Measured in trials: improved. A lab change is not the same as a health benefit.	^{17 16}
IBS symptom score (7x7 questionnaire)	Biological association	Very low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	¹⁸
Foot function index (heel pain)	Biological association	Very low certainty	Measured in trials: lowered. A lab change is not the same as a health benefit.	⁶

L. Active compounds

Connected to	Kind of connection	Evidence status	Context	Studies
d-Limonene ((R)-(+)-limonene)	Biological association	Mixed findings	Studied for anxiety-like behaviour, inflammation and cancer markers mostly in animals and cells; two small human studies of limonene (a vaporized trial with THC and an oral breast-cancer pilot). Preparation or compound: Citrus peel oils; cannabis resin; some thyme types; many other plants	^{40 29 8}
l-Limonene ((S)-(-)-limonene)	Biological association	In vitro	Less studied than d-limonene; the same human liver enzymes oxidise both forms in the lab. Preparation or compound: Reported for the cannabis variety Finola in one study	^{4 30}
Limonene hydroperoxides (oxidation products)	Biological association	Observational	Strong skin sensitisers; limonene-1-hydroperoxide was the most potent in one study. Preparation or compound: Form when limonene is exposed to air	^{7 2 5}
Perillic acid (breakdown product)	Biological association	Human	Main circulating metabolite after high oral doses; it did not concentrate in breast tissue. Preparation or compound: Made in the body from limonene	^{47 29 34}
Perillyl alcohol (breakdown product)	Biological association	Human	A minor limonene metabolite in the 4-volunteer oral study (less than 0.1% of the dose in urine). Preparation or compound: Made in the body from limonene (small amounts)	^{37 30}
Limonene-1,2-diol and limonene-8,9-diol (breakdown products)	Biological association	Human	Limonene-8,9-diol accounted for about 32% of an oral dose in urine in 4 volunteers; limonene-1,2-diol about 4.3%. CID 94217 is for the 1,2-diol. Preparation or compound: Made in the body from limonene	^{37 34}
Limonene oxide (1,2-epoxide)	Biological association	Animal	In male rats, the minor metabolite d-limonene-1,2-oxide binds to the kidney protein alpha-2u-globulin, which a review links to the rat-specific kidney damage. Preparation or compound: Minor metabolite in rats	¹³
Beta-phellandrene	Biological association	Not studied	Not studied here. Listed because some lab methods may not separate it cleanly from limonene. Preparation or compound: Cannabis and other plants

Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 25, 2026).

Evidence at a glance: what changed in 11 lab markers

Tap a number to show only those markers. Counts are markers, not people.

Other722

The evidence

The research centre for Limonene. Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.

Evidence by outcome

Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).

How we rate evidence

High certainty

Several well-run trials or reviews agree; further research is unlikely to change the picture much.

Moderate certainty

Good trials point the same way, but some doubt remains.

Low certainty

Small, short or inconsistent trials. The finding could change with better research.

Very low certainty

Very little or very weak human data. Treat as a possibility only.

Mixed findings

Trials or reviews disagree with each other.

Not enough evidence

Not enough human research to say either way.

Evidence against

Good research found no benefit, or found harm.

We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We searched PubMed and read abstracts of about 50 sources, read the FDA flavouring lists through the Electronic Code of Federal Regulations, read PubChem for identity and hazard classifications, and ran the PubChem identity check. Only abstracts were read for papers. Certainty ratings are the compiler's own reading. IARC, EFSA, JECFA, EU cosmetics rules, LiverTox and LactMed were not read. The lab numbers are from public regulator datasets and published papers, not our own testing.

Study library: every study we checked 53

Design Research type Year from Search

Study	Design	People	Product, dose, length	Result
Amorim 2016 Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species. PLoS One · PMID 27088973 · DOI	Animal research mouse	Mice	Essential oils of lemon (C. limon), C. latifolia, C. aurantifolia and C. limonia, and pure limonene, by mouth Essential oils 10 to 100 mg/kg · vs Controls	Oils from C. limon, C. aurantifolia and C. limonia reduced inflammation; similar amounts of pure limonene did the same. The authors link the effect of lemon and C. limonia oils to their large limonene content. C. aurantifolia oil caused bone marrow toxicity in mice, which the authors link to its citral. Anti-inflammatory in mice; one citrus oil was toxic Methods, limits and funding Outcomes: Inflammation in formalin and carrageenan models, pain on a hot plate, bone marrow toxicity Limitations: Mice; oral doses; shows citrus oils differ and not all are harmless. Funding and conflicts: Not stated in the abstract. Read: abstract
Audrain 2014 Allergy to oxidized limonene and linalool is frequent in the U.K. British Journal of Dermatology · PMID 24702129 · DOI	Observational	4731 Consecutive patients in 13 UK dermatology departments, 2011 to 2012	Patch tests with limonene hydroperoxides 0.3%, linalool hydroperoxides 1.0% and the stabilised forms 10% Oxidised isolated compounds Patch test Patch test · vs Stabilised (non-oxidised) terpenes	237 patients (5.0%) reacted to limonene hydroperoxides. Only 11 (0.2%) reacted to the stabilised terpenes alone. Testing the oxidised forms captured 97% of positive reactions. Irritant reactions were also common. 5.0% positive to oxidised limonene; almost none to the fresh form alone Methods, limits and funding Outcomes: Positive patch-test reactions Limitations: Dermatology clinic patients; some positive reactions can be irritant rather than allergic. Funding and conflicts: Not stated in the abstract. Read: abstract
Blevins 2022 Evaluation of the anti-inflammatory effects of selected cannabinoids and terpenes from Cannabis Sativa employing human primary leukocytes. Food and Chemical Toxicology · PMID 36228902 · DOI	Laboratory research cell	Human immune cells (PBMC) in culture	Five cannabis terpenes including D-limonene, and six cannabinoids Isolated compounds 0.001 to 10 micromolar Cell culture · vs Vehicle	Cannabinoids had more effect than terpenes. Alpha-pinene was the most active terpene. Limonene had no effect on any of the parameters tested. No effect of limonene on human immune cells in this test Methods, limits and funding Outcomes: 21 immune responses per compound (proliferation, activation, cytokines, phagocytosis) Limitations: Cell culture only; low concentrations. Funding and conflicts: Not stated in the abstract. Read: abstract
Booth 2017 Terpene synthases from Cannabis sativa. PLoS One · PMID 28355238 · DOI	Lab analysis plant	Cannabis sativa hemp variety Finola (gene and enzyme study)	Cannabis terpene synthase enzymes Plant trichomes	Cannabis makes its terpene-rich resin in glandular trichomes on the female flower. Nine terpene synthases were found; their products make up most of the terpenes of Finola resin, including beta-myrcene, (E)-beta-ocimene, (-)-limonene, (+)-alpha-pinene, beta-caryophyllene and alpha-humulene. Cannabis enzymes make (-)-limonene in this hemp variety Methods, limits and funding Outcomes: Genes and enzymes that make cannabis terpenes Limitations: One hemp variety (Finola), not drug-type cannabis; other varieties may make other forms. Funding and conflicts: Not stated in the abstract. Read: abstract
Brared Christensson 2014 Positive patch test reactions to oxidized limonene: exposure and relevance. Contact Dermatitis · PMID 25099087 · DOI	Observational	2900 Consecutive dermatitis patients in six countries (Australia, Denmark, UK, Singapore, Spain, Sweden)	Oxidised R-limonene 3.0% in petrolatum (0.33% limonene hydroperoxides) patch test Oxidised isolated compound Patch test Patch test	5.2% of 2900 patients (range 2.3 to 12.1% between centres) had a positive reaction. Exposure to limonene-containing products was judged probably relevant in 36% of limonene-allergic patients, and over 70% in Barcelona and Copenhagen. About 1 in 20 clinic patients reacted Methods, limits and funding Outcomes: Positive reactions; exposure to limonene products; relevance Limitations: Patients who already had dermatitis and were referred to clinics, so the rate is higher than it would be in the general public; relevance judged by clinicians. Funding and conflicts: Not stated in the abstract. Read: abstract
Burke 2024 Randomized placebo controlled trial of phytoterpenes in DMSO for the treatment of plantar fasciitis. Scientific Reports · PMID 39085322 · DOI	Controlled trial	62 Adults with plantar fasciitis (heel pain)	Topical solution of camphor, menthol, eugenol, eucalyptol and vanillin; limonene (1%), 15% DMSO and rosemary oil were added to help skin absorption Plant terpenes in DMSO 1 ml applied twice a day 10 days · vs Placebo solution	78.1% of the treated group reported an 85% or greater drop in total pain score by day 10; the placebo had no effect (p < 0.01). Large reported pain drop with the mixture Methods, limits and funding Outcomes: Foot function index (pain score) Limitations: Limonene was only 1% of the mix and was used to help the other ingredients pass through skin, so this trial says nothing about limonene as a pain reliever. DMSO is itself active on skin. Funding not stated in the abstract. Funding and conflicts: Not stated in the abstract. Registration: ClinicalTrials.gov NCT05467631 Read: abstract
Christensson 2008 Limonene hydroperoxide analogues differ in allergenic activity. Contact Dermatitis · PMID 19076885 · DOI	Observational mouse	Mice (local lymph node assay) and patients with known allergy to oxidised limonene	Oxidised and non-oxidised limonene and limonene hydroperoxides Isolated compounds · vs Non-oxidised limonene	Pure limonene was a very weak sensitiser, but oxidised limonene was much stronger in mice. One hydroperoxide, limonene-1-hydroperoxide, was the most potent and gave more positive tests in allergic patients. Oxidation greatly increases the allergy risk Methods, limits and funding Outcomes: Skin-sensitising strength in mice; patch-test reactions in allergic patients Limitations: Mouse assay plus a patient test; number of patients not in the abstract. Funding and conflicts: Not stated in the abstract. Read: abstract
Crowell 1999 Prevention and therapy of cancer by dietary monoterpenes. Journal of Nutrition · PMID 10082788 · DOI	Review rat and mouse	Review of animal and cell research	Dietary monoterpenes including d-limonene Isolated compounds	The review says d-limonene makes up more than 90% of orange peel oil and has chemopreventive activity against rodent mammary, skin, liver, lung and forestomach cancers, and chemotherapeutic activity against rodent mammary and pancreatic tumours. It lists several possible mechanisms and notes phase I trials under way. Rodent anti-cancer data; mechanisms uncertain Methods, limits and funding Outcomes: Chemoprevention and treatment in rodents Limitations: A 1999 review of animal work; not a statement about people. Funding and conflicts: Not stated in the abstract. Read: abstract
Dei Cas 2021 Characterization of chemotype-dependent terpenoids profile in cannabis by headspace gas-chromatography coupled to time-of-flight mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis · PMID 34111731 · DOI	Lab analysis plant	33 20 THC-dominant and 13 CBD-dominant cannabis flower samples	Cannabis flower, terpene analysis Inflorescence	D-Limonene made up 6.2% of total terpenes in CBD-dominant and 7.2% in THC-dominant samples, among the main terpenes (beta-caryophyllene, beta-myrcene, terpinolene, alpha-humulene, limonene, alpha-pinene, beta-pinene, cis-beta-ocimene). The method can also spot artificial additives such as hexyl butyrate ester. Limonene is a mid-sized part of the terpene mix Methods, limits and funding Outcomes: Terpene content of the flower Limitations: 33 samples; shares of the terpene total, not amounts in the flower. Funding and conflicts: Not stated in the abstract. Read: abstract
Falk-Filipsson 1993 d-limonene exposure to humans by inhalation: uptake, distribution, elimination, and effects on the pulmonary function. Journal of Toxicology and Environmental Health · PMID 8421324 · DOI	Pharmacokinetic study	Human volunteers in an exposure chamber (number not in the abstract)	Inhaled d-limonene vapour Isolated compound About 10, 225 and 450 mg per cubic metre of air 2 hours at light exercise, on three occasions · vs Lowest exposure	About 70% of inhaled limonene was taken up. Blood clearance was high, suggesting ready breakdown. About 1% left unchanged in breath and 0.003% in urine. A long slow phase in blood suggested build-up in body fat. Vital capacity fell after the high exposure. No irritation or central nervous system symptoms were reported. High lung uptake; slow release from fat; a small fall in lung capacity at the highest exposure Methods, limits and funding Outcomes: Uptake, blood clearance, elimination, lung function, symptoms Limitations: Workplace-style vapour exposure, not cannabis vapour; number of volunteers not in the abstract; 1993. Funding and conflicts: Not stated in the abstract. Read: abstract
Giovannoni 2023 Determination of variability of terpenes and terpenoids in Cannabis sativa by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. Journal of Chromatography A · PMID 36463647 · DOI	Lab analysis plant	20 Ten plants of each of two cannabis strains grown under controlled conditions	Cannabis flower, terpene analysis Inflorescence	High amounts of beta-myrcene, alpha-pinene, beta-pinene, limonene, (E)-beta-ocimene, beta-caryophyllene, alpha-humulene, (E)-nerolidol and linalool were found in both strains. Variability between plants grown together was about 20% for terpenes above 20 micrograms per gram. Limonene is common; plants of one strain differ by about 20% Methods, limits and funding Outcomes: Terpene amounts and plant-to-plant variability Limitations: Two strains only. Funding and conflicts: Not stated in the abstract. Read: abstract
Goes 2012 Effect of sweet orange aroma on experimental anxiety in humans. Journal of Alternative and Complementary Medicine · PMID 22849536 · DOI	Controlled trial	40 Healthy male volunteers	Inhaled sweet orange (Citrus sinensis) essential oil Essential oil 2.5, 5 or 10 drops; tea tree oil (2.5 drops) or water (2.5 drops) as controls Single inhalation before an anxiety test · vs Tea tree oil and water	People exposed to the 2.5 and 10 drop doses showed no significant rise in state anxiety, tension or loss of tranquillity during the test, unlike the control groups. Physiological changes (heart rate, muscle activity) were not prevented in any group. Self-rated anxiety did not rise during a stress test; body measures were not changed Methods, limits and funding Outcomes: State anxiety, subjective tension, tranquillity, sedation, heart rate, muscle activity during a Stroop colour-word stress test Limitations: Men only, 40 people split into five groups of about 8; single exposure; the abstract does not describe the 5-drop group result; orange oil is a mixture, limonene not tested alone. Funding and conflicts: Not stated in the abstract. Read: abstract
Hard 1994 Risk assessment of d-limonene: an example of male rat-specific renal tumorigens. Critical Reviews in Toxicology · PMID 7945892 · DOI	Review rat	Review of animal and mechanism data	d-Limonene Isolated compound	d-Limonene causes kidney tumours only in male rats, where it makes a liver-made protein (alpha-2u-globulin) pile up in kidney cells. The authors say people do not have this protein in the needed quantity or type, and that d-limonene is not genotoxic, so they conclude it poses no carcinogenic or nephrotoxic risk to humans. The male-rat tumours are judged not relevant to humans Methods, limits and funding Outcomes: Why d-limonene causes kidney tumours in male rats and whether this applies to people Limitations: A 1994 review; its conclusion is the authors' risk assessment, not a human study. Funding and conflicts: Research support from US government sources (publication-type tag). Read: abstract
Herwig 2025 Classification of Cannabis Strains Based on their Chemical Fingerprint - A Broad Analysis of Chemovars in the German Market. Cannabis and Cannabinoid Research · PMID 39137353 · DOI	Lab analysis plant	140 140 medicinal cannabis flowers on the German market	Cannabis flower, terpene analysis Inflorescence	There was no statistical link between terpene profiles and the genetic (sativa, indica or hybrid) labels. The authors say terpene profiles are very mixed and that there was no relation between terpenes and estimated pharmacological effect. Terpene profiles did not match the labels Methods, limits and funding Outcomes: Terpene profiles versus sativa/indica/hybrid labels and expected effects Limitations: Terpene analysis only; estimated effects are not measured effects. Funding and conflicts: Not stated in the abstract. Read: abstract
Hirota 2012 Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinae-treated mice. Inhalation Toxicology · PMID 22564095 · DOI	Animal research mouse	Mice with dust-mite-induced asthma	Inhaled limonene Isolated compound · vs Untreated asthma mice	Limonene lowered IL-5, IL-13, eotaxin, MCP-1 and TGF-beta1 in lung fluid, reduced mucus-cell changes, airway muscle thickening and fibrosis, and reduced airway over-reactivity to acetylcholine. Less allergic airway inflammation in mice Methods, limits and funding Outcomes: Airway cytokines, tissue changes, airway reactivity Limitations: Mice; no human data. Inhaled limonene that has oxidised in air is a known skin allergen, and its lung effects in people were not studied here. Funding and conflicts: Not stated in the abstract. Read: abstract
Igimi 1976 The use of d-limonene preparation as a dissolving agent of gallstones. American Journal of Digestive Diseases · PMID 790944 · DOI	Case series	4 People with cholesterol gallstones retained in the bile duct after surgery	Mixture of 97.0 parts d-limonene with 2.1 parts polysorbate 80 and 0.9 part sorbitan monooleate Medical solvent preparation	Three cases were successfully treated; in a fourth, treatment was tried instead of surgery and some stones partly dissolved. No complaints after more than 2 years of follow-up in some cases. Stones dissolved in three of four cases described Methods, limits and funding Outcomes: Dissolution of retained stones; complaints afterwards Limitations: Four cases; given by doctors through a drain placed in the bile duct, with a special rubber catheter; not a food, not a drink, not something to take by mouth. Funding and conflicts: Not stated in the abstract. Read: abstract
Igimi 1991 Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent. Digestive Diseases and Sciences · PMID 1988264 · DOI	Case series	200 200 people with retained gallstones in the bile ducts	d-Limonene preparation injected directly into the bile system by doctors Medical solvent preparation	Stones disappeared completely in 96 cases (48%), partly in 29 (14.5%), partly with a chelating agent in 16 (8%), and the treatment was ineffective in 59 (24.5%). The authors advise careful watching for side effects and frequent liver and pancreas tests during treatment. Complete clearance in about half of 200 people Methods, limits and funding Outcomes: Whether retained stones disappeared Limitations: No comparison group; a specialist hospital procedure, not something people can do at home; the authors call for liver and pancreas monitoring. Funding and conflicts: Not stated in the abstract. Read: abstract
Ivashkin 2022 Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial. PLoS One · PMID 35704960 · DOI	Controlled trial	56 Adults with irritable bowel syndrome (IBS) or IBS with functional dyspepsia	Food supplement with menthol, limonene and gingerol, added to standard treatment Mixture of three compounds 30 days · vs Placebo plus standard treatment	After 30 days the supplement group's total score was lower (borderline illness) than the placebo group's (mild illness), p = 0.009. No significant change in gut microbiota. No obvious side effects. Lower symptom score with a three-ingredient supplement Methods, limits and funding Outcomes: Symptom severity (7x7 questionnaire); gut microbiota Limitations: Three ingredients, so the result cannot be credited to limonene; 56 people; the abstract does not say who funded it. Funding and conflicts: Not stated in the abstract. Registration: ClinicalTrials.gov NCT04484467 Read: abstract
Karlberg 1997 Contact allergy to oxidized d-limonene among dermatitis patients. Contact Dermatitis · PMID 9165203 · DOI	Observational	People with dermatitis who were patch tested	Patch tests with air-exposed (oxidised) d-limonene and with its hydroperoxide fraction Oxidised isolated compound Patch test · vs Standard series	Air exposure turns d-limonene into oxygen-containing products that are strong contact allergens. The share of positive reactions to oxidised d-limonene was similar to several allergens in the standard series. Patients reacting to d-limonene often also reacted to fragrance mix, balsam of Peru and colophony. Oxidised limonene is a real contact allergen Methods, limits and funding Outcomes: Positive patch-test reactions Limitations: Clinic patients with dermatitis, not the general population; the abstract gives no numbers. Funding and conflicts: Not stated in the abstract. Read: abstract
Kathem 2024 Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-kB/AP-1 Pathway. Biomolecules · PMID 38540754 · DOI	Animal research mouse	Mice given a bacterial toxin (LPS)	Oral limonene Isolated compound 100 and 200 mg/kg Pretreatment before LPS · vs LPS without limonene	Limonene lowered kidney stress markers (urea, creatinine) and the cytokines TNF-alpha, IL-1beta and COX-2, suppressed TLR4/NF-kB/AP-1 signalling (not IRF3) and activated Nrf2. Anti-inflammatory signals in mice Methods, limits and funding Outcomes: Sepsis score, kidney markers, gut cytokines and signalling Limitations: Mice; very high doses compared with food; NIH-funded (tag). Funding and conflicts: Not stated in the abstract. Read: abstract
Kim 2013 Safety evaluation and risk assessment of d-Limonene. Journal of Toxicology and Environmental Health Part B · PMID 23573938 · DOI	Review animal and human	Review of toxicology data	d-Limonene Isolated compound	d-Limonene has low toxicity in standard animal tests. Skin irritation and sensitisation were reported after wide use in consumer products, and oxidation products or metabolites act as skin irritants. The male-rat kidney tumours are considered not relevant to humans. The liver was identified as a critical target organ after oral dosing. The review concludes d-limonene appears to pose no serious risk at the exposures it assessed, but that skin irritation justifies regulation in cosmetics. Low systemic toxicity; skin is the main human concern Methods, limits and funding Outcomes: Overall safety and risk assessment Limitations: A review that assessed consumer exposures; it does not cover heated or inhaled cannabis products. Funding and conflicts: Not stated in the abstract. Read: abstract
Komori 1995 Effects of citrus fragrance on immune function and depressive states. Neuroimmunomodulation · PMID 8646568 · DOI	Controlled trial	12 People with depression	Citrus fragrance (the abstract does not say which citrus oil) Fragrance · vs Not clear from the abstract	The authors report that the antidepressant doses needed could be markedly reduced, that hormone levels and immune function normalised, and that the treatment was "rather more effective than antidepressants". Authors report lower antidepressant need in 12 people Methods, limits and funding Outcomes: Antidepressant doses needed, neuroendocrine hormone levels, immune function Limitations: Only 12 people; a 1995 abstract with no numbers; control and blinding not described; the claim of being more effective than antidepressants is not supported by a comparison shown in the abstract. Limonene is not named. Treat as a lead, not as evidence. Funding and conflicts: Not stated in the abstract. Read: abstract
Lehrner 2000 Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients. Physiology & Behavior · PMID 11134689 · DOI	Controlled trial	72 Dental patients waiting for treatment, aged 22 to 57	Ambient odour of orange (essential oil of Citrus sinensis) diffused in the waiting room Essential oil During the wait · vs No odour in the air	Compared with controls, women exposed to orange odour had lower state anxiety, a more positive mood and higher calmness. The abstract reports this effect for women only. Lower anxiety and better mood in women; no such result is reported for men Methods, limits and funding Outcomes: Self-reported state and trait anxiety, mood, alertness, calmness Limitations: Orange oil is a mixture; limonene was not measured or tested alone. Self-report. A smell cannot be hidden from the person, so blinding is not possible. Effect seen in women only. Funding and conflicts: Not stated in the abstract. Read: abstract
Lehrner 2005 Ambient odors of orange and lavender reduce anxiety and improve mood in a dental office. Physiology & Behavior · PMID 16095639 · DOI	Controlled trial	200 Dental patients aged 18 to 77, half women and half men	Ambient odour of orange or of lavender (essential oils) Essential oils During the wait for dental treatment · vs Music condition; no odour and no music	Compared with the control condition, both the orange and the lavender odour reduced anxiety and improved mood in patients waiting for dental treatment. Lower anxiety and better mood versus no odour Methods, limits and funding Outcomes: Anxiety, mood, alertness, calmness Limitations: Orange oil is a mixture; limonene was not tested alone. Self-report; an odour cannot be blinded; waiting-room setting only. No numbers in the abstract. Funding and conflicts: Not stated in the abstract. Read: abstract
Liktor-Busa 2021 Analgesic Potential of Terpenes Derived from Cannabis sativa. Pharmacological Reviews · PMID 34663685 · DOI	Narrative review	Review	Cannabis terpenes including limonene Review	The review says terpenes including beta-myrcene, alpha-pinene, limonene and linalool, and the sesquiterpenes beta-caryophyllene and alpha-humulene, may contribute to cannabis's anti-inflammatory and pain-relieving properties, and sets out to analyse the evidence. Terpenes may contribute; evidence mostly preclinical Methods, limits and funding Outcomes: Pain-related evidence for cannabis terpenes Limitations: Only the abstract was read; the abstract does not give limonene-specific results. Funding and conflicts: Not stated in the abstract. Read: abstract
Lima 2013 Anxiolytic-like activity and GC-MS analysis of (R)-(+)-limonene fragrance, a natural compound found in foods and plants. Pharmacology Biochemistry and Behavior · PMID 22995322 · DOI	Animal research mouse	Mice	Inhaled (+)-limonene Isolated compound 0.5% and 1.0% vapour Single exposure · vs Control	At 0.5% and 1.0%, inhaled (+)-limonene significantly changed all the maze measures in the direction of lower anxiety. The effect of 1% was not blocked by flumazenil (a blocker of the benzodiazepine site). Anxiolytic-like behaviour in mice Methods, limits and funding Outcomes: Elevated plus maze (a standard anxiety test), effect of flumazenil Limitations: Mice; inhalation of a fixed vapour concentration; no human link. Funding and conflicts: Not stated in the abstract. Read: abstract
Maltzman 1989 The prevention of nitrosomethylurea-induced mammary tumors by d-limonene and orange oil. Carcinogenesis · PMID 2702727 · DOI	Animal research rat	Rats	d-Limonene and orange oil in the diet (route and amounts not in the abstract) Isolated compound and orange oil	d-Limonene and orange oil prevented rat mammary cancers caused by a chemical carcinogen, and the effect was limited to the promotion and progression stage. Fewer chemically induced breast tumours in rats Methods, limits and funding Outcomes: Chemically induced mammary tumours Limitations: Rats; a chemical-induced model; 1989; no human link. Funding and conflicts: Not stated in the abstract. Read: abstract
Meehan-Atrash 2019 Aerosol Gas-Phase Components from Cannabis E-Cigarettes and Dabbing: Mechanistic Insight and Quantitative Risk Analysis. ACS Omega · PMID 31592479 · DOI	Lab analysis n/a	Laboratory vaporiser and dabbing tests	THC alone and THC mixed with terpenes, heated Cannabis extract components · vs THC alone	Users of cartridge vaporisers and dabs may be exposed to degradants such as methacrolein, benzene and methyl vinyl ketone. THC alone and mixed with terpenes gave similar products, but added terpenes led to higher levels of gas-phase products. Levels were lower than for smoking cannabis. Added terpenes raised breakdown products in a lab test Methods, limits and funding Outcomes: Gas-phase breakdown products Limitations: Laboratory test of a terpene mixture, not limonene on its own; not a human study. Funding and conflicts: Not stated in the abstract. Read: abstract
Miller 2013 Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Cancer Prevention Research · PMID 23554130 · DOI	Clinical trial	43 Women with newly diagnosed operable breast cancer	Oral limonene Isolated compound 2 grams a day 2 to 6 weeks before surgery	Limonene concentrated in breast tissue (mean 41.3 micrograms per gram). Tumour cyclin D1 fell by 22% (p = 0.002); Ki67 and caspase-3 changed little. No significant change in leptin, adiponectin, TGF-beta1, IGFBP-3 or IL-6; a small, significant rise in IGF-I. Reached breast tissue; one tumour marker (cyclin D1) fell; no clinical outcome measured Methods, limits and funding Outcomes: Limonene and metabolite levels in blood and breast tissue; tumour markers (cyclin D1, Ki67, cleaved caspase-3); blood markers Limitations: Open-label pilot with no placebo group; marker changes are not patient outcomes; the authors call for placebo-controlled trials. NIH-funded (research support tag). Funding and conflicts: NIH extramural research support (publication-type tag); no conflict statement in the abstract. Read: abstract
Miyazawa 2002 Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metabolism and Disposition · PMID 11950794 · DOI	Laboratory research in-vitro	Human liver microsomes from 62 people and recombinant human enzymes	(+)- and (-)-limonene Isolated compounds	Both mirror forms of limonene were oxidised to carveols and perillyl alcohols. CYP2C9 (and CYP2C19) were the main enzymes in human liver tissue, and recombinant CYP2C8, 2C9, 2C18, 2C19 and 3A4 all did it. CYP2B6 did not. Limonene is broken down mainly by CYP2C9 and CYP2C19 in the lab Methods, limits and funding Outcomes: Which liver enzymes break down limonene Limitations: Laboratory enzyme work; no human interaction was tested. Funding and conflicts: Not stated in the abstract. Read: abstract
Nascimento 2025 Effectiveness of aromatherapy with sweet orange oil (Citrus sinensis L.) in relieving pain and anxiety during labor. Explore (New York) · PMID 39577393 · DOI	Controlled trial	84 Pregnant women in labour (42 per group), Brazil	Inhaled sweet orange essential oil Essential oil 250 microlitres inhaled During labour · vs 250 microlitres of distilled water	The orange oil group had lower pain over time (p = 0.0411) and lower anxiety (p < 0.0001), and lower mean blood pressure, heart rate, respiratory rate and fetal heart rate (p < 0.0001). The authors suggest limonene is the active part, but this was not tested. Lower reported pain and anxiety versus water Methods, limits and funding Outcomes: Pain on a visual scale, state anxiety (STAI-E), blood pressure, heart rate, respiratory rate, fetal heart rate Limitations: Single-blind; a smell cannot be hidden; the cause is attributed to limonene in the discussion without testing it; the fetal heart rate finding was not interpreted in the abstract. Funding and conflicts: Not stated in the abstract. Read: abstract
National Toxicology Program 1990 NTP Toxicology and Carcinogenesis Studies of d-Limonene (CAS No. 5989-27-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP Technical Report Series · PMID 12704437	Animal research rat and mouse	F344/N rats and B6C3F1 mice, both sexes (50 per group in the 2-year studies)	d-Limonene by gavage in corn oil Isolated compound (more than 99% pure) Rats: 75 or 150 mg/kg (males), 300 or 600 mg/kg (females); mice: 250 or 500 mg/kg (males), 500 or 1,000 mg/kg (females); 5 days a week 103 weeks (plus 16-day, 13-week and 21-day studies) · vs Vehicle control (corn oil)	Clear evidence of kidney tumours (tubular cell adenomas and adenocarcinomas) in male rats, with kidney damage typical of male-rat alpha-2u-globulin nephropathy. No tumour evidence in female rats or in mice of either sex. In high-dose male mice, liver cells with abnormal numbers of nuclei and enlarged cells were seen. d-Limonene was not mutagenic in the Salmonella, mouse lymphoma cell or hamster cell tests. Male-rat kidney tumours; no tumours in female rats or mice; not mutagenic in tests Methods, limits and funding Outcomes: Survival, body weight, organ lesions, tumours, genetic toxicity tests Limitations: Very high gavage doses in animals; the male-rat kidney mechanism is considered by the reviewers below not to apply to people. Funding and conflicts: US National Toxicology Program (government). Read: abstract
Pesonen 2014 Occupational contact dermatitis caused by D-limonene. Contact Dermatitis · PMID 25141986 · DOI	Case series	14 14 workers with occupational contact allergy to limonene (Finland, 2008 to 2013)	Limonene in cleaning products, hand cleansers and scented cosmetics Exposure at work	Allergy was seen in workers using limonene-containing machine-cleaning detergents and hand cleansers, surface cleaners and dishwashing liquids, and, in three, leave-on cosmetics. Cleaning products and hand cleansers are important sources Methods, limits and funding Outcomes: Source of exposure Limitations: Case series from one clinic; no rate can be derived. Funding and conflicts: Not stated in the abstract. Read: abstract
Poon 1996 Identification and characterization of limonene metabolites in patients with advanced cancer by liquid chromatography/mass spectrometry. Drug Metabolism and Disposition · PMID 8723738	Pharmacokinetic study	People with advanced cancer given oral limonene in a phase I trial	Oral limonene Isolated compound	Limonene was rapidly converted to hydroxylated and carboxylated products. Five main plasma metabolites: limonene-1,2-diol, limonene-8,9-diol, perillic acid, an isomer of perillic acid and dihydroperillic acid. Urine held glucuronides of several of these. Rapid conversion to several metabolites Methods, limits and funding Outcomes: Metabolites in plasma and urine Limitations: Patients with advanced cancer taking very high oral doses; number of people not in the abstract. Funding and conflicts: Not stated in the abstract. Read: abstract
Ravichandran 2018 Review of toxicological assessment of d-limonene, a food and cosmetics additive. Food and Chemical Toxicology · PMID 30075315 · DOI	Review animal and human	Review of toxicology data	d-Limonene (R-(+)-limonene) Isolated compound	The review says d-limonene is rapidly absorbed in animals and people, forms metabolites including perillic acid and dihydroperillic acid, and in rodents causes kidney damage in male rats only (not valid for humans), liver effects and nervous system effects. It reports no genotoxic, immunotoxic or carcinogenic effects and calls it a low-toxicity additive. It adds that the toxicity of metabolites and of breakdown products formed during storage of citrus juices is not known. Low toxic additive; breakdown products not well studied Methods, limits and funding Outcomes: Absorption, metabolism, toxic effects Limitations: A review of food and cosmetic exposure. Funding and conflicts: Not stated in the abstract. Read: abstract
Russo 2011 Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology · PMID 21749363 · DOI	Narrative review	Review	Cannabis terpenoids including limonene Review	The review explores cannabis terpenoids (limonene, myrcene, alpha-pinene, linalool, beta-caryophyllene, caryophyllene oxide, nerolidol, phytol), notes that terpenoids share a precursor with phytocannabinoids and are food flavours classed as generally recognised as safe by the FDA and others, and proposes possible synergy with THC. It says synergy, if proven, would make new products possible. Hypothesis paper; not proof Methods, limits and funding Outcomes: Possible entourage effects Limitations: The synergy it describes was proposed, not shown, in 2011; the same author is a co-author of the 2024 limonene trial. Funding and conflicts: Not stated in the abstract. Read: abstract
Schmidt 2017 R-Limonene metabolism in humans and metabolite kinetics after oral administration. Archives of Toxicology · PMID 27325307 · DOI	Pharmacokinetic study	4 Four healthy volunteers	Single oral dose of R-limonene Isolated compound 100 to 130 micrograms per kilogram of body weight Single dose; urine collected for 24 hours; blood up to 5 hours in two people	Metabolites peaked 1 to 2 hours after the dose and fell quickly, with half-lives of 0.7 to 2.5 hours. About 32% of the dose appeared in urine as limonene-8,9-diol, 4.3% as limonene-1,2-diol, 2.0% as perillic acid, and about 5% (estimate) as dihydroperillic acid. Elimination was complete within 24 hours. Fast metabolism and elimination in four people Methods, limits and funding Outcomes: Limonene and metabolites in blood and urine Limitations: Four volunteers; a tiny single dose; says nothing about effects or safety. Funding and conflicts: Not stated in the abstract. Read: abstract
Shimada 2002 Species differences in the metabolism of (+)- and (-)-limonenes and their metabolites, carveols and carvones, by cytochrome P450 enzymes in liver microsomes of mice, rats, guinea pigs, rabbits, dogs, monkeys, and humans. Drug Metabolism and Pharmacokinetics · PMID 15618705 · DOI	Laboratory research in-vitro	Liver microsomes from seven species	(+)- and (-)-limonene Isolated compounds	Humans, monkeys, rats and mice made carveols and perillyl alcohols but not carvones. In humans, CYP2C9 and CYP2C19 were the major enzymes handling carvone. The authors say it remains unclear whether species differences explain why only male rats develop kidney toxicity. Human limonene metabolism differs in detail from other animals Methods, limits and funding Outcomes: Species differences in limonene metabolism Limitations: Laboratory enzyme work. Funding and conflicts: Not stated in the abstract. Read: abstract
Song 2021 Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum. Phytomedicine · PMID 33548867 · DOI	Animal research mouse	Mice and PC-12 cells	Injected limonene Isolated compound Before behaviour testing · vs Saline injection	Limonene-treated mice moved more and spent more time in open arms. Striatal dopamine and the proteins tyrosine hydroxylase and GAD-67 rose, and GABA release in PC-12 cells was enhanced. The anti-anxiety effect and the GABA increase were blocked by an adenosine A2A receptor blocker. Anxiolytic-like effect in mice that depended on the A2A receptor Methods, limits and funding Outcomes: Elevated plus maze, dopamine and GABA markers in the striatum, effect of an A2A receptor blocker Limitations: Injected rather than inhaled or eaten; mice and cell culture only. Funding and conflicts: Not stated in the abstract. Read: abstract
Spindle 2024 Vaporized D-limonene selectively mitigates the acute anxiogenic effects of delta-9-tetrahydrocannabinol in healthy adults who intermittently use cannabis. Drug and Alcohol Dependence · PMID 38498958 · DOI	Controlled trial	20 Healthy adults who use cannabis intermittently	Vaporized d-limonene alone, vaporized THC alone, and both together Isolated compounds, inhaled by vaporizer THC 15 or 30 mg; d-limonene 1 or 5 mg; same doses together; a 12-person subset also had 30 mg THC with 15 mg d-limonene Nine double-blind outpatient sessions per person (ten for the 12-person subset) · vs Placebo	d-Limonene alone did not differ from placebo. THC alone produced the usual cannabis effects. Anxiety-like ratings fell as the d-limonene dose rose, and 30 mg THC plus 15 mg d-limonene gave significantly lower ratings of "anxious/nervous" and "paranoid" than 30 mg THC alone. Other effects were unchanged. d-Limonene blood levels rose with dose and did not change THC blood levels. Lower anxious and paranoid ratings with the highest d-limonene dose given with THC; no change in other effects Methods, limits and funding Outcomes: Subjective drug effects, cognitive and psychomotor performance, vital signs, blood levels of THC and d-limonene Limitations: Small trial (20 people), healthy volunteers who already use cannabis, vaporized pure compounds, short-term, one site; the effect was seen at the highest dose in a 12-person subset. The authors say it should be tested with oral products. It does not show that limonene inside cannabis flower works the same way. Funding and conflicts: Not stated in the abstract. Read: abstract
Stojanovic 2014 Composition of headspace volatiles and essential oils of three Thymus species. Natural Product Communications · PMID 25532293	Lab analysis plant	Three thyme species (above-ground parts)	Thyme headspace volatiles and essential oils Above-ground parts	In the headspace volatiles of two samples of Thymus praecox subsp. jankae, limonene was 7.5% and 17.8% of the total, alongside alpha-pinene, myrcene and beta-pinene. Limonene is a smaller part of thyme volatiles Methods, limits and funding Outcomes: Composition of volatiles Limitations: One example of a non-citrus plant; amounts vary by plant and chemotype. Funding and conflicts: Not stated in the abstract. Read: abstract
Sukakul 2022 Contact allergy to oxidized linalool and oxidized limonene: Patch testing in consecutive patients with dermatitis. Contact Dermatitis · PMID 34561893 · DOI	Observational	5773 Patients with dermatitis, patch tested 2013 to 2020	Patch tests with oxidised limonene and oxidised linalool Oxidised isolated compounds Patch test Patch test	Contact allergy rates were 5.1% for oxidised limonene and 7.0% for oxidised linalool, with significantly rising trends over the years. Patients were younger and mostly female. The authors say more work is needed on clinical relevance before recommending routine screening. 5.1% positive to oxidised limonene, rising over time Methods, limits and funding Outcomes: Prevalence of contact allergy and its trend over time Limitations: Retrospective clinic data from one setting. Funding and conflicts: Not stated in the abstract. Read: abstract
Sun 2007 D-Limonene: safety and clinical applications. Alternative Medicine Review · PMID 18072821	Narrative review	Review of d-limonene	d-Limonene Isolated compound	The author says d-limonene is a major constituent of orange, lemon, mandarin, lime and grapefruit oils, is listed as generally recognised as safe as a flavour, has fairly low toxicity, and has been used to dissolve cholesterol gallstones and, because of a gastric acid neutralising effect, for heartburn and reflux. A phase I trial showed a partial response in one breast cancer patient and stable disease for more than six months in three colorectal cancer patients. Narrative summary; no new data Methods, limits and funding Outcomes: Safety and clinical uses as summarised by the author Limitations: A narrative review in a journal that carries supplement-related content, not a systematic review. Its heartburn and reflux statement is not backed by a trial in the abstract. Some of its wording is more positive than the underlying studies. Funding and conflicts: Not stated in the abstract. Read: abstract
US Food and Drug Administration 2026 US Code of Federal Regulations Title 21, section 182.60: Synthetic flavoring substances and adjuvants (and section 182.20: Essential oils, oleoresins, and natural extractives) eCFR (API; text version dated 2026-10-01, retrieved 2026-10-25) · Source	Authoritative guidance n/a	n/a	n/a	Section 182.60 lists "Limonene (d-, l-, and dl-)" among synthetic flavouring substances and adjuvants "generally recognized as safe for their intended use". Section 182.20 lists essential oils that are generally recognised as safe for their intended use, including lemon, lime, sweet orange and bitter orange oils. Section 182.60 lists "Limonene (d-, l-, and dl-)" among synthetic flavouring substances and adjuvants "generally recognized as safe for their intended use". Section 182.20 lists essential oils that are generally recognised as safe for their intended use, including lemon, lime, sweet orange and bitter orange oils. Methods, limits and funding Outcomes: Whether limonene and citrus oils are on the FDA's generally-recognised-as-safe lists for food flavouring Limitations: GRAS status for food use as a flavour. It says nothing about inhaling, vaping, or heating limonene, or about use in cannabis products. Funding and conflicts: n/a Read: full-text
US National Library of Medicine (PubChem) 2026 PubChem: GHS classification for D-limonene (aggregated from company notifications to the ECHA C&L Inventory) PubChem PUG-View API (retrieved 2026-10-25) · Source	Authoritative guidance n/a	n/a	n/a	Aggregated from 2,981 reports by companies in 72 notifications: flammable liquid and vapour (H226, over 99.9% of notifications); causes skin irritation (H315, over 99.9%); may cause an allergic skin reaction (H317, 100%); very toxic to aquatic life (H400 96%, H410 94.1%); may be fatal if swallowed and enters airways (H304, 32.6%). PubChem notes that classifications vary between notifications. Aggregated from 2,981 reports by companies in 72 notifications: flammable liquid and vapour (H226, over 99.9% of notifications); causes skin irritation (H315, over 99.9%); may cause an allergic skin reaction (H317, 100%); very toxic to aquatic life (H400 96%, H410 94.1%); may be fatal if swallowed and enters airways (H304, 32.6%). PubChem notes that classifications vary between notifications. Methods, limits and funding Outcomes: Hazard classifications notified for pure d-limonene Limitations: These are classifications that companies notified for the pure chemical, not a regulator's decision and not about low-level food or aroma exposure. Funding and conflicts: n/a Read: full-text
US National Library of Medicine (PubChem) 2026 PubChem compound records for limonene: CID 440917 (D-limonene, (R)-(+)), CID 439250 ((S)-(-)-limonene), CID 22311 (limonene, no mirror form given) PubChem REST API (retrieved 2026-10-25) · Source	Authoritative guidance n/a	n/a	n/a	CID 440917: (+)-Limonene, IUPAC (4R)-1-methyl-4-prop-1-en-2-ylcyclohexene, C10H16, 136.23; synonyms include D-Limonene, 5989-27-5, (R)-(+)-Limonene, Carvene, (+)-Dipentene. CID 439250: Limonene, (-)-, (4S) form. CID 22311: 1-methyl-4-prop-1-en-2-ylcyclohexene; synonyms include LIMONENE, Dipentene, 138-86-3, DL-Limonene. Related CIDs read: perillic acid 1256, perillyl alcohol 10819, limonene oxide 91496, carveol 7438, limonene-1,2-diol 94217, beta-phellandrene 11142. CID 440917: (+)-Limonene, IUPAC (4R)-1-methyl-4-prop-1-en-2-ylcyclohexene, C10H16, 136.23; synonyms include D-Limonene, 5989-27-5, (R)-(+)-Limonene, Carvene, (+)-Dipentene. CID 439250: Limonene, (-)-, (4S) form. CID 22311: 1-methyl-4-prop-1-en-2-ylcyclohexene; synonyms include LIMONENE, Dipentene, 138-86-3, DL-Limonene. Related CIDs read: perillic acid 1256, perillyl alcohol 10819, limonene oxide 91496, carveol 7438, limonene-1,2-diol 94217, beta-phellandrene 11142. Methods, limits and funding Outcomes: Identity, formula, IUPAC names and synonyms of limonene and related compounds Limitations: Database record, not a study. Funding and conflicts: n/a Read: full-text
Vigushin 1998 Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Chemotherapy and Pharmacology · PMID 9654110 · DOI	Clinical trial	42 32 people with refractory solid tumours (phase I) plus 10 with breast cancer (limited phase II)	Oral d-limonene Isolated compound 0.5 to 12 g per square metre of body surface per day 21-day cycles (99 courses in phase I)	The maximum tolerated dose was 8 g/m2 per day; nausea, vomiting and diarrhoea limited higher doses. One breast cancer patient had a partial response lasting 11 months; three colorectal patients had prolonged stable disease; the phase II breast cancer group had no responses. Main blood metabolites were perillic acid, dihydroperillic acid, limonene-1,2-diol and uroterpenol. Well tolerated up to a limit; one partial response and three cases of stable disease; no responses in phase II Methods, limits and funding Outcomes: Toxicity, maximum tolerated dose, blood levels of d-limonene and metabolites, tumour response Limitations: No control group; very advanced cancer; huge doses compared with food or aroma exposure; responses in a few people cannot be credited to limonene. Funding and conflicts: Not stated in the abstract. Read: abstract
Wang 2025 Effects of a cannabidiol/terpene formulation on sleep in individuals with insomnia: a double-blind, placebo-controlled, randomized, crossover study. Journal of Clinical Sleep Medicine · PMID 39167421 · DOI	Controlled trial	125 Adults with insomnia	Oral formulation of CBD with eight terpenes, THC-free Mixture: CBD plus linalool, myrcene, phytol, limonene, alpha-terpinene, alpha-terpineol, alpha-pinene and beta-caryophyllene CBD 300 mg plus 1 mg of each terpene At least 4 days a week for 4 weeks · vs Placebo (crossover)	A small gain in slow-wave plus REM sleep: 1.3% of the night (standard error 0.60; 95% CI 0.1 to 2.5; p = .03). No effect on total sleep time or heart rate. No adverse events reported. About 1.3 percentage points more deep plus REM sleep, by wrist tracker (0.1 to 2.5) Methods, limits and funding Outcomes: Percent of the night in slow-wave plus REM sleep, measured with a wrist-worn tracker Limitations: A mixture: the effect cannot be put down to limonene, which was 1 mg of nine ingredients. Sleep measured by a consumer-style wrist device, not a sleep lab. Funding is not stated in the abstract. Funding and conflicts: Not stated in the abstract. Registration: ClinicalTrials.gov NCT05233761 Read: abstract
Wolffenbuttel 2018 Citrus essential oils inhalation by mice: Behavioral testing, GCMS plasma analysis, corticosterone, and melatonin levels evaluation. Phytotherapy Research · PMID 29168240 · DOI	Animal research mouse	Mice	Inhaled orange essential oils (Citrus sinensis and Citrus aurantium), 10% solution vaporised Essential oils 10% solution, 30 minutes Single exposure · vs Imipramine as a positive control; control air	Inhaled 10% Citrus sinensis oil produced an anxiolytic-like and sedative effect. Melatonin and corticosterone did not change. Oil components were detected in plasma. Anxiolytic-like and sedative effect of whole orange oil in mice Methods, limits and funding Outcomes: Anxiety-like, sedative and antidepressant-like behaviour; plasma melatonin and corticosterone; oil components in plasma Limitations: Whole oil, not limonene alone; mice. Funding and conflicts: Not stated in the abstract. Read: abstract
Zhang 2019 Antidepressant-like Effect of Citrus sinensis (L.) Osbeck Essential Oil and Its Main Component Limonene on Mice. Journal of Agricultural and Food Chemistry · PMID 30905156 · DOI	Animal research mouse	Mice with chronic unpredictable mild stress	Inhaled navel orange essential oil and inhaled limonene Essential oil and isolated compound · vs Untreated stressed mice; positive control not stated	Orange oil inhalation reduced depression-like behaviour. Limonene was the most abundant compound in the air and in mouse brain after sniffing. Limonene inhalation restored behaviour, calmed the hypothalamic-pituitary-adrenal stress axis and raised monoamine levels, with lower BDNF signalling in the hippocampus. Antidepressant-like effects in stressed mice Methods, limits and funding Outcomes: Depression-like behaviour, stress hormone axis, brain chemicals Limitations: Mice; no human link; the direction of the BDNF change is as the abstract states. Funding and conflicts: Not stated in the abstract. Read: abstract
d'Alessio 2013 Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans. Life Sciences · PMID 23665426 · DOI	Mixed rat	Rats with chemically induced colitis; cell cultures; elderly healthy people (observational part)	Oral d-limonene (animals); orange peel extract containing d-limonene (people) Isolated d-limonene (rats, cells); orange peel extract (people) 10 mg/kg by mouth in rats; human dose not in the abstract People took the extract for 56 days · vs Ibuprofen comparison and untreated rats	In rats, d-limonene lowered gut inflammation scores about as much as ibuprofen and lowered blood TNF-alpha. In cells it blocked NF-kB movement and raised gut cell barrier resistance. In an observational study of orange peel extract in elderly healthy people, blood markers, especially IL-6, fell. Lower inflammation signals in rats and cells; fall in IL-6 in an uncontrolled human part Methods, limits and funding Outcomes: Gut inflammation scores, blood TNF-alpha, NF-kB movement in cells, gut cell barrier, blood inflammation markers in people Limitations: The human part was observational and used an orange peel extract, not pure limonene; the database tags the paper as a randomised trial but the abstract describes the human part as observational. Check the full paper before relying on it. Funding and conflicts: Not stated in the abstract. Read: abstract
de Groot 2019 Limonene Hydroperoxides. Dermatitis · PMID 31433385 · DOI	Narrative review	Review	Limonene hydroperoxides Review	Limonene is widely used in cosmetics and household products. Positive patch tests to pure limonene were rare, but exposure to air forms hydroperoxides with far stronger sensitising power, and routine testing finds high rates of positive reactions. The author warns that some positive reactions may be false-positive irritant responses. Hydroperoxides are important fragrance allergens Methods, limits and funding Outcomes: Contact allergy to limonene oxidation products Limitations: Review, no new data. Funding and conflicts: Not stated in the abstract. Read: abstract
do Vale 2002 Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown. Phytomedicine · PMID 12587690 · DOI	Animal research mouse	Mice	Limonene (also citral and myrcene tested separately), injected into the abdomen Isolated compound 50 to 200 mg/kg for most tests; 5 mg/kg in the maze Single injections · vs Vehicle control	Limonene lowered movement at 100 and 200 mg/kg and relaxed muscle even at the lowest dose tested (50 mg/kg). At 200 mg/kg it lengthened barbiturate sleeping time about 2.6 times. In the plus maze there was no anxiolytic effect; the authors describe a slight anxiogenic type of effect (a small fall in open-arm entries even at 5 mg/kg). Sedative and muscle-relaxing at high injected doses; no anti-anxiety effect Methods, limits and funding Outcomes: Open-field movement, rota-rod muscle relaxation, barbiturate sleeping time, elevated plus maze Limitations: Mice; injected, not inhaled or eaten; doses far above food or aroma exposure. This contradicts the mouse papers above that found anti-anxiety effects. Funding and conflicts: Not stated in the abstract. Read: abstract

What we do not know yet

What the evidence supports: everything is low, very-low or insufficient certainty. Most is from animals, cells, whole oils or mixtures.
The best human study is a 20-person vaporizer trial of pure compounds; it has not been repeated, and oral products and real cannabis flower were not tested.
No trial tested limonene alone for anxiety disorders, depression, sleep, pain, reflux or inflammation.
No human interaction study with prescription drugs and no data in pregnancy, breastfeeding, children or older adults.
Nothing is known about long-term inhalation of vaporized limonene, or whether limonene amounts on labels are accurate.
Our lab data do not say whether d- or l-limonene was measured, and one dataset's limonene peak may overlap with beta-phellandrene.

How new research is added

New studies are found by a saved PubMed search and are placed in a review queue. A person reads each one before it changes any evidence rating or safety wording. New publications never change ratings automatically.

Lab markers

What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".

Other 12

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Self-rated anxiety (state anxiety)

Lowered in trials

How anxious a person says they feel right now on a questionnaire.

Low certainty

Results and what it means

Why it was measured

It is the usual quick way to test whether a scent or treatment calms people before a stressful event.

Statistical vs. clinical meaning

Consistent direction in four small trials; effect sizes are not given in most abstracts.

Safety implication

None reported in these trials. Oxidised orange oil can cause skin allergy (see Safety).

Study	Result	People	Product
²³	Lower state anxiety, better mood and more calmness in women exposed to orange odour than in controls.	72 dental patients	Ambient orange odour versus no odour
²⁴	Orange and lavender odours both lowered anxiety and improved mood compared with no odour.	200 dental patients	Orange or lavender odour versus music or nothing
¹²	No significant rise in state anxiety during a stress test at 2.5 and 10 drops of sweet orange oil, unlike controls.	40 healthy men	Inhaled sweet orange oil versus tea tree oil or water
³¹	Lower anxiety (p < 0.0001) and pain (p = 0.0411) in labour.	84 pregnant women	Inhaled sweet orange oil versus water

^{23 24 12 31}

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"Anxious/nervous" and "paranoid" ratings after THC

Lowered in trials

How strongly a person rates feeling anxious or paranoid after taking THC.

Low certainty

Results and what it means

Why it was measured

These feelings are among THC's most common unwanted effects.

Statistical vs. clinical meaning

Statistically significant in a small trial; size not in the abstract.

Safety implication

The other effects of THC, including thinking and movement tests, were unchanged, so limonene should not be taken to make THC safer for driving.

Study	Result	People	Product
⁴⁰	30 mg THC plus 15 mg d-limonene gave significantly lower ratings than 30 mg THC alone. d-Limonene alone matched placebo. Other effects were unchanged.	20 healthy adults (12 in the combined-dose session)	Vaporized THC with or without d-limonene

⁴⁰

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Elevated plus maze (open-arm time) in mice

Mixed results in trials

A raised maze with open and closed arms. Mice that are less anxious spend more time in the open arms.

Very low certainty

Results and what it means

Why it was measured

A standard animal test for anti-anxiety effects.

Statistical vs. clinical meaning

Results point in different directions in animals.

Safety implication

Not applicable to people.

Study	Result	People	Product
²⁶	Inhaled limonene (0.5% and 1%) changed all maze measures toward lower anxiety; not blocked by flumazenil.	Mice	Inhaled (+)-limonene
³⁹	Limonene raised open-arm preference and locomotion; blocked by an A2A receptor antagonist.	Mice	Injected limonene
⁵³	No anxiolytic effect; a small fall in open-arm entries (slight anxiogenic type) with limonene.	Mice	Limonene injected at 5 mg/kg and above

^{26 39 53}

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Barbiturate sleeping time in mice

Raised in trials

How long a mouse stays asleep after a sleep-inducing drug. A longer time suggests a sedating effect.

Very low certainty

Results and what it means

Why it was measured

A quick animal test for sedative effects.

Statistical vs. clinical meaning

One mouse study at a very high injected dose.

Safety implication

Suggests limonene could add to sedatives at high doses; not tested in people.

Study	Result	People	Product
⁵³	At 200 mg/kg, limonene lengthened barbiturate sleep about 2.6 times; it also lowered movement and relaxed muscle.	Mice	Limonene injected into the abdomen

⁵³

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Share of the night in slow-wave plus REM sleep

Raised in trials

The percentage of sleep time in deep (slow-wave) and dreaming (REM) sleep, estimated by a wrist device.

Very low certainty

Results and what it means

Why it was measured

A proxy for how restorative sleep may be.

Statistical vs. clinical meaning

Small gain from a mixture; cannot be credited to limonene.

Safety implication

No adverse events were reported.

Study	Result	People	Product
⁴⁸	+1.3% of the night (95% CI 0.1 to 2.5; p = .03) with a CBD plus eight-terpene mix versus placebo. No change in total sleep time.	125 adults with insomnia	Oral CBD 300 mg plus 1 mg each of eight terpenes including limonene

⁴⁸

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Cyclin D1 in breast tumour tissue

Lowered in trials

A protein that helps cells divide. Lower levels can mean slower tumour-cell growth.

Very low certainty

Results and what it means

Why it was measured

A marker used in pilot cancer prevention studies.

Statistical vs. clinical meaning

A marker change in an uncontrolled pilot.

Safety implication

A small, significant rise in blood IGF-I was also seen.

Study	Result	People	Product
²⁹	22% reduction in tumour cyclin D1 (p = 0.002); Ki67 and cleaved caspase-3 changed little.	43 women with early breast cancer	Oral limonene 2 g a day for 2 to 6 weeks, open-label

²⁹

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Blood IL-6 (inflammation signal)

Mixed results in trials

A protein made during inflammation. Higher levels mean more inflammatory activity.

Very low certainty

Results and what it means

Why it was measured

A common blood marker of inflammation.

Statistical vs. clinical meaning

Opposite findings in two small human studies with different preparations.

Safety implication

None identified.

Study	Result	People	Product
⁵¹	IL-6 fell in elderly healthy people taking an orange peel extract (observational part).	Elderly healthy volunteers	Orange peel extract for 56 days
²⁹	No significant change in serum IL-6 after limonene in women with breast cancer.	43 women	Oral limonene 2 g a day

^{51 29}

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Gut inflammation score and blood TNF-alpha in rats

Lowered in trials

A microscope-based score of damage in the gut, and the level of the inflammation protein TNF-alpha in the blood.

Very low certainty

Results and what it means

Why it was measured

Standard measures in an animal model of colitis.

Statistical vs. clinical meaning

One rat model.

Safety implication

Not applicable.

Study	Result	People	Product
⁵¹	d-Limonene by mouth (10 mg/kg) lowered the score about as much as ibuprofen and lowered TNF-alpha.	Rats with induced colitis	Oral d-limonene

⁵¹

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Airway cytokines and over-reactivity in asthma mice

Lowered in trials

Inflammation proteins in lung fluid and how strongly airways narrow in response to acetylcholine.

Very low certainty

Results and what it means

Why it was measured

Standard measures in an animal asthma model.

Statistical vs. clinical meaning

One mouse study.

Safety implication

Not tested in people.

Study	Result	People	Product
¹⁵	Inhaled limonene lowered IL-5, IL-13, eotaxin, MCP-1 and TGF-beta1 and reduced airway over-reactivity.	Mice with dust-mite-induced asthma	Inhaled limonene

¹⁵

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Disappearance of retained gallstones

Improved in trials

Whether stones left in the bile duct are gone on follow-up imaging.

Very low certainty

Results and what it means

Why it was measured

The direct goal of the procedure.

Statistical vs. clinical meaning

Uncontrolled series.

Safety implication

Authors advise frequent liver and pancreas tests.

Study	Result	People	Product
¹⁷	Complete disappearance in 96 of 200 (48%), partial in 29 (14.5%).	200 people with retained stones	d-Limonene preparation injected into the bile system
¹⁶	Success in three of four described cases.	4 people	d-Limonene, polysorbate 80 and sorbitan monooleate through a bile-duct drain

^{17 16}

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IBS symptom score (7x7 questionnaire)

Lowered in trials

A questionnaire that scores how severe gut symptoms were over the past week.

Very low certainty

Results and what it means

Why it was measured

The standard way to follow IBS symptoms.

Statistical vs. clinical meaning

A mixture; limonene not isolated.

Safety implication

No obvious side effects reported.

Study	Result	People	Product
¹⁸	Lower total score with the menthol, limonene and gingerol supplement than with placebo at the last visit (p = 0.009).	56 adults with IBS	Three-ingredient supplement for 30 days

¹⁸

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Foot function index (heel pain)

Lowered in trials

A questionnaire scoring pain and ability to use the foot.

Very low certainty

Results and what it means

Why it was measured

A validated measure for heel pain.

Statistical vs. clinical meaning

A mixture; limonene was a skin-absorption helper.

Safety implication

None reported in the abstract.

Study	Result	People	Product
⁶	78.1% of treated people reported at least an 85% drop in total pain score by day 10; no change on placebo.	62 adults with plantar fasciitis	Topical terpene mix with 1% limonene in DMSO

⁶

Safety

What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.

Main points to know 4

Oxidised limonene is a common skin allergen. Fresh limonene is a weak allergen, but when it sits in air it forms hydroperoxides that are strong ones. In patch-test clinics, about 5% of people with dermatitis reacted: 5.2% of 2,900 patients in six countries, 5.0% of 4,731 in the UK, and 5.1% of 5,773 in one later series. These are people already seen for skin problems, so the rate in the general public is lower. Cleaners, hand cleansers and scented products are the usual sources. Observational ^{5 2 42 7 52 33}
At food and scent levels, reviews call limonene low in toxicity. Two toxicology reviews describe d-limonene as a low-toxicity food and cosmetic additive. They say the main human concern is skin irritation and allergy. Those reviews looked at food, cosmetic and cleaning-product exposure, not at heated or concentrated cannabis products. Review ^{21 35}
Pure limonene or concentrated oils are not for swallowing or for children. Companies notify the pure chemical as a flammable liquid that irritates skin, may cause an allergic skin reaction, and, in about a third of notifications, may be fatal if swallowed and enters the airways. Keep pure terpene oils, essential oils and cleaning products out of reach of children. Authoritative guidance ⁴⁵
No approved medical use, and limited human safety data for inhaling it. Limonene is a food flavour and fragrance, not an approved medicine for any condition we found. Human safety data come from patch tests, a chamber study of inhaled vapour, one small vaporized trial and cancer trials with huge oral doses. Nothing studied long-term inhalation of vaporized limonene from cannabis. Review ^{40 10 47}

Side effects 7

Effect	How often	Severity and recovery	Evidence
Allergic contact dermatitis (itchy, red, sometimes blistering rash) from oxidised limonene Rates come from patients already referred for skin problems and tested with oxidised limonene. Some positive tests may be irritant rather than allergic.	About 5% of dermatitis clinic patients tested positive (5.0 to 5.2% in two large series; 5.1% in a later series)	moderate Not described in the abstracts	Observational ^{5 2 42}
Skin irritation from limonene products A review reports skin irritation after wide consumer use; workers using limonene hand cleansers and cleaning products developed contact allergy.	No rate found	mild to moderate Not described in the abstracts	Review ^{21 33}
Nausea, vomiting and diarrhoea at very high oral doses Doses were grams per square metre a day, far above food or scent exposure.	Dose-limiting in a phase I cancer trial of 32 people	moderate Not described in the abstract	Clinical trial ⁴⁷
Small fall in lung capacity (vital capacity) after a high-level inhaled exposure The volunteers reported no irritation and no central nervous system symptoms. This was workplace-style vapour, not vaporized cannabis.	Seen at the highest exposure (about 450 mg per cubic metre for 2 hours); number of volunteers not in the abstract	mild Not described in the abstract	Pharmacokinetic study ¹⁰
Sedation, muscle relaxation and longer barbiturate sleep in mice at high injected doses Muscle relaxation even at the lowest dose tested (50 mg/kg); sleep about 2.6 times longer at 200 mg/kg. Not tested in people.	Mice only	moderate Not described in the abstract	Animal research ⁵³
Kidney tumours in male rats (not in female rats or in mice) Reviewers say the mechanism needs a rat-specific protein and is not relevant to people. We list it for completeness.	Kidney tubule adenomas or adenocarcinomas in male rats in the 2-year US National Toxicology Program study (see studies)	serious (in rats) Not applicable	Animal research ^{32 13}
Liver cell changes in high-dose male mice NTP found no increase in mouse tumours. A review names the liver as a critical target organ after oral dosing in animals.	Cells with abnormal numbers of nuclei in 32 of 50 high-dose male mice versus 8 of 49 controls; enlarged cells in 38 of 50 versus 23 of 49 (NTP)	unknown Not described	Animal research ^{32 21}

Liver

No human case of liver injury from limonene was found in the sources read, and LiverTox was not read. In animals, the National Toxicology Program saw liver-cell changes in high-dose male mice, and a toxicology review names the liver as the critical target after oral dosing. The doctors who gave limonene directly into the bile duct for gallstones advised frequent liver and pancreas tests during treatment. ^{32 21 17}

How often. No human rate was found.

Monitoring. No agency monitoring advice was read. Hospital authors advised liver and pancreas tests for the bile-duct procedure only.

This is a safety connection. It is not evidence that Limonene supports liver health.

Medicines and supplements 4

With	Why it matters	Importance	Evidence	What to do
THC (cannabis) cannabis	In a small trial, vaporized d-limonene did not change THC blood levels, and the highest dose lowered "anxious" and "paranoid" ratings. It did not change THC's other effects.	Not shown to make THC safer for driving or thinking tasks, because those effects were unchanged.	Controlled trial Low certainty ⁴⁰	Do not assume limonene removes the risks of THC. Impairment from THC still applies.
Sedatives: sleeping pills, benzodiazepines, barbiturates, opioids, alcohol prescription	In mice, limonene lengthened barbiturate sleep at 200 mg/kg injected and relaxed muscle.	Unknown in people.	Animal research Very low certainty ⁵³	Tell your doctor or pharmacist if you use concentrated limonene products with sedating medicines or alcohol.
Drugs processed by liver enzymes CYP2C9 or CYP2C19 prescription	In human liver tissue in the lab, limonene was broken down mainly by CYP2C9 and CYP2C19 (and, in recombinant enzymes, also CYP2C8, 2C18 and 3A4).	Unknown. These tests show limonene is a substrate; they do not show it changes other drugs' levels. No human interaction study was found.	Laboratory research Very low certainty ^{30 38}	If you take prescription medicines, ask a pharmacist before using concentrated limonene products.
Other fragrance allergens (fragrance mix, balsam of Peru, colophony, linalool) allergy	Patients reacting to oxidised d-limonene often also reacted to fragrance mix, balsam of Peru and colophony. Oxidised linalool and oxidised limonene allergy are also reported together.	If you have a known fragrance allergy, limonene in scented products can matter.	Observational Low certainty ^{19 42}	People with fragrance allergy should read product ingredient lists and ask a dermatologist about patch testing.

Who should check first 6

Situation	Advice	Evidence
Known fragrance or limonene allergy, or hand dermatitis	Avoid products that contain limonene (it appears on ingredient lists) and avoid old, air-exposed citrus oils on the skin. Ask a dermatologist about patch testing.	Observational ^{5 19}
Pregnancy and breastfeeding	No human safety data on concentrated limonene or on vaporized limonene were found. Citrus fruit as food is not what this is about. Ask your doctor before using cannabis products, essential oils or supplements.	Gap
Children, teenagers and older adults	No studies of limonene in these groups were found for cannabis use or supplements. The risks of THC for teenagers, such as effects on thinking, mental health and dependence, and for older adults are covered in the THC profile. Limonene has not been shown to change those risks.	Gap
Mental health conditions, including a history of psychosis or severe anxiety	The one limonene and THC trial was in healthy adults. Nothing is known for people with these conditions. The mental health risks of THC are covered in the THC profile; do not treat limonene as a safeguard.	Gap ⁴⁰
Asthma, chronic lung disease, or a child or pet that swallowed pure oil	No study tested vaporized limonene in people with lung disease, and heated terpene mixtures made more breakdown products in a lab test. If pure terpene oil is swallowed and the person coughs, chokes, or has trouble breathing, get emergency help and call a poison centre.	Authoritative guidance ^{45 28}
Driving and machinery	In a trial where THC and limonene were given together, THC's effects on thinking and movement were not reduced by limonene. In mice, high doses of limonene were sedating. Do not drive or use machinery after THC, or if you feel drowsy.	Controlled trial ^{40 53}

Overdose, product quality and regulators

Summary. Reviews describe d-limonene as low in toxicity at food and consumer levels. High-dose animal studies found kidney effects in male rats (judged not relevant to people) and liver changes in male mice. In people, skin allergy to oxidised limonene is the best-documented problem.

Animal. NTP 2-year gavage study (rats and mice): clear evidence of kidney tumours in male rats, with signs of male-rat alpha-2u-globulin kidney damage; no tumour evidence in female rats or in mice. Deaths and weight loss occurred at the highest doses in short-term studies. Not mutagenic in Salmonella, mouse lymphoma and hamster cell tests.

Human doses studied. 100 to 130 micrograms per kilogram once, by mouth, in 4 volunteers; 2 g a day for 2 to 6 weeks in 43 women; 0.5 to 12 g per square metre a day in 32 cancer patients; vaporized 1 to 15 mg in a lab trial; chamber exposure to about 10, 225 and 450 mg per cubic metre of air for 2 hours.

High dose or long term signals. Nausea, vomiting and diarrhoea at very high oral doses in cancer patients; a small fall in vital capacity after the highest chamber exposure.

Overdose response. Not described in the sources read. Pure limonene carries an aspiration hazard if swallowed according to about a third of company notifications.

Genotoxicity. NTP: d-limonene was not mutagenic in the tests used. Reviews say it is not genotoxic.

Limonene is a very common natural terpene and is also added as a flavour. Oxidised limonene (air-exposed) is the safety issue for skin. Terpene numbers on a cannabis label are one batch result, and no study we read tested whether limonene figures on labels are accurate.

Oxidation on the shelf. Limonene readily reacts with oxygen to form strong skin allergens, so old or poorly stored products with limonene can be worse for allergy than fresh ones. Testing with the oxidised form captured 97% of positive reactions in a UK audit. ^{19 2 7}

Natural variation. Ten plants of one strain grown together varied by about 20% in terpenes above 20 micrograms per gram. A 2025 analysis of 140 medicinal cannabis flowers found terpene profiles did not match sativa, indica or hybrid labels. ^{11 14}

Added flavours and heated products. A headspace method could spot artificial flavour added to cannabis. In a laboratory test of vaporizers and dabbing, adding terpenes to THC raised gas-phase breakdown products compared with THC alone. The test used a terpene mixture, not limonene alone. ^{9 28}

Body	Action	Date
US Food and Drug Administration (Code of Federal Regulations, Title 21, section 182.60) (United States)	Lists "Limonene (d-, l-, and dl-)" among synthetic flavouring substances and adjuvants that are generally recognised as safe for their intended use as food flavourings. Section 182.20 also lists lemon, lime, sweet orange and bitter orange oils as essential oils generally recognised as safe for their intended use. source	2026-10-25
Company hazard notifications to the European Chemicals Agency's classification and labelling inventory (as summarised by PubChem) (European Union / EEA)	For pure d-limonene, companies' notifications most often list flammable liquid and vapour, skin irritation, may cause an allergic skin reaction, and very toxic to aquatic life; about a third also list may be fatal if swallowed and enters airways. PubChem notes these are aggregated company notifications and vary. source	2026-10-25

When to get medical help

A child or adult swallowed pure limonene, terpene oil or a citrus-oil cleaner and is coughing, choking, wheezing or has trouble breathing (get emergency help and call a poison centre).
A rash that spreads quickly, blisters, or swells the face or lips after skin contact with a product containing limonene.
Trouble breathing, chest tightness or wheezing after breathing vapour, especially in someone with asthma.
A person who cannot be woken or whose breathing is slow after combining sedating products with alcohol or sleep medicines.
Severe anxiety, confusion, or loss of touch with reality after using cannabis products (see the THC profile).

Stop using the product and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.

General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.

Frequently asked questions

What is limonene?

Limonene is a small citrus-smelling molecule made by many plants, including orange and lemon peel, some thyme types and cannabis. It is a monoterpene with the formula C10H16. d-Limonene is the form most studied.

^{46 43}

Which plants contain limonene?

Citrus peel oils are the best-known source: a review says d-limonene is more than 90% of orange peel oil. Cannabis, some thyme types and many other plants also make it. Amounts vary by plant and batch.

^{8 43 9 41}

Is limonene in cannabis the same as in oranges?

Both are called limonene and share the formula C10H16, but it comes in two mirror-image forms. Safety studies mostly used d-limonene. One study of a hemp variety found cannabis enzymes make (-)-limonene. Our lab data do not say which form was measured.

^{46 4 21}

Does limonene reduce anxiety?

Evidence is limited. One small trial in 20 healthy adults found a high vaporized dose lowered anxious and paranoid ratings after THC; alone it matched placebo. Orange scent lowered self-rated anxiety in small trials, but those used whole oil. Mouse results are mixed. It is not a treatment for anxiety.

^{40 23 24 12 31 53}

Does limonene make THC safer or change how cannabis feels?

Not shown. In the one trial, limonene did not change THC blood levels or THC's effects on thinking and movement; only anxious and paranoid ratings fell, at the highest dose. No study tested limonene inside cannabis flower. Do not drive or make risky choices after THC.

⁴⁰

Does a lemon or citrus strain name mean more limonene?

Not in the numbers we have. In Nevada medians, Super Lemon Haze was among the lowest and Lemon Cherry Gelato was much higher. The same strain name also varies a lot between samples. A name is marketing, not a measurement.

^{14 11}

Can limonene cause a skin allergy?

Yes, mainly when it has reacted with air. In dermatitis clinics, about 5% of patients tested positive to oxidised limonene (5.0 to 5.2% in large series). Cleaners, hand cleansers and scented products are common sources. If a product with limonene makes your skin itch or blister, stop using it and ask a clinician.

^{5 2 42 33}

Is limonene safe?

Reviews call d-limonene low in toxicity as a food and cosmetic ingredient; skin irritation and allergy are the main human concerns. Pure limonene is flammable and dangerous if swallowed and breathed into the lungs. Safety of long-term vaporizing is unknown, and a lab test found terpenes added to THC raised breakdown products in vape and dab aerosol.

^{21 35 45 28}

Is limonene a cancer treatment?

No. Rodent studies found fewer chemically induced mammary tumours. In people, a phase I trial in 42 patients found it tolerated up to a limit with one partial response, and a 43-woman pilot found a 22% fall in one tumour marker. There is no placebo-controlled trial. Do not use limonene instead of cancer treatment.

^{27 47 29}

Does limonene help heartburn or gallstones?

No trial of limonene for heartburn was found. For gallstones, doctors used a limonene solvent through a bile-duct drain in a hospital procedure that cleared stones in 48% of 200 people. That is not something to take by mouth or do at home.

^{43 17 16}

Is limonene safe in pregnancy, for children or for older adults?

We found no human data for concentrated limonene or vaporized limonene in these groups. Ask your doctor or pharmacist before using essential oils, supplements or cannabis products. Risks of THC for teenagers and older adults are covered in the THC profile.

Is limonene approved or regulated?

In the US, limonene is listed among food flavouring substances generally recognised as safe for their intended use. That is a food flavour status and says nothing about vaping, heating or cannabis products. Companies also notify pure limonene as a skin irritant and sensitiser.

^{44 45}

Explore by health goal

Editorial transparency

Written by: AlternativeMed editorial team. Research compiled with AI assistance, then checked against PubMed records.
Medical review: None. This page has not been reviewed by a physician or pharmacist.
First published: 2026-10-25
Last substantive update: 2026-10-25
How we research: We searched PubMed and read abstracts of about 50 sources, read the FDA flavouring lists through the Electronic Code of Federal Regulations, read PubChem for identity and hazard classifications, and ran the PubChem identity check. Only abstracts were read for papers. Certainty ratings are the compiler's own reading. IARC, EFSA, JECFA, EU cosmetics rules, LiverTox and LactMed were not read. The lab numbers are from public regulator datasets and published papers, not our own testing.
How we rate evidence: See "How we rate evidence" in the Evidence tab.
Independence: No product is promoted on this page. No affiliate links are shown, and none will be added for limonene. This page is information, not a recommendation to use it.

Sources 53

Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.

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Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.