Spilanthes

Other Names

Acmella oleraceaAcmella uliginosaAgnamafanaAgrião do BrasilAgrião do ParáAkarkarAkarkaraAkarkara IraniAkkarakaramAlphabet plantAustralian cressBidens acmellaBidens ocymifoliaBidens oleraceaBlainvillea acmellaBrazil cressBrède mafanaBrède mafaneBuzz buttonsCeruchis Gaertn.Cotula dichotomaCotula pyrethariaCresson de ParaDesflemaderaDesflematoriaDesi AkarkaraElectric daisyEyeball plantHemmugaluHusarenknopfblumeIsocarpha pyrethrariaJambúJambuJambu PhoolJin kou caoJin niu kouMandal Poo ChediNim-nimNovacaine plantPara cressParacressParakarseParakrassiPellitoryPhak khraat hua wanPigeon-coopPimenteiraPipulkaPirazhaPyrethraria dichotomaPyrethrum acmellaPyrethrum spilanthusSalad cressSichuan buttonsSpilanthe de ChineSpilanthe des teinturiersSpilanthes acmellaSpilanthes acmella var. calvaSpilanthes acmella var. oleraceaSpilanthes calvaSpilanthes fuscaSpilanthes oleraceaSpilanthes paniculataSpilanthes radicansSpilanthus L.Spot plantSzechuan buttonsTandvärksplantaTannpineplanteTingflowersToothache plantVerbesina acmella印度金鈕扣

Synopsis

Spilanthes: A Comprehensive Reference Article

1. Identity, Taxonomy, and Nomenclature

The common name Spilanthes refers to a cluster of closely related medicinal plants in the family Asteraceae (tribe Heliantheae), historically placed in the genus Spilanthes Jacq. but subject to extensive taxonomic revision. Spilanthes is a genus of African and South American plants in the tribe Heliantheae within the family Asteraceae. Numerous species once included in Spilanthes are now considered members of other genera; the best known of these is the toothache plant, which was formerly Spilanthes acmella but is now considered part of its own genus and referred to as Acmella oleracea.

The taxonomy of this plant complex is notoriously complicated. The genus Acmella, a member of Asteraceae (conserved name, Compositae), embraces 30 species and nine additional infraspecific taxa dispersed in tropical and subtropical areas. Since the genus shows extremely complicated patterns from a morphological and chromosomal perspective, it has been very difficult to demarcate the taxa, and it is sometimes mentioned interchangeably with the genus Spilanthes, even in recently published papers. A. oleracea, the most distinguished and recognized species for its medicinal purpose, is sometimes described as identical to Spilanthes acmella (L.) Murr., which has the officially accepted name Blainvillea acmella (L.) Philipson (World Flora Online, 2025). In chromosome studies, Spilanthes has a chromosome number of 16, whereas Acmella has 12 or 13. Jansen recircumscribed the genus and restored the generic status of Acmella, which had long been subsumed to a section under Spilanthes by earlier taxonomists.

In practice, the trade literature and most pharmacological research uses the names Spilanthes acmella (L.) Murr., Acmella oleracea (L.) R.K. Jansen, and Spilanthes oleracea interchangeably, often referring to the same or closely related plant material. The search and data collection in one comprehensive 2025 review was performed using the primary keyword Acmella oleracea, Spilanthes acmella, a term frequently misused by many researchers. Throughout this article, Spilanthes or S. acmella is used as the collective common name covering this entire plant complex, as is conventional in the herbal supplement literature.

Common Names and Regional Designations

Toothache plant (English, most widespread)
Jambu (Brazil, Amazon region)
Para cress / Paracress (English, food use)
Buzz buttons / Electric daisy / Szechuan buttons (culinary / novelty food industry)
Akarkara (Ayurvedic tradition, India)

Spilanthes acmella is an herbaceous plant that belongs to the family Asteraceae. It is used in traditional medicine throughout Asia and South America, where it is known as Jambu. The leaves are used for culinary purposes, and the flowers have been used for their numbing and pain-relieving properties, earning the plant such common names as the toothache plant. In addition, it has been noted to relieve stomatitis, have taste-activating properties, and to induce a salivary response.

Botanical Description

Typically, these plants are annual herbs or short-lived perennials, approximately a half-meter tall with prostrate or ascending cylindrical hairy stems and simple ovate opposite leaves with stipules. They belong to the family Asteraceae, the tribe Heliantheae, and the subtribe Ecliptinae, and have characteristic flower heads that distinguish individual species. These are annual or perennial herbs with branching stems usually reaching 10 to 20 centimetres in length, growing prostrate or erect. The oppositely arranged leaves are smooth-edged or toothed and usually have rough or soft hairs. The flower heads are distinctive cone-shaped or button-like structures; spilanthol is found in higher concentrations in the flowers of the plant than in the leaves.

Geographic Distribution

Spilanthes acmella is an important medicinal plant found in tropical and subtropical countries, mainly India and South America, and is popularly known as the toothache plant. The genus Acmella is native to the Americas and has been introduced to Asia, Africa, the Pacific islands, and Australia. One familiar species is Acmella oleracea, which has been widely cultivated for centuries; it is used for food and medicine, and as an insecticide and an ornamental plant.

Common Forms and Preparations

Spilanthes is commercially available in several forms as a dietary supplement and cosmetic ingredient:

Dried whole plant / flower heads: Used for decoctions and infusions, particularly in traditional settings.
Hydroalcoholic tinctures: Fresh or dried aerial parts extracted in ethanol or cane alcohol, applied topically or taken orally.
Standardized dry extracts in capsule or tablet form: One commercially reported preparation is SA3X capsules, which contain 500 mg of Spilanthes acmella extract standardized to 3.5% spilanthol, thus delivering 17.5 mg spilanthol per capsule.
Topical/cosmetic preparations: Creams, serums, and ointments, particularly for anti-wrinkle and oral-care applications.
Fresh culinary use: The leaves are eaten as a vegetable in India; fresh as well as broiled leaves are used in dishes, and raw leaves are used as flavoring for salads, soups, and meats.

2. Traditional and Historical Use

S. acmella's medicinal uses have been documented for centuries, particularly in traditional systems across India and among tribal communities, reflecting a rich ethnobotanical heritage.

Oral Health and Toothache

The most pervasive and cross-cultural traditional use of Spilanthes is for dental pain. In the tropics and subtropics, these plants are widely used in traditional medicine; the major use in all these systems of medicine is for toothache, where the fresh flower head and/or leaves is chewed or placed in tooth cavities to relieve pain. The most traditional use of this plant is to reduce toothache all over India as well as South America.

India and Ayurvedic Tradition

Other important traditional uses of the herb include treatment of rheumatism, use as a sialagogue for stammering and tongue paralysis, as an antipyretic, and for sore throat and gum infections. In India, juice of the inflorescence of S. acmella is used to treat mouth ulcers. Spilanthes acmella has been well documented for its uses as a spice, as an antiseptic, antibacterial, antifungal, and antimalarial treatment, and as a remedy for toothache, flu, cough, rabies diseases, and tuberculosis.

Africa

Ethiopian traditional healers use the crushed aerial parts in a paste dressing for external injuries. Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria.

Southeast Asia and Other Regions

In Java, it is used to treat stomatitis; the tribal people of Bangladesh use the leaves and flowers to treat leucorrhoea. In Cameroon, the plant is used for treating snake bites and articular rheumatism. Documented literature reports the traditional uses of S. acmella not only against dental problems but also in skin care cosmetics due to its anti-wrinkle properties, as a digestive aid, in obesity control, as an immunomodulatory agent, antimalarial, antifungal, and antibacterial agent, and for the treatment of fever and rheumatism.

South America (Amazonian / Brazilian Tradition)

Acmella oleracea is a plant species widely used in traditional Amazonian medicine to treat sexual dysfunction. Hydroethanolic preparations of Acmella oleracea are used in the north of Brazil as a female aphrodisiac. The plant, known locally as jambu, is also an important culinary ingredient in the traditional cuisine of Pará state in northern Brazil.

Additional Traditional Uses Across Cultures

Other traditional uses of Spilanthes acmella include its use as a stomachic, stimulant, and antidiarrhoeal agent, and it is used rarely against tuberculosis. Many researchers have proposed that the whole plant has local anaesthetic, anti-inflammatory, antioxidant, aphrodisiac, antinociceptive, immunomodulatory, and insecticidal effects.

3. Key Constituents and Active Compounds

Alkylamides / N-Alkylamides

Alkylamides are predominantly found in this genus and have been shown to possess varied biological activities; they act on cannabinoid type 2 receptors, both dependently and independently, and have also been found to possess useful immunomodulatory effects as chemotaxonomic markers.

Spilanthol (Affinin)

Spilanthol (affinin), a plant bioactive, is an N-alkylamide classified as (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide, first isolated from Heliopsis longipes. It is the principal and most studied bioactive compound in the plant. In general, spilanthol is an N-isobutylamide; from a chemical standpoint, it has been found to be pungent in flavor and has capabilities to stimulate salivation. (2E, 6Z, 8E)-N-isobutylamide-2,6,8-decatrienamide is the molecular formula determined for spilanthol. Spilanthol possesses a powerful bitter savor and is expected to produce general local astringency and anesthetic effects.

The principal pungent and bioactive N-isobutylamide compound, spilanthol, is known to modulate chemosensory receptors and ligands associated with these receptors. Affinin or spilanthol is an alkamide mainly derived from plants of the Asteraceae family; the most important affinin-producing plants belong to the genera Acmella (Spilanthes), Heliopsis, and Wedelia, particularly A. oleracea and H. longipes.

Acmellonate

The main constituents, "spilanthol" and "acmellonate", are sometimes used to reduce the pain associated with toothaches and can induce saliva secretion. Acmellonate is a long-chain unsaturated 2-ketol ester isolated from the plant, chemically distinct from the alkylamide spilanthol.

Other Alkylamides

Other N-isobutylamides, such as undeca-2E,7Z,9E-trienoic acid isobutylamide and undeca-2E-en-8,10-diynoic acid isobutylamide, as well as 2E-N-(2-methylbutyl)-2-undecene-8,10-diynamide; 2E,7Z-N-isobutyl-2,7-tridecadiene-10,12-diynamide; and 7Z-N-isobutyl-7-tridecene-10,12-diynamide from S. acmella, have been reported.

Phenolic Compounds, Flavonoids, and Other Constituents

These bioactivities were attributed to bioactive compounds such as phenolics, flavonoids, and alkamides. The phytochemical composition of S. acmella includes components such as triterpenoids, α- and β-amyrin esters, and alkaloids, particularly rich in N-isobutylamides and alkylamides. It also contains stigmasterol and myricyl alcohol; spilanthol, the main constituent, is involved in various biological activities such as antimicrobial, immunomodulatory, antioxidant, anti-inflammatory, hepatoprotective, diuretic, antinociceptive, and insecticidal actions. The leaves additionally contain vitamins A, C, and K, lutein, and magnesium.

4. Mechanisms of Action

Analgesia / Antinociception: TRP Channel Modulation

The potential mechanism of action of Spilanthes acmella as a topical anaesthetic may be related to conduction obstruction in nerve fibres. The antinociceptive properties of S. acmella have been investigated; the suggested mechanism of action involves enhanced gamma-aminobutyric acid (GABA) release and modification or blockage of transient receptor potential channels subfamily V member 1 (TRPV1) and subfamily A member 1 (TRPA1).

In an acute pain mouse model, Acmella oleracea has been reported to have antiallodynic and anti-oedematogenic activities due to alkylamides, and in particular spilanthol. The molecular mechanism has been described for spilanthol, demonstrated to act as a modulator of TRPA1 receptors and as a TRPV1 antagonist, thus promoting analgesic effects.

Vasodilation: Cannabinoid and TRP Receptors

Affinin (spilanthol) displays a great variety of biological activities, including antinociceptive effects associated with activation of the NO/cGMP pathway and TRPV1 channels. Research has demonstrated that this alkamide induces a vasodilatory effect, which was partly dependent on the presence of endothelium. Evidence indicates that spilanthol activates vascular endothelial cannabinoid receptors (CB1 and eCB), as well as endothelial TRPA1 and TRPV1 channels.

Anti-Inflammatory: NF-κB / COX-2 / iNOS Pathways

Hexane and chloroform extracts of Spilanthes acmella were found to suppress nitric oxide production in stimulated macrophages at 80 µg/mL by 72% and 85%, respectively. Isolated spilanthol demonstrated dose-dependent prevention of macrophage activation with 60% and 20% production of nitric oxide at 90 and 360 µM concentrations, respectively. These inhibitory properties were accompanied by less nitric oxide synthetase and cyclooxygenase-2 (COX-2) mRNA and protein content, less cytokine production from macrophages, and less NF-κB activation in the nucleus.

The molecular mechanism of S. acmella in reducing oxidative stress and inflammatory targets such as inducible nitric oxide synthase (iNOS), transcription factors of the nuclear factor-κB family (NF-κB), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) signalling pathways has been discussed in the literature.

Antipyretic: Flavonoid-Mediated COX/LOX Inhibition

The antipyretic activity of Spilanthes acmella demonstrated in experimental study is attributed to the presence of flavonoids, which are predominant inhibitors of either cyclo-oxygenase or lipo-oxygenase.

Cosmetic/Anti-Wrinkle: Neuromuscular (Botox-Like) Action

The potential benefits in anti-wrinkle applications are linked to the plant's main active molecule, the N-alkylamide spilanthol. The potential mechanism of action of A. oleracea extracts is not fully elucidated, but it has been proposed that spilanthol may be a rapid-acting topical muscle relaxant that can "rapidly and progressively inhibit the repeated contractions of facial expression muscles (botox-like action), thus achieving claimed instantaneous effect on facial expression lines and wrinkles." When applied locally or subcutaneously in formulations, spilanthol works by blocking the release of acetylcholine, the neurotransmitter responsible for causing muscular contractions. By inhibiting its release, spilanthol temporarily reduces muscle activity, leading to smoother-looking skin with diminished wrinkles and fine lines.

Immunomodulation

Alkylamides have been shown to possess varied biological activities; they act on cannabinoid type 2 receptor-dependent and -independent pathways and have also been found to possess useful immunomodulatory effects. Studies have demonstrated that the anti-inflammatory effects of spilanthol on lipopolysaccharide-activated murine macrophage model RAW 264.7 suggested that spilanthol can inhibit pro-inflammatory mediator production at the transcriptional and translational levels.

5. Scientific Evidence by Area of Use

5.1 Oral Health, Local Anaesthesia, and Toothache

Evidence strength: Preclinical strong; limited human clinical data available.

Animal model studies provide a strong preclinical basis for local anaesthetic activity. An aqueous extract of S. acmella Murr. was tested for local anaesthetic action by intracutaneous wheal in guinea pigs and by plexus anaesthesia in frogs, using 2% xylocaine as the standard drug. The test drug at concentrations of 10% and 20% produced 70.36% and 87.02% anaesthesia respectively by the intracutaneous wheal, compared to 97.22% anaesthetic effect produced by 2% xylocaine (p < 0.001). The mean onset of anaesthesia with the test drug was 5.33±0.57 min compared to 2.75±0.31 min (p < 0.001) for the standard drug in the plexus anaesthesia model.

At the clinical level, the efficacy of A. oleracea as a topical anaesthetic gel was found safe and effective in a study on buccal mucosa. An S. acmella mucoadhesive film was shown to be effective, and an S. acmella Murr gel was found to be a good intraoral topical anaesthetic in a comparative trial with 2% lignocaine gel in children. These findings are reported from small-scale clinical evaluations; large, well-powered randomized controlled trials are lacking.

5.2 Anti-Inflammatory and Analgesic Effects

Evidence strength: Preclinical (in vitro and animal); no large human RCTs.

The anti-inflammatory activity of Spilanthes acmella has been evaluated using carrageenan-induced hindpaw oedema in animals; carrageenan is a standard phlogistic agent. The extract was found to produce considerable dose-dependent inhibition of paw oedema, which was less than the standard drug. Researchers also demonstrated the analgesic activity of S. acmella using acetic acid-induced abdominal constriction and the tail-flick method. The former procedure evaluates peripherally acting analgesics, while the latter indicates the involvement of the central nervous system.

One pilot study explored the adjuvant use of Acmella oleracea in a combination preparation for chronic pain. In this pilot study, 48 medical cannabis-treated subjects were supplemented with a dietary supplement containing a combination of standardized Zingiber officinalis and Acmella oleracea extracts in phytosome (Mitidol), coenzyme Q10 phytosome (Ubiqsome), and group B vitamins (B1, B6, and B12), twice daily for 90 days. Pain intensity was measured by the visual analogue scale (VAS), pain type evaluated by the Italian Pain Questionnaire (QUID), and possible reduction of therapeutic and/or painkiller doses were recorded. This study, however, used a combination product; the independent contribution of Spilanthes cannot be isolated from these results.

5.3 Musculoskeletal Disorders (Arthritis, Osteoporosis, Muscle Injury)

Evidence strength: Preliminary; largely preclinical with a small body of clinical evidence.

Plants in the genus Acmella, including Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella oleracea, contain various bioactive compounds that have demonstrated anti-inflammatory, analgesic, and anti-arthritic properties. A 2025 systematic review evaluated the clinical and preclinical evidence supporting the use of plants from the Acmella genus for the treatment of musculoskeletal disorders such as arthritis, osteoporosis, muscle injuries, and joint inflammation. The extracts from these plants were shown to decrease inflammation, enhance joint health, relieve pain, and stimulate osteogenic activity; these effects may be attributed to several active compounds found in these plants. Available evidence suggests that Spilanthes acmella and Blainvillea acmella have the potential to treat osteoporosis; Acmella oleracea and Acmella uliginosa have potential for treatment of osteoarthritis, while Spilanthes acmella is used to treat myopathies. Further research is needed to establish the efficacy, optimal dosing, and safety of these plants.

5.4 Aphrodisiac / Sexual Function

Evidence strength: Preliminary; one human population study and some small clinical evidence, with significant methodological limitations.

A potential natural alternative for sexual dysfunction is the plant Acmella oleracea, which has long been used in traditional medicine as a potent sexual stimulant. With respect to the chemical composition and pharmacological properties, spilanthol, the main phytochemical compound, has been demonstrated to be a potential alternative that can be used to enhance sexual activity.

In a previous clinical trial, topical application of an A. oleracea-based product to the male genitalia was demonstrated to result in an improvement in sexual response, with the authors' speculating that the observed increases in patients' sexual desire and satisfaction were probably associated with the tingling sensation experienced following application of the cream to the glans.

A longitudinal population-based study was carried out to determine the extent of increase or decrease in muscle mass and sexual frequency over a period of 3 weeks and 2 months in 240 males consuming SA3X capsules (500 mg of Spilanthes acmella extract, standardized to 3.5% spilanthol). The results reflected Spilanthes acmella to be a potent muscle gainer and aphrodisiac. This study lacks a control arm and should be interpreted with caution. S. acmella ethanolic flower extract increased levels of testosterone, follicle-stimulating hormone, and luteinizing hormone in animal studies.

5.5 Antimalarial Activity

Evidence strength: Moderate preclinical (in vitro and in vivo animal); no human clinical trials.

The isolated alkylamides, spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC50s of 16.5 µg/mL and 41.4 µg/mL on Plasmodium falciparum strain PFB, and IC50s of 5.8 µg/mL and 16.3 µg/mL for the chloroquine-resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced parasitaemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitaemia) at 50 mg/kg. No human clinical trials for malaria have been identified.

5.6 Antifungal and Antimicrobial Activity

Evidence strength: In vitro only; results are mixed across species and extraction methods.

In vivo studies showed that spilanthol did not have any antimicrobial activity, whereas the Spilanthes extract showed antimicrobial activity, indicating that other metabolites should be examined for this activity. The aqueous, ethanol, and hexane extracts of S. americana and the methanol extracts of S. calva did not show activity against C. albicans, and the chloroform, methanol, and water extracts of S. acmella whole plants did not show significant activity against Entamoeba histolytica at 1,000 µg/mL. Hexane and chloroform extracts of S. acmella completely inhibited the growth of S. cerevisiae with a MIC of 256 µg/mL. Petroleum ether extracts of S. acmella flower heads showed good inhibition zones against Fusarium oxysporum, F. moniliforme, Aspergillus niger, and Aspergillus parasiticus. Overall, antimicrobial and antifungal effects are extract-type and species-specific, and clinical human data are absent.

5.7 Antioxidant Activity

Evidence strength: In vitro; no clinical human trials.

The antioxidant potential of S. acmella has been measured by total phenolic content (TPC), total flavonoid content (TFC), DPPH, and superoxide anion radical scavenging (SOD) and thiobarbituric acid reactive substance (TBARS) assays. This review revealed that S. acmella might have a potential role as a reservoir of bioactive agents contributing to observed antioxidant, anti-inflammatory, and health beneficial effects.

5.8 Antipyretic Activity

Evidence strength: Animal models only.

The antipyretic activity was determined by yeast-induced pyrexia in rats, with aspirin 300 mg/kg used as the standard drug. Dose-dependent temperature reduction was observed; the extract was active but less potent than aspirin at the doses tested. No human fever-reduction trials have been reported.

5.9 Cosmetic / Anti-Wrinkle Applications

Evidence strength: In vitro muscle-fibre data (supporting mechanism); limited small human/cosmetic studies.

In the context of research, it was observed that spilanthol, notably in the form of an Acmella oleracea extract, was able to effectively inhibit contractile activity in subcutaneous face muscles. This observation formed the basis of a patent filed by the cosmetics company Gattefossé (European Patent EP1722864 / US Patent 7,531,193), claiming a botulinum toxin-like effect.

In commercial applications, S. acmella flower extract has been added to products such as Gatuline (from Gattefossé) and Antiwrinkle Firming Light Cream (from Laboratories SVR) for its anti-aging properties. In an analysis featured in the Journal of Cosmetic Dermatology, researchers conducted a double-blind, randomized, placebo-controlled trial, finding that a topical product containing Acmella extract notably enhanced the look of facial wrinkles and fine lines within a four-week period. Another study published in the Journal of Ethnopharmacology demonstrated that a cream containing Acmella extract was effective in reducing the depth of forehead wrinkles and improving overall skin texture.

5.10 Insecticidal Activity

Evidence strength: In vitro / laboratory; no clinical relevance for human supplementation.

Laboratory studies have shown spilanthol to have insecticidal activity against mosquitoes, the Egyptian cotton worm, and various ticks. The plant's active compound, spilanthol, shows potent insecticidal properties against mosquito species at low concentrations.

6. Body Systems and Health Areas of Association

Based on the peer-reviewed literature, Spilanthes has been associated with the following body systems:

Oral and Dental Health: Local anaesthesia, toothache relief, gum infections, stomatitis, mouth ulcers, sialagogue effects.
Immune System: Immunomodulatory effects via cannabinoid receptor and alkylamide pathways; macrophage regulation.
Musculoskeletal System: Anti-inflammatory and analgesic activity; preliminary evidence for arthritis, osteoporosis, and myopathies.
Cardiovascular/Vascular System: Vasorelaxant activity via endothelial NO and prostacyclin pathways; flower parts have shown vasorelaxation activity.
Reproductive/Endocrine System: Aphrodisiac/sexual stimulant use; androgenic effects noted in animal studies.
Integumentary System (Skin): Cosmetic anti-wrinkle and anti-aging applications; antimicrobial topical uses.
Urinary System: Diuretic effects observed in animal models.
Gastrointestinal System: Traditional use as stomachic, antidiarrhoeal, and digestive stimulant.
Neuromuscular System: Facial muscle relaxation for cosmetic use; GABA-modulating activity linked to anticonvulsant effects in preclinical models.

A comprehensive 2024 pharmacological review found that A. oleracea contains a variety of phytochemicals, including spilanthol, which exhibit diverse pharmacological activities such as antioxidant, anti-inflammatory, immunomodulatory, antinociceptive, pronociceptive, antibacterial, antifungal, antidiabetic, diuretic, and vasorelaxant effects.

7. Dosage Forms and Reported Doses

No official pharmacopeial monograph establishing a standardized human dose for Spilanthes as a dietary supplement has been identified in available literature. The following doses are reported from studies or clinical preparations, as stated in the cited sources:

Standardized extract capsules (oral, human population study): SA3X capsules contain 500 mg of Spilanthes acmella extract standardized to 3.5% spilanthol, delivering 17.5 mg spilanthol. This was used in a longitudinal study of 240 males over 3 weeks to 2 months.
Spilanthol (isolated compound, animal antimalarial): In a murine malaria model, spilanthol was given at 2.5 mg/kg twice daily; water extract at 25 mg/kg; ethanol extract at 25 mg/kg, for four days.
Aqueous extract (animal local anaesthetic / antipyretic): The test drug in concentrations of 10% and 20% produced 70.36% and 87.02% anaesthesia in guinea pigs, respectively.
Adjuvant clinical supplement (combination product): In a pilot human study, 48 subjects received a combination supplement containing standardized Zingiber officinalis and Acmella oleracea extracts in phytosome, twice daily for 90 days. Specific Spilanthes dose within this product was not isolated in the source.
Anti-inflammatory macrophage studies (in vitro): Hexane and chloroform extracts suppressed nitric oxide production at 80 µg/mL; isolated spilanthol demonstrated dose-dependent effects at 90 and 360 µM concentrations.

No standardized, validated clinical dosing guidelines for Spilanthes as a dietary supplement have been established in the peer-reviewed literature. The doses above are for reference as described in their specific research contexts only.

8. Safety Considerations and Drug Interactions

No formal clinical human trials on the toxicology of Acmella have been completed, but it is generally considered safe. Reviews highlight the significant medicinal potential of A. oleracea while also identifying areas for further research, particularly regarding its toxicological impacts on humans and animals.

Reproductive and Developmental Toxicity

In vivo studies suggest potential teratogenic effects with high doses of a hydroethanolic extract of A. oleracea. A zebrafish study provides specific context: teratogenic effects were observed in offspring embryos, including tail deformation, cardiac and yolk oedema, scoliosis, and growth retardation, most prominent in groups born from progenitors exposed to the highest concentrations (100 and 200 µg/L); but only the occurrence of yolk and cardiac oedema had a statistically significant difference compared to the control group. Overall, the data showed that treatment caused no detrimental changes in progenitors regarding their gonads or fertility but caused some potentially teratogenic activity in embryos, which may be due to the action of spilanthol's metabolites.

CYP Enzyme Inhibition

In vitro studies suggest spilanthol significantly inhibits CYP2E1. Clinical relevance has yet to be determined, although drugs in this class include those used in general anaesthesia such as isoflurane and sevoflurane.

Diuretic Drug Interaction

In animal studies, S. acmella has loop diuretic activity and may have additive effects with other diuretic drugs. Care should be exercised if using diuretics, as Acmella can have a diuretic effect.

Androgenic / Hormonal Effects

S. acmella ethanolic flower extract increased levels of testosterone, follicle-stimulating hormone, and luteinizing hormone in animal studies. In animal studies, S. acmella may increase testosterone levels; this is potentially relevant for those taking antiandrogen drugs such as bicalutamide, flutamide, or abiraterone.

Allergenicity

Contact allergy risk exists for individuals who are allergic to members of the Asteraceae family. A case of painful lip swelling was reported in a 42-year-old man who presented to the emergency department; the suspected cause was an appetizer of "Szechuan buttons" ingested several days earlier, in the absence of any other explanation.

Acute Toxicity Data (Preclinical)

Preclinical acute toxicity data for the closely related alkamide affinin (spilanthol) showed an LD50 of 1,442.2 mg/kg (oral, mice), compared to hexahydroaffinin (LD50 ≥ 5,000 mg/kg, oral) and capsaicin (LD50 = 489.9 mg/kg, oral). These are animal toxicology data and do not directly translate to human safety thresholds.

Summary of Known Interactions

CYP2E1 substrates (e.g., isoflurane, sevoflurane): Potential inhibition in vitro; clinical significance unestablished.
Diuretic drugs: Potential additive loop-diuretic effect.
Antiandrogen drugs (bicalutamide, flutamide, abiraterone): Animal data suggest possible testosterone elevation.
Asteraceae allergy: Potential for cross-reactivity.
Pregnancy: Possible teratogenic signals at high doses in animal/zebrafish models; human data absent.

References

Health Conditions

Health conditions that Spilanthes may help support.

No conditions available.

Body Systems

Body systems that Spilanthes may help support.

No body systems available.