Melanotan I vs Melanotan II: Approval, Evidence and Safety Signals

The biggest difference is that Melanotan I is the same molecule as an approved drug, and Melanotan II is not. Melanotan I is afamelanotide, sold as the Scenesse implant, which FDA approved in 2019 for adults with a rare light-sensitivity disorder called erythropoietic protoporphyria (EPP). Melanotan II is a different, ring-shaped peptide that acts on several melanocortin receptors, and we found no approval for it from any regulator (a DailyMed search on September 30, 2026 returned no label for melanotan, and only Scenesse for afamelanotide). No trial has compared the two head to head, and vials sold online under either name are unapproved products, not the Scenesse implant.

At a glance

How they work differently

Both are lab-made copies of alpha-melanocyte-stimulating hormone (alpha-MSH), the signal that tells skin cells to make dark pigment. The difference is in the shape and in which receptors they switch on.

Melanotan I is a straight-chain peptide. The Scenesse label describes it as a melanocortin receptor agonist that binds predominantly to MC1-R, the pigment receptor in skin, and says it raises production of the dark pigment eumelanin independently of sunlight or artificial UV (Scenesse prescribing information, DailyMed, label dated May 2026). Melanotan II is a lactam-bridged cyclic peptide built from a fragment of alpha-MSH (Dorr et al., Life Sciences, 1996), and the researchers who tested it in men called it a non-selective melanocortin receptor agonist (Wessells et al., International Journal of Impotence Research, 2000). A review of the field says activating melanocortin receptors in the brain can trigger spontaneous erections, and MT-II is the one of the pair that went into erectile-dysfunction studies (King et al., Current Topics in Medicinal Chemistry, 2007).

A 2006 history of the two compounds puts the split plainly: the linear MT-I was tested clinically for tanning, and the cyclic MT-II for erectile dysfunction (Hadley and Dorr, Peptides, 2006). The erection and desire studies we found were all of MT-II. Our single-compound guides go deeper: Melanotan I and Melanotan II.

What the evidence shows

Head to head. We searched PubMed on September 30, 2026 for human studies that compared the two and found none. Studies of each compound use different people, different products, different routes and different endpoints, so lining up their numbers would be unreliable. What follows is each compound's evidence on its own terms.

Melanotan I. This is the only compound in the pair with randomized, placebo-controlled trials. In two multicenter trials of the implant in adults with EPP (74 patients in the European Union, 94 in the United States), time in direct sunlight without pain was longer with afamelanotide than with placebo (median 69.4 versus 40.8 hours in the US trial and 6.0 versus 0.8 hours in the EU trial), quality of life improved, and adverse events were mostly mild (Langendonk et al., New England Journal of Medicine, 2015). That is a result in patients with an inherited disease, under clinical supervision, with a sterile licensed product. For healthy-volunteer tanning, the evidence is a study of seven volunteers, where a short course of MT-I under the skin darkened the face, neck and forearm and raised eumelanin in skin biopsies (Dorr et al., Photochemistry and Photobiology, 2000). In vitiligo, a randomized trial of 55 people found faster and greater repigmentation when the implant was added to narrowband UVB light than with light alone; nausea and minor infections were among the events noted in the combination group (Lim et al., JAMA Dermatology, 2015). Vitiligo is not an approved use.

Melanotan II. Human evidence is three small studies from the 1990s and 2000. A pilot in three healthy men found increased pigmentation in two of them, along with nausea, spontaneous erections and, in one man at the highest dose reached, significant sleepiness and fatigue (Dorr et al., 1996). In a double-blind crossover study of ten men with psychogenic erectile dysfunction, eight developed clinically apparent erections after MT-II (Wessells et al., Journal of Urology, 1998). A follow-up in 20 men with erectile dysfunction reported erections in 17 without sexual stimulation, increased desire after 13 of 19 MT-II doses versus 4 of 21 placebo doses, and severe nausea in 12.9% of participants at the dose tested (Wessells et al., 2000). Those studies show the effects exist. They do not measure safety at any scale, and we found no larger controlled trial.

A plain reading. The evidence is stronger for Melanotan I than for Melanotan II because it has randomized trials and a regulator's review behind it, but only for the approved implant in EPP. For the reasons most buyers search these names (tanning, sexual effects), both compounds rest on a handful of small early studies, and neither set of studies tells you what an unsupervised vial does.

Side effects and risks compared

Melanotan I, the approved implant. In three vehicle-controlled trials of 244 adults with EPP, the most common reactions were implant-site reactions (21% on Scenesse versus 10% on vehicle), nausea (19% versus 14%), skin hyperpigmentation (4% versus 0%) and melanocytic nevus (4% versus 2%). The label warns that it may darken existing moles and freckles, recommends regular full-body skin examinations, and notes serious hypersensitivity reactions, including anaphylaxis, reported after approval (Scenesse label). Those numbers come from supervised use of a licensed implant, not from vials.

Melanotan II. There is no label and no incidence data. What exists is trial observations (nausea, yawning, sleepiness) and case reports. One report describes a man who injected internet-bought product and developed a racing heart, tremors, muscle breakdown and kidney injury, with mass spectrometry confirming the substance was MT-II (Nelson et al., Clinical Toxicology, 2012). Another describes ischemic priapism after an MT-II injection that needed surgical decompression, and notes only two earlier such reports in the literature (Mallory et al., Sexual Medicine, 2021). A separate case of low-flow priapism after a melanotan injection did not specify which melanotan in its abstract (Dreyer et al., BMJ Case Reports, 2019). FDA's own page on bulk substances flagged in its compounding review lists Melanotan II with published case reports of melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism (FDA, content current as of April 22, 2026).

What they share. A 2017 dermatology review said afamelanotide has been thoroughly tested for its approved use, but that illegal melanotans are likely risky: uncertain preparation and dosage, and case reports tying unregulated use of both melanotan I and II to changes in existing moles and new atypical moles. It counted four case reports of melanoma emerging from existing moles during or shortly after use and said conclusive evidence of a link is lacking (Habbema et al., International Journal of Dermatology, 2017). Many reports do not say which melanotan was used. Case reports cannot give a rate, so nobody can say from this literature which compound is riskier when used without supervision. The serious reports we found that name a specific compound (muscle and kidney injury, ischemic priapism) name Melanotan II.

What is in the vial. An independent analysis of MT-II vials bought from three online shops found impurities of about 4% to 6% in vials from two of them, and peptide content below the labelled amount in every case (Breindahl et al., Drug Testing and Analysis, 2015). That is one study from 2015 and it did not include MT-I.

What the lab tests show

As of September 30, 2026, VendorVerify's database has three Melanotan I vials from two vendors, with purity from 99.72% to 99.85% and all three measuring about 5% to 8% over their labelled amount. One vial has an endotoxin result, a pass. The database has one Melanotan II vial: 99.93% pure and about 13% over label. None of the four met our failure definition (empty, under 95% pure, more than 20% under label, or more than 50% over).

That is four vials in total, so the numbers cannot rank one compound against the other or say anything about a vendor. Purity and amount also say nothing about sterility or endotoxin, or about the safety signals above. Results pages: Melanotan I and Melanotan II.

Because we don't have enough lab data on either compound to rank vendors for it, here are the highest-ranked vendors across all compounds right now. A vendor's overall record is a signal, not a guarantee for a compound they have never had tested.

Buying smarter

With this little compound-specific data, the general checks do the work. Look at each vendor's full record and how many reports sit behind the score. Treat a vendor-posted COA as a starting point (how to read a peptide COA, fake peptide COAs). Independent identity, purity and quantity testing on your own vial is the only way to know what you have, and endotoxin testing matters for anything injected; how to get a peptide tested walks through it. Given how few results exist for either compound, submitting a report adds real information. If a report comes back with a fail, stop using that batch, tell anyone who bought from the same run, and bring the report to the vendor.

Database figures are from VendorVerify as of September 30, 2026. This isn't medical advice; Scenesse is the only approved form of Melanotan I and is prescribed for one condition, and vials sold online under either name are unregulated research chemicals.