Melanotan 2 darkens the skin without sunlight. In the first human study, published in 1996, five small doses given under the skin were enough to visibly darken the face, upper body and buttocks. The effect was measured with an instrument, not only judged by eye. Below you will find how the peptide switches on a tan, what the researchers at the University of Arizona measured and how melanotan 2 differs from its older relative, which became an approved drug.
How does melanotan 2 produce a tan?
Melanotan 2 mimics the natural hormone alpha-MSH, which tells pigment cells to produce dark pigment. These cells are melanocytes, which sit in the lowest layer of the epidermis. On their surface is the MC1R receptor. When alpha-MSH or its synthetic counterpart binds to this receptor, the melanocyte switches production to eumelanin.
Eumelanin is a brown-black pigment responsible for a dark, lasting skin tone. The second pigment, pheomelanin, is yellow-red and protects less against radiation. A natural tan after sun exposure forms along the same pathway, only the starting signal is skin damage from ultraviolet light. Melanotan 2 delivers that signal directly, so the melanocyte does not have to wait for UV radiation.
What is melanotan 2?
Melanotan 2 is a short, ring-shaped fragment of the alpha-MSH hormone, built from seven amino acids. It was designed by scientists at the University of Arizona in Tucson, the same team that had earlier created melanotan 1. The ring is formed by a lactam bond between two amino acids. This structure protects the molecule from the enzymes that quickly break down the natural hormone.
The authors of the first clinical study called melanotan 2 a superpotent melanotropic analogue. In laboratory tests it had a very strong effect on pigment cells. PT-141, or bremelanotide, comes from the same family of molecules and was developed later as a drug for sexual dysfunction.
What did the first human study of melanotan 2 show?
The first human study of melanotan 2 found darker skin after only five doses. The paper was published in Life Sciences in 1996. Three healthy men took part. For two weeks they received a subcutaneous injection from Monday to Friday, alternating between melanotan 2 and saline. The participant did not know which one he received on a given day.
The starting dose was 0.01 mg per kilogram of body weight. Two participants were gradually raised to 0.03 mg/kg and one to 0.025 mg/kg. One week after the last dose, two of the three men had clearly darker skin on the face, upper body and buttocks. The change was confirmed by measuring light reflected from the skin, a method that turns colour into a number.
The researchers concluded that melanotan 2 has a tanning effect in humans after only five low doses given every other day. They named 0.025 mg/kg per day as the dose for further phase 1 studies. This recommendation is not advice for anyone. It is a number from the protocol of one study in three people.
| What was measured | Result in the 1996 study |
|---|---|
| Number of participants | 3 healthy men |
| Route | subcutaneous, every other weekday for 2 weeks |
| Doses | 0.01 to 0.03 mg/kg |
| Skin darkening | in 2 of 3 people: face, upper body, buttocks |
| When visible | one week after the last dose |
| Other effects | mild nausea, yawning with stretching, spontaneous erections for 1-5 hours |
What does melanotan 2 do besides tanning?
Melanotan 2 does not act only on the skin, because melanocortin receptors are also found in the brain. In the 1996 study the participants developed a typical pattern of yawning and stretching. It coincided with spontaneous erections that lasted from one to five hours after the dose. Mild nausea that needed no medication was reported at most doses.
At the highest dose, 0.03 mg/kg, one of the two participants felt grade 2 drowsiness and fatigue on the World Health Organization scale. It was this effect on erections that steered further work on this family of molecules towards drugs for sexual dysfunction. PT-141 grew out of that research, described in more detail in the guide on melanotan 2 and PT-141.
What do studies of similar tanning peptides show?
Most of the data on tanning without sun come from studies of melanotan 1, an older alpha-MSH analogue from the same laboratory. Melanotan 1 acts on the same MC1R receptor but has a different, linear structure. Its results show how skin responds to melanotropins, although they cannot be transferred directly to melanotan 2.
- JAMA, 1991. 28 healthy men received 10 injections over 12 days. The skin darkened both in people who tan poorly and in those who tan easily. After placebo there was no change. The skin was darkest one to three weeks after the last dose, even though the participants used a high-factor sunscreen throughout.
- Photochemistry and Photobiology, 2000. In seven volunteers the amount of eumelanin in forearm skin rose by an average of 98 percent, and in forehead skin by 49 percent. The amount of pheomelanin did not change. The tan was therefore made of the dark, protective pigment.
- Archives of Dermatology, 2004. People who combined melanotan 1 with sun exposure tanned more deeply than the sun-only group. The tan lasted at least three weeks longer. The group without the peptide needed 50 percent more time in the sun to reach the same shade. In one part of the study, the skin of people on the peptide also had 47 percent fewer sunburn cells after irradiation.
These three papers show the mechanism that also works for melanotan 2. A synthetic melanotropin switches melanocytes to eumelanin, and the tan keeps deepening for several weeks after dosing ends.
How does melanotan 2 differ from melanotan 1 and afamelanotide?
Melanotan 2 is shorter and more potent than melanotan 1, but it acts more broadly, because it also stimulates receptors in the brain. Melanotan 1 received the international name afamelanotide. Under the brand name Scenesse it was approved in the European Union on 22 December 2014. The indication is prevention of phototoxic reactions in adults with erythropoietic protoporphyria, a rare disease in which sunlight causes severe skin pain.
| Feature | Melanotan 2 | Melanotan 1 (afamelanotide) |
|---|---|---|
| Structure | 7 amino acids, closed in a ring | full alpha-MSH chain, linear |
| Main effect in studies | tan, spontaneous erections, nausea | tan |
| Status | not approved, research material | drug Scenesse, implant under the skin every 2 months |
| Largest study | 3 people (1996) | 168 patients in two trials (2015) |
In trials published in the New England Journal of Medicine in 2015, afamelanotide extended the time patients could spend in the sun without pain. In the US part the median was 69.4 hours against 40.8 hours on placebo. This was the first proof that a synthetic melanotropin gives the skin real protection from light, not just colour.
What is not known about melanotan 2?
Melanotan 2 has not been through large clinical trials and is not approved as a drug in any country. The only published tanning study covered three people and lasted two weeks. There are no data on use over many months, or on how long the tan lasts after dosing ends.
The New Zealand dermatology service DermNet describes darkening of existing moles and the appearance of new ones in people using melanotan 2. Such changes make it harder for a dermatologist to assess the skin, so moles are worth having checked by a doctor before research starts and regularly during it. The status of peptides sold as research material is described in the guide on the legal status of peptides.
Where to buy melanotan 2 and how much does it cost?
In the shop, melanotan 2 comes in vials of 10 mg lyophilised powder from two brands. MT-2 10 mg Genheal costs 25 EUR. MT-2 10 mg Bio-Peptide also costs 25 EUR. Both versions, a description of the molecule and the price per milligram are on the melanotan 2 page.
The vial contains a powder that is dissolved in bacteriostatic water before use. The whole procedure is described step by step in the guide on how to reconstitute peptides. Undissolved powder is best kept in the fridge, away from light.
Frequently asked questions
Does melanotan 2 tan without sun?
Yes. In the 1996 study the skin of two of the three participants darkened after five doses, without deliberate sunbathing. Similar peptides darkened the skin even in people using sunscreen.
How soon does a tan appear after melanotan 2?
In the 1996 study the darkening was measured one week after the last dose. In studies of melanotan 1 the skin was darkest one to three weeks after dosing ended.
How does melanotan 2 act on the skin?
It binds to the MC1R receptor on melanocytes and switches them to producing eumelanin, the dark pigment. This is the same pathway that the sun triggers.
How does melanotan 2 differ from melanotan 1?
Melanotan 2 is shorter, closed in a ring and also acts on receptors in the brain. Melanotan 1, or afamelanotide, is approved in the EU as the drug Scenesse, while melanotan 2 has no approval.
Is melanotan 2 an approved drug?
No. Melanotan 2 is not approved in any country and is sold as research material. Only the related afamelanotide and bremelanotide, or PT-141, are approved.
This is information about published research, not medical advice. The choice of treatment belongs to a doctor.
Sources
- Dorr RT, Lines R, Levine N et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sciences, 1996, 58(20): 1777-1784. https://doi.org/10.1016/0024-3205(96)00160-9
- Levine N, Sheftel SN, Eytan T et al. Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin. JAMA, 1991, 266(19): 2730-2736. https://pubmed.ncbi.nlm.nih.gov/1658407/
- Dorr RT, Dvorakova K, Brooks C et al. Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-alpha-MSH in humans. Photochemistry and Photobiology, 2000, 72(4): 526-532. https://pubmed.ncbi.nlm.nih.gov/11045725/
- Dorr RT, Ertl G, Levine N et al. Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Archives of Dermatology, 2004, 140(7): 827-835. https://doi.org/10.1001/archderm.140.7.827
- Langendonk JG, Balwani M, Anderson KE et al. Afamelanotide for Erythropoietic Protoporphyria. New England Journal of Medicine, 2015, 373(1): 48-59. https://doi.org/10.1056/NEJMoa1411481
- European Medicines Agency. Scenesse (afamelanotide), European public assessment report. https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse
- DermNet. Melanotan II. https://dermnetnz.org/topics/melanotan-ii