Melanotan I and II: one became a licensed drug, the other a mole-changing tanning jab

“Melanotan” is two different synthetic peptides developed at the University of Arizona, and the split between them is the whole story [1]. Melanotan I, now called afamelanotide, went through proper trials and is an approved medicine in Europe and the US for erythropoietic protoporphyria, a rare disease in which sunlight causes severe pain [6–8]. Melanotan II was never approved for anything. It is sold online as a tanning injection, and dermatologists have published case reports of changing moles and melanoma in people using it [9,10].

What the two peptides are

Both are copies of α-melanocyte-stimulating hormone (α-MSH), the body’s signal for pigment cells to make melanin, redesigned to resist breakdown and bind more strongly [1].

The difference in shape matters. Melanotan II is shorter and ring-shaped and acts on melanocortin receptors much less selectively [13]. That broader action is thought to explain why it causes erections and nausea as well as tanning [3], and a close relative of it, bremelanotide, went on to become a sexual desire drug [1].

The 1991 JAMA study was Melanotan I

The best-known early human tanning trial, published in JAMA in 1991, is sometimes cited as evidence for Melanotan II. It wasn’t about Melanotan II. The compound was [Nle4, D-Phe7]-α-MSH [2], the same molecule later developed as afamelanotide [8], in other words Melanotan I. The pilot study of Melanotan II in people wasn’t published until 1996 [3].

The result showed that human skin could be darkened without ultraviolet light [2]. The developers hoped such a tan might lower skin cancer risk in fair-skinned people [1], but we found no trial that has tested that.

Melanotan II in people

The first Melanotan II study, in 1996, was a pilot phase I trial in three healthy men [3]. It reported mild nausea at most doses, grade II sleepiness and fatigue in one of two men at the highest dose, a stretching-and-yawning pattern, and spontaneous erections lasting one to five hours. Two of the three men showed increased pigmentation of the face, upper body and buttocks a week after dosing ended [3].

The erection finding redirected research. In a double-blind crossover in 10 men with erectile dysfunction of psychological origin, 8 developed erections on Melanotan II [4]. A second crossover in 10 men with physical risk factors for erectile dysfunction found erections after 12 of 19 Melanotan II injections vs 1 of 21 placebo doses; 4 of the 19 injections caused severe nausea [5]. Those are tiny studies from the developers’ own group, and Melanotan II went no further as a medicine.

Afamelanotide: the version that worked

Afamelanotide’s approved use has nothing to do with cosmetic tanning. People with erythropoietic protoporphyria (EPP) build up a light-sensitive compound in the skin, and even short sun exposure causes intense burning pain.

What afamelanotide looks like outside trials

A Swiss clinic followed 39 people with EPP treated with afamelanotide between 2016 and 2018 [16]. Before treatment, the median time they could spend in sunlight before a painful reaction was 10 minutes; on treatment it rose to a median of 180 minutes. The worst reaction’s pain score fell from a median of 10 to 6 out of 10, and 97.4% of patients kept up their implants [16]. That’s observational data without a comparison group, but for a disease where people had been planning their lives around avoiding daylight, it is a striking change, and the gap between these figures and the more modest trial medians is worth noting.

Quality of life improved in both randomised trials, and adverse events were mostly mild [6]. The trials were funded by the manufacturer, Clinuvel, among others [6]. The European Medicines Agency authorised afamelanotide as Scenesse in December 2014 under “exceptional circumstances”: the agency said complete information on benefits couldn’t be obtained, partly because the disease is so rare, and the company must supply longer-term data from a patient registry [7]. The FDA approved it in 2019 to increase pain-free light exposure in adults with EPP [8].

Even in this controlled setting, the FDA label warns that it can darken existing moles and freckles and recommends a full-body skin check twice a year [8]. In the placebo-controlled trials, new or changed moles (“melanocytic nevus”) were reported in 4% on afamelanotide vs 2% on placebo, and nausea in 19% vs 14% [8].

Why Melanotan II is a different risk

The contrast between the two peptides isn’t only about paperwork. Afamelanotide is given as a 16 mg implant every two months by a trained clinician, to a defined patient group, with skin checks twice a year [8]. Melanotan II bought online is self-injected at doses people pick themselves, often alongside deliberate sun or sunbed exposure. Its trial record amounts to a handful of men in small studies in the 1990s, with frequent nausea and, in one study, severe nausea after about one injection in five [3,5]. Nobody has run a trial of it as a tanning product, so there are no controlled data on moles, skin cancer or long-term use.

The unlicensed market and the mole problem

Melanotan II sold online is a different proposition. When researchers bought vials from three online shops, all claiming 10 mg, the vials held between 4.32 and 8.84 mg, and two shops’ products had 4.1% to 5.9% unknown impurities [14].

The skin reports are case reports, which can’t prove cause, but they share a pattern:

• A 20-year-old woman developed a melanoma on her buttock three months after a 3- to 4-week course of self-injected Melanotan II combined with sunbed use [10].
• A German report described new moles appearing, and existing ones darkening, within 24 hours of a single Melanotan II injection [11].
• A teenager with a hereditary syndrome of multiple atypical moles had changes in her moles after melanotan injections and sunbed use [12].

A 2017 Dutch review counted four published cases of melanoma arising in existing moles during or shortly after melanotan use and noted rising reports of new, sometimes atypical moles [9]. The authors were careful to say conclusive evidence of a causal link is lacking [9]. Part of the difficulty is that people who inject tanning products often use sunbeds as well, which independently raises melanoma risk.

Other reported harms are rarer. A Swedish team described a kidney infarction most likely linked to Melanotan II and reviewed earlier reports of muscle breakdown and kidney failure [13].

Is melanotan legal in the UK?

The short answer is that Melanotan II has never been approved as a medicine anywhere, and the MHRA treats products that meet the legal definition of a medicine as unlicensed, which is why it has kept removing them from sale.

Afamelanotide (Scenesse) is a prescription implant approved for EPP in the EU and US, given by trained clinicians [7,8]. Melanotan II has never been approved as a medicine anywhere. In the UK, the MHRA says melanotan II products that meet the legal definition of a medicine must be authorised before they can be sold, and it has been removing such products from sale for over 10 years; between 2011 and 2021 it received 13 Yellow Card reports of suspected reactions [15]. The MHRA also notes that injectable melanotan II isn’t automatically classed as a medicine, and nasal sprays sold without medical claims generally aren’t regulated as medicines [15], which is one reason these products remain easy to find.

What is still open

• Whether Melanotan II raises melanoma risk, or whether the case reports reflect sunbed use and pre-existing moles.
• The long-term skin effects of repeated afamelanotide implants over many years.
• Whether a sunless tan from these peptides protects against sunburn or skin cancer, a hypothesis never tested in an outcome trial.
• What most online melanotan products actually contain.

What this means

Our position is that Melanotan II should not be used, and the case for that does not rest on a missing trial. Two things are already established. First, the moles: a 20-year-old developed a melanoma on her buttock three months after a short course of self-injected Melanotan II, new moles appeared within 24 hours of a single injection, and a review counted four melanomas arising in existing moles [9–12]. Second, the supply: vials sold online as 10 mg held between 4.32 and 8.84 mg, and two shops’ products carried 4.1% to 5.9% unknown impurities [14]. A drug that redirects the skin’s pigment cells, is dosed by guesswork and arrives with unknown impurities is a risk we would not take for a tan, and we think you should not either.

The approval of afamelanotide does not launder Melanotan II. Afamelanotide is a fixed 16 mg implant placed every two months by a trained clinician, in a defined patient group, with a full-body skin check twice a year [8]. Every part of that scaffolding is what makes it a medicine: the dose, the route, the monitoring, the follow-up. Self-injecting a vial bought online, at a dose you choose, alongside sunbed exposure, strips all of it away. The two peptides share a family resemblance, not a safety record.

Where the evidence is genuinely thin, we will say so: no controlled trial has tested Melanotan II as a tanning product, and the case reports cannot establish cause on their own, because people who inject tanning peptides often use sunbeds as well. That fact cuts one way here. A trial of Melanotan II as a tanning product will never be run, because nothing funds it, so the melanoma risk will stay unquantified indefinitely. An unmeasured risk that is never going to be measured is not a small one. It is one you carry without a number attached.

Educational content only — not medical advice. Many peptides discussed on HPR are not approved for human use. Talk to a qualified clinician before making any decision about your health.