Pentapeptide-18
Neurotransmitter-inhibiting peptide
Also Leuphasyl, Pentapeptide 18, Leuphasyl peptide
- Evidence
- CAnimal and cell studies
- FDA status
- Cosmetic ingredientas of 2026-10-26
- Route
- Topical
- Studies cited
- 2 human0 animal or cell
It is a cream ingredient sold as a Botox alternative for expression lines. Two small studies of 20 people each had no comparison group, so the proof is weak.
Sold for
Pentapeptide-18 is sold as a topical alternative to botulinum toxin that softens expression lines, usually paired with acetyl hexapeptide-8 (Argireline).
Studies say
Two small uncontrolled studies in 20 volunteers each report shorter or fewer wrinkles after weeks of use, one of them with retinol in the same cream, which is grade C support at best.
Why grade C. The human evidence is two small uncontrolled studies: a 20-volunteer, two-month test of pentapeptide-18 creams at three strengths, in which only the strongest reduced measured wrinkle length, and an eight-week test in 20 women of a cream that also contained retinol. Neither had a vehicle or placebo control, and the manufacturer has not published its own trial data. Uncontrolled series put it at C for expression lines. 13
FDA. Pentapeptide-18 is a cosmetic ingredient, sold under the trade name Leuphasyl. Cosmetic ingredients in the United States are not reviewed or approved by the FDA before sale, so there is no FDA approval to cite for or against it. 2
Written from 3 cited sources. Fact-checked 2026-10-27: 10 claims checked, 5 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Softening expression lines
- Can a US doctor prescribe it?
- No prescription; it is a cosmetic ingredient.
- Properly tested in people?
- Not properly: animal or lab studies, or small uncontrolled human reports. Two reports of 20 people each.
Evidence checklist
- Randomised controlled trial Maker's test only; no peer-reviewed trialno
- Human study over 100 people No independent human studyno
- More than one research group Only manufacturer datano
- Clinical outcomes, not surrogate markers No clinical outcomeno
- Human safety data beyond case reports No formal safety studyno
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Pentapeptide-18 is a synthetic chain of five amino acids designed by Lipotec (now part of Lubrizol) and marketed as Leuphasyl. It is formulated into creams and serums aimed at expression lines around the eyes and forehead, and it is usually sold alongside acetyl hexapeptide-8, the ingredient better known as Argireline. 2
Because it is used in cosmetics and not in drugs, pentapeptide-18 has never gone through a drug approval process anywhere. Published papers group it with the neurotransmitter-inhibiting peptides, alongside acetyl hexapeptide-8. 13
How it works
The manufacturer describes pentapeptide-18 as an enkephalin mimic. Enkephalins are small opioid peptides the body makes; when they bind receptors on nerve endings they reduce the release of acetylcholine, the chemical signal that tells a muscle to contract. The claim is that a topical peptide can reach those nerve endings and dampen the signal enough to relax the small muscles behind expression lines. Whether a water-soluble peptide applied to skin reaches the neuromuscular junction in meaningful amounts has not been shown in published work. 12
What human research shows
A 2014 study from a Romanian pharmacy faculty applied creams with three concentrations of pentapeptide-18 to the forehead and eye area of 20 volunteers for two months and tracked wrinkles with a 2D skin imaging device. Only the strongest cream produced a clear change: wrinkle length fell by an average of 34.7% between the eyebrows and 28.4% around the eyes. There was no vehicle-only comparison and wrinkle depth was not measured, so the result cannot separate the peptide from the cream base or from measurement drift. 1
A 2024 Polish study put pentapeptide-18 and retinol together into lipid nanoparticles in a night cream and tested it for eight weeks in 20 women with signs of skin aging, reporting fewer wrinkles and better hydration. Retinol has its own evidence for wrinkles, so the study says little about pentapeptide-18 alone. Supplier data on the ingredient are only available behind a login on trade listings and have not been published in a journal. 32
| Study | Model | Finding |
|---|---|---|
| Dragomirescu 2014, Leuphasyl creams | Humans, n=20 volunteers, three concentrations, two months, no control | Only the strongest cream reduced measured wrinkle length, by 34.7% between the eyebrows and 28.4% around the eyes. 1 |
| Pawłowska 2024, retinol plus pentapeptide-18 cream | Humans, n=20 women, eight weeks, no placebo, combined with retinol | Fewer wrinkles and better hydration were reported, but the effect cannot be attributed to the peptide. 3 |
Safety
The 2014 study reported no side effects in its 20 volunteers, and the 2024 study reported that the nanoparticle form reduced the irritation usually seen with retinol. Cosmetic peptides of this type are used at low concentrations, but there is no formal safety study of pentapeptide-18 alone, and two short studies of 20 people cannot detect uncommon reactions. 13
Questions for your clinician
- Is there any independent trial of this ingredient?
- What does the maker's own test actually show?
- Are there wrinkle treatments with controlled data?
Questions people ask
Is pentapeptide-18 the same as Argireline?
No. Argireline is acetyl hexapeptide-8, a six-amino-acid peptide that targets a different step in the release of acetylcholine. Pentapeptide-18 is a five-amino-acid peptide described as working one step upstream, and the two are often sold together on the theory that they add up. 12
Does pentapeptide-18 need FDA approval?
No. Cosmetic ingredients in the United States are not approved by the FDA before they are sold. The FDA can act against a cosmetic that is unsafe or makes drug claims, but there is no approval to look up for pentapeptide-18. 2
What does the research actually show?
Very little. Two small studies without a placebo or plain-cream comparison, 20 people each, report fewer or shorter wrinkles after two months, and one of them combined the peptide with retinol. No controlled trial of pentapeptide-18 has been published, and the manufacturer has not published its data. 13
Citations
- Dragomirescu 2014, Cosmetics (MDPI): the efficiency and safety of Leuphasyl, a botox-like peptide mdpi.com
- SpecialChem: Lubrizol Leuphasyl (pentapeptide-18) product listing specialchem.com
- Pawłowska 2024, Life: retinol and pentapeptide-18 loaded lipid nanocarriers in anti-acne and anti-aging creams doi.org