Argireline is the trade name of acetyl hexapeptide-8, a six-amino-acid peptide sold as a topical alternative to botulinum toxin. It is in 452 leave-on and rinse-off cosmetic products by the last industry count, and in one of the cheapest serums on the market. This page reads the human studies as they were published, the one skin-penetration study run by FDA, and the safety review the cosmetics industry commissioned, and then puts the number on the bottle next to the numbers in the papers.
What it is and what it is designed to do
The peptide's sequence is Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2. Its designers, at the Universitas Miguel Hernández in Alicante, built it to mimic the N-terminal end of SNAP-25, one of the three proteins that form the SNARE complex a nerve ending needs to release neurotransmitter. Botulinum toxin A cuts SNAP-25; the peptide is meant to compete with it. In cell assays the original paper reports it "significantly inhibited neurotransmitter release with a potency similar to that of BoNT A, although as expected, it displayed much lower efficacy than the neurotoxin" (Blanes-Mira et al., International Journal of Cosmetic Science 2002). That is the whole mechanism claim: the same target as botulinum toxin, much weaker, and from the outside of the skin rather than inside the muscle.
The human studies
| Study | Design | People | Concentration and vehicle | Duration | Result as reported | Funding or affiliation |
|---|---|---|---|---|---|---|
| Blanes-Mira 2002, Int J Cosmet Sci | Open application, no control described in the abstract | "healthy women volunteers", number not given | 10% in an oil-in-water emulsion | 30 days | Skin topography: wrinkle depth reduced "up to 30%" | Universitas Miguel Hernández, Alicante; the paper introduces the peptide |
| Wang 2013, Am J Clin Dermatol | Randomized, placebo-controlled, 3 to 1 | 60 Chinese subjects | Argireline, concentration not in the abstract; twice daily to periorbital wrinkles | 4 weeks | Subjective global assessment: 48.9% efficacy vs 0% on placebo; silicone-replica roughness parameters all decreased (p < 0.01), none on placebo | Second Hospital of Xi'an Jiaotong University; no industry funder named |
| Raikou 2018, J Cosmet Dermatol | Randomized, four arms (peptide, tripeptide-10-citrulline, both, neither) | 24 volunteers | Acetyl hexapeptide-3 (an older name for the same peptide) | 60 days | Roughness parameters cR2 and cR3 and transepidermal water loss improved versus the no-peptide arm at 20 and 60 days | Technological Educational Institute of Athens |
| An 2022, Ann Dermatol | Double-blind, randomized, split-face; the peptide in a dissolving hyaluronic-acid microneedle patch, not a serum | 52 Korean women | Not stated | 29 days, weekly 4-hour application | Wrinkle and hydration improved in all groups; the peptide patch beat the plain patch (p < 0.05) | CHA University; a patch study, not a topical-serum study |
The 2013 trial is the one that carries the weight. It is randomized, placebo-controlled and measured with an instrument as well as by eye, and its authors reported it as safe and well tolerated. Its limits are the ones a reader should hold onto: 60 people, four weeks, one site, and a primary outcome that was a global assessment by graders. The 2002 paper is a proof of concept by the peptide's designers; the abstract does not say how many women took part or whether anyone used a vehicle without the peptide. A 2025 review of the ingredient (PMC12193160) also cites a 2015 study by Tadini and colleagues that found no significant change in elasticity or water content against placebo; we could not obtain that paper, so we report it as cited.
What is missing is as informative as what exists: no trial longer than 60 days, no dose-ranging study, no comparison with a retinoid, and no comparison with botulinum toxin, the product it is marketed against.
Does it get in? FDA's penetration study
The mechanism requires the peptide to reach nerve endings under the skin. In 2015, scientists at FDA's Center for Food Safety and Applied Nutrition applied a commercial oil-in-water emulsion containing 10% acetyl hexapeptide-8 to human cadaver skin and hairless guinea-pig skin in diffusion cells for 24 hours, then washed, tape-stripped and separated the layers. The result, as a percentage of the applied dose: most of the peptide was washed from the surface; 0.22% remained in the stratum corneum of human skin (0.54% in guinea pig), falling with each tape strip; 0.01% was found in the epidermis of both; none is reported in the receptor solution beneath (Kraeling et al., Cutaneous and Ocular Toxicology 2015).
The 2025 review notes that an earlier study had reported 30% of the peptide crossing the stratum corneum in two hours, and calls the results contradictory; it concludes that "achieving therapeutic concentrations" through the lipophilic stratum corneum "is challenging" and that penetration is insufficient to reach muscle, so that injection would be necessary for a neuromuscular effect. The trials above reported changes in wrinkle depth and roughness all the same. Either a small amount at the epidermis is enough for some effect, or the effect measured was something other than the mechanism claimed, such as hydration or film-forming. The papers do not settle which.
Safety: the 0.005% ceiling and the 10% bottle
The Cosmetic Ingredient Review is the industry-funded panel that assesses cosmetic ingredients in the United States. Its final report on acetyl hexapeptide-8 amide states: "the Panel ... concluded that Acetyl Hexapeptide-8 Amide is safe in the present practices of use in cosmetics at concentrations up to 0.005%. The Panel further concluded that the available data are insufficient to make a determination that Acetyl Hexapeptide-8 Amide is safe in cosmetic formulations at concentrations greater than 0.005%." The figure comes from a 2019 concentration-of-use survey by the Personal Care Products Council, which reported a maximum of 0.005% in leave-on eye lotions and face and neck products, and 0.000005% in rinse-off products; 2020 registration data listed the ingredient in 452 products. The report also says: "The Panel is aware of products with higher use concentrations, but whether these products are drugs or cosmetics remains unknown," and that use concentrations above 0.005% "are unsupported by the available safety test data." The reasoning for safety at 0.005% rests partly on a calculated log P of −6.3, meaning percutaneous absorption is unlikely (CIR report).
Now the bottle. The Ordinary's Argireline Solution 10% lists its ingredients as "Aqua (Water), Propanediol, Acetyl Hexapeptide-8, Trisodium Ethylenediamine Disuccinate, Gellan Gum, Sodium Chloride, Isoceteth-20, Dimethyl Isosorbide, Potassium Sorbate, Phenoxyethanol, Chlorphenesin", and sells for $9.70 per 30 mL (theordinary.com, 2026-09-05). Ten percent is 2,000 times the highest concentration the safety panel assessed and the concentration used in every human trial in the table. Two things are true at once: the trials at 10% reported no irritation or toxicity over 30 days to 60 days, and the body that assesses cosmetic-ingredient safety has said the data are insufficient above 0.005%. A buyer of a 10% product is relying on the short trials, not on a safety assessment.
The name on the label
"Acetyl hexapeptide-8" and "acetyl hexapeptide-3" are the same peptide; the INCI name changed, and older papers and some products use the older number. A product listing either is listing Argireline. "Argireline Amplified" and similar suffixes are supplier trade names for formulations of the same peptide; the ingredient list is the check.
What not to mix it with
The Ordinary's page lists direct acids, direct vitamin C, resveratrol and ferulic acid, salicylic acid and its multi-antioxidant serum as not to be combined with the product. No published study tests any of those pairings. Peptides in general are less stable at low pH, which would explain the acids and vitamin C; the list is a formulation rule from one brand and should be read as that.
Products that state the concentration
Few do. The Ordinary states 10% in the product name and lists the peptide third. Most other products list acetyl hexapeptide-8 somewhere in the ingredient order without a percentage, which, given the 0.005% survey maximum, usually means far less than 10%. We will add products here as we verify their disclosed concentrations from the manufacturer's own page; we do not rank them, because no product has been through our review standard.
What the evidence does not show
It does not show an effect past 60 days; it does not show a dose-response; it does not show equivalence to botulinum toxin, or to any retinoid, on any endpoint; and it does not show that the peptide reaches the muscle whose paralysis is the marketing premise. It does show, in one randomized trial and three smaller studies, measurable changes in skin roughness and graded wrinkle appearance over a month or two at 10%.
Sources and dates
Opened 2026-09-05: Blanes-Mira et al. 2002 (PubMed 18498523; the record carries a 2010 indexing date), Wang et al. 2013 (PubMed 23417317), Raikou et al. 2018 (PubMed 28150423), An et al. 2022 (PubMed 33911590), Kraeling et al. 2015 (PubMed 24754410), the 2025 review PMC12193160, the CIR final report on acetyl hexapeptide-8 amide, and The Ordinary's US product page. Corrections and additional trials go to the contact page; our review standard is on the testing notes page.