Melanotan-II

Origin and structure

Melanotan II is a shortened, chemically locked copy of α-melanocyte-stimulating hormone (α-MSH), the 13-amino-acid hormone that signals pigment cells to make melanin. Chemists working with Victor Hruby and Mac Hadley at the University of Arizona in Tucson described it in 1989 as one of a series of ring-shaped α-MSH fragments. They kept the active core, replaced methionine with norleucine and phenylalanine with its mirror-image D-form, and joined two side chains with a lactam bridge so that the peptide closes into a ring. The result, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, has seven amino acids, and in lizard-skin tests it was about 90 times as potent as α-MSH.

It came out of the same Arizona melanocortin programme as melanotan I, the longer, linear analogue later developed as afamelanotide. The same group took melanotan II into people in the 1990s: first a three-man pilot on tanning, which also recorded spontaneous erections, then two small trials in men with erectile dysfunction. Larger trials never followed. They did for its near-twin bremelanotide (PT-141), while melanotan II now circulates mainly as an unlicensed tanning injection bought online or in gyms, nicknamed the 'Barbie drug'.

How it is thought to work

Melanotan II binds the MC1, MC3, MC4 and MC5 melanocortin receptors with high affinity, so it is not selective. MC1 receptors sit on melanocytes, the pigment cells of the skin; activating them increases melanin production and darkens the skin. MC4 receptors are found on nerve cells in many parts of the brain and spinal cord, and their activation is thought to explain the rest of what melanotan II does: the erections, the stretching and yawning that came before them in the first volunteers, the nausea and the loss of appetite.

That spread of targets is the main difference from its relatives. Afamelanotide was developed for its action on the MC1 receptor in the skin. Bremelanotide differs from melanotan II only at the end of the chain, a free acid where melanotan II has an amide; it too activates several receptor types, and its US label names MC1 and MC4 as the ones that matter at the approved dose and lists skin darkening among its side effects.

Is melanotan II approved?

No. No regulator in the EU, the US or anywhere else has authorised a medicine containing melanotan II, and it never went through the trials that could support one. In the Netherlands it is not a registered medicine, so it may not be sold, advertised or supplied for use in people; it is available only as research material, which is the basis on which our shop sells it. Dutch doctors have documented what happens when it is used anyway: dermatologists from Bussum, Leiden and Rotterdam reviewed the risks in 2017, noting that several national health authorities had issued warnings, and internists in Gouda described a young man with a poisoning reaction in the Nederlands Tijdschrift voor Geneeskunde in 2022.

In the United States it is an unapproved drug. The FDA placed melanotan II in Category 2 of its compounding lists, for bulk substances that may pose significant safety risks. Its reasons: possible immune reactions caused by aggregation or peptide impurities, and published case reports of melanoma, posterior reversible encephalopathy syndrome (sudden brain swelling with headache, seizures or loss of vision), a sympathomimetic toxidrome and priapism. The nomination was later withdrawn by the party that made it, and the FDA's page, last updated in April 2026, now lists melanotan II under nominations withdrawn, with the same safety concerns still written beside it.

Two relatives are approved medicines, and neither approval covers melanotan II. Afamelanotide (melanotan I) is approved as Scenesse, an implant for the rare light intolerance erythropoietic protoporphyria. Bremelanotide is approved in the US as Vyleesi, since 2019, for low sexual desire in premenopausal women; it has no marketing authorisation in the EU.

In sport melanotan II is prohibited at all times. The WADA list does not name it, but class S0 bans any pharmacological substance that no health authority has approved for human therapeutic use, and the Dopingautoriteit's Dutch translation of the 2026 list carries the same wording.

What the research shows

Almost everything known about melanotan II in people comes from three small studies by the Arizona group, published between 1996 and 2000, with 23 men in total. The only tanning data come from three of them, and no study lasted longer than two weeks. Since then the human literature has consisted of case reports from unlicensed use and laboratory tests of products sold online.

• Phase 1 pilot (Dorr et al., Life Sciences 1996): 3 healthy men received melanotan II and saline on alternating weekdays for two weeks, single-blind. Two had more pigmentation of the face, upper body and buttocks one week after the last dose, measured by skin reflectance. Mild nausea occurred at most dose levels, one of the two men on the highest dose had moderate (grade II) drowsiness and fatigue, and spontaneous erections came and went for 1 to 5 hours after each dose, with their onset coinciding with stretching and yawning.
• Psychogenic erectile dysfunction (Wessells et al., Journal of Urology 1998): a double-blind, placebo-controlled crossover trial in 10 men. Eight developed erections on melanotan II; the time with more than 80% rigidity at the tip of the penis averaged 38 minutes, against 3 minutes on placebo. Nausea, stretching and yawning, and reduced appetite were reported more often than on placebo, but none needed treatment.
• Erectile dysfunction with physical risk factors (Wessells et al., Urology 2000): the same design in 10 men. Erections followed 12 of 19 melanotan II injections against 1 of 21 placebo doses, rigidity time averaged 45.3 minutes against 1.9, and sexual desire was higher after melanotan II than after placebo. Severe nausea followed 4 of the 19 injections.
• Product quality (Breindahl et al., Drug Testing and Analysis 2015): vials sold online by three shops as 10 mg contained between 4.32 and 8.84 mg of melanotan II, and the vials from two shops held 4.1 to 5.9% unidentified impurities.

Moles, melanoma and other warnings

In the trials the side effects were nausea, sometimes severe, stretching and yawning, reduced appetite, drowsiness and fatigue, and spontaneous erections. Those trials were too small and too short to pick up rarer or slower harm.

The larger concern comes from case reports of unlicensed use. Dermatologists keep describing existing moles that darken and new, sometimes dysplastic moles in people using melanotan I or II. By 2017 the Dutch review counted four published melanomas that had arisen in existing moles during or shortly after melanotan use, and the FDA still cites melanoma case reports in 2026. Conclusive evidence that melanotan causes melanoma is lacking: these are single cases, and melanotan is mostly used as part of a tanning routine with sunbeds or sunbathing, which raise melanoma risk on their own. For people with many or atypical moles, that uncertainty matters most.

Other reports describe acute reactions: a sympathomimetic poisoning picture (the 2022 Gouda case: a 27-year-old man who reached the emergency department two hours after an injection and was treated with lorazepam, potassium and intravenous fluids), priapism (a painful erection that will not go away), and posterior reversible encephalopathy syndrome. With unlicensed products the dose and the contents are uncertain, as the 2015 vial analysis showed.

Melanotan II, melanotan I and bremelanotide

The three names are easy to mix up. Melanotan I (afamelanotide) is a linear analogue of the full 13-amino-acid α-MSH, approved as Scenesse, an implant placed under the skin by specialist centres for erythropoietic protoporphyria. Melanotan II is the shorter, cyclic analogue described here, never approved. Bremelanotide (PT-141) is almost the same molecule as melanotan II and is the only one of the two that completed phase 3 trials.

Bremelanotide's US label shows what this receptor profile does in larger controlled numbers. In the phase 3 trials nausea affected 40% of 627 women against 1.3% of 620 on placebo, and flushing 20%; blood pressure rose transiently by up to 6 mmHg systolic after each dose; and focal darkening of the face, gums and breasts appeared in 1% of women using it at most eight times a month, but in 38% after eight daily doses, and did not always fade after stopping. Melanotan II has never been through comparable trials, so its rates are unknown.

Frequently asked questions

Is melanotan II legal in the Netherlands?

It is not a registered medicine in the Netherlands or anywhere else, so it may not be sold, advertised or supplied for use in people, including as a tanning injection. Buying and selling it as research material is a different status, which our guide on research-use-only products in the Netherlands explains. For athletes under anti-doping rules it is prohibited however it was obtained.

Can melanotan II cause melanoma?

Nobody knows. There are no studies that could answer it, only case reports: new and darkening moles are described repeatedly, and by 2017 four melanomas arising in existing moles during or shortly after melanotan use had been published. Melanotan is mostly used alongside sunbeds or sunbathing, so the reports do not prove cause, but dermatologists and the FDA treat the signal seriously, particularly for people with many or atypical moles or a history of melanoma.

What is the difference between melanotan II and PT-141?

Chemically very little: PT-141 (bremelanotide) has a free acid where melanotan II has an amide at the end of the chain. The difference is in the evidence. Bremelanotide went through two 24-week phase 3 trials with more than 1,200 women and is approved in the US as Vyleesi for low sexual desire in premenopausal women. Melanotan II stopped after studies in 23 men and has no approval anywhere.

Melanotan I or melanotan II: what is the difference?

Melanotan I is afamelanotide, a linear analogue of the whole α-MSH hormone that acts mainly on the pigment cells of the skin and is approved, as the Scenesse implant, for the light intolerance erythropoietic protoporphyria. Melanotan II is a shorter, ring-shaped analogue that also acts in the brain, which is why it causes nausea, yawning, erections and loss of appetite as well as tanning, and it has never been approved.

Is melanotan II banned in sport?

Yes, at all times, in and out of competition. The WADA list does not name it, but class S0 covers every pharmacological substance without approval for human therapeutic use by any health authority, and melanotan II has none. The Dopingautoriteit applies the same list in the Netherlands. See our guide on peptides and the doping list.

Has melanotan II been tested in humans?

Only in three small studies from the University of Arizona between 1996 and 2000, with 23 men in total and no exposure longer than two weeks: one pilot in which 2 of 3 men tanned, and two placebo-controlled crossover trials in men with erectile dysfunction. No further human trial has been published since.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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