Nigellone

Nigellone at a Glance

Nigellone is the constituent of black seed (Nigella sativa) that carries the herb’s respiratory reputation. When older texts explain why black seed was used for asthma, wheeze and bronchitis, nigellone is the name they reach for ^{1,2Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →Reference 2Wienkötter N et al. · 2008The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearanceView study →}.

It is also the constituent with the most confused identity on the plant. Chemical registries treat “nigellone” as a straight synonym of dithymoquinone — a defined dimer of thymoquinone with the formula C₂₀H₂₄O₄ ^{13,19Reference 13Salehi B et al. · 2021ReviewNigella plants — traditional uses, bioactive phytoconstituents, preclinical and clinical studiesView study →Reference 19Imran M et al. · 2022Clinical trialNigella sativa L. and COVID-19: a glance at the anti-COVID-19 chemical constituents, clinical trials, inventions, and patent literatureView study →}. The pharmacology papers that made the name famous describe something else: an amorphous carbonyl polymer, called “polythymoquinone” by the researchers who isolated it ^{1,3,4Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →Reference 3El-Dakhakhny M et al. · 2002AnimalNigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from ratsView study →Reference 4El-Dakhakhny M · 1965Studies on the Egyptian Nigella sativa LView study →}. Whether those are the same substance has never actually been demonstrated.

The evidence is thin, old and largely from one research lineage. There is one properly reported isolated-organ study supporting the bronchodilator claim ^{2Reference 2Wienkötter N et al. · 2008The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearanceView study →}, one mast-cell study ^{1Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →}, one eicosanoid study ^{3Reference 3El-Dakhakhny M et al. · 2002AnimalNigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from ratsView study →} — and beyond that, a scatter of assays in which dithymoquinone is consistently the least active of black seed’s quinones ^{9,10,11Reference 9Marsik P et al. · 2005In vitroIn vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1- and -2-catalyzed prostaglandin E2 biosynthesesView study →Reference 10Tesarova H et al. · 2011Determination of oxygen radical absorbance capacity of black cumin (Nigella sativa) seed quinone compoundsView study →Reference 11Halamova K et al. · 2010In vitroIn vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levelsView study →}. Do not read thymoquinone’s much larger evidence base onto this molecule.

Nigellone vs. Dithymoquinone

This is the first thing to settle, because almost every secondary source gets it wrong in one direction or the other.

The registry position: they are the same compound. Chemical databases list nigellone as a synonym of dithymoquinone (CAS 39461-20-6, C₂₀H₂₄O₄, MW 328.4) — the trans-anti [2+2] cyclobutane photodimer of thymoquinone, a benzoquinone-fused cage whose structure was settled by single-crystal X-ray diffraction in 2012 ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}. Modern reviews follow suit and write “dithymoquinone (nigellone)” or “Nigellone (DTQ)” without comment ^{13,19Reference 13Salehi B et al. · 2021ReviewNigella plants — traditional uses, bioactive phytoconstituents, preclinical and clinical studiesView study →Reference 19Imran M et al. · 2022Clinical trialNigella sativa L. and COVID-19: a glance at the anti-COVID-19 chemical constituents, clinical trials, inventions, and patent literatureView study →}.

The pharmacology position: nigellone is a polymer. The researchers who introduced the name describe something less defined. El-Dakhakhny’s own 1965 paper compares the seed’s “active principle” (thymoquinone) with “its dihydro compound” (thymohydroquinone) and “its polymer” — the latter being nigellone ^{4Reference 4El-Dakhakhny M · 1965Studies on the Egyptian Nigella sativa LView study →}. His 2002 paper writes the name as “nigellone (polythymoquinone)” ^{3Reference 3El-Dakhakhny M et al. · 2002AnimalNigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from ratsView study →}. Chakravarty’s mast-cell study opens: “Nigellone is the carbonyl polymer of thymoquinone” ^{1Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →}. A dimer is, strictly, the n = 2 member of a polymer series, so the two descriptions are not incompatible — but they are not the same claim either.

What is missing is the bridge. No primary paper published a structural characterisation — NMR, mass spectrum, crystal structure — of the material actually dosed in the nigellone pharmacology studies. Dithymoquinone’s own structure was only nailed down in 2012, decades after those studies ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}. So the equivalence rests on assertion, not on analysis.

The literature around the name is genuinely unreliable in both directions. A 2024 review states that thymohydroquinone is “also known as DTQ or hydrothymoquinone” — conflating the hydroquinone with the dimer, which are different molecules with different formulae ^{20Reference 20Alberts A et al. · 2024ReviewNigella sativa: a comprehensive review of its therapeutic potential, pharmacological properties, and clinical applicationsView study →}. An agronomy study measures the “nigellone oil content” of black cumin seed as a field response variable, using the name for a whole oil fraction rather than a compound at all ^{18Reference 18Al-Kayssi AW et al. · 2011Impact of soil water stress on nigellone oil content of black cumin seeds grown in calcareous-gypsifereous soilsView study →}.

Our verdict. This page treats nigellone and dithymoquinone as one entry with two names and an unresolved boundary: dithymoquinone is the defined dimer, and it is almost certainly what modern papers mean by nigellone — but the mid-century bronchodilator work was done on a polymeric preparation that was never structurally characterised, and the safest reading is that its identity with pure dithymoquinone is assumed rather than proven. Where a finding belongs to one and not the other, it is said which.

A Photodimer, and Possibly an Artefact

If nigellone is dithymoquinone, then a second question follows immediately: is it a plant product at all?

Dithymoquinone forms from thymoquinone by light. The photodimerisation was first described more than 150 years ago, and the classic preparation — Smith and Tess, 1944 — is simply a thin polycrystalline film of thymoquinone left in indirect daylight for seven days ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}. The reaction is a solid-state [2+2] cycloaddition and it is efficient: irradiating thymoquinone under two ordinary fluorescent tubes drives it essentially to completion in 48 hours, at better than 99.8% conversion ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}. Any quinone-rich oil sitting in a clear bottle on a shelf is running a slow version of this reaction.

The compositional data are consistent with that reading:

• It is detectable in oil. The reference HPLC method for black seed quantifies thymoquinone, dithymoquinone, thymohydroquinone and thymol together in a commercial N. sativa seed oil sample ^{7Reference 7Ghosheh OA et al. · 1999High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.)View study →}. So it is genuinely present in products.
• It is frequently absent from the seed. A compiled survey of Nigella essential-oil analyses records dithymoquinone as not detected across multiple independent studies of N. sativa and N. damascena seed oil ^{13Reference 13Salehi B et al. · 2021ReviewNigella plants — traditional uses, bioactive phytoconstituents, preclinical and clinical studiesView study →}. A detailed metabolite mapping of the seed lists the volatile pool as p-cymene, thymohydroquinone, thymoquinone, γ-terpinene and α-thujene, with carvacrol appearing on maturation — and no dimer at all ^{14Reference 14Botnick I et al. · 2012Distribution of primary and specialized metabolites in Nigella sativa seeds, a spice with vast traditional and historical usesView study →}.
• The quinones are explicitly flagged as light- and heat-sensitive. A supercritical-CO₂ extraction study frames the four quinonic phenols of the seed as “thermally labile or photosensitive” volatiles whose recovery depends on how gently the material is handled ^{16Reference 16Tiruppur Venkatachallam SK et al. · 2010Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxideView study →}.

Taken together, the balance of evidence favours dithymoquinone being largely a conversion product of thymoquinone — driven by light, heat, storage and processing — rather than a primary seed metabolite. That is not a settled conclusion, and it deserves a dedicated study; it is offered here as the reading the available data support.

It matters practically. If the dimer forms on the shelf, then its content in a given bottle of black seed oil is a measure of how that oil was handled, not of the plant it came from — and any “nigellone content” figure without a stated storage and light history is close to meaningless.

The Bronchodilator Tradition

This is the claim the molecule exists for, and it needs handling carefully.

What the tradition says. Black seed has a long folk record in asthma, cough and bronchitis; the standard pharmacology review of the plant opens by naming asthma among the conditions it is used for, and notes that the oil “increases respiration” ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}. Nigellone is the constituent to which mid-twentieth-century Egyptian pharmacology attributed that effect ^{4,5Reference 4El-Dakhakhny M · 1965Studies on the Egyptian Nigella sativa LView study →Reference 5Mahfouz M · 1961Mode of action of nigelloneView study →}.

What can actually be verified is very little. The primary sources are two:

• El-Dakhakhny, 1965 — Studies on the Egyptian Nigella sativa L. IV. Some pharmacological properties of the seeds’ active principle in comparison to its dihydro compound and its polymer ^{4Reference 4El-Dakhakhny M · 1965Studies on the Egyptian Nigella sativa LView study →}. The record exists and the title is unambiguous about the three-way comparison, but the paper predates abstracts in the index and its contents cannot be read from the database entry.
• Mahfouz & El-Dakhakhny, 1961 — a one-page Mode of Action of Nigellone item in Biochemical Pharmacology ^{5Reference 5Mahfouz M · 1961Mode of action of nigelloneView study →}. A meeting abstract, not a full report.

The clinical reports frequently alluded to — nigellone given by mouth to asthmatic children and adults in 1960s Egypt — could not be located in either PubMed or Crossref. They may exist in non-indexed Egyptian journals; they may be a citation that has propagated without a source. Either way, there is no verifiable clinical evidence for nigellone in asthma, and it will not be cite an approximation of one.

The one modern experiment is real, and it is favourable. Wienkötter and colleagues tested nigellone and thymoquinone on isolated trachea and on mucociliary transport ^{2Reference 2Wienkötter N et al. · 2008The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearanceView study →}:

• Nigellone produced concentration-dependent inhibition of trachea contracted by Ba²⁺ (a depolarising stimulus); thymoquinone did so only at high concentrations.
• Contractions induced by leukotriene D₄ were inhibited by both.
• The cholinergic route (carbachol) was “hardly involved” — a useful mechanistic exclusion.
• Mucociliary clearance was highly increased by nigellone (217.5 vs 505.0 seconds per 12 mm) and only slightly modified by thymoquinone.

The authors’ conclusion is worth quoting in substance: nigellone, but not thymoquinone, may be useful in respiratory disease ^{2Reference 2Wienkötter N et al. · 2008The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearanceView study →}. That is a rare instance of a minor constituent outperforming the marker compound, and it is the strongest single result here.

The caveat is equally important. This is an isolated-organ study from a single group, and M. El-Dakhakhny is a co-author — the same investigator behind the original 1960s claim. It is best read as a modern, properly reported continuation of that research lineage rather than as independent replication. Nothing has confirmed it since; a broad review of plant tracheal relaxants places N. sativa among the relaxant herbs but does not add isolate-level nigellone data ^{21Reference 21Shakeri F · 2015ReviewA review of the relaxant effect of various medicinal plants on tracheal smooth muscle, their possible mechanism(s) and potencyView study →}.

What It's Used For

Setting the respiratory work aside, the picture is thin and unusually negative. Where dithymoquinone has been tested head-to-head against black seed’s other quinones, it is repeatedly the weakest of the set.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every score here is capped low for the same reason: there is no human evidence for this molecule at all, and several rows are held down by explicitly negative findings rather than by absence of testing.

01Bronchodilation and Airway ClearanceShaky26%One isolated-organ study, favourable and mechanistically specific — but single-lab and un-replicated ^{2Reference 2Wienkötter N et al. · 2008The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearanceView study →}

02Mast Cell Stabilisation and Histamine ReleaseShaky22%One in-vitro rat mast-cell study with a defined calcium/PKC mechanism ^{1Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →}

03Lipoxygenase and Cyclo-oxygenase InhibitionShaky20%Measured in cell-free and leukocyte assays — but far weaker than thymoquinone ^{3,9Reference 3El-Dakhakhny M et al. · 2002AnimalNigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from ratsView study →Reference 9Marsik P et al. · 2005In vitroIn vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1- and -2-catalyzed prostaglandin E2 biosynthesesView study →}

04Cytotoxicity in Tumour Cell LinesShaky14%Cytotoxic at high micromolar concentrations in human tumour lines ^{8Reference 8Worthen DR et al. · 1998In vitroThe in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa LView study →}

05Antioxidant and Antimicrobial ActivityShaky8%Mostly a negative record — no ORAC/DPPH effect, not among the antiyeast actives ^{10,11Reference 10Tesarova H et al. · 2011Determination of oxygen radical absorbance capacity of black cumin (Nigella sativa) seed quinone compoundsView study →Reference 11Halamova K et al. · 2010In vitroIn vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levelsView study →}

Mechanisms

Read the last two rows as carefully as the first four. Two of the activities most often assumed for a black seed quinone — antioxidant capacity and insulin secretion — were tested for nigellone and were not found.

Pharmacokinetics

There are no pharmacokinetic data for nigellone or dithymoquinone: no absorption study, no oral bioavailability figure, no distribution, metabolism, half-life or plasma assay in any species. This is a total absence, not a thin dataset.

Two structural points are worth flagging as inference rather than measurement. Dithymoquinone is a rigid, fused cyclobutane bis-quinone of MW 328 — roughly double thymoquinone’s mass, far less volatile, and with the reactive quinone C=C bonds consumed in the dimerisation, so it should behave quite differently from the parent both chemically and in the body. And if the pharmacologically studied nigellone is genuinely a polymer of undefined chain length, then pharmacokinetics is not merely unmeasured but ill-defined — you cannot characterise the disposition of a substance without a molecular weight.

Clinical Trials

There are no clinical trials of nigellone or dithymoquinone — none completed, planned or terminated in any register located. The frequently alluded-to mid-twentieth-century Egyptian reports of oral nigellone in bronchial asthma could not be found in PubMed or Crossref and are treated here as unverified. The substantial clinical record for Nigella sativa belongs to the seed, the fixed oil and thymoquinone-standardised preparations, and does not transfer to this constituent.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule sits in an unusual position: almost everything published about it is isolate work, and that is exactly why the picture looks so modest.

The isolate record is small but genuinely isolate. Nigellone or dithymoquinone as a purified preparation has been put on isolated trachea ^{2Reference 2Wienkötter N et al. · 2008The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearanceView study →}, on primary mast cells ^{1Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →}, on leukocyte 5-lipoxygenase alongside the whole oil and thymoquinone ^{3Reference 3El-Dakhakhny M et al. · 2002AnimalNigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from ratsView study →}, into cell-free COX assays ^{9Reference 9Marsik P et al. · 2005In vitroIn vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1- and -2-catalyzed prostaglandin E2 biosynthesesView study →}, into DPPH/ORAC ^{10Reference 10Tesarova H et al. · 2011Determination of oxygen radical absorbance capacity of black cumin (Nigella sativa) seed quinone compoundsView study →}, into antifungal broth dilution ^{11Reference 11Halamova K et al. · 2010In vitroIn vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levelsView study →}, onto human tumour lines ^{8Reference 8Worthen DR et al. · 1998In vitroThe in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa LView study →}, and onto Vero cells with SARS-CoV-2 ^{12Reference 12Esharkawy ER et al. · 2022In vitroIn vitro potential antiviral SARS-CoV-19 activity of natural product thymohydroquinone and dithymoquinone from Nigella sativaView study →}. Several of those experiments ran thymoquinone and thymohydroquinone in the same plate, which is the best possible design for this question. The verdict from those head-to-head comparisons is consistent: this is the least active member of the set, except in the airway.

The plant record does not belong to it. Every clinical and animal result for black seed — glycaemic, lipid, anti-inflammatory, hepatoprotective, antimicrobial — is attributable, per the reference pharmacology review, chiefly to thymoquinone ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}. Where nigellone was tested alongside the oil in an animal-adjacent model, it did not reproduce the oil’s effect: N. sativa oil lowered blood glucose in streptozotocin-diabetic rats over six weeks, but neither the oil, nor nigellone, nor thymoquinone stimulated insulin release from isolated pancreatic islets ^{17Reference 17El-Dakhakhny M et al. · 2002The hypoglycemic effect of Nigella sativa oil is mediated by extrapancreatic actionsView study →}.

And a third problem, specific to this compound: the tested material may not be the named one. Because the pharmacology preparations were never structurally characterised (see Nigellone vs. Dithymoquinone), even the isolate studies carry an identity caveat that most compound pages never need.

Prevalence in Nature

Nigellone is, in practice, a Nigella entry — but a shaky one, because its occurrence in the intact plant is not securely established.

Where it is reported. The reference HPLC method for black seed quantifies dithymoquinone alongside thymoquinone, thymohydroquinone and thymol in commercial N. sativa seed oil ^{7Reference 7Ghosheh OA et al. · 1999High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.)View study →}, and it appears in the volatile profile of supercritical-CO₂ seed extracts ^{16Reference 16Tiruppur Venkatachallam SK et al. · 2010Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxideView study →}. Review compilations routinely list it among the seed’s terpenoid/quinone constituents ^{13,19Reference 13Salehi B et al. · 2021ReviewNigella plants — traditional uses, bioactive phytoconstituents, preclinical and clinical studiesView study →Reference 19Imran M et al. · 2022Clinical trialNigella sativa L. and COVID-19: a glance at the anti-COVID-19 chemical constituents, clinical trials, inventions, and patent literatureView study →}.

Where it is absent. Compiled essential-oil analyses of N. sativa and N. damascena record dithymoquinone as not detected in study after study ^{13Reference 13Salehi B et al. · 2021ReviewNigella plants — traditional uses, bioactive phytoconstituents, preclinical and clinical studiesView study →}. A detailed seed metabolite map — which resolved the volatile pool down to γ-terpinene, α-thujene, p-cymene, thymohydroquinone, thymoquinone and carvacrol, and even located the nigellidine/nigellicine alkaloids to the seed coat — does not report a dimer at all ^{14Reference 14Botnick I et al. · 2012Distribution of primary and specialized metabolites in Nigella sativa seeds, a spice with vast traditional and historical usesView study →}.

The most economical explanation is the one set out above: the dimer forms from thymoquinone under light and heat, so it shows up in oils that have been extracted, bottled and stored, and is missing from careful analyses of fresh seed ^{6,16Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →Reference 16Tiruppur Venkatachallam SK et al. · 2010Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxideView study →}. On that reading its “prevalence in nature” is largely a prevalence in product.

For context, the seed itself is >30% fixed oil rich in linoleic acid, plus a volatile fraction of roughly 0.4–0.5% built around thymoquinone ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}. Whatever share of that fraction the dimer occupies, it is small, variable and — critically — not reported with a defensible number anywhere verifiable. The hole is logged in the compound’s gaps tracker.

Discovery & Synthesis

The chemistry came first, by a century. The photodimerisation of thymoquinone to dithymoquinone was described in the 1800s, and the first substantial procedure was published by Smith and Tess in 1944: evaporate a concentrated ethereal solution of thymoquinone to a thin polycrystalline film, leave it in indirect daylight for seven days, and crystallise the product from ethanol as pale yellow needles ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}.

The name came from Egypt. Thymoquinone was isolated from black seed essential oil by El-Dakhakhny in 1963 ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}, and it was the same Alexandria group — Mahfouz and El-Dakhakhny, around 1960–61 — that introduced nigellone as the name for the polymeric thymoquinone material and proposed a mode of action for it ^{5Reference 5Mahfouz M · 1961Mode of action of nigelloneView study →}, with the comparative pharmacology of principle, dihydro compound and polymer following in 1965 ^{4Reference 4El-Dakhakhny M · 1965Studies on the Egyptian Nigella sativa LView study →}.

The structure was settled last. Despite the reaction being known for 150 years, dithymoquinone’s structure was only confirmed by single-crystal X-ray diffraction in 2012, by Myers and colleagues at MD Anderson, who also developed the practical preparation still used for reference standards: dissolve thymoquinone in ethyl acetate, irradiate the solid-state film under two 32-watt fluorescent tubes for 48 hours (>99.8% conversion), crystallise from 2-propanol, and obtain a 55% yield of a single trans-anti isomer via a [2+2] cycloaddition ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}.

Manufacture today: none, commercially. Nigellone is not produced or sold as an isolate. It is made in laboratories by irradiating thymoquinone, which is itself cheaply available ^{6Reference 6Myers AL et al. · 2012A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinoneView study →}. Human exposure is via black seed oil, and whatever dimer that oil contains it very likely made itself.

Patents: not yet researched.

Toxicity & Safety

Nigellone carries an unknown flag, and that is the honest badge rather than a placeholder.

There is no toxicology package of any kind — no acute or repeat-dose study, no LD₅₀, no genotoxicity, no reproductive data, no human safety report, and no pharmacokinetics — for either the polymer or the purified dimer.

The widely repeated reassurance is unsupported. Chakravarty’s 1993 paper states that “the polymer is far less toxic but retains much of the pharmacologic properties of thymoquinone” ^{1Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →}. That sentence has been recycled for three decades. It appears in the paper as an assertion with no accompanying toxicology, and nothing since has tested it.

What isolate data exist point the other way, mildly. Dithymoquinone was cytotoxic to human tumour cell lines at IC₅₀ 78–393 µM ^{8Reference 8Worthen DR et al. · 1998In vitroThe in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa LView study →}, and in Vero cells it was reported to show “high cytotoxicity” with a selectivity index of only 1.4 — meaningfully worse than thymohydroquinone in the same experiment ^{12Reference 12Esharkawy ER et al. · 2022In vitroIn vitro potential antiviral SARS-CoV-19 activity of natural product thymohydroquinone and dithymoquinone from Nigella sativaView study →}. These are cell-line observations at concentrations far above realistic exposure, not a hazard finding, but they do not support “far less toxic”.

The reassuring context is the plant, not the molecule. Black seed itself is characterised in the reference review as having “a very low degree of toxicity”, with no significant adverse liver or kidney effects on extended dosing and only isolated contact-dermatitis reports ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}. That is a statement about a food, and it does not license conclusions about a concentrated isolate.

Safety at a Glance

❔ Toxicity unknown

• Dietary exposure is trace and the parent food is well tolerated. Black seed has a very low reported toxicity profile across extended animal dosing ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}.
• No toxicology exists for this compound at all. No acute, repeat-dose, genotoxicity, reproductive, or pharmacokinetic data for nigellone or dithymoquinone in any species.
• The “far less toxic than thymoquinone” claim is unsupported. It is an uncited assertion in a 1993 abstract ^{1Reference 1Chakravarty N · 1993Inhibition of histamine release from mast cells by nigelloneView study →}; cell-line data point mildly the other way ^{8,12Reference 8Worthen DR et al. · 1998In vitroThe in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa LView study →Reference 12Esharkawy ER et al. · 2022In vitroIn vitro potential antiviral SARS-CoV-19 activity of natural product thymohydroquinone and dithymoquinone from Nigella sativaView study →}.
• The substance’s identity is unresolved. Safety statements about a defined dimer may not apply to the uncharacterised polymer that the pharmacology was done on — and vice versa.
• Do not transfer thymoquinone’s or black seed’s evidence here. The herb’s trial record, dosing and cautions track the quinone fraction, chiefly thymoquinone ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}.

Dosage

There is no established or studied human dose for nigellone. It is not sold as an isolated supplement, no modern trial has administered it, and the mid-twentieth-century Egyptian reports of oral nigellone in asthma could not be located or verified — so no historical figure can be quoted either.

Exposure happens through black seed — ground seed or cold-pressed oil — where whatever dimer is present arrived largely by way of light and storage rather than by design. Dosing for the herb belongs on the nigella monograph, and where black seed products are standardised at all, they are standardised to thymoquinone, not to this constituent ^{15Reference 15Ali BH · 2003ReviewPharmacological and toxicological properties of Nigella sativaView study →}.

Nothing here is a dosing recommendation.

References

1. Chakravarty N (1993). Inhibition of histamine release from mast cells by nigellone. Annals of Allergy. https://pubmed.ncbi.nlm.nih.gov/7680846/
2. Wienkötter N, Höpner D, Schütte U, Bauer K, Begrow F, El-Dakhakhny M, Verspohl EJ (2008). The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearance. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/18219598/
3. El-Dakhakhny M, Madi NJ, Lembert N, Ammon HP (2002). Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/12065147/
4. El-Dakhakhny M (1965). Studies on the Egyptian Nigella sativa L. IV. Some pharmacological properties of the seeds’ active principle in comparison to its dihydro compound and its polymer. Arzneimittel-Forschung 15(10):1227–1229. https://pubmed.ncbi.nlm.nih.gov/4380349/
5. Mahfouz M, El-Dakhakhny M (1961). Mode of action of nigellone. Biochemical Pharmacology 8:160. https://doi.org/10.1016/0006-2952(61)90726-2
6. Myers AL, Zhang YP, Kramer MA, Bornmann WG, Kaseb A, Yang P, Tran HT (2012). A practical synthesis and X-ray crystallographic analysis of dithymoquinone, a photodimer of thymoquinone. Letters in Organic Chemistry. https://pubmed.ncbi.nlm.nih.gov/24883052/
7. Ghosheh OA, Houdi AA, Crooks PA (1999). High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). Journal of Pharmaceutical and Biomedical Analysis. https://pubmed.ncbi.nlm.nih.gov/10698539/
8. Worthen DR, Ghosheh OA, Crooks PA (1998). The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Research. https://pubmed.ncbi.nlm.nih.gov/9673365/
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