TL;DR
Melanotan I is better known by its real medical name, Afamelanotide: an implant (brand name Scenesse) approved for a rare condition called erythropoietic protoporphyria (EPP), where ordinary sunlight causes severe pain and skin damage. It works by boosting the skin's own dark pigment so light does less harm, which is also why unregulated "Melanotan I" gets sold off-label as a tanning product. The approved implant is only given by a clinician in a clinical setting; injectable versions sold online are a different, unverified product with no licence in Ireland. There's no dosing information on this page because none is published for that off-label use, and this guide keeps the two products clearly separate throughout.
What is Melanotan I?
Melanotan I, known by its pharmaceutical name Afamelanotide, is an alpha-melanocyte-stimulating hormone (alpha-MSH) analogue that acts as a selective agonist at the melanocortin-1 receptor (MC1R), expressed on melanocytes. Unlike many peptides discussed in a research context, Afamelanotide has genuine, licensed medicinal status: it is approved by the European Medicines Agency (since 2014, under the brand name Scenesse) and by the US FDA (since 2019) for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP), a rare genetic disorder causing severe light-induced skin pain and damage.
It is important to distinguish two very different things that both get called "Melanotan I." The approved product, Scenesse, is administered as a subcutaneous implant by a healthcare professional in a specialist clinical setting, under strict regulatory control. Separately, unregulated injectable "Melanotan I" products sold online or through grey-market channels are not the same regulated pharmaceutical product — they carry a different (and largely unverified) risk, purity and quality profile, and are not licensed by the HPRA or any equivalent regulator for use in Ireland. This guide distinguishes the approved medicinal use of afamelanotide (Scenesse implant, for EPP) from the unregulated research/off-label use of injectable Melanotan I throughout.
How strong is the evidence?
| Evidence Type |
Status |
| Human RCT |
✔ |
| Observational |
✔ |
| Animal Studies |
✔ |
| In Vitro |
✔ |
| Regulatory Approval |
✔ (EMA 2014 & FDA 2019 — Scenesse implant, EPP only. Unregulated injectable "Melanotan I" products are not the licensed product.) |
How does Melanotan I work?
Afamelanotide (Melanotan I) is a selective agonist at the melanocortin-1 receptor (MC1R) expressed on the surface of melanocytes in the skin. Binding of the peptide to MC1R stimulates intracellular signalling that upregulates tyrosinase activity and shifts melanin synthesis toward eumelanin, the darker, more photoprotective form of skin pigment, as opposed to the lighter, less protective pheomelanin.
This increase in eumelanin content provides a physical barrier that reduces the penetration of UV and visible light into the skin, which is the mechanistic basis for Scenesse's approved use in erythropoietic protoporphyria: by increasing baseline skin pigmentation, afamelanotide reduces the severity of phototoxic reactions triggered by light exposure in EPP patients, who otherwise cannot tolerate normal levels of sunlight or even some indoor lighting.
What has Melanotan I been studied for?
Erythropoietic Protoporphyria Photoprotection (Approved Indication)
The core, regulator-approved application of afamelanotide is photoprotection in EPP. Phase 3 clinical trial data, most notably the landmark study by Langendonk JG and colleagues published in the New England Journal of Medicine, demonstrated meaningful increases in pain-free time in sunlight for EPP patients receiving afamelanotide implants compared to placebo.
Vitiligo Repigmentation Research
Afamelanotide has been studied, often in combination with narrowband UVB (NB-UVB) phototherapy, for its potential to enhance repigmentation in patients with vitiligo. Research led by groups including Grimes PE and colleagues has examined combined afamelanotide plus NB-UVB protocols against NB-UVB alone.
General Photoprotection and Skin Cancer Prevention Research
Beyond EPP, afamelanotide has been studied in populations at elevated skin cancer risk, including organ transplant recipients, as a potential adjunct for reducing UV-induced DNA damage. Pilot work by Harms J and colleagues explored this preventive photoprotection angle in immunosuppressed populations.
Cosmetic Tanning and Off-Label/Grey-Market Use
Historically, unregulated injectable Melanotan I products have been marketed and used off-label for cosmetic tanning purposes without medical supervision. This use sits entirely outside the licensed indication and dosing form (the Scenesse implant) and outside any regulatory oversight, and is not supported by the clinical trial evidence base underpinning the approved product.
What did the studies actually find?
| Study / Model |
Reported Effect |
| Langendonk JG et al. 2015 (NEJM) |
Afamelanotide implants significantly increased daily pain-free time in direct sunlight for EPP patients versus placebo across two randomised Phase 3 trials. |
| Biolcati G et al. long-term real-world data |
Sustained improvement in phototoxic reaction frequency and quality of life in EPP patients receiving repeated afamelanotide implants over extended follow-up periods. |
| Lim HW et al. phototoxicity studies |
Reported reduction in phototoxic reaction severity and frequency associated with increased skin eumelanin content following afamelanotide administration. |
| Grimes PE et al. vitiligo study |
Afamelanotide combined with NB-UVB produced greater repigmentation of vitiligo lesions compared to NB-UVB monotherapy in a randomised trial. |
| Harms J et al. transplant recipient pilot study |
Preliminary evidence of reduced UV-induced skin damage markers in organ transplant recipients receiving afamelanotide, in a small pilot cohort. |
What has Melanotan I been studied alongside?
- Afamelanotide + narrowband UVB (NB-UVB) phototherapy → Research rationale: Investigated in vitiligo repigmentation trials, where afamelanotide-driven melanocyte stimulation is combined with UVB-driven melanocyte activation to study additive repigmentation effects versus NB-UVB alone.
- Afamelanotide + routine photoprotection measures (sunscreen, protective clothing) → Research rationale: Studied as a combined approach in EPP management research, positioning afamelanotide as an adjunct to, not a replacement for, standard physical photoprotection.
⚠️ Stack combinations listed for research reference only. Not safety or efficacy guidance.
Why there are no doses on this page
This site does not publish doses, durations or frequencies for any compound. Published research protocols for this compound vary considerably between studies in design, intensity and duration. Those details are not something to copy from a fitness website — anyone researching this compound should read the primary literature directly and talk to a doctor who knows their bloods.
What side effects were reported?
- Nausea
- Headache
- Fatigue
- Implant site reactions/nodules
- Mild darkening of naevi (moles), clinically monitored with repeated use
- Flushing
Skin surveillance is recommended with repeated afamelanotide use given the observed effect on naevi pigmentation; this is actively monitored in both the approved clinical use and the research literature.
Melanotan I at a glance
- CAS Number
- 75921-69-6
- Molecular Formula
- C63H93N17O14
- Molecular Weight
- Approximately 1297.5 g/mol
- Half-Life
- Plasma half-life of a few hours for the free peptide; the Scenesse implant is designed for sustained release over approximately 2 months
- Synonyms
- Afamelanotide, Melanotan I, [Nle4-D-Phe7]-alpha-MSH (related but distinct from NDP-MSH), Scenesse (brand name), CUV1647
- Research Classification
- Melanocortin-1 receptor (MC1R) agonist, alpha-MSH analogue
The research this page cites
- Langendonk JG et al. 2015 — Afamelanotide for Erythropoietic Protoporphyria. — New England Journal of Medicine — [Human RCT]
- Biolcati G et al. 2015 — Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. — British Journal of Dermatology — [Observational / Human]
- Harms JH et al. 2009 — Mitigating photosensitivity of erythropoietic protoporphyria patients by an agonistic analog of alpha-melanocyte stimulating hormone. — Photochemistry and photobiology — [Pilot Human Study]
- Lim HW et al. 2015 — Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. — JAMA Dermatology — [Human RCT]
- Fabrikant J et al. 2013 — A review and update on melanocyte stimulating hormone therapy: afamelanotide. — Journal of drugs in dermatology — [Review]
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