Acetyl hexapeptide-8

A synthetic six-amino-acid peptide, listed on ingredient labels as Acetyl Hexapeptide-8 and also sold under the older name acetyl hexapeptide-3 and the trade name Argireline. It is often marketed by comparing it to Botox.

Sold as

Applied to the skin (gel, cream, serum)

Legal status in the EU

A cosmetic ingredient under EU Regulation 1223/2009, which involves no check that it works before sale. Under article 20 and the annex to Regulation 655/2013, claims have to be backed by "adequate and verifiable evidence". Claiming that a product relaxes muscles or replaces an injectable treatment can push it into the legal definition of a medicine in Directive 2001/83/EC, which covers substances intended to restore, correct or modify how the body works.

The sequence matches amino acids 12–17 (EEMQRR) at one end of a protein called SNAP-25, which you can read directly in the UniProt entry P60880. The idea is that the peptide competes with SNAP-25 for its place in the machinery nerve cells use to release their signal, and so dampens that signal. Any effect wears off, and it depends on the peptide reaching the nerve endings inside the muscle — which is exactly the weak point when you rub something on the skin.

Part of the bodyWhat happensHow it is knownKind of evidence

The skin's surface, and the lines you can see

This is the only thing anyone has measured in living people, and the measurements do not agree with each other. The first published human test found the crow's-foot lines around the eye became shallower over a month. Two later trials found less. One, using a camera system, found no difference between the treated side of a face and the untreated side. The other, using a suction probe, found no change in the skin's springiness, though a different measure of how the skin stretches did shift on the face. Nothing in any of these trials measured a muscle.

Measured in people, in four small short studies that point in different directions. 10 women over 30 days, with a silicone mould taken from the skin beside the eye: 30% shallower wrinkles, against 10% for the same cream without the peptide. 60 people in China over 4 weeks: a combined anti-wrinkle score of 48.9% in the peptide group. 19 women over 4 weeks, with the peptide on one side of the face and the identical serum without it on the other. No significant difference, p = 0.83 between the sides. 40 women aged 35 to 55 over 4 weeks: no change in skin springiness.

Studies in people disagree

Source [02]Source [09]Source [10]Source [11]

The eyelid muscle, in people whose eyelids clamp shut

This is the one place a muscle effect has been looked for in people. Blepharospasm is a condition in which the muscles around the eye squeeze shut without warning. It is treated with botulinum toxin injections every three months. A cream was rubbed on the eyelids on top of those injections to see whether it made the injections last longer. The people on the peptide took a little longer to go back to how they were, but the difference was called a trend rather than a result.

Measured in 24 adults with blepharospasm, 23 of them analysed. They applied a 0.005% cream to the eyelids twice a day for about 7 months, alongside their usual injections. It took 3.7 months to return to baseline on the peptide, against 3.0 months on a cream with no peptide. Four of the twelve on the peptide went 3.3 to 7.1 months. A later trial run by the US National Institute of Neurological Disorders and Stroke was terminated with 8 people enrolled. At 2 months its eyelid-spasm scores were worse on the peptide than on the dummy cream: 6 on the stronger cream and 7 on the weaker one, against 4.33. A higher score means worse.

One small study

Source [12]Source [13]

How fast water escapes through the skin

Skin constantly loses a little water to the air. How fast it does that is a standard way of asking whether the outer barrier is in good condition. In one small trial that rate differed between the group using the peptide on its own and the group using no peptide at all. The authors concluded the peptide lowered it. This is an effect on the outer skin, not on a muscle.

Measured in 24 healthy volunteers randomised to four groups for 60 days: the peptide alone, a second peptide alone, both together, or neither. Water loss through the skin differed significantly between the peptide-alone group and the no-peptide group at 20 days (p = 0.025) and again at 40 days. A measure of the skin's surface texture also differed between those same two groups at 20 days. At 60 days the significant differences were between other pairs of groups, not between peptide alone and no peptide.

One small study

Source [09]Source [14]

Oil on the skin, and the look of scars

One Italian clinic looked back at its own patients who had used a 10% gel-cream on scars and other marks. It reported the treated spot became more elastic and produced less oil than the skin around it. That is the only comparison there was, so nothing here says what would have happened without the gel. A randomised trial of the oil question was run at the University of California, Davis, and its results have never been posted.

Reported in 26 patients in Modena, Italy, looked at after the fact with no control group. The published abstract gives no numbers at all. The 2025 review adds one: enlarged openings of the skin's oil glands were smaller by up to 85%. The University of California, Davis trial put a 10% lotion on one half of 14 people's faces and a plain moisturiser on the other. It ran 4 weeks, finished in February 2016, and has posted no results.

One small study

Source [01]Source [15]Source [16]

The dead outer layer of the skin, and how far the peptide gets past it

Almost all of it stays on top. When a 10% emulsion was left on human skin in a laboratory for a day, most was simply washed off the surface. A tiny fraction stayed in the dead outer layer and a tinier fraction reached the living layer under it. None at all was found deeper down, or in the fluid beneath the skin. A different experiment, using only the isolated dead outer layer rather than whole skin, found much more got through. That is the disagreement at the centre of this compound.

Measured on skin in a laboratory, never in a living person. On human cadaver skin over 24 hours: 0.22% of the applied amount in the dead outer layer, and 0.01% in the living layer below. Nothing in the deeper layer or the fluid underneath. On isolated dead outer layer from surgery donors: 30% of a 0.05% water solution reached the collecting chamber within 2 hours. Nobody has ever measured what happens to the peptide inside a living body — no absorption, distribution or breakdown data exist in any species.

Only seen in a dish, not in a body

Source [01]Source [09]

The muscles that pull your face into an expression

This is the target the whole idea depends on, and no study in a person has ever shown the peptide reaching it or acting on it. In a test tube the peptide stops three proteins snapping together into the structure a nerve uses to dump its chemical signal onto a muscle. In dishes of hormone-releasing cells it cut that dumping by about a third. In laboratory muscle-contraction tests it cut contraction by about a quarter. All of that needed amounts far above anything a cream has been shown to deliver.

Seen only in test tubes, dishes of cells and laboratory models. The docking structure was blocked at 1 and 2 millimoles per litre, and was gone completely at 2. Adrenal cells released 30% less of their hormone at 100 micromoles per litre. In muscle-contraction tests — cells grown together in a dish, and a millimetre-long worm used as a laboratory model — 100 parts per million cut contraction by 26%. The 2025 review states plainly that none of the human application studies confirmed any effect on muscle contraction.

Only seen in a dish, not in a body

Source [01]Source [09]

The evidence is small, short studies, pulled together in a 2025 review in Int J Mol Sci (26:5722). Wang and colleagues (2013) ran a multi-centre study in 60 Chinese participants over four weeks and reported a 48.9% overall anti-wrinkle effect — a composite score, not a measurement of wrinkle depth. Tadini and colleagues (2015) found no significant change in skin elasticity after four weeks, and Raikou and colleagues (2017) found only a marginal reduction in skin roughness after 20 days. An independent randomised triple-blind study at Mahidol University (NCT01381484, 70 participants, 10% gel, three months) finished in September 2009, but its results were never posted.

The trials that measured anything measured it fast and stopped early. The 2002 study took moulds of the skin at 15 and 30 days, and reported wrinkle depth down 20% by day 15 and 30% by day 30. Water loss through the skin differed from the no-peptide group at 20 days and again at 40 days. Most wrinkle trials ran 4 weeks. The longest topical trial of any kind ran about 7 months, on eyelids, as an add-on to botulinum toxin injections. Nothing has been measured beyond that, and no study has followed anyone after stopping.

What was measuredWhat happenedIn whomHow it is known

Depth of the lines beside the eye

30% shallower with the peptide, against 10% shallower with the identical cream that had no peptide in it, measured from a silicone mould of the skin. The 10% was not flagged as statistically significant, and the report states the cream without the peptide caused no significant change in skin topography.

10 healthy women, cream applied twice a day for 30 days, one side of the face against the other, moulds taken at 0, 15 and 30 days.

One small study

Source [09]

A combined anti-wrinkle score

48.9% in the peptide group. This is a pooled score, not a measurement of wrinkle depth. The published abstract gives no matching figure for the dummy cream, so there is no comparison number to set beside it. Wrinkle depth was separately reported as reduced (p < 0.01), again without a number.

60 people in China, randomised 3 to 1 to peptide or dummy cream, applied twice a day for 4 weeks.

One small study

Source [02]

Wrinkle score from a photographic camera system

No significant change on either side of the face, and no significant difference between the peptide side and the plain side (p = 0.83). A skin-age score from the same camera also did not move (p = 0.80 between sides).

19 women recruited at a plastic surgery clinic. The same hyaluronic-acid serum went on both sides of the face, with the peptide added on one side only, twice a day for 4 weeks.

One small study

Source [10]

Springiness of the skin, measured with a suction probe

Unchanged after 4 weeks, on both the face and the forearm, with and without the peptide. A separate measure of how evenly the skin stretches in different directions did improve on the face with the peptide. Water held in the outer layer rose on the face with both creams, including the one without the peptide.

40 healthy women aged 35 to 55, twice a day on the face and the forearm for 4 weeks, measured at 2 and 4 weeks. The formulation held 10% of an Argireline solution, and that solution held 0.05% acetyl hexapeptide-3; the paper does not state the final strength in the product.

One small study

Source [11]

Water escaping through the skin

Significantly different between the group using the peptide alone and the group using no peptide at all. That held at 20 days (p = 0.025) and again at 40 days. The authors concluded the peptide lowered it. A measure of the skin's surface texture also differed between those same two groups at 20 days. At 60 days the significant differences were between other pairs of groups.

24 healthy volunteers randomised to four groups for 60 days: the peptide alone, a second peptide alone, both together, or neither.

One small study

Source [09]Source [14]

How long an eyelid-spasm treatment kept working

3.7 months to return to the starting score with the peptide cream, against 3.0 months with a cream with no peptide. The authors called this a trend, not a difference. Four of the twelve people on the peptide went between 3.3 and 7.1 months.

24 adults with blepharospasm already receiving botulinum toxin injections every 3 months (23 analysed), cream applied to the eyelids twice a day for about 7 months.

One small study

Source [12]

Eyelid-spasm score at 2 months, in the trial that was stopped early

6 on the stronger cream and 7 on the weaker one, against 4.33 on the dummy cream, where a higher score is worse. Two people in each peptide group and three on the dummy were measured, so these numbers carry almost no weight. They are recorded here because the trial was stopped and the result was posted anyway.

8 adults with blepharospasm in a US government trial that ran from November 2012 and was terminated in May 2015.

One small study

Source [13]

The size of enlarged openings of the skin's oil glands, at a treated spot

Reported smaller by up to 85%, alongside more elastic skin and less oil at the treated spot than in the skin around it. The published report gives no numbers of its own; the 85% appears in a later review. The only comparison was the surrounding skin — there was no control group and no randomisation, so this describes what one clinic saw.

26 patients in Modena, Italy, with surgical scars, skin tags, wrinkles and other marks, reviewed after the fact.

One small study

Source [01]Source [15]

Putting it on the skin is generally well tolerated, and no serious side effects were reported in the studies reviewed. How much actually gets in is disputed: the 2025 review cites one experiment where around 30% crossed the membrane and another where only 0.22% got past the outer layer of skin, which makes claims about its effect hard to judge. Injecting it is not cosmetic use — the same review describes cases of Mycobacterium abscessus infection after injection into the skin.

EffectWhat it feels likeHow often

A deep skin infection after it was injected rather than rubbed onSerious

A 45-year-old woman had the peptide injected into her forehead and temples. A week later the injection sites broke out in lesions. The pus grew Mycobacterium abscessus, a stubborn germ from the same family as the one that causes tuberculosis. It is hard to treat and easily mistaken for an ordinary skin infection. She needed two antibiotics together for five months. The lesions settled but left scars and darkened patches. Injecting this peptide is not what the cosmetic ingredient is for.

Not measured. One case has been published, and the authors say it was the first of its kind reported anywhere.

Source [17]

A serious event recorded in the eyelid trial that was stoppedSerious

The person was driving and was in a car crash. The registry note says they were on the study cream and reported that worsening of their eyelid spasm may have contributed. It is listed as a serious adverse event without any finding that the cream caused it. The dummy group also had one serious event, an inflamed eyelid margin.

1 of the 3 people on the stronger cream. The trial had 8 people in total, so a single event fills a large share of the arm.

Source [13]

Mild irritation of the eyelid

It was minor, settled by itself, and did not require anything to be changed about the treatment. Puffiness of the lower eyelid was also recorded once in the later trial that was stopped early.

4 of 24 people in the seven-month eyelid trial — 2 on the peptide and 2 on the cream with no peptide, which is the same rate in both.

Source [09]Source [13]

An allergy that builds up with repeated contact

The test applied a trade-name mixture containing 0.05% of the peptide in water to the same patch of skin over and over. That is the standard way of provoking this kind of allergy. Nobody reacted. The report gave no details of how the test was run. The strength tested was far below the 10% that appears on some product labels.

0 of 50 people in the one repeated patch test that has been reported.

Source [09]

Stinging, redness, dryness or itching where it is put on

A 2025 review of 10 studies covering 312 people reported no significant adverse effects in any trial. Absence of reports across a few hundred people, over a few weeks each, is not the same as a measured rate. None of these studies was designed to find rare problems.

None reported, but the studies are small. They are 8 people over 60 days who were asked about each of these by name, 19 women over 4 weeks, and 26 patients in an Italian clinic.

Source [09]Source [18]

These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.

Blanes-Mira and colleagues 2002, the first published human test, in the same paper that described the peptide — wrinkles beside the eye

An oil-in-water emulsion containing 10% acetyl hexapeptide-8, applied twice a day to one side of the face

30 days, with measurements at 0, 15 and 30 days

Source [09]

Wang and colleagues 2013, anti-wrinkle study in 60 people in China

Applied twice a day. The published abstract does not state the strength; the 2025 Int J Mol Sci review reports the formulation as 10%

4 weeks

Source [01]Source [02]

Tadini and colleagues 2015, skin mechanics in 40 women aged 35 to 55

A formulation holding 10% of an Argireline solution, that solution itself holding 0.05% acetyl hexapeptide-3, applied twice a day to the forearm and the face. The paper does not state the final strength of the peptide in the product

4 weeks

Source [11]

Lungu and colleagues 2013, eyelid spasm in 24 adults already having botulinum toxin injections

An emulsion containing 0.005% acetyl hexapeptide-8, applied twice a day to the eyelids only

About 7 months, started the day after a botulinum toxin injection

Source [09]Source [12]

NCT01750346, the US government eyelid-spasm trial that was terminated with 8 people enrolled

Creams at 0.025% and 0.05% acetyl hexapeptide-8, against a dummy cream. The registry does not state how often they were applied

Followed to 2 months for the main measurement, with further checks to 7 months; the trial ran from November 2012 and was terminated in May 2015

Source [13]

NCT01381484, the largest independent trial, in wrinkles around the eye at Mahidol University — completed in September 2009 with no results ever posted

A 10% Argireline gel, applied twice a day over the face and around the eyes

3 months

Source [03]

What people report

• Whether any of it ever reaches a facial muscle in a living person. The central claim has never been demonstrated in a body, only in test tubes and dishes.
• Whether it reduces the chemical signal from nerve to muscle in a person at any strength that a cream can deliver.
• What happens to it once it is past the skin. No study in any species has measured how it is absorbed, where it goes, how it is broken down or how it leaves.
• What repeated use does over months or years — no short-term, subchronic or chronic toxicity study exists.
• Whether it affects fertility, pregnancy or an unborn child: no developmental or reproductive study exists.
• Whether it raises or lowers cancer risk — no cancer study has been done.
• Whether it is safe above 0.005%: the US expert panel said in 2025 that the data are not sufficient to judge stronger formulations.
• How strong the products actually are, because most published studies say "10%" without stating whether that means 10% peptide or 10% of a diluted supplied solution.
• Whether the wrinkle change some studies found comes from anything to do with muscle, or simply from a cream sitting on the outer skin and holding water in it.
• What the largest independent trial found — 70 people, a 10% gel, three months, finished in September 2009 and never published.
• What happens after stopping: no trial has followed anyone once they put the cream down.

Is it Botox in a bottle?

No. Botulinum toxin is injected directly into a muscle, where it stops the nerve signalling to that muscle. This peptide is rubbed on the surface of the skin, and the laboratory work says almost none of it gets past the dead outer layer. On human skin, 0.22% of the applied amount stayed in that outer layer, 0.01% reached the living layer beneath, and none was found any deeper. The test-tube experiments that block the nerve signal needed amounts in the millimoles per litre — far above anything shown to arrive in a person. The one trial in a real muscle condition put the cream on top of botulinum toxin injections rather than instead of them.

Source [09]Source [12]

Does it actually reduce wrinkles?

The trials disagree, and they are all small. The 2002 study of 10 women found lines beside the eye 30% shallower over 30 days, against 10% for the same cream without the peptide. A 2013 study of 60 people in China reported a combined anti-wrinkle score of 48.9%, with no matching figure given for the dummy cream. Against that, a 2023 study put the peptide on one side of 19 women's faces for 4 weeks and found no significant difference between the sides. A 2015 study of 40 women found no change in skin springiness. A 2025 review of 10 studies covering 312 people concluded that all of them reported decreases in wrinkle and scar prominence. Whether the decrease was statistically meaningful varied from study to study.

Source [09]Source [10]Source [18]

Products say 10%, but a safety panel says 0.005%. Which is it?

Both numbers are real and they have never been reconciled in public. The US Cosmetic Ingredient Review surveyed the industry in 2019 across 452 products. It found the ingredient in use at up to 0.005% in leave-on products and up to 0.000005% in wash-off ones. Its expert panel concluded in 2025 that the ingredient is safe at up to 0.005%, and that there is not enough data to judge anything stronger. Meanwhile several published studies describe emulsions containing 10% of it, and 10% appears on product labels. One of those studies, Tadini 2015, makes the trap plain: its formulation held 10% of a supplied Argireline solution, and that solution held only 0.05% of the peptide. The other papers do not say which they mean, so the two sets of figures cannot be compared directly.

Source [09]Source [11]Source [19]

Was there ever a proper large trial?

Three registered trials exist and none of them settled anything. The largest was run at Mahidol University in Thailand: 70 people, a 10% gel twice a day for three months, randomised and triple-blind. It finished in September 2009 and no results have ever been posted. A trial at the University of California, Davis put a 10% lotion on one half of 14 people's faces for four weeks. It finished in February 2016 and posted no results either. The one trial that did post results, run by a US government neurology institute, was terminated with 8 people enrolled.

Source [03]Source [13]Source [16]

What about injecting it instead?

There is one published case and it went badly. A 45-year-old woman had it injected into her forehead and temples and broke out in lesions a week later. The pus grew Mycobacterium abscessus, a stubborn germ that took five months of two antibiotics to clear, and she was left with scars and darkened skin. Beyond that single report, nobody has ever measured what happens to this peptide once it is inside a body. There are no absorption, distribution or breakdown studies in any species, and no repeat-dose toxicity studies of any length.

Source [09]Source [17]

Does it do anything other than wrinkles?

Two things have been measured and neither is about muscles. In a 24-person study, water escaping through the skin was lower with the peptide than without it after 20 days. That is a barrier effect in the outer skin. At one Italian clinic, 26 patients using a 10% gel-cream were reported to have more elastic skin, less oil, and enlarged oil-gland openings smaller by up to 85%. The comparison was the skin around the treated spot, not a control group. The randomised trial built to test the oil question properly, at the University of California, Davis, has never posted its results.

Source [01]Source [14]Source [15]Source [16]

Each letter represents one amino acid.

1. [01]Acetyl Hexapeptide-8 in Cosmeceuticals — A Review of Skin Permeability and Efficacy. Int J Mol Sci 2025;26(12):5722 (2025)
2. [02]Wang Y m.fl. The anti wrinkle efficacy of synthetic hexapeptide (Argireline) in Chinese Subjects. J Cosmet Laser Ther 2013 (60 deltagare, 4 veckor, samlad antirynkeffekt 48,9 %) (2013)
3. [03]ClinicalTrials.gov API: NCT01381484, Efficacy and Safety of Topical Argireline in the Treatment of Periorbital Wrinkles (Mahidol University, 70 participants, randomised triple-blind, completed September 2009, hasResults = false) (2009)
4. [04]UniProt P60880 (SNP25_HUMAN) – FASTA sequence showing EEMQRR at residues 12–17
5. [05]PubChem: Acetyl hexapeptide-8 (CID 71587772) – the entry gives C35H62N14O11S and a structure whose first residue is drawn incorrectly against Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2
6. [06]Commission Regulation (EU) No 655/2013 on common criteria for claims made about cosmetic products (EUR-Lex, CELEX 32013R0655) (2013)
7. [07]Directive 2001/83/EC on the Community code relating to medicinal products for human use (EUR-Lex, CELEX 32001L0083) (2001)
8. [08]WADA: World Anti-Doping Code International Standard – Prohibited List 2026 (i kraft 1 januari 2026) (2026)
9. [09]CIR revised tentative safety assessment of Acetyl Hexapeptide-8 Amide as used in cosmetics, released 16 December 2020 — clinical studies section, describing the Blanes-Mira 2002 study of 10 women over 30 days with silicone imprints (2020)
10. [10]Effects of Argireline in a skin serum on skin surface wrinkles using the Visia Complexion Analysis camera system — split-face study in 19 women, 4 weeks (GMS Interdiscip Plast Reconstr Surg) (2023)
11. [11]Tadini KA et al. Acetyl hexapeptide-3 in a cosmetic formulation acts on skin mechanical properties — clinical study, 40 women aged 35 to 55, 4 weeks (Braz J Pharm Sci) (2015)
12. [12]Lungu C et al. Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy. Eur J Neurol 2013;20(3):515-518 (2013)
13. [13]ClinicalTrials.gov API: NCT01750346, Placebo Controlled Double Blind Study of Acetyl Hexapeptide-8 in Treatment of Blepharospasm (NINDS, terminated, enrollment 8 actual, results first posted 10 November 2016) (2016)
14. [14]Raikou V et al. The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study. J Cosmet Dermatol 2017;16(2):271-278 (2017)
15. [15]Palmieri B et al. Skin scars and wrinkles temporary camouflage in dermatology and oncoesthetics: focus on acetyl hexapeptide-8 (Clin Ter 2020, 26 patients, retrospective, no numeric results in the abstract) (2020)
16. [16]ClinicalTrials.gov API: NCT02597777, Pilot Randomized Double-Blind Controlled Trial of Topical Acetyl Hexapeptide-8 and the Cosmetic Appearance of Oily Skin (UC Davis, 14 participants, completed February 2016, hasResults = false) (2016)
17. [17]Mycobacterium abscessus infection after facial injection of argireline: A case report (World Journal of Clinical Cases, 2021) (2021)
18. [18]Lum K et al. Acetyl Hexapeptide-8 as a Topical Alternative to Botulinum Toxin: A Review of the Literature. J Drugs Dermatol 2025;24(4) — 10 studies, 312 participants (2025)
19. [19]Safety Assessment of Acetyl Hexapeptide-8 Amide as Used in Cosmetics — final Expert Panel conclusion (International Journal of Toxicology 2025;44(2_suppl):54S-63S) (2025)