Cosmetic & skin

Leuphasyl (pentapeptide-18)

Also called Pentapeptide-18, [D-Ala2]-Leu-enkephalin, H-Tyr-D-Ala-Gly-Phe-Leu-OH, YaGFL

Leuphasyl is the trade name of pentapeptide-18, a small lab-made peptide used in anti-wrinkle creams and serums. It is modeled on enkephalins, natural nerve-signaling peptides, and is often described as a 'Botox-like' ingredient you rub on instead of inject. Human evidence is very thin: there is no controlled study of the peptide on its own, and the few published skin studies either give no results in their abstract or tested it mixed with retinol.

Early human dataSome small human studies exist; evidence is limited.

New · under editorial review. Added October 30, 2026 by our automated research, with every claim sourced. A person has not checked this page yet; treat it with extra care. How we research

All printable flashcards

Illustrative chain. The exact sequence has not been published in a source we could verify.

Overview

How it works

Proposed, not shown in human skin: authors describe pentapeptide-18 as acting like an enkephalin. It is said to bind enkephalin receptors on nerve cells at the nerve-muscle junction, which would reduce the release of the signal chemical acetylcholine and so relax the small facial muscles that form expression lines ²³. These statements in the papers are not backed by their own experiments, and a 2020 review cites the manufacturer's own documents, not peer-reviewed studies, for some supporting claims (such as a boost when combined with Argireline) ⁵. Whether enough of the peptide passes through the skin to reach those nerve endings has not been shown in the sources reviewed.

What research shows

Human cosmetic study (Romania, 2014): creams with 0.5%, 1% or 2% Leuphasyl were applied over the brow and eye-area muscles, and frown-line changes were measured with an imaging device. The abstract does not report results, group size or whether there was a control group, and the full text could not be opened for this review ².
Combination study (Poland, 2024; 20 women aged 30–65, 8 weeks): each volunteer used an eye cream with retinol plus pentapeptide-18 in lipid nanoparticles and a base cream without these actives. Total wrinkle area fell 20% vs 11% with the base cream. There was no placebo group, randomization or blinding was not described, and the peptide's own effect cannot be separated from retinol's ³.
Combination study (Poland, 2024; an anti-aging group of 20 women, 8 weeks; a second group of 20 tested anti-acne creams): a night cream with retinol plus pentapeptide-18 nanoparticles cut wrinkle counts by 29% on the forehead and 18% around the eyes vs 6% and 9% with the base cream. Again no placebo group, no blinding described, and retinol was present ⁴.
Lab studies: pentapeptide-18 showed no toxicity to cultured human skin cells (HaCaT) up to 1 mg/mL, and computer models suggested it may bind skin-aging enzymes such as MMP-13; these are not human results ⁷.
Cell study: versions of pentapeptide-18 with an added D-tyrosine reduced melanin in pigment cells and a 3D skin model; this tested modified peptides, not Leuphasyl itself ⁶.
A 2026 systematic review (published as a letter) of topical 'Botox-like' peptides for wrinkles included 11 studies, mostly of acetyl hexapeptide-8 (Argireline); none tested Leuphasyl ¹².

Doses studied in people

Study or label	Dose used	Source
Human cosmetic study (2014; abstract only, group size not reported), topical cream — product concentration, not a dose	Emulsions containing 0.5%, 1% or 2% Leuphasyl applied to the skin over the brow and eye-area muscles	²

Leuphasyl is only used on the skin. The figures shown are cream concentrations from one published study, reported only from its abstract and not recommended; there are no human studies of injected or oral use.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

Vial	Liquid added	Concentration	Per unit (0.01 mL)
5 mg	1 mL	5 mg/mL	50 mcg	Open in calculator
5 mg	2 mL	2.5 mg/mL	25 mcg	Open in calculator
5 mg	3 mL	1.67 mg/mL	16.7 mcg	Open in calculator
10 mg	1 mL	10 mg/mL	100 mcg	Open in calculator
10 mg	2 mL	5 mg/mL	50 mcg	Open in calculator
10 mg	3 mL	3.33 mg/mL	33.3 mcg	Open in calculator

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

The two 2024 volunteer studies asked participants to report any adverse effects, but neither paper presents adverse-event results, so tolerability of the peptide is not documented ³⁴.
In lab tests it did not harm cultured human skin cells at concentrations up to 1 mg/mL ⁷.
Pentapeptide-18 is chemically the same as [D-Ala2]-Leu-enkephalin, a laboratory enkephalin analog ¹. Its effects if absorbed into the body have not been studied in the cosmetic sources reviewed.
Long-term safety of daily use is unknown; the 2024 volunteer studies lasted 8 weeks ³⁴.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA: Not an FDA-approved drug. In the US it is used as a cosmetic ingredient; FDA does not approve cosmetics or their ingredients (other than color additives) before sale ⁸. FDA says products that claim to change skin structure, such as removing wrinkles, are drugs rather than cosmetics ⁹.
Compounding: Not named on FDA's 503A bulk drug substance category lists (updated May 14, 2026) ¹⁰.
Sports (WADA): Not named on the WADA 2026 Prohibited List ¹¹.
Other: EU cosmetic (CosIng) and Cosmetic Ingredient Review status could not be verified from a primary source in this review.

Rules change often. See Legal status of peptides for how these categories work.

History

Leuphasyl was developed as a cosmetic ingredient by the Spanish company Lipotec; a 2020 review cites a 2005 Lipotec document for it and notes that the synergy claims with Argireline come from the maker ⁵. The first peer-reviewed human study we found was a Romanian study published in 2014 that tested creams with 0.5%, 1% and 2% Leuphasyl; only its abstract could be checked, and it gives no group size or results ². Later papers (2020–2026) have mainly been lab, cell and computer-modeling studies, plus two 2024 Polish volunteer studies of creams that combined it with retinol ³⁴⁶⁷.

Common questions

What is Leuphasyl?

It is the trade name for pentapeptide-18, a five-amino-acid peptide (Tyr-D-Ala-Gly-Phe-Leu) used in anti-wrinkle skin care ¹³. Chemically it is [D-Ala2]-Leu-enkephalin, a modified enkephalin ¹.

Does Leuphasyl work like Botox?

It is described as 'Botox-like' because it is thought to reduce nerve signals to facial muscles, but that idea has not been proven in human skin ²⁵. A 2026 systematic review of these 'Botox-like' skin peptides found no Leuphasyl studies to include, and none compared it with Botox ¹².

What does the human evidence show?

Very little. There is no controlled study of the peptide on its own. One 2014 study tested 0.5–2% creams, but its abstract gives no results ². Two 2024 studies saw fewer wrinkles with creams that also contained retinol, so the peptide's own effect is unclear ³⁴.

Is Leuphasyl FDA-approved?

No. It is a cosmetic ingredient, and FDA does not approve cosmetic ingredients before sale ⁸. Products claiming to remove wrinkles count as drugs under FDA rules ⁹.

Is it safe?

It did not harm skin cells in the lab ⁷. The small human studies did not publish any adverse-event data, and they lasted 8 weeks or less, so safety in people, especially long-term, is not well documented ³⁴.

Is Leuphasyl banned in sport?

It is not named on the WADA 2026 Prohibited List ¹¹.

Related compounds

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Argireline (acetyl hexapeptide-8)

acetyl hexapeptide-8 · acetyl hexapeptide-3 (older INCI name)

Argireline is a short lab-made peptide used in anti-wrinkle creams and serums.

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SNAP-8 (acetyl octapeptide-3)

Acetyl octapeptide-3 · Acetyl glutamyl heptapeptide-3

SNAP-8 is a short lab-made peptide used in anti-wrinkle creams and serums.

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Palmitoyl pentapeptide-4 (Matrixyl)

Matrixyl · Pal-KTTKS

Palmitoyl pentapeptide-4, sold under the trade name Matrixyl, is a skin-care ingredient made of five amino acids joined to a fatty acid.

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GHK-Cu

Copper tripeptide-1 · Copper peptide

GHK-Cu is a tiny three-amino-acid peptide (GHK) bound to copper.

Sources

Wondering how to judge the claims made about compounds like this one? The Academy track Thinking clearly about peptide claims walks through it. You can try the Academy free first.

Last reviewed 2026-10-30 · How we research · Found an error? See our corrections policy.