A five-amino-acid enkephalin copy from Lipotec, sold in creams next to Argireline to quiet the nerve signal behind expression lines.
Also called Pentapeptide-18, Leuphasyl peptide, [D-Ala2]-Leu-enkephalin, D-Ala2-leucine-enkephalin, Tyr-D-Ala-Gly-Phe-Leu
When Leuphasyl's status or evidence changes, it's in the next morning's email.
Leuphasyl is the trade name for pentapeptide-18, five amino acids: Tyr-D-Ala-Gly-Phe-Leu. It is a copy of leu-enkephalin, one of the body's own opioid-type signaling peptides, with one amino acid swapped for its mirror-image D form, and the same molecule is listed in PubChem as [D-Ala2]-leucine-enkephalin. Lipotec, the Spanish company that also sells Argireline and was bought by Lubrizol in 2012, patented it as an anti-wrinkle ingredient with a 2005 priority date.
The human data come from Lipotec's patent. Twenty people with crow's feet used a cream containing the peptide twice daily for 4 weeks, and wrinkle depth fell 11.6% on silicone skin casts. The patent does not describe a placebo group or statistics, and the listed concentration is ambiguous. In the same patent, Leuphasyl lowered nerve-cell signal release by 12% in a lab dish, Argireline alone by 18%, and the two together by 37%, which is the basis for selling them as a pair.
No independent human trial has been published. Recent peer-reviewed work from Istanbul is computer modeling, spectroscopy and cell toxicity tests, and one of those papers found it was toxic to two cancer cell lines in a dish. Whether it crosses the skin, and whether it acts on opioid receptors in skin or nerves when applied as a cream, has not been studied. It is a cosmetic ingredient, not a drug.
What it binds to, and what happens inside the body after that, step by step.
Enkephalins are the body's own peptides that dampen nerve activity. Lipotec designed Leuphasyl to mimic them so that the nerves serving facial muscles fire less and release less acetylcholine. In the patent's lab tests, 1 mM of the peptide reversibly reduced firing in rat sensory nerve cells and cut stimulated signal release by 12%. The patent reports a larger drop when it was combined with Argireline, which is why Lipotec sells them as a pair. None of this has been measured in human facial nerves or muscle.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
The only human data is a 20-person, 4-week test in Lipotec's own patent, which reported 11.6% shallower crow's feet without a described placebo group or statistics. Everything else is lab work: nerve-cell tests in the patent and independent computer modeling and cell toxicity studies. No independent human trial has been published.
20 people with crow's feet, cream twice daily for 4 weeks; supplier data in a patent, not peer-reviewed
Wrinkle depth on silicone skin casts fell 11.6% from day 0 to day 28; no placebo group or statistical test is described.
Read the studyRat sensory nerve cells and a lab glutamate-release assay
At 1 mM the peptide reversibly reduced nerve firing and cut stimulated glutamate release 12%; with Argireline the drop was 37% versus 18% for Argireline alone.
Read the studyComputer docking and HaCaT human skin cell cultures; independent Istanbul study
Leuphasyl bound the collagen-degrading enzyme MMP-13 in computer models and was not toxic to skin cells up to 1 mg/mL.
Read the studyComputer docking and cancer cell lines
Leuphasyl docked to cancer-related targets including EGFR and was most toxic to MDA-MB-231 breast and PC3 prostate cancer cells in a dish.
Read the studySpectroscopy and computer modeling
Describes the peptide's structure and predicted binding to inflammation and aging pathways; no cell or human outcome was measured.
Read the studyFormulation stability tests
Lipid nanoparticles carrying retinol and pentapeptide-18 stayed stable over 4 weeks of storage; efficacy was not tested.
Read the studyWhen a new Leuphasyl study in people is published, the daily email covers it.
These are questions the published research has not answered.
No product containing Leuphasyl is approved as a medicine by the FDA.
Sold in topical cosmetics, which FDA does not review for efficacy before sale. It is not an approved drug anywhere. A distributor lists the commercial ingredient as water, glycerin and pentapeptide-18 from Lipotec in Spain. No Cosmetic Ingredient Review safety assessment specific to pentapeptide-18 was found. It is an enkephalin analog but is not named on the WADA list; the WADA narcotics section is a closed list of named drugs that does not include it.
When the FDA or WADA changes Leuphasyl's status, it's in the next morning's email.
No human half-life has been published for Leuphasyl, so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.
This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
In one lab nerve test in Lipotec's patent, the pair cut signal release 37% versus 18% for Argireline alone. No human trial has tested the pair.
It is a synthetic enkephalin copy. The only human test reported an 11.6% drop in wrinkle depth, without a described control, which is not comparable to Botox.
It is an enkephalin analog, but no study has measured it in blood or urine after skin use. WADA's narcotics list does not name it.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Lipotec's patent describes the combination as additive or synergistic.
EvidenceSupported only by a lab nerve test in Lipotec's patent (37% versus 18% for Argireline alone); no human trial of the pair has been published.
Sold as a pre-dissolved cosmetic ingredient; a distributor advises sealed original containers, protected from light, refrigerated when possible.
Follow the cosmetic product's packaging and expiry date; no independent stability data are published.
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