Evidence Grade E — Very limited evidence. 2 published studies. 0 registered clinical trials.
Medically reviewed by a licensed medical professional
Leuphasyl is a cosmetic peptide ingredient designed to reduce expression lines by mimicking natural pain-signalling peptides (enkephalins) to decrease nerve activity at the skin surface. It is used primarily in combination with Argireline. At 570 Da, it is the closest cosmetic peptide to the skin penetration threshold, potentially offering better absorption than larger competitors. It has no pharmaceutical approval.
Leuphasyl is also known by these brand and alternate names:
2 published studies: 2 human, 0 animal, 1 in-vitro, 0 reviews
Leuphasyl has no pharmaceutical authorisation. It is used as a cosmetic ingredient. Industry-sponsored studies report wrinkle reduction of approximately 11–12% when used alone, with potentially greater effects when combined with Argireline (#133).
The evidence base consists of small, primarily industry-sponsored cosmetic studies. As a cosmetic peptide with a proposed mechanism of action at nerve endings beneath the skin surface, the same penetration questions that apply to Argireline are relevant. It is a topical cosmetic ingredient.
Research suggests Leuphasyl mimics enkephalin neuropeptides and may interact with opioid receptors on nerve endings in the skin. The proposed result is reduced acetylcholine release and decreased muscle contraction. These proposed mechanisms are based on the compound's structural similarity to enkephalin rather than on demonstrated topical activity in human skin.
Research suggests industry-sponsored studies report approximately 11-12% wrinkle reduction when used alone, with potentially greater effects in combination with Argireline. One independent study provides additional support. No large double-blind randomised controlled trials exist. The evidence base is small but slightly broader than most cosmetic peptides due to the independent study. The same skin penetration questions that apply to all cosmetic peptides are relevant, though Leuphasyl's smaller size may partly mitigate this concern.
PeptideTrace tracks 0 registered clinical trials for Leuphasyl sourced from ClinicalTrials.gov.
No trials registered on ClinicalTrials.gov for this compound.
Leuphasyl (Pentapeptide-18) is a 5-amino acid synthetic peptide with the sequence Tyr-D-Ala-Gly-Phe-Leu, containing a D-alanine at position 2. Its molecular weight is 569.65 Da (CAS 64963-01-5). Developed by Lipotec (Lubrizol), Leuphasyl is an enkephalin analog designed as a topical neuromuscular relaxant for cosmetic wrinkle reduction. The D-alanine incorporation enhances resistance to enzymatic degradation.
Research suggests Leuphasyl mimics enkephalin neuropeptides and binds to delta and mu opioid receptors on presynaptic nerve terminals. Receptor activation triggers Gi protein signaling, leading to calcium channel closure and potassium channel opening. This reduces acetylcholine release at the neuromuscular junction, producing localized muscle relaxation. The mechanism is complementary to Argireline/SNAP-8 (which act downstream at the SNARE complex), as Leuphasyl operates upstream at the receptor level, providing a rationale for combination use.
Lipotec (2005) conducted a 28-day study showing Leuphasyl alone produced 11.64% wrinkle reduction, Argireline alone produced 16.26%, and the combination achieved 24.62% with maximum individual improvement of 46.53%, suggesting synergy. Dragomirescu (2014, N=20, open-label, 60 days) reported 34.7% frontal wrinkle reduction, 28.4% periorbital reduction, and 11.31% depth reduction. The synergistic rationale (upstream opioid receptor plus downstream SNARE complex) provides a mechanistic basis for combination formulations.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
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GHK has no pharmaceutical authorisation. Small cosmetic studies of the copper-complexed form (GHK-Cu) have reported improvements in skin appearance measures. No pharmaceutical clinical trials for injectable use have been completed. As with GHK-Cu (#85), the cosmetic evidence base for topical use should be distinguished from claims about injectable use. Gene expression profiling studies have reported broad effects, but observational genomic changes do not constitute evidence of therapeutic efficacy. This entry overlaps substantially with GHK-Cu (#85).
GHK-Cu has no pharmaceutical authorisation from any regulatory agency. It is widely available as a cosmetic ingredient in over-the-counter skincare products, where it is marketed for skin conditioning. A small study comparing GHK-Cu cream to vitamin C and retinoic acid creams reported improvements in skin appearance measures. No pharmaceutical clinical trials for injectable GHK-Cu have been completed. The compound's cosmetic use (topical, in formulated skincare products) should be clearly distinguished from its unregulated availability as an injectable research compound. These represent fundamentally different risk profiles.
Argireline has no pharmaceutical authorisation. It is widely available as a cosmetic ingredient in over-the-counter skincare products. Small industry-sponsored studies have reported wrinkle depth reductions of 17–30% with topical application. The key scientific question is whether sufficient peptide penetrates intact skin to reach neuromuscular junctions and produce a meaningful effect. The molecule's size exceeds the conventional limit for transdermal absorption. Argireline's cosmetic use in formulated skincare products represents a fundamentally different risk profile from injectable use.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
