Melanotan 1 vs Melanotan 2: differences, evidence and safety

Verdict: Melanotan 1 is afamelanotide, an FDA- and EMA-approved implant (Scenesse) for the light-sensitivity disorder erythropoietic protoporphyria. Melanotan 2 is unapproved anywhere we checked; its human evidence is three small trials published 1996–2000 plus case reports of serious harm.

Melanotan 1 (MT-1) has the stronger record by a wide margin. Two randomized, placebo-controlled phase 3 trials showed that afamelanotide implants increased pain-free time in sunlight for people with erythropoietic protoporphyria (EPP) [Human RCT, n=74 and n=94] (Langendonk 2015), and the FDA approved it in October 2019 (FDA approval letter). Melanotan 2 (MT-II) triggered erections in small trials [Human RCT, n=10] (Wessells 1998), but it was never approved, and the FDA notes published case reports of melanoma, a brain-swelling syndrome and priapism (FDA). Neither is approved for cosmetic tanning.

Item	Melanotan 1 (afamelanotide)	Melanotan 2
US FDA status	Approved October 8, 2019 as Scenesse implant for adults with phototoxic reactions from EPP (FDA); not approved for tanning	Not approved for any use; a 2017 review called afamelanotide the only approved alpha-MSH analogue at the time (Habbema 2017)
Compounding (503A/503B)	Approved product; not on FDA’s Category 2 safety-risk list	Was in Category 2; now listed as “nominated but withdrawn”, with FDA’s safety concerns still posted (FDA); no next step announced
EU	Authorised December 22, 2014, under exceptional circumstances (EMA)	Not authorised
WADA 2026	Not named; as an approved drug it falls outside S0 (WADA 2026 List)	Not named; applying S0’s wording (substances with no current regulatory approval are banned at all times), it would fall under S0, as we found no approval for it
Strongest evidence	Approved label; two phase 3 RCTs	Small crossover RCTs (n=10 each); case reports of harm
Human trials	NCT01605136, NCT00979745, NCT06109649 (vitiligo, running)	Published 1996–2000, before trial registration was routine; none completed on ClinicalTrials.gov
Next regulatory step	None announced in the sources checked; the vitiligo phase 3 trial (NCT06109649) passed its estimated primary completion (December 2025) with no results posted	None announced
Last checked	2026-10-04	2026-10-04

What changed (October 2026): Clinuvel’s July 2026 update on afamelanotide’s vitiligo trials (210 patients enrolled, results expected in December 2026) is added, and the sport section covers the 2027 WADA List.

Melanotan 1 vs Melanotan 2 at a glance

Feature	Melanotan 1	Melanotan 2
What it is	Afamelanotide, a linear 13-amino-acid alpha-MSH analogue	A cyclic 7-amino-acid alpha-MSH analogue
Brand	Scenesse (Clinuvel)	None
Main receptor	Binds mainly MC1R, the pigment receptor on skin cells	Non-selective: several melanocortin receptors, including brain ones
Main research focus	Light-sensitivity disorders (EPP, vitiligo, polymorphic light eruption)	Tanning, then erectile dysfunction
Best human evidence	Two phase 3 RCTs in EPP (NEJM 2015)	Two crossover RCTs in erectile dysfunction, n=10 each (Urology 2000)
Approval	FDA (2019), EU (2014), for EPP only	None
WADA	Not named on the List	Not named; falls under S0 by that class’s wording (non-approved substances)
Route studied	Under the skin (injection, then a slow-release implant)	Under the skin (injection)
Tanning onset in studies	Peak 1–3 weeks after a course ended	Visible 1 week after dosing ended (n=3)
Main safety concerns	Nausea, implant-site reactions, darker moles, rare anaphylaxis	Nausea, spontaneous erections, priapism, mole changes, melanoma case reports
Product quality	Regulated, made to approved standards	Unregulated; dose and purity unreliable

What is Melanotan 1?

Melanotan 1 was built at the University of Arizona as a longer-lasting copy of alpha-melanocyte-stimulating hormone (alpha-MSH), the hormone that tells skin cells to make the dark pigment eumelanin (Hadley and Dorr 2006). Under the name afamelanotide it became the first alpha-MSH analogue given to human volunteers (Minder 2017). Today it is sold as Scenesse, a small dissolving rod placed under the skin by a trained health professional. In the US it is approved to increase pain-free light exposure in adults with a history of phototoxic reactions from EPP, a rare inherited condition in which light on the skin causes severe pain (Scenesse label). It is not approved for cosmetic tanning.

What is Melanotan 2?

Melanotan 2 came from the same Arizona group: a truncated, ring-shaped (cyclic) peptide that was tested for tanning and then for erectile dysfunction (Hadley and Dorr 2006). Its sexual effects were found by accident during the tanning studies (Hadley 2005). A Melanotan 2 analogue, PT-141, was then being readied for phase 3 trials (Hadley and Dorr 2006); as bremelanotide, the FDA approved it in 2019 as Vyleesi for low sexual desire in premenopausal women (Vyleesi label). Melanotan 2 itself was never approved; what circulates under that name is sold online, in gyms and in tanning salons (Langan 2010).

How they work differently

• Melanotan 1: binds mainly the melanocortin-1 receptor (MC1R) on pigment cells and raises eumelanin production without sunlight [Approved label] (Scenesse label). Melanotan 2: a non-selective melanocortin agonist (Wessells 2000) whose sexual effects arise in the brain (Hadley 2005).
• Melanotan 1: in seven volunteers, forearm eumelanin rose 98% a week after injections ended, while the reddish pigment pheomelanin did not change [Human, n=7] (Dorr 2000). Melanotan 2: two of three volunteers developed darker skin on the face, upper body and buttock [Human, n=3] (Dorr 1996).
• Melanotan 1: side effects in an early volunteer study were limited to occasional stomach upset and facial flushing [Human, n=3] (Ugwu 1997). Melanotan 2: the brain effects show up as yawning, stretching, nausea and spontaneous erections lasting 1–5 hours after a dose (Dorr 1996).

Vyleesi, an approved relative of Melanotan 2, illustrates the broader receptor profile: its label lists MC1R and MC4R activity, nausea in 40% of users and patchy skin darkening (Vyleesi label).

Evidence head-to-head

Outcome	Melanotan 1 best evidence	Melanotan 2 best evidence
Tanning in healthy people	Human RCT, n=28: darkening in both skin-type groups studied (I–II and III–IV), none on placebo (JAMA 1991)	Human pilot, n=3: darker skin in 2 of 3 (Life Sci 1996)
Sunburn protection	Human phase 1, n=8: 47% fewer sunburn cells (Arch Dermatol 2004)	No human data
Pain-free sun time in EPP	Human RCTs, n=74 and n=94; approved label (NEJM 2015)	No human data
Vitiligo repigmentation	Human RCT, n=55: 48.64% vs 33.26% with light therapy alone (JAMA Dermatol 2015)	No published human data
Erections	No human data	Human crossover RCT, n=10: erections in 8 of 10 (J Urol 1998)
Sexual desire	No human data	Human crossover RCTs, n=20: higher desire after 68% of doses vs 19% placebo (IJIR 2000)
Long-term safety	Label safety pool of 244 adults; up to 8 years of use reported in EPP (review)	No controlled data; case reports only

The EPP trials are the most encouraging data for either peptide. In the US trial, people on afamelanotide had a median of 69.4 pain-free hours in direct sunlight over six months versus 40.8 hours on placebo; in the European trial, phototoxic reactions fell from 146 to 77 [Human RCT] (Langendonk 2015). The trials were funded by the manufacturer, and the EMA authorised the drug under exceptional circumstances because complete benefit data could not be collected in such a rare disease (EMA). The Melanotan 2 trials are small and short; the second crossover study, in men with organic-risk erectile dysfunction, found erections after 12 of 19 injections versus 1 of 21 placebo doses [Human RCT, n=10] (Wessells 2000). How we grade these levels is explained in how we compare peptides.

Vitiligo is afamelanotide’s next possible use. In a filing dated 2026-07-28, Clinuvel reported that its phase 3 trial CUV105 had enrolled 210 patients worldwide, comparing SCENESSE plus narrowband UVB light with the light alone over 20 weeks, with the share of patients reaching 50% repigmentation (T-VASI50) as the main end point; it expects topline results in December 2026. A second trial, CUV107, in 300 patients with darker skin (Fitzpatrick types IV to VI), is expected to start in November 2026 (Clinuvel, SEC Form 6-K). As of 2026-10-27, afamelanotide is not approved for vitiligo in the US or the EU, and these are company statements, not results.

Which fits which goal?

• Melanotan 1 has more evidence for protecting people with EPP from light-triggered pain [Approved label], for darkening skin without UV exposure [Human RCT, n=28] (Levine 1991), and for speeding repigmentation in vitiligo alongside light therapy [Human RCT, n=55] (Lim 2015).
• Melanotan 2 has more evidence for triggering erections in men with erectile dysfunction, from two crossover trials of 10 men each [Human RCT] (Wessells 2000). The analogue taken forward for commercial development was PT-141, not Melanotan 2 (Hadley and Dorr 2006).
• Cosmetic tanning: neither has an approval for it. Melanotan 1 has the cleaner tanning data, but only in supervised studies with pharmaceutical-grade product.

These are statements about evidence, not recommendations. A clinician who knows the person’s history and skin is the one to decide whether any treatment is appropriate; this page is general information, as set out in the medical disclaimer.

Can they be combined?

No controlled human study has tested the combination, so nothing is known about whether taking both changes either peptide’s effects or risks. Every published Melanotan 2 trial tested it alone (Wessells 2000), as did the afamelanotide trials behind its approval (Langendonk 2015). A review of unregulated use found that case reports of new and changing moles involve both melanotan I and II products (Habbema 2017).

Safety and regulatory status

Melanotan 1 (Scenesse)

In three placebo-controlled trials of 244 adults with EPP, the most common side effects were implant-site reactions (21% vs 10% on placebo) and nausea (19% vs 14%); skin darkening (4% vs 0%) and new moles (4% vs 2%) were also more frequent [Approved label] (Scenesse label). Serious allergic reactions, including anaphylaxis, have been reported since approval. Safety in children and in pregnancy has not been established, and no carcinogenicity studies were run. A review of afamelanotide reported no late effects in volunteers followed 25 years after first exposure (Minder 2017).

Melanotan 2

Melanotan 2 has no controlled long-term safety data. In one erectile dysfunction trial, severe nausea followed 4 of 19 injections [Human RCT, n=10] (Wessells 2000). Case reports describe:

• new moles and darkening of existing ones within 24 hours of a single injection (Schulze 2014);
• melanoma arising from existing moles during or shortly after melanotan use, in four reports, without proof of cause (Habbema 2017);
• muscle breakdown (rhabdomyolysis) and kidney dysfunction after an internet-bought injection, confirmed as Melanotan 2 by lab testing (Nelson 2012), and a kidney infarction most likely linked to it (Peters 2020);
• priapism, a painful erection that will not subside, needing surgery in one case (Mallory 2021) and leaving erectile function unrecovered at four weeks in another (Dreyer 2019).

A systematic review of sudden-onset moles grouped melanotan with immunosuppressants and chemotherapy as suspected causes in 41% of 179 cases; 16% of cases had at least one abnormal (dysplastic) mole (Burian 2019).

By jurisdiction

• United States: afamelanotide is approved only as Scenesse for EPP (FDA). Melanotan 2 has no approval; the FDA’s compounding page cites immunogenicity risk and case reports of melanoma, encephalopathy, sympathomimetic toxicity and priapism (FDA).
• European Union: Scenesse is authorised for preventing phototoxicity in adults with EPP and is prescribed only in specialist centres (EMA).
• United Kingdom: the MHRA has raised the risk of blood-borne infection from needle sharing and the potential impurity of unlicensed melanotan products (Langan 2010).
• Sport: the 2026 WADA List names neither peptide. Its S0 class bans at all times any substance with no current regulatory approval for human use; applying that wording, Melanotan 2, which has no approval we could find, would fall under S0 (WADA). The 2027 List, in force from 2027-01-01, also names “peptides” in general in S0 (USADA athlete advisory); Melanotan 2 is still not named.

For the wider picture on unapproved peptides, see are peptides safe?

How long do effects take in studies?

• Melanotan 1, tanning: darkening peaked 1 to 3 weeks after a 12-day course ended [Human RCT, n=28] (Levine 1991), and was still visible 3 weeks after the last dose in a small study [Human, n=3] (Ugwu 1997). Combined with sunlight, the tan lasted at least 3 weeks longer than sun alone [Human, n=8] (Dorr 2004).
• Melanotan 1, EPP: the benefits were measured over 6 and 9 months (Langendonk 2015).
• Melanotan 1, vitiligo: facial repigmentation was reached at 41 days versus 61 days with light therapy alone [Human RCT, n=55] (Lim 2015).
• Melanotan 2: erections came within hours of a dose; skin darkening was measured 1 week after dosing ended [Human, n=3] (Dorr 1996).