Pentapeptide-18
Also known as: Leuphasyl, Tyr-Ala-Gly-Phe-Leu, Leu-enkephalin analog
Key Facts: Pentapeptide-18
- Category
- Skin & Hair
- FDA Status
- Not FDA Approved
- Clinical Status
- Cosmetic ingredient, usually paired with Argireline in anti-wrinkle serums. Not an FDA-approved drug: cosmetics and their ingredients (except color additives) do not need FDA approval before sale, and this peptide has never been through drug trials. Efficacy data is small and mostly manufacturer-funded.
- Banned in Sport (WADA)
- Not on the WADA Prohibited List (2026). It is a topical cosmetic ingredient, and skincare use is not a known anti-doping issue.
- Administration
- Topical (serums, creams)
- Typical Dose
- About 2-5% of the commercial solution in a finished product
- Frequency
- Once or twice daily
- Duration
- 28 days to 2 months in studies; ongoing use to maintain any effect
How does Pentapeptide-18 work?
Pentapeptide-18 is Tyr-Ala-Gly-Phe-Leu, a close copy of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) with one amino acid swapped. The theory is that it binds enkephalin receptors on nerve endings, which dampens nerve activity and lowers acetylcholine release at the junction with facial muscles. Argireline works at a different step (the SNARE complex inside the nerve ending), which is why the two get marketed as a combo. The same big caveat as Argireline applies: it is sold on a nerve-to-muscle mechanism, but nobody has shown in living skin that a topical cream delivers enough peptide to the muscle to do this.
What does the research show?
The most quoted numbers come from a Lipotec study: about 11% wrinkle reduction with 5% Leuphasyl alone over 28 days in a small panel, and about 25% with 5% Leuphasyl plus 5% Argireline. The company calls that synergy, but on its own figures the combination roughly equals the two effects added together, so 'synergistic' is a stretch. The one journal paper we found is Dragomirescu and colleagues (2014, Cosmetics, MDPI), which tested 0.5%, 1% and 2% emulsions around the eyebrows and eyes for efficacy and safety. Trade summaries say only the 2% cream gave a significant improvement after two months in about 20 volunteers; we could not read the full paper to confirm the numbers. A 2020 review of cosmetic peptides lists it among the neurotransmitter-inhibitor peptides and notes that much of the support comes from the manufacturer. Bottom line: safe enough as a skincare ingredient and plausible on paper, but expect subtle softening at most, not anything close to an injection.
What doses have been studied?
Typical Dosingⓘ
Community experience
About 2-5% of the commercial solution in a finished product
0.5-5% in published and manufacturer studies (percent of the ingredient, not pure peptide)
Once or twice daily
These are cosmetic formulation levels, not personal doses. It is usually combined with Argireline. There is no injectable or oral use with human data, and it does not work like a botulinum toxin injection.
Research Dosingⓘ
Scientific studies
Typical cosmetic formulation levels from manufacturer and published data. Not a dosing recommendation.
Doses from Studies
0.5%, 1% and 2% emulsions on eyebrow and eye areas
Manufacturer combination data with Argireline
Review citing manufacturer (Lipotec) data - Errante et al. 2020, Front Chem ↗
Duration
28 days to 2 months in studies; ongoing use to maintain any effect
Administration
Topical (serums, creams)
When and how is Pentapeptide-18 taken?
Best Time to Take
Morning and/or evening, on clean skin
Once or twice daily, ongoing
Food Recommendation
With or without food
Why This Timing?
Timing has no known effect on a topical peptide; consistent daily use is what the studies tested.
What are the side effects of Pentapeptide-18?
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Generally well tolerated in cosmetic use
- ●Mild irritation or redness (uncommon)
- ●Contact allergy possible, as with any skincare ingredient
References
- https://www.mdpi.com/2079-9284/1/2/75
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7662462/
- https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1618306/full
- https://www.fda.gov/cosmetics/cosmetics-laws-regulations/it-cosmetic-drug-or-both-or-it-soap
Research This Peptide Further
Frequently Asked Questions
What does Pentapeptide-18 do?
Pentapeptide-18 is Lipotec's Leuphasyl, a 'Botox-like' cosmetic peptide modeled on enkephalins, the body's own calming neuropeptides. It is mostly sold alongside Argireline, with the claim that the two relax expression lines better together. It is a cosmetic ingredient, and the evidence is small and mostly manufacturer-run.
How does Pentapeptide-18 work?
Pentapeptide-18 is Tyr-Ala-Gly-Phe-Leu, a close copy of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) with one amino acid swapped. The theory is that it binds enkephalin receptors on nerve endings, which dampens nerve activity and lowers acetylcholine release at the junction with facial muscles. Argireline works at a different step (the SNARE complex inside the nerve ending), which is why the two get marketed as a combo. The same big caveat as Argireline applies: it is sold on a nerve-to-muscle mechanism, but nobody has shown in living skin that a topical cream delivers enough peptide to the muscle to do this.
Is Pentapeptide-18 FDA approved?
No, Pentapeptide-18 is not currently FDA approved. Current status: Cosmetic ingredient, usually paired with Argireline in anti-wrinkle serums. Not an FDA-approved drug: cosmetics and their ingredients (except color additives) do not need FDA approval before sale, and this peptide has never been through drug trials. Efficacy data is small and mostly manufacturer-funded.
Is Pentapeptide-18 banned in sport?
Not on the WADA Prohibited List (2026). It is a topical cosmetic ingredient, and skincare use is not a known anti-doping issue.
What are the side effects of Pentapeptide-18?
Reported side effects include: Generally well tolerated in cosmetic use, Mild irritation or redness (uncommon), Contact allergy possible, as with any skincare ingredient. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Pentapeptide-18?
Community-reported common dose: About 2-5% of the commercial solution in a finished product (Once or twice daily). Range: 0.5-5% in published and manufacturer studies (percent of the ingredient, not pure peptide). Administration: Topical (serums, creams). Community-reported doses. Not medical advice. Consult healthcare provider.
Related Peptides
Peptides commonly compared with Pentapeptide-18 or used in similar applications.
GHK-Cu
Clinical TrialsGHK-Cu is the copper(II) complex of GHK, a naturally occurring human tripeptide (glycyl-L-histidyl-L-lysine) found in blood plasma, saliva and urine, whose levels decline with age. It is researched and widely used in cosmetic skincare for skin regeneration, wound healing, collagen support and anti-aging. It is not an FDA-approved drug; it appears in over-the-counter cosmetics and as a research or compounded peptide, with most human evidence coming from small topical-skincare studies.
Skin & HairSnap-8
ResearchSNAP-8 (Acetyl Octapeptide-3) is a synthetic eight-amino-acid topical cosmetic peptide, an extended cousin of Argireline that adds two residues to the same SNAP-25 mimic sequence. It is marketed as a needle-free way to soften expression lines, especially on the forehead and around the eyes. It is a cosmetic ingredient, not an approved drug, and the human evidence behind it is thin and mostly comes from the manufacturer.
Skin & HairArgireline
ResearchArgireline is the trade name for acetyl hexapeptide-8 (sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, also called acetyl hexapeptide-3), a synthetic peptide sold in anti-aging creams as a topical, needle-free alternative to Botox. It is designed to relax the muscle contractions behind expression lines. It is a cosmetic ingredient, not an FDA-approved drug, and the human efficacy data are genuinely mixed rather than settled.
Skin & HairMatrixyl
ResearchMatrixyl is the trade name (Sederma) for palmitoyl pentapeptide-4, also written Pal-KTTKS, a collagen-fragment peptide attached to a fatty acid so it can cross skin. Unlike Botox-mimic peptides, it does not touch muscle: it signals skin cells to rebuild collagen, so it is aimed at fine lines, firmness and skin texture rather than expression wrinkles. It is a cosmetic ingredient with one of the better-documented topical studies in the peptide space, though far short of drug-grade proof.
Skin & HairMatrixyl 3000
ResearchMatrixyl 3000 is Sederma's follow-up to the original Matrixyl, a fixed pair of two fatty-acid-tagged peptides: palmitoyl tripeptide-1 (Pal-GHK) and palmitoyl tetrapeptide-7 (Pal-GQPR). The idea is a one-two punch: one peptide tells skin to rebuild collagen, the other calms the low-grade inflammation that wears collagen down. It is a cosmetic ingredient aimed at firmness, fine lines and aging skin, with supportive but mostly company-generated evidence.
Skin & HairCopper Peptide AHK-Cu
ResearchAHK-Cu is a synthetic copper-bound tripeptide, alanine-histidine-lysine complexed with a copper ion, engineered mainly for hair and scalp products. It is the lesser-known sibling of the naturally occurring GHK-Cu copper peptide, designed in the lab specifically to push hair follicles to keep growing. It is a cosmetic and research ingredient, not an approved hair-loss drug, and its evidence is essentially limited to one notable lab study.
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