Supplement
Toothache plant is a flowering herb whose blooms contain spilanthol, a compound that numbs the mouth and calms irritated tissue. No main use stands out, but the best-supported human findings involve erectile function, where three trials of one branded extract found improved scores over one to three months, and testosterone rose in men with erectile dysfunction. The evidence is limited, since all the human work came from a single research group, and most of the wider research on pain and inflammation was in animals or cells.
Sources: PMID 35541293; PMID 36818267; PMID 35898380
- Updated
- How we grade
- 18 studies cited
- Best evidence
- Grade C
- Conditions studied
- 0
- Outcomes
- 7
- Graded outcomes
- 0043
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Local Anesthetic / Analgesic Effect Multiple animal studies demonstrate antinociceptive effects of spilanthol-rich extracts via Na+ channel blockade, opioidergic/serotoninergic/GABAergic activation, and TRPV1/CB receptor interaction. Local anesthetic activity confirmed in guinea pig and frog models. One observational cohort (103 patients) showed ~37% pain score reduction for chronic low back pain, though this used a combination product with Boswellia serrata. | Improves (the measure goes down) | Moderate effect | 6 studies | 103 people | ||
Studies that measured local anesthetic / analgesic effect
| ||||||
| Erectile Function Three human trials (RCTs and longitudinal) using SA3X (500 mg S. acmella extract) reported improved erectile function scores over 1-3 months in men with ED. An animal study in male rats showed dose-dependent increases in mounting and intromission frequency. All human trials are from a single research group using a branded extract, requiring independent replication. | Improves (the measure goes up) | Moderate effect | 5 studies | 350 people | ||
Studies that measured erectile function
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| Anti-inflammatory Activity In vitro, spilanthol dose-dependently suppressed iNOS, COX-2, IL-1β, IL-6, and TNF-α in macrophages via NF-κB inactivation. In rodent models, topical spilanthol reduced allergic inflammation in atopic dermatitis (reducing IgE, blocking MAPK pathways) and attenuated 5-FU-induced intestinal mucositis. Anti-inflammatory effects also demonstrated in a pancreatitis model. | Improves (the measure goes down) | Moderate effect | 5 studies | |||
Studies that measured anti-inflammatory activity
| ||||||
| Testosterone Levels In a double-blind RCT, SA3X supplementation increased serum testosterone by ~22 ng/dL over 3 months in men with ED. A longitudinal study of 326 men confirmed a significant increase from 309.84 to 332.27 ng/dL by month 3 (p<0.01). An animal study showed dose-dependent testosterone increases in male rats. All human data from a single research group. | Improves (the measure goes up) | Small effect | 4 studies | 350 people | ||
Studies that measured testosterone levels
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| Diuretic Effect In rats, Spilanthes acmella flower extract produced significant diuretic activity. A mechanistic study showed spilanthol reduces NKCC2 phosphorylation and AQP2 membrane expression in mouse kidney tissue by lowering cAMP via increased cytosolic Ca²⁺, producing furosemide-like natriuretic and kaliuretic responses. No human data available. | Improves (the measure goes up) | Small effect | 2 studies | |||
| Ejaculatory Latency A pilot clinical study found that a topical nano-formulation spray containing Acmella oleracea extract, applied 5 minutes before intercourse for 12 weeks, increased intravaginal ejaculatory latency time from 193 to 293 seconds in men with premature ejaculation, with good tolerability and no systemic side effects. | Improves (the measure goes up) | Moderate effect | 1 study | 30 people | ||
| Oral Health (Periodontal) A small RCT of 30 patients with chronic generalized periodontitis found that local drug delivery of Acmella oleracea gel as adjunct to scaling and root planing showed clinical and microbiological improvements, though the formulation also included Acacia catechu. | Improves (the measure goes up) | Small effect | 30 people | |||
Key findings
- Local Anesthetic / Analgesic EffectImproves (the measure goes down)
- Erectile FunctionImproves (the measure goes up)
- Anti-inflammatory ActivityImproves (the measure goes down)
Safety notes in the studies
- Multiple animal studies demonstrate antinociceptive effects of spilanthol-rich extracts via Na+ channel blockade, opioidergic/serotoninergic/GABAergic activation, and TRPV1/CB receptor interaction.
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- Grade C
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Studies cited
18 studies from PubMed
- Efficacy and Safety of Acmella oleracea and Boswellia serrata Extract as Add-On Therapy for Chronic Low Back Pain: An Observational, Real-World Cohort Study
- Clinical Safety of a Pharmaceutical Formulation Containing an Extract of Acmella oleracea (L.) in Patients With Premature Ejaculation: A Pilot Study
- Alkylamides from Acmella oleracea: antinociceptive effect and molecular docking with cannabinoid and TRPV1 receptors
- Randomized, Triple-Blinded, Placebo-Controlled Trial of SA3X (Spilanthes acmella) for the Management of Erectile Dysfunction
- Effect of SA3X (Spilanthes acmella) Supplementation on Serum Testosterone Levels in Males with Erectile Dysfunction -- A Parallel Double-Blind Randomized Controlled Trial
- Evaluation of Serum Testosterone Levels Following Three Months of SA3X (Spilanthes acmella) Supplementation
- Local effects of natural alkylamides from Acmella oleracea and synthetic isobutylalkyl amide on neuropathic and postoperative pain models in mice
- Pharmacological potential of alkylamides from Acmella oleracea flowers and synthetic isobutylalkyl amide to treat inflammatory pain
- Topical Spilanthol Inhibits MAPK Signaling and Ameliorates Allergic Inflammation in DNCB-Induced Atopic Dermatitis in Mice
- Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
- Spilanthol, the Principal Alkylamide from Acmella oleracea, Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice
- Action of the hydroethanolic extract of the flowers of Acmella oleracea (L.) R.K. Jansen on the reproductive performance of Wistar females rats: A popular female aphrodisiac from the Amazon
- Spilanthol from Acmella Oleracea Lowers the Intracellular Levels of cAMP Impairing NKCC2 Phosphorylation and Water Channel AQP2 Membrane Expression in Mouse Kidney
- Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice
- Spilanthes acmella ethanolic flower extract: LC-MS alkylamide profiling and its effects on sexual behavior in male rats
- Preliminary studies on local anesthetic and antipyretic activities of Spilanthes acmella Murr. in experimental animal models
- Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators
- Diuretic activity of Spilanthes acmella flowers in rats