Marjoram

Marjoram (Origanum majorana L.): A Comprehensive Reference

1. Identity and Botanical Classification

1.1 Names and Taxonomy

Origanum majorana L. — known as Sahtar or Zaatar in traditional medicine and currently named sweet marjoram — is a medicinal plant of the family Lamiaceae, a perennial herb of the genus Origanum. Its accepted botanical synonym is Majorana hortensis, while the plant is most commonly known as sweet marjoram. The word Origanum originates from the Greek word oros, meaning "mountain," and ganos, meaning "joy" or "light," giving the genus its association with the phrase "joy of mountains."

Various other aromatic herbs of the genus Origanum are also called marjoram. Pot marjoram (O. onites) is cultivated for its aromatic leaves and used to flavor food. Oregano, or wild marjoram (O. vulgare), is a popular culinary herb native to Europe and Asia. Historically, both O. majorana (sweet marjoram) and O. vulgare (wild marjoram / oregano) have been called marjoram. The physical similarity of the plants and difficulty with proper identification have been a historical problem that has persisted to recent times, meaning all history and folklore must be considered in a broad context.

1.2 Botanical Description and Geographic Distribution

Origanum majorana L. is a tender, bushy perennial hairy herb, up to about 0.6 m; leaves are 5–20(−35) × 5–10(−15) mm, glabrous to tomentose, not papillose, ovate to ovate elliptic-spatulate, obtuse or acute, rounded or attenuate at base; flowers are purple, rarely white, in compact heads, forming a terminal trichotomous panicle. It is an aromatic plant with a distinctive tangy odour and a bitter taste.

The plant is native to Greece, Cyprus, and Turkey; however, it has also been cultivated in Morocco, Egypt, Tunisia, Algeria, and elsewhere. O. majorana is found in the flora of Türkiye, especially in Southern Anatolia, where it is referred to as "Mercanköşk" as well as by various local names such as "Kekik otu," "Göğe kekiği," "Kahve otu," "Guy otu," "Sebso," and "Sebzo."

1.3 Common Forms and Preparations

The pharmacopoeial herbal substance, Origani majoranae herba, consists of the dried flowering shoots of Origanum majorana L. containing not less than 5 ml/kg of essential oil (in the dried herbal substance) (Farmakopea Polska X, 2014). Marjoram is encountered in several distinct preparations:

• Dried herb and herbal tea (infusion): The aerial parts with flowers are used as powder for oral use or prepared as an infusion at 5% as an herbal tea, as a spasmolytic and to help digestion.
• Essential oil: The plant contains up to 5% volatile oil (usually less than 1%), consisting primarily of terpinen-4-ol and (+)-cis-sabinene hydrate. The essential oil is obtained by steam distillation of the aerial parts.
• Topical ointment: An ointment described in the Farmakopea Polska (1995 and 2014) corresponds to an extract with a ratio of herbal substance to extraction solvent of 1:5, using ethanol 96% V/V and white petroleum jelly as the extraction medium.
• Hydroalcoholic and aqueous extracts: Used in research and phytotherapy preparations, obtained from the aerial parts of the plant.
• Culinary use: The food industry widely uses the dried leaves of sweet marjoram as flavoring agents for dressings and in the formulation of aromatized and fortified wines such as vermouth and bitters.

2. Traditional and Historical Use

2.1 Ancient Mediterranean and Classical Antiquity

Hippocrates (460–370 B.C.) used O. majorana as an antiseptic agent. Aristotle reportedly documented it as an anti-poison. In ancient Egypt, marjoram was used to disinfect and preserve food, and its oil was massaged onto the forehead and into the hair. Dioscorides named it "sampsouchon."

In most of the historical record, origanums have been portrayed in a very positive light, associated with love, protection, purification, healing, and happiness, and steeped in religious tradition and myth.

2.2 Traditional Mediterranean and Middle Eastern Medicine

Origanum majorana L., commonly known as sweet marjoram, has been used for a variety of diseases in traditional and folklore medicines, including gastrointestinal, ocular, nasopharyngeal, respiratory, cardiac, rheumatologic, and neurological disorders.

This species is widely used in traditional medicine for the treatment of many diseases such as allergies, hypertension, respiratory infections, diabetes, stomach pain, and intestinal antispasmodic. This species is also used in the traditional medicine of Mediterranean countries to treat respiratory diseases such as influenza, cough, and the common cold, as well as for its sedative and gastrointestinal antispasmodic effects.

2.3 European Folk and Pharmacopoeial Tradition

It is traditionally indicated in Poland "for relief of nasal rhinitis, suitable for cutaneous use in paediatric practice." Literature supports the traditional use of Origanum majorana herba for more than 30 years in the EU as a traditional herbal medicinal product used for relief of irritated skin around the nostrils, applied as a small amount of ointment spread around the nostrils, two to four times daily.

Different parts of this plant are utilized to treat several ailments, including cough, cramps, and acute diarrhea. Several beneficial properties, including expectorant, carminative, antiseptic, antispasmodic, hepatoprotective, cardioprotective, antitumor effects, and notable anti-inflammatory and antioxidant activities, have been attributed to the plant.

2.4 Traditional Hormonal and Gynecological Use

In traditional medicine, marjoram herb (Origanum majorana) is locally reputed for its ability to restore hormonal balance and to regulate the menstrual cycle. The uses of marjoram are also similar to related species: it is traditionally applied against digestive problems and bronchial diseases.

3. Key Constituents and Active Compounds

3.1 Essential Oil (Volatile Fraction)

Monoterpene hydrocarbons are found in the essential oil of O. majorana. Terpinene-4-ol and cis-sabinene hydrate are the two main oxygenated monoterpenes isolated from O. majorana. The full list of active components includes monoterpene hydrocarbons (such as α-pinene, β-pinene, camphene, and γ-terpinene), oxygenated monoterpenes — particularly terpinene-4-ol, cis-sabinene hydrate, and terpineol — phenolic compounds particularly flavonoids (such as apigenin, hesperetin, quercetin, kaempferol), and phenolic glycosides (such as arbutin).

In most studies, the compounds detected in greatest abundance are terpinen-4-ol, cis-sabinene hydrate, and γ-terpinene. Researchers have classified O. majorana into two main chemotypes based on qualitative criteria: the first is the terpinen-4-ol/cis-sabinene hydrate chemotype, and the second belongs to the carvacrol/thymol type. Phytochemical studies on O. majorana essential oil have reported variations in the volatile compositions according to geographical origins.

A representative GC-MS analysis of O. majorana essential oil illustrates typical quantitative composition: in one study, the essential oil contained terpinen-4-ol (24.92%), trans-sabinene hydrate (25.18%), γ-terpinene (6.48%), cis-sabinene hydrate (5.44%), p-cymene (4.72%), sabinene (4.53%), α-terpineol (4.43%), and α-terpinene (3.00%) as the main constituents. GC and GC/MS analysis has revealed the presence of 38 components represented mainly by oxygenated monoterpenes (64.01–71.4%), monoterpene hydrocarbons (21.73–29.92%), and sesquiterpene hydrocarbons (1.47–4.05%), with main components terpinen-4-ol (29.13–32.57%), cis-sabinene hydrate (19.9–29.27%), trans-sabinene hydrate (3.5–11.61%), γ-terpinene (2.11–8.20%), bornyl acetate (1.52–2.94%), and linalool (1.05–1.39%).

The often-cited higher contents of terpinen-4-ol, α-terpinene, and γ-terpinene in the essential oil are partly due to rearrangements that occur during the distillation process.

3.2 Non-Volatile (Polar) Phytochemicals

The occurrence of flavonoid aglycons and glycosides, hydroxyquinone derivatives (hydroxyquinone, arbutin, methylarbutin), tannins, and phenolic acids (rosmarinic acid, caffeic acid, caftaric acid, chlorogenic acid, protocatechuic acid) have been described from the hydroalcoholic, ethyl acetate, and water extracts of the plant.

Supercritical CO₂ extraction has obtained essential oil with variable amounts of cis-sabinene hydrate, terpinene-4-acetate, 1-terpinen-4-ol, α-terpineol, trans-sabinene hydrate, spathulenol, caryophyllene, linalool, carvacrol, and α-bergamatone. The phenolic compounds identified in the essential oils are hydroxycinnamic acids like rosmarinic acid, ferulic acid, caffeic acid, coumarinic acid, and hydroxybenzoic acids like vanillic acid, syringic acid, and p- and m-hydroxybenzoic acid. Hydroalcoholic extracts accommodate high amounts of phenolic acids, flavonoids, and flavonoid glycosides, which are major contributors to the antioxidant activity of the marjoram extracts.

Among the identified phytochemicals are thymol, carvacrol, tannins, hydroquinone, arbutin, methyl arbutin, vitexin, orientin, thymonin, triacontan, sitosterol, cis-sabinene hydrate, limonene, terpinene, camphene, and flavonoids such as diosmetin, luteolin, and apigenin.

Additional constituents include ursolic acid, a triterpenoid with anti-inflammatory and antioxidant effects; linalool, a terpene alcohol with calming and analgesic properties; carvacrol, which exhibits antimicrobial and anti-inflammatory activities; and flavonoids such as apigenin, known for its anti-inflammatory and antioxidant effects, and luteolin, recognized for its antioxidant and anti-inflammatory activities.

The constituents include 1% to 2% of an essential oil containing terpinenes and terpinols, plus tannins, bitter compounds, carotenes, and vitamin C. These substances give sweet marjoram stomachic, carminative, antispasmodic, and weak sedative properties.

3.3 Chemotype Variability

A historical sample of marjoram more than 60 years old was analyzed and its composition compared to standard material from the European herb market. The extract contained high amounts of terpinen-4-ol, thus resembling the distilled essential oil. The high content of carvacrol, normally never present in standard material from cultivation, gave an indication of the heterogeneity of marjoram in former times, and confirmed the opinion that cultivated marjoram is a chemovariety selected a long time ago.

4. Mechanisms of Action

4.1 Antioxidant Mechanisms

Pharmacological studies have demonstrated that the high antioxidant potential of marjoram is attributed to its phenolic monoterpenes, including thymol and carvacrol, as well as other phenolic compounds such as eriganoside and rosmarinic acid. Hydroalcoholic extracts accommodate high amounts of phenolic acids, flavonoids, and flavonoid glycosides, which are major contributors to the antioxidant activity of the marjoram extracts.

4.2 Anti-Inflammatory Mechanisms

In vitro, Origanum inhibited pro-inflammatory cytokines such as IL-6, NO, and TNF in LPS-stimulated macrophages, provided anti-inflammatory activity, and facilitated wound healing in human keratinocytes. Furthermore, several in vivo studies support the promising protective effects of Origanum in various models of inflammation and oxidative stress, including gastritis, cardiotoxicity, and LPS-induced endotoxemia models.

4.3 Antimicrobial Mechanisms

Monoterpenes have been reported to be the dominant antimicrobial constituents of the essential oil, and some monoterpenes are responsible for its antimicrobial activity — particularly sabinene hydrate and terpinen-4-ol. In efflux pump inhibitory assays, the essential oil exhibited substantial activity, especially in E. coli ATCC 25922 strain. Among the EO constituents, sabinene was identified as an efflux pump inhibitor in sensitive Escherichia strains. In S. aureus strains, EO and sabinene hydrate exhibited moderate potency on the drug-resistant phenotype.

γ-Terpinene, terpinen-4-ol, sabinene, sabinene hydrate, and linalool were found to be effective inhibitors of biofilm formation (inhibition 36–86%) on E. coli ATCC 25922 and S. aureus MRSA ATCC 43300.

4.4 Gastroprotective Mechanisms

Marjoram at doses of 250 and 500 mg/kg of body weight significantly decreased the incidence of ulcers, basal gastric secretion, and acid output in rat models. Furthermore, the extract replenished the ethanol-induced depleted gastric wall mucus and non-protein sulfhydryls (NP-SH) contents and significantly lowered the increase in the concentration of malondialdehyde (MDA).

4.5 Neuroprotective Mechanisms

Rosmarinic acid, a major phytochemical in O. majorana extract, can mitigate LPS-induced cognitive deficits, neurodegeneration, and the overproduction of proinflammatory cytokines in the hippocampus and cortex, and reverse the oxidant-antioxidant balance in a rat model of LPS-induced neuroinflammation. Additionally, O. majorana essential oil has been shown to enhance brain-derived neurotrophic factor (BDNF) expression, further supporting cognitive function improvement in Alzheimer's disease models.

4.6 Endocrine and Metabolic Mechanisms

Marjoram's bioactive components, including flavonoids and phenolic compounds, exhibit potent antioxidant activity, countering oxidative stress commonly associated with PCOS. Mechanistically, marjoram activates peroxisome proliferator-activated receptors (PPARs), enhancing insulin sensitivity and reducing metabolic dysfunctions.

5. Scientific Evidence by Area of Use

5.1 Polycystic Ovary Syndrome (PCOS) and Hormonal Effects

Human/clinical evidence:

A pilot study aimed to investigate the effects of marjoram tea on the hormonal profile of women with polycystic ovary syndrome (PCOS) in a randomised, double-blind, placebo-controlled trial. Twenty-five patients were assigned to receive marjoram tea or a placebo tea twice daily for 1 month (intervention group: n = 14; placebo group: n = 11).

Marjoram tea significantly reduced DHEA-S and fasting insulin levels (P < 0.05) by a mean (SD) of 1.4 (0.5) μmol L⁻¹ and 1.9 (0.8) μU mL⁻¹, respectively. In comparison to the placebo group, the change was only significant for DHEA-S (P = 0.05) but not for insulin (P = 0.08). HOMA-IR was not reduced significantly in the intervention group (P = 0.06), although the change was significant compared to the placebo group (P < 0.05).

The results obtained in the present study show beneficial effects of marjoram tea on the hormonal profile of PCOS women because it was found to improve insulin sensitivity and reduce the levels of adrenal androgens.

Preclinical evidence:

In a DHEA-induced rat model of PCOS, marjoram treatment significantly reduced oxidative stress by decreasing nitric oxide (NO) and increasing total antioxidant capacity (TAC). Hormonal analysis revealed that high-dose marjoram (100 mg/kg) normalized progesterone, estradiol, testosterone, and FSH levels. Body weight gain was also reduced with marjoram treatment, especially at the higher dose.

Recent preclinical research demonstrates that marjoram increases estradiol levels, decreases insulin and glucose concentrations, and addresses hormonal imbalances, with proposed ovulation-inducing effects. These effects are supported by clinical trials, highlighting marjoram's potential as a natural alternative for ovulation induction in women with PCOS.

Evidence strength: The only human study is a small pilot RCT (n = 25) with a 1-month intervention. Differences relative to placebo were statistically significant only for DHEA-S. Results are preliminary; larger, longer trials are needed before clinical conclusions can be drawn.

5.2 Dysmenorrhea (Menstrual Pain)

Clinical evidence:

In a controlled clinical study on menstrual pain in high school girls, the abdomen was massaged once using clary sage, marjoram, cinnamon, ginger, and geranium in a base of almond oil. The level of menstrual pain was assessed using a visual analogue scale at baseline and twenty-four hours afterward. The reduction of menstrual pain was significantly higher in the aromatherapy group than in the acetaminophen control group. Using multiple regression, aromatherapy massage was found to be more highly associated with reduction in the level of menstrual pain. These findings suggest that aromatherapy massage may be an effective treatment for menstrual pain, though it could not be verified whether the positive effects derived from the aromatherapy, the massage, or both.

Subjects in the treatment group received a ten-minute abdominal massage using essential oils — clary sage, marjoram, cinnamon, ginger, and geranium — in a 1:1:0.5:1.5:1.5 ratio, diluted in almond oil at a final concentration of 5%.

Evidence strength: Preliminary. The blend nature of the intervention (multiple oils combined) makes it impossible to isolate marjoram's specific contribution. No human trials on marjoram monotherapy for dysmenorrhea have been identified in the peer-reviewed literature.

5.3 Antimicrobial Activity

In vitro evidence:

In a published study, the essential oil contained terpinen-4-ol (24.92%) and trans-sabinene hydrate (25.18%) as the main constituents. The antibacterial activity of the EO and its constituents terpinen-4-ol, α-terpinene, and linalool was assessed against sensitive and drug-resistant S. aureus and E. coli strains, with MIC values of 0.125–0.250% for EO.

A 95% methanol extract prepared from the aerial parts of O. majorana was tested in vitro on 14 clinical isolates and one ATCC strain of Helicobacter pylori. Origanum majorana proved very active against the used Helicobacter strains; the minimal inhibitory concentration (MIC) was also identified for the extract (around 2.50 mg/mL for all but one strain).

Origanum majorana EO contained high levels of terpinen-4-ol (34.2%) and indicated moderate antibacterial activity against multidrug-resistant Salmonella strains, compared to Thymus satureioides which demonstrated the highest efficacy with the lowest MIC (0.15 mg/mL).

Evidence strength: O. majorana essential oils showed remarkable antimicrobial, antioxidant, anticancer, anti-inflammatory, antimutagenic, nephroprotective, and hepatoprotective activities in laboratory studies. However, further investigations regarding the evaluation of molecular mechanisms of identified compounds against human cancer cell lines, inflammatory processes, and microbial infections are needed to validate pharmacodynamic targets. All antimicrobial evidence is from in vitro laboratory studies; no human clinical trials have established clinical antimicrobial efficacy.

5.4 Gastroprotective and Antiulcer Effects

Preclinical evidence:

The antiulcerogenic activity of the ethanol extract was evaluated in hypothermic restraint stress-, indomethacin-, and necrotizing agent-induced ulcers and in basal gastric acid secretion using a pylorus-ligated Shay rat model. Marjoram at doses of 250 and 500 mg/kg of body weight significantly decreased the incidence of ulcers, basal gastric secretion, and acid output. The extract replenished the ethanol-induced depleted gastric wall mucus and non-protein sulfhydryl (NP-SH) contents and significantly lowered the concentration of malondialdehyde (MDA). Ulcer-preventing potential was further confirmed by histopathological assessment.

Evidence strength: Preclinical only (rat models). No human clinical trials on gastroprotection have been identified.

5.5 Hepatoprotective Effects

Preclinical evidence:

A study investigated the antioxidative and hepatoprotective effects of methanolic extract of Origanum majorana L. (OM) on hepatic disorder and tissue damage induced by bile duct ligation (BDL) in rats. Twenty-eight male Wistar rats were randomly divided into 4 groups, and animals received vehicle or methanolic extract of OM at 300 mg/kg/day for 7 consecutive days by oral gavage. Biochemical profiles in a separate acute toxicity study indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels.

Evidence strength: Preclinical only. The hepatoprotective signal is consistent across multiple animal studies, but human clinical evidence is absent.

5.6 Neuroprotection and Cognitive Function

Preclinical evidence:

A study assessed the phytochemical characteristics of Origanum majorana L. hydroalcohol extract and its neuroprotective activities in a murine neuroinflammatory model. Oxidative stress was induced in vitro by hydrogen peroxide, and Swiss albino mice were injected intraperitoneally with OM extract at a dose of 100 mg/kg for 12 days, with 250 μg/kg LPS daily starting from day 6 to induce neuroinflammation.

A study showed strong antioxidant properties of Origanum majorana that protected neurons from haloperidol-induced cognitive and motor deficits by decreasing oxidative stress. Flavonoids, phenolic acids, and terpenoids in O. majorana exhibit antioxidant, anti-inflammatory, and cholinergic activity modulations crucial in Alzheimer's disease pathology. Research indicates that O. majorana's phytochemicals, particularly rosmarinic acid and thymol, possess strong antioxidant and anti-inflammatory effects, which are critical in combating neuroinflammation and oxidative stress associated with Alzheimer's disease.

Evidence strength: Preclinical only (in vitro and rodent/zebrafish models). No human trials on neuroprotection or cognitive function have been identified.

5.7 Antioxidant Activity

Pharmacological investigations have shown that essential oils and extracts from O. majorana exhibit different biological properties, particularly antibacterial, antifungal, antioxidant, antiparasitic, antidiabetic, anticancer, nephrotoxicity-protective, anti-inflammatory, analgesic and anti-pyretic, hepatoprotective, and antimutagenic effects. The antioxidant activity has been validated in multiple laboratory models using DPPH and FRAP assays, but no dedicated clinical trials measuring antioxidant biomarker changes in humans as a primary endpoint have been identified in the peer-reviewed literature for marjoram alone.

5.8 Antidiabetic Potential

The findings of pharmacological investigations have marked an important correlation between the traditional use of O. majorana as an anti-diabetic agent and its biological effects in laboratory studies. This evidence base remains preclinical (cell and animal models); no standalone human trials for glycemic outcomes have been identified.

6. Body Systems and Health Areas

Based on the peer-reviewed literature, the following body systems and health areas are associated with Origanum majorana:

• Gastrointestinal system: Gastrointestinal conditions are among the primary disease areas in traditional and folklore medicines. Historically used as a stomachic, carminative, and antispasmodic, with preclinical evidence for gastroprotection and antiulcer activity.
• Endocrine and reproductive system: Early studies suggest that marjoram improves insulin sensitivity, reduces DHEA-S and fasting insulin levels, and modulates inflammatory markers and oxidative stress. Human pilot data exist specifically for PCOS.
• Respiratory system: Marjoram is used in the traditional medicine of Mediterranean countries to treat respiratory diseases such as influenza, cough, and the common cold.
• Musculoskeletal system: Traditional use as an antispasmodic and analgesic for muscle pain and spasm.
• Nervous system: Several in vivo studies support the protective effects of Origanum in models of oxidative stress, and strong antioxidant properties have been shown to protect neurons from haloperidol-induced cognitive and motor deficits by decreasing oxidative stress.
• Liver/hepatic system: Preclinical hepatoprotective evidence based on liver enzyme reductions and bile duct ligation models.
• Integumentary (skin) system: Traditionally used as a herbal medicinal product for relief of irritated skin around the nostrils. Also investigated in anti-acne and antimicrobial topical applications.
• Immune/anti-infective: Antimicrobial activity against a wide range of bacterial, fungal, and parasitic pathogens demonstrated in vitro.

7. Dosage Forms and Reported Dosages

Dosages below are those reported in the cited scientific literature and regulatory documents only.

• Herbal tea (infusion): Prepared as an infusion at 5% as an herbal tea, used for spasmolytic and digestive purposes.
• Human PCOS pilot study — tea: Twenty-five patients were assigned to receive marjoram tea or a placebo tea twice daily for 1 month (intervention group: n = 14; placebo group: n = 11).
• Topical ointment (pharmacopoeial, Poland): A traditional herbal medicinal product used for relief of irritated skin around the nostrils; a small amount of the ointment is spread around the nostrils two to four times daily.
• Antiulcer study (rat, oral extract): Marjoram ethanol extract at doses of 250 and 500 mg/kg of body weight significantly decreased the incidence of ulcers, basal gastric secretion, and acid output.
• Hepatoprotective study (rat, oral extract): Animals received methanolic extract of OM at 300 mg/kg/day for 7 consecutive days by oral gavage.
• Neuroprotective study (mouse, intraperitoneal extract): Swiss albino mice were injected intraperitoneally with OM extract at a dose of 100 mg/kg for 12 days.
• PCOS rat study (oral): High-dose marjoram at 100 mg/kg normalized progesterone, estradiol, testosterone, and FSH levels in a DHEA-induced rat PCOS model.
• Essential oil aromatherapy/topical blend (dysmenorrhea study): A ten-minute abdominal massage using essential oils — clary sage, marjoram, cinnamon, ginger, and geranium — in a 1:1:0.5:1.5:1.5 ratio, diluted in almond oil at a final concentration of 5%, was administered to subjects in the treatment group.

No standardized human oral dosage for O. majorana supplements has been established by any major regulatory body or pharmacopoeia as of the reviewed literature.

8. Safety Considerations and Interactions

8.1 General Toxicological Profile

In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420. The extract preserved fibroblast viability above 90% across all tested concentrations (10–200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg.

Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses.

Toxicological evaluation confirmed the safety and innocuity of this species and supported its medicinal uses. An acute toxicity test showed a large margin of safety of the extract in mice.

8.2 EMA Assessment and Regulatory Safety Data

Intoxications due to herbal preparations are not reported and no cases of overdose have been documented. There are no reports on drug interactions recorded in the EMA assessment report on Origanum majorana herba.

O. majorana preparations are contraindicated in patients with hypersensitivity to the active substance.

8.3 Potential Genotoxicity at High Doses

Comet and micronucleus assays revealed dose-dependent DNA damage in vitro, suggesting genotoxic potential at higher exposures. This finding was observed in cell-based experiments with methanolic extract and requires follow-up to clarify its relevance to typical human exposures. Systematic in vivo and in vitro safety assessments remain limited.

8.4 Use in Pediatric Populations

Marjoram is traditionally indicated in Poland "for relief of nasal rhinitis, suitable for cutaneous use in paediatric practice." The EMA assessment notes, however, that due to lack of adequate safety and efficacy data, the use of oral preparations in pediatric populations is not established.

8.5 Pregnancy and Emmenagogue Considerations

The EMA and traditional sources note that marjoram has historically been regarded as an emmenagogue (capable of stimulating menstrual flow). The EMA assessment report notes that due to lack of scientific data on reproductive safety, the use of O. majorana oral preparations in pregnancy and lactation is not recommended. This is a traditional caution reflected in the pharmacopoeial and regulatory record, though formal clinical reproductive toxicology data in humans are absent.

8.6 Adverse Event Reports

An adverse event of gastrointestinal disorder was reported in relation to use of a combination product containing Levisticum officinale, Melissa officinalis, Origanum majorana, Phosphorus, Pulsatilla vulgaris, and Vitex agnus-castus. This adverse event related to a combination product in which Origanum majorana is not the main component. Thus, it is not possible to relate the observed GI disorders with only one component of the product. Moreover, this adverse event has not been found reported elsewhere, neither in the literature nor in the pharmacovigilance system of the marketed products.

8.7 Drug Interactions

No cases of overdose have been documented and there are no reports on drug interactions in the EMA assessment literature. Given the preliminary human evidence showing effects on insulin sensitivity and adrenal androgen production, theoretical interactions with antidiabetic medications and hormone therapies warrant monitoring in clinical settings, though this has not been formally evaluated in human studies.

8.8 Allergic Sensitivity

As a member of the Lamiaceae family, individuals with known sensitivities to related plants (e.g., oregano, thyme, basil) may show cross-reactivity. Among references reviewed in the EMA addendum process, 82 references related to safety revealed no new signs of toxicity.

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