# Leuphasyl (pentapeptide-18)

Enkephalin-mimic expression-line peptide, sold as argireline's partner; hard to find alone, barely reviewed.

- Page: https://peprank.xyz/peptides/pentapeptide-18
- Category: Skin & hair (Supplement)
- Also known as: pentapeptide-18; Leuphasyl (Lipotec trade name, now Lubrizol); Tyr-D-Ala-Gly-Phe-Leu ([D-Ala2]-leucine-enkephalin); enkephalin-mimic 'Botox-like' peptide
- Routes: Topical
- Safety tier: Strict: Caution · Balanced: Clean · Evidence only: Clean
- Risk axes (0 none to 3 severe): Seen harm 0, Mechanism 1, Data gap 2, Silent harm 0, Product 0
- Positive: 55% of 1 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #5 of 23 supplements
- Graded reports: 1 (Positive 1)
- Evidence: Small human studies — one uncontrolled 20-volunteer study (2014, Romania) found 2D wrinkle traces shrank about 35% between the brows and 28% around the eyes with a 2% cream over two months, and a 2024 Polish study used it with retinol in lipid nanocarriers; otherwise supplier, cell and computer-model data. No placebo-controlled trial of the peptide alone
- Access: Supplement
- Onset: Weeks
- Lasts: Hours per application; nothing persists after stopping
- Cost per month: ≈ €4–27 (researchers' estimate)
- Updated: 2026-10-30

## What users report

Too few reports to judge. Leuphasyl is hard to buy on its own (a user pointed to Skin Deva, and DIY suppliers sell the raw solution), and most people meet it unknowingly inside multi-peptide 'Botox-alternative' serums next to argireline, Matrixyl and SYN-AKE, where nobody can credit it. One user of a Skin Deva serum saw an improvement in forehead lines after two weeks; another, who says they are biased toward the compounding pharmacy they buy from, credits it with GHK-Cu for smoother, tighter skin. A German microneedled treatment (NoTox) combining it with argireline drew questions but no outcome reports. The score is closer to a placeholder than a verdict. Felt nothing: Too few reports to count (2, one promotional).

**Effects:** claimed: softer expression lines on forehead and around the eyes; one user: visible improvement within two weeks

**Downsides:** hard to find as a single-ingredient product; no meaningful user record

**Caveat:** Pentapeptide-18 is [D-Ala2]-leucine-enkephalin, an opioid-receptor agonist long used in pharmacology research; the cosmetic story is that it damps acetylcholine release at the nerve ending. At cosmetic levels on intact skin there is no evidence it reaches nerves or the circulation, and peptides of this kind do not cross into the brain, so no opioid-like effect is expected. The 2014 paper miscalls it 'pentapeptide-3'. This verdict covers creams; microneedled 'NoTox' treatments put it deeper and have no published safety data.

**Typical use:** 2% of the Leuphasyl solution was the effective level in the one human study; finished serums rarely say. Apply over the muscles that make the lines (between the brows, crow's feet) once or twice daily.

**Getting it:** Over-the-counter cosmetic: a Skin Deva serum one user bought for it, the raw Lipotec solution from DIY suppliers (Lotioncrafter), and multi-peptide serums such as DNA Code's and Meder's Myo-fix alongside argireline; in Germany some clinics microneedle it in as 'NoTox'.

**Stacked with:** Argireline (The supplier designed it as argireline's partner: argireline at SNARE assembly, Leuphasyl upstream at the enkephalin receptor.); GHK-Cu (topical) (One user's pairing.)

## Risk profile

- **Seen harm 0/3:** No serious adverse events in the 20-volunteer study, the 2024 nanocarrier study or first-hand reports; exposure is modest and mostly hidden inside multi-peptide serums, so the zero is weak reassurance.
- **Mechanism 1/3:** Chemically [D-Ala2]-leucine-enkephalin, an opioid-receptor agonist; a systemic or central opioid effect would need it to cross intact skin and the blood-brain barrier, which a hydrophilic pentapeptide used at a fraction of a percent of a dilute solution is not shown to do. Speculative, hence 1.
- **Data gap 2/3:** Small human studies only: an uncontrolled 20-person study and a volunteer study of a retinol combination; no placebo-controlled trial, no CIR assessment, and nothing on microneedled use.
- **Silent harm 0/3:** The only plausible harms at cosmetic exposure are irritation or contact allergy, noticed at once and gone on stopping.
- **Product 0/3:** Bought as finished over-the-counter serums; DIY mixing of the raw solution and clinic microneedling ('NoTox') are minority channels, the latter delivering it below the barrier with no safety data.
- **Never if:** known allergy to a product containing it; pregnancy and breastfeeding (no reproductive data; opioid-receptor agonist by design)

## Top reports

- Positive, skin-hair: “I use the Skin Deva brand and so far (it's been two weeks) can see an improvement. I bought it directly from their website” — [r/30PlusSkinCare](https://www.reddit.com/r/30PlusSkinCare/comments/1ffxk95/skincare_products_with_leuphasyl/lnqdsmr/)

## Studies

- [Dragomirescu et al., The Efficiency and Safety of Leuphasyl, a Botox-Like Peptide (Cosmetics 2014)](https://www.mdpi.com/2079-9284/1/2/75) (open-label, n=20, 2014): Creams with 0.5%, 1% and 2% Leuphasyl applied over the corrugator and orbicularis muscles for two months: only 2% gave important improvement, with wrinkle-trace size down 34.7% between the brows and 28.4% around the eyes on 2D imaging; no wrinkle disappeared. No control group.
- [Pawłowska et al., Retinol and Oligopeptide-Loaded Lipid Nanocarriers as Effective Raw Material in Anti-Acne and Anti-Aging Therapies (Life 2024)](https://doi.org/10.3390/life14101212) (open-label, 2024): Semi-solid formulations with retinol and pentapeptide-18-loaded solid lipid nanoparticles reduced sebum and facial wrinkle counts in volunteers, with less retinol irritation; pentapeptide-18's own share is not separable.

## Sources

- [Lipotec Leuphasyl technical paper (supplier mechanism and claims)](https://alfaspa.ua/pdf/Peptide-Clinicals/Leuphasyl%20technical%20paper.pdf)
- [Lotioncrafter: Leuphasyl peptide solution (pentapeptide-18)](https://lotioncrafter.com/products/leuphasyl)
- [r/30PlusSkinCare: Skincare products with leuphasyl?](https://www.reddit.com/r/30PlusSkinCare/comments/1ffxk95/skincare_products_with_leuphasyl/)