Melanotan I, II and afamelanotide: research and regulation

Key points

• Melanotan I and II are synthetic analogues of the hormone alpha-MSH, designed at the University of Arizona. Melanotan I is the same compound as afamelanotide, which is approved only as an implant for adults with erythropoietic protoporphyria (EPP): in the EU since 22 December 2014 and in the US since October 2019 [1][2][3].
• Melanotan II is not approved by any regulator we could check. Regulators in the US, UK, Australia, Ireland and Denmark describe melanotan products sold for tanning as unlicensed or unapproved [14][15][16][17][19][20][21].
• Evidence on unlicensed products is case reports and reviews of them, not trials. They describe mole changes, several melanomas, and kidney, muscle and genital complications. None proves cause [22][23][24].
• A vial labelled “Melanotan-1” is an unapproved product whose contents nobody has verified for you. The tier-list verdict below is “not supported”.

What melanotan I and II are

Alpha-melanocyte-stimulating hormone (alpha-MSH) darkens skin by acting on melanocytes. In 1980 a University of Arizona group reported an analogue with norleucine at position 4 and D-phenylalanine at position 7. It was 26 times as potent as alpha-MSH in one lab assay and resisted breakdown by serum enzymes [5]. That linear peptide became melanotan I. Melanotan II is a different, cyclic peptide from the same programme [6].

The university says Victor Hruby, Robert Dorr and the late Mac Hadley developed, patented and first tested the molecule in Arizona, originally to tan skin before sun exposure and so reduce cancer risk. The university licensed it to a company called Melanotan Inc. in 1995 [7].

Competitive Technologies’ 2005 annual report describes the next steps. It licensed sunless-tanning rights to Melanotan Corporation, which sublicensed them to EpiTan Ltd, an Australian company [8]. A separate licence for sexual dysfunction went to Palatin Technologies. Competitive Technologies terminated it by notice in September 2007 and received an $800,000 payment, reported on 28 January 2008 [9]. The later EPP work was by Clinuvel, the applicant named in the FDA’s approval release [1]. We could not verify how EpiTan became Clinuvel.

Early human work was small. Three phase 1 studies of melanotan I with ultraviolet light or sunlight used 8, 12 and 8 volunteers [11]. A study of 7 volunteers reported tanning at 3 of 8 body sites [10]. The first melanotan II study had 3 men; it recorded nausea, yawning and spontaneous erections [12]. Hadley wrote that the sexual effect was found by accident during tanning studies [13].

Afamelanotide (Scenesse): the approved relative

Afamelanotide is melanotan I as a regulated drug. It is a prescription implant [2].

	United States	European Union
Decision	Approved 8 October 2019 [1]	Authorised 22 December 2014 [3]
Wording	“to increase pain free light exposure in adult patients with a history of phototoxic reactions” from EPP [2]	“Prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP)” [3]
Basis	Two vehicle-controlled trials [2]; Priority Review and Orphan designation [1]	Authorised “under exceptional circumstances” because complete data could not be provided [3]

The US label reports two trials. CUV039 enrolled 93 adults (48 on Scenesse, 45 on vehicle) for 180 days. The median time in direct sunlight on pain-free days was 64.1 hours against 40.5 hours. CUV029 enrolled 74 (38 and 36) for 270 days; the median was 6.0 hours against 0.75 hours on a different measure [2]. These are patient diaries of sun exposure, not cancer outcomes. The EMA page describes a six-month study of 93 patients with 116 hours on average against 61 on placebo [3]. We could not tell from the pages whether this is the same trial as CUV039; the measures differ.

Across the three trials in the safety pool (244 adults), implant-site reactions occurred in 21% against 10%, nausea in 19% against 14%, skin hyperpigmentation in 4% against 0%, and melanocytic nevus in 4% against 2%. The label says it may darken existing moles and freckles and recommends a full-body skin examination twice a year [2]. The EMA says it must not be used with reduced liver or kidney function [3]. The UK and German status of Scenesse was not checked.

Bremelanotide (Vyleesi): another approved melanocortin drug

Bremelanotide is a cyclic melanocortin receptor agonist approved in the US (initial approval 2019) for premenopausal women with acquired, generalized hypoactive sexual desire disorder [4]. Its structure resembles melanotan II’s, with a free acid end in place of an amide [4][12]. The label’s trials were two 24-week placebo-controlled studies in 1,247 women. The desire score rose by 0.5 against 0.2 in one and 0.6 against 0.2 in the other. Satisfying sexual events did not differ. Nausea affected 40%, and focal skin darkening 1% on placebo-controlled use. The label says the mechanism is unknown, and it is contraindicated in uncontrolled hypertension or known cardiovascular disease [4]. Related compounds on this site: PT-141. We did not check EU status.

Why melanotan II is not approved

We found no marketing application, approval or label for melanotan II in the documents we opened. Published records show it was tested for erectile dysfunction and that its analogue PT-141 was the one Palatin carried forward [6][9]. We could not find a company or regulator document that states why melanotan II itself was dropped, so we do not give a reason. What can be said is that it has no approved indication, and regulators say so: the FDA called it an unapproved new drug in 2016 [14], and Australia’s TGA said in August 2026 that no melanotan II products are on its register [19]. We did not search every national register, so the claim is limited to what we could verify. Compound pages: melanotan I and melanotan II.

What regulators say about unlicensed melanotan

• United States (FDA, 2016). In a notice to the owner of Melanocorp, who had pleaded guilty to conspiracy, the FDA said melanotan II was an unapproved new drug sold as an injectable tanning product. It added that the company had made claims about skin cancer and rosacea [14].
• United Kingdom (MHRA, 2021 and 2024). The MHRA says that injectable pens containing melanotan II are medicines, while a nasal spray counts only if sold with claims to treat or prevent disease. Selling, supplying or advertising unauthorised medicines is not permitted. It had 13 Yellow Card reports for 2011 to 2021 and 16 for 2012 to 2022, with the caveat that reports do not prove cause and under-reporting is unknown [15][16].
• Australia (TGA, 2017, 2025, 2026). The TGA says melanotan I and II are not on its register and are prescription-only. It lists side effects including darkened skin, moles and freckles, and, for melanotan II, kidney dysfunction and brain swelling reports. In 2026 it reported a seized batch of nasal sprays estimated at 0.7 to 1.8 times the labelled amount and 27 infringement notices [17][18][19].
• Ireland and Denmark. The Danish Medicines Agency said in 2011 that melanotan is not authorised in Denmark, Europe or the United States [20]. In 2023 the HPRA said melanotan 2 is not authorised by any medicines regulator, as reported by the Irish Times; we read the report, not the HPRA page [21].
• EU and Germany. We found no EMA statement on melanotan and did not check BfArM.

“Research use only” is a seller’s label, not a regulatory category. The MHRA says it decides case by case whether a product is a medicine [15].

Risks and unknowns

The evidence is case reports and reviews of case reports. No randomized trial of unlicensed melanotan in tanners exists in what we found.

Moles and melanoma. A 2017 review in the International Journal of Dermatology (Habbema and colleagues) said case reports link melanotan I and II to changes in existing moles and new dysplastic nevi, and that four case reports describe melanomas arising in existing moles. It added that conclusive evidence is lacking [22]. A 2019 systematic review of eruptive nevi (93 articles, 179 patients) listed melanotan among the suspected causes, found 5 associated melanomas, and said the data could not assess malignant risk [23]. Later reports describe a 20-year-old woman with melanoma found three months after a course of melanotan II plus sunbed use [24]; melanoma in situ [25]; an oral mucosal melanoma in a 22-year-old using a nasal spray [26]; and five melanomas in situ in one patient who also used tanning beds and anabolic hormones [27]. Sunbeds and personal risk confound each of these.

Other harms. Single case reports describe rhabdomyolysis [28], renal infarction [29], priapism [30] and posterior reversible encephalopathy syndrome [31]. A 2026 systematic review of tanning agents (68 studies) lists rhabdomyolysis, renal infarction and priapism [32].

Contents. A forensic laboratory reported one vial labelled melanotan II with 30% purity [33], and the TGA found inconsistent amounts [19]. The MHRA and TGA also mention infection risk from injecting [16][17].

Not studied. Long-term cancer risk, the incidence of any harm, and safety in people with many moles are unknown.

What the tier list claims: a vial labelled “Melanotan-1”

On 22 October 2026 @Hoostethics posted “ranking looksmaxxing techniques” [34]. We read the post text through the fxtwitter mirror and looked at the image. Melanotan sits in the S tier, shown as a vial labelled “Melanotan-1”; fake tan is in C. The list gives no criteria. See also our tier-list check and sunless tanning evidence.

Tested against the sources:

• Melanotan I exists as a drug, but as an EPP implant, not a cosmetic tanner [1][3].
• The tanning data for melanotan I are phase 1 studies of 7 to 12 volunteers [10][11].
• A vial sold online is not that implant. We found no published analysis of vials labelled “Melanotan-1”, so its content is unverified. Analyses of melanotan II products found low purity and wide variation [19][33].
• The harm reports cover melanotan I and II together [22].

Verdict: not supported. An S placement implies top value, and the evidence offers an approved rare-disease drug, small early trials, case reports of melanoma, and regulator warnings.

Frequently asked questions

Is melanotan the same as Scenesse? Melanotan I and afamelanotide are the same peptide. Scenesse is the approved implant for adults with EPP. A vial sold as melanotan is an unapproved product with unverified contents [2][3].

Is melanotan II approved anywhere? We found no approval. The FDA, TGA and European regulators call it unapproved or unlicensed [14][19][20][21].

Does melanotan cause melanoma? Unknown. Case reports describe melanoma in people who used it, usually with sunbeds. Reviews say no proof of cause exists and risk cannot be quantified [22][23][24].

What is the difference between melanotan II and Vyleesi? Vyleesi (bremelanotide) is an approved drug for premenopausal women with low sexual desire; its label warns about blood pressure and skin darkening [4]. Melanotan II has no approval.

Sources

1. FDA (reprinted by BioSpace), “FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder” (8 Oct 2019). https://www.biospace.com/fda-approves-first-treatment-to-increase-pain-free-light-exposure-in-patients-with-a-rare-disorder (reprint of the FDA release; the fda.gov page was not reachable)
2. DailyMed, “SCENESSE (afamelanotide) implant, prescribing information” (revised 5/2026; effective 11 May 2026). https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48&type=display
3. European Medicines Agency, “Scenesse: EPAR” (page updated 7 Oct 2026). https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse
4. DailyMed, “VYLEESI (bremelanotide) injection, prescribing information” (effective 13 Nov 2025). https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf&type=display
5. Sawyer TK et al., “4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone”, PNAS (1980). https://pubmed.ncbi.nlm.nih.gov/6777774/
6. Hadley ME, Dorr RT, “Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization”, Peptides (2006). https://pubmed.ncbi.nlm.nih.gov/16412534/
7. University of Arizona Cancer Center, “UA-discovered drug for skin disease approved for patients in Europe” (29 Oct 2014, updated 3 Nov 2014). https://cancercenter.arizona.edu/news/2014/10/ua-discovered-drug-skin-disease-approved-patients-europe
8. Competitive Technologies Inc, Form 10-K for fiscal year ended 31 July 2005 (SEC EDGAR). https://www.sec.gov/Archives/edgar/data/0000102198/000114420405031650/v026984_10k.htm
9. Competitive Technologies Inc, Form 8-K (28 Jan 2008, SEC EDGAR). https://www.sec.gov/Archives/edgar/data/0000102198/000136086508000002/ctt8-k1222008.txt
10. Dorr RT et al., “Increased eumelanin expression and tanning is induced by a superpotent melanotropin in humans”, Photochem Photobiol (2000). https://pubmed.ncbi.nlm.nih.gov/11045725/
11. Dorr RT et al., “Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers”, Arch Dermatol (2004). https://pubmed.ncbi.nlm.nih.gov/15262693/
12. Dorr RT et al., “Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study”, Life Sci (1996). https://pubmed.ncbi.nlm.nih.gov/8637402/
13. Hadley ME, “Discovery that a melanocortin regulates sexual functions in male and female humans”, Peptides (2005). https://pubmed.ncbi.nlm.nih.gov/15996790/
14. FDA, “Notice of Opportunity for Hearing: Manookian, Edward” (5 Aug 2016). https://www.fda.gov/regulatory-information/electronic-reading-room/notice-opportunity-hearing-nooh-manookian-edward-8516
15. MHRA, response to FOI 21/1237 on melanotan II Yellow Card reports (20 Dec 2021). https://assets.publishing.service.gov.uk/media/67bc97a898ea2db44fadddb1/FOI_21-1237_.pdf
16. MHRA, response to FOI 24/274, “Side effects reports of melanotan II products” (17 Apr 2024). https://assets.publishing.service.gov.uk/media/669fbd3aa3c2a28abb50d55a/Final_Redaction_FOI_24_274.pdf
17. TGA, “Melanotan: Illegal therapeutic goods”, consumer alert (3 Nov 2017; read via Internet Archive copy). https://www.tga.gov.au/alert/melanotan-illegal-therapeutic-goods
18. TGA, “Don’t risk using tanning products containing melanotan” (24 Jan 2025; read via Internet Archive copy). https://www.tga.gov.au/news/blog/dont-risk-using-tanning-products-containing-melanotan
19. TGA, “Melanotan II tanning peptide products found to be inconsistently dosed” (17 Aug 2026; read via Internet Archive copy). https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/melanotan-ii-tanning-peptide-products-found-be-inconsistently-dosed
20. Danish Medicines Agency, “Warning against the tanning product Melanotan” (20 Jun 2011). https://laegemiddelstyrelsen.dk/en/pharmacies/medicines-imported-from-abroad/warnings-against-products/warning-against-the-tanning-product-melanotan/
21. The Irish Times, “Purported tanning aid advertised on social media may cause serious health issues, regulator warns” (10 Aug 2023), reporting an HPRA warning. https://www.irishtimes.com/health/2023/08/10/purported-tanning-aid-advertised-on-social-media-may-cause-serious-health-issues-regulator-warns
22. Habbema L et al., “Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review”, Int J Dermatol (2017). https://pubmed.ncbi.nlm.nih.gov/28266027/
23. Burian EA, Jemec GBE, “Eruptive Melanocytic Nevi: A Review”, Am J Clin Dermatol (2019). https://pubmed.ncbi.nlm.nih.gov/31119650/
24. Hjuler KF, Lorentzen HF, “Melanoma associated with the use of melanotan-II”, Dermatology (2014). https://pubmed.ncbi.nlm.nih.gov/24355990/
25. Ong S, Bowling J, “Melanotan-associated melanoma in situ”, Australas J Dermatol (2012). https://pubmed.ncbi.nlm.nih.gov/22724573/
26. Alsabbagh Y et al., “Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma?”, Int J Oral Maxillofac Surg (2025). https://pubmed.ncbi.nlm.nih.gov/40210573/
27. Vadner, Smith, “Five primary melanomas in situ in a patient with recent tanning bed use, melanotan exposure, and anabolic hormone use”, JAAD Case Rep (2026); only the title and record were read. https://pubmed.ncbi.nlm.nih.gov/42328529/
28. Nelson ME et al., “Melanotan II injection resulting in systemic toxicity and rhabdomyolysis”, Clin Toxicol (2012). https://pubmed.ncbi.nlm.nih.gov/23121206/
29. Peters et al., “Melanotan II: a possible cause of renal infarction”, CEN Case Rep (2020). https://pubmed.ncbi.nlm.nih.gov/31953620/
30. Dreyer et al., “Melanotan-induced priapism: a hard-earned tan”, BMJ Case Rep (2019). https://pubmed.ncbi.nlm.nih.gov/30796078/
31. Kaski D et al., “Melanotan and the posterior reversible encephalopathy syndrome”, Ann Intern Med (2013); only the title and record were read. https://pubmed.ncbi.nlm.nih.gov/23648958/
32. “Insights into Tanning Biology and Tanning Products”, J Clin Aesthet Dermatol (2026), systematic review of 68 studies. https://pubmed.ncbi.nlm.nih.gov/41890775/
33. “Barbie drug identification: Not a child’s play”, J Forensic Sci (2024). https://pubmed.ncbi.nlm.nih.gov/39302005/
34. @Hoostethics on X, “ranking looksmaxxing techniques.” (22 Oct 2026); text and image read through the fxtwitter mirror. https://x.com/Hoostethics/status/2113302148750758106

This article is information, not medical advice.