Pentapeptide-18 (INCI name), [D-Ala2]-Leu-enkephalin
A five-amino-acid copy of leu-enkephalin, one of the body’s own opioid peptides, with its second amino acid, glycine, replaced by D-alanine. It’s marketed, often alongside Argireline, to soften expression lines by calming nerve signals to facial muscles.
None of these uses is approved. Uses tested in people come first, then claims that rest on animal studies or user reports.
Trial: tested in people, with the result. Animal: cell or animal studies only. No study: nothing published supports it.
Every compound’s uses, by body system: evidence map, and by condition: conditions A to Z.
Category 2 is FDA’s list of bulk substances that may present significant safety risks in compounding. The 503A bulks list adds substances that pharmacies may compound with. Advisory committee votes are advice; FDA makes the final decision. Sport status follows the WADA Prohibited List in force since January 1, 2026; athletes should confirm with their anti-doping organization. Checked October 5, 2026. Status outside the US checked October 7, 2026 against EMA, MHRA, Health Canada and TGA records. By country: EU, UK, Canada, Australia. Status of every compound.
Pentapeptide-18 is leu-enkephalin, one of the body’s own opioid peptides, with its second amino acid changed to D-alanine. In lab tests this compound binds opioid receptors, mainly the delta type, which damp nerve-cell activity; its maker reports it reduced release of a nerve signaling chemical from cultured neurons, more so combined with Argireline. No study shows it reaches the nerve endings that control facial muscles through skin.
AnimalMainly from cell and animal studies; not shown in people.
Whether it passes through skin to nerve endings, whether it has any opioid effect in people, and whether wrinkle changes in tests come from nerve effects, is unknown.
Supplier data
Maker’s test: cream with 5% Leuphasyl solution (about 25 ppm peptide), twice daily around the eyes for 28 days.
Finished products contain 3–10% of the supplier solution, about 15–50 ppm peptide; “10% Leuphasyl” doesn’t mean 10% pure peptide.
Continuous, shown over 26 weeks
The ways Leuphasyl is most often run, each tagged with where it comes from.
The supplier solution is only 0.05% peptide. It’s added to a finished product, often with Argireline, never used neat.
14 people aged 39–64: crow’s-feet wrinkles 11.6% shallower on average (maximum 23.6%); with 5% Argireline added, 24.6% (15 people). Unpublished, no statistics.
Dragomirescu 2014, 20 volunteers, no control group: only 2% clearly helped (wrinkle size 34.7% and 28.4% smaller).
Applied over the muscles that form expression lines, such as between the brows and around the eyes. Topical only; never inject it.
Nothing special. Skip it and use the next application as usual.
Maker’s test: crow’s-feet wrinkles 11.6% shallower with Leuphasyl alone and 24.6% with Argireline added. Supplier data only, unpublished.
TrialIn 20 volunteers using 2% Leuphasyl, wrinkle size fell 34.7% between the brows and 28.4% around the eyes, with no control group or statistics (Dragomirescu 2014).
TrialSkin irritation or redness
Patch-test first. Stop if it doesn’t settle.
No side effects described in two 20-person skin studies
Studies were small and short, so rare reactions can’t be ruled out.
Eye irritation
Keep it out of the eyes. Rinse with water if it gets in.
Stop and see a doctor for a spreading rash, swelling, blistering or hives, or eye pain after contact.
The side effects people ask about most, answered one by one. Each answer says where it comes from.
Not reported: studied in people and not reported. No data: no human safety data. A side effect that hasn’t been reported can still happen, especially with long or high-dose use. Any of these across every compound: the side-effect finder.
No product label covers Leuphasyl, so these come from human studies and from precautions based on how it works. Most important first.
Precaution: follows from how it works or from a related drug, and hasn’t been tested. This isn’t a complete list: a pharmacist or doctor can check a specific medicine or condition. Every documented interaction, by medicine: drug interactions.
What’s known about pregnancy, breastfeeding, kidney and liver problems, age and surgery. Where nothing has been studied, the row says so.
Precaution: not studied, so the caution follows from how it works or from a related drug. Ages are given as approved or studied; this site never gives doses for children. Across every compound: pregnancy, breastfeeding, kidney disease, liver disease, older adults and surgery.
The maker pairs them for an additive effect: 24.6% vs 16.3% for Argireline alone in its unpublished 28-day test, without published statistics.
2 key published human studies, with how many people took part. Animal studies aren’t listed here.
Only the 2% emulsion clearly helped: wrinkle size fell 34.7% between the brows and 28.4% around the eyes on average; no statistics or safety data were reported.
Dragomirescu et al., Cosmetics 2014, doi:10.3390/cosmetics1020075
Forehead wrinkle count fell 29% and eye-area count 18% with the nanoparticle cream vs 6% and 9% with the base; retinol’s share can’t be separated.
Pawłowska et al., Life (Basel) 2024, PMID 39459512
No ongoing trial of Leuphasyl is registered, and none has finished recently without publishing its results. Checked on ClinicalTrials.gov, October 7, 2026. Every compound: trials under way.
Leuphasyl’s human evidence is the maker’s unpublished 28-day test (about 14 people per group, no published statistics), a 20-person study without a control group and a retinol cream study in 20 women. No peer-reviewed controlled trial of it alone exists. Its nerve-calming action rests on lab tests, and skin absorption and any opioid effect in people are unmeasured. Pure-powder mixes, long-term use and injection are untested.
Leuphasyl is used on the skin, so the math is a dilution, not a syringe dose.
| Powder | Serum volume | Strength | Percent | ppm |
|---|---|---|---|---|
| 10 mg | 100 mL | 0.1 mg/mL | 0.01% | 100 ppm |
| 10 mg | 200 mL | 0.05 mg/mL | 0.005% | 50 ppm |
| 10 mg | 400 mL | 0.025 mg/mL | 0.003% | 25 ppm |
| 10 mg | 1,000 mL | 0.01 mg/mL | 0.001% | 10 ppm |
The maker supplies it as a water and glycerin solution with 0.05% peptide (500 ppm). Its 5% test level equals about 25 ppm, roughly 10 mg of pure peptide in 400 mL of serum.
Every compound side by side: the half-life chart and the storage chart.
Every compound’s numbers: the identifiers table.
The maker supplies a water and glycerin solution with 0.05% peptide (500 ppm), used at 3–10%, so finished products hold about 15–50 ppm. Pure powder is 2,000 times stronger than that solution.
A five-amino-acid copy of leu-enkephalin, one of the body’s own opioid peptides, with its second amino acid, glycine, replaced by D-alanine. It’s marketed, often alongside Argireline, to soften expression lines by calming nerve signals to facial muscles.
Pentapeptide-18 is leu-enkephalin, one of the body’s own opioid peptides, with its second amino acid changed to D-alanine. In lab tests this compound binds opioid receptors, mainly the delta type, which damp nerve-cell activity; its maker reports it reduced release of a nerve signaling chemical from cultured neurons, more so combined with Argireline. No study shows it reaches the nerve endings that control facial muscles through skin. Whether it passes through skin to nerve endings, whether it has any opioid effect in people, and whether wrinkle changes in tests come from nerve effects, is unknown.
Not approved as a drug in the US or EU; used as a cosmetic ingredient. Cosmetics don’t need FDA approval before sale. Never nominated for FDA’s compounding bulk lists; it isn’t on any of FDA’s 503A or 503B category lists (May 2026 and March 2025 versions).
From human studies (Supplier data): Maker’s test: cream with 5% Leuphasyl solution (about 25 ppm peptide), twice daily around the eyes for 28 days. From community reports, not established: Finished products contain 3–10% of the supplier solution, about 15–50 ppm peptide; “10% Leuphasyl” doesn’t mean 10% pure peptide. These are the amounts sources reference, not recommendations.
No product label covers Leuphasyl, so these come from human studies and from precautions based on how it works. Anyone thinking of injecting it: It is a cosmetic ingredient, not made to injectable standards, and has never been tested by injection in people; chemically it’s an enkephalin-like opioid peptide. Anyone mixing pure powder at high strength: The maker’s test used about 25 ppm peptide; stronger mixes haven’t been tested for benefit or safety. Pregnancy or breastfeeding: No human safety data exist.
Before mixing: Freezer (about −20 °C) for long-term storage, kept dry. After mixing: Fridge (2–8 °C); use within about 4 weeks. This is common practice; no product label covers it.
No. Not named on the 2026 list. It’s a topical cosmetic ingredient; though it’s an enkephalin-like opioid peptide, S7 bans only named narcotics, and it isn’t one of them.
Yes. The human studies section lists 2 published studies. The largest, from 2014, included 20 people. Only the 2% emulsion clearly helped: wrinkle size fell 34.7% between the brows and 28.4% around the eyes on average; no statistics or safety data were reported.
Trial 2 months, in 20 volunteers using emulsions of up to 2% Leuphasyl without a control group. A trade report describes 6 months alongside toxin injections.
Animal Sold for creams and serums; skin absorption hasn’t been measured. As the opioid research peptide [D-Ala2]-Leu-enkephalin it was studied in animal tissue; human injection is untested.
No study There’s no label and no overdose data. It binds opioid receptors in lab tests, but no study has measured blood levels after skin use. Call Poison Help (1-800-222-1222), or emergency services for severe symptoms.
For the protocol details
For how it works, who should avoid it and the limits of the evidence
For uses, the side-effect questions, special situations, trials, identifiers and status outside the US
Doses tagged Community come from public dosing guides and user reports, checked against at least two of them. Those sites aren’t named here because many of them sell peptides or earn commissions on them.