Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-15. ← Back to Evidence Library

Melanotan I (afamelanotide): what the evidence says

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

What "No human data" means here: for protection against sunburn or skin cancer in healthy people, we found nothing at all in human trials.

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What is it?

Afamelanotide makes pigment cells produce more eumelanin, the brown-black pigment. In EPP, that extra pigment filters some of the light that triggers pain. A darker skin color or a higher eumelanin level is a change you can measure, not proof of a health benefit by itself. Melanotan II is non-selective: it switches on several melanocortin receptors, including MC1R on pigment cells and MC3R and MC4R in the brain. Afamelanotide is thought to darken skin mainly by switching on MC1R, the skin-pigment receptor. ^R23

The approved product vs. the gray-market vial: Scenesse is a solid rod-shaped implant that slowly releases the drug, made under regulatory oversight. Gray-market "melanotan I" is sold as powder in vials for injection. Even if the vial holds the same molecule, it is a different product, and a gray-market vial is not the approved product.

Does it work?

Human EPP, approved Scenesse implant (approval-trial evidence; this does not apply to gray-market use): - Langendonk 2015 (NEJM): two double-blind placebo-controlled trials, 74 patients in the EU and 94 in the US. In the US trial, median (middle-value) pain-free time in direct sunlight over 6 months was 69.4 hours vs 40.8 on placebo (P = 0.04, meaning a gap this size would be unusual if the drug did nothing). In the EU trial, it was 6.0 vs 0.8 hours over 9 months (P = 0.005), with fewer painful light reactions (77 vs 146). Quality of life improved in both. Funded by Clinuvel Pharmaceuticals, with US NIH grants (NHLBI, NIDDK) also listed. ^R4 - Long-term use: an observational study of 115 patients in Rome and Zurich over up to 8 years, and a German post-approval safety study of 200 patients, reported lasting quality-of-life gains and continued use. Neither had a placebo group. The German study was funded by Clinuvel. Three authors are paid by Clinuvel (one also owns stock), and the others received Clinuvel research support. ^{R7, R8}

Human Vitiligo: Lim 2015, 55 adults, light therapy plus afamelanotide vs light therapy alone (no placebo implant). Re-pigmentation was faster and greater with the combination (48.6% vs 33.3% at day 168), mainly in people with darker skin types (IV to VI). Caution [UNVERIFIED: funding statement not read (no free full text); the page's "company-supplied drug" claim is unconfirmed] A small Singapore study is published only as a letter. ^{R16, R21}

Human Acute stroke: 6 patients, no comparison group, Clinuvel-sponsored, with three Clinuvel employees as authors. Mainly a safety and feasibility test. One patient died of a second stroke, judged unrelated. ^R17

Human Cosmetic tanning: Dorr 2000, 7 healthy volunteers with skin that tans (six men, one woman), a short course of injections (schedule in the study table). Funded by US NIH grants (NIDDK, NCI). Skin darkened at 3 of 8 measured sites (face, neck, forearm), and forearm eumelanin roughly doubled. No comparison group and no long-term follow-up. Other early University of Arizona volunteer studies exist. Caution [UNVERIFIED: earlier 1990s tanning studies not reviewed] ^R1

Is it safe?

• Human Approved implant (FDA label, three placebo-controlled trials, 125 on drug vs 119 on placebo): implant-site reaction 21% vs 10%; nausea 19% vs 14%; throat pain 7% vs 5%; cough 6% vs 3%; tiredness 6% vs 3%; skin darkening 4% vs 0%; dizziness 4% vs 3%; mole (melanocytic nevus) 4% vs 2%. Serious allergic reactions, including anaphylaxis, have been reported since approval. The label says it can darken existing moles and freckles and recommends a full-body skin check twice a year. ^R10
• Human In the EPP trials: adverse events (problems reported after use, which may or may not have been caused by the drug) were mostly mild. Serious adverse events were not thought to be drug-related. ^R4
• Human Moles: in 15 EPP patients, existing moles changed under a dermatoscope (a magnifying skin-exam tool) after implants and returned to how they looked before treatment by 12 months, with no signs of melanoma and no new moles. ^R14
• Caution Unregulated "melanotan" (I and II): a 2017 review describes case reports of changes in existing moles, new abnormal moles, and four melanomas arising in moles during or soon after melanotan use. It notes that a direct causal link has not been shown, and most reports don't separate melanotan I from II. ^R15
• Dropouts vs placebo: Caution [UNVERIFIED: dropout numbers by group in Langendonk 2015 not checked; abstract only] In the long-term Italian/Swiss study, 23% stopped, mostly for reasons such as pregnancy or cost, and 3 because it didn't meet their expectations. ^R7
• Unknown Nothing is known about repeated self-injection of gray-market powder, or about long-term use in healthy people seeking a tan.

Is it legal?

• EU: Scenesse authorised Dec 22, 2014, "prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP)," marketing authorisation holder Clinuvel Europe Limited (EMA medicines data, checked Oct 15, 2026). It was approved under "exceptional circumstances" (a route used when full data can't be collected for a rare disease). EU orphan designations also exist for other uses, which are not approvals. ^{R11, R12}
• US (FDA): Scenesse, NDA 210797, approved Oct 8, 2019, "to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria." It must be implanted by a health professional trained in Clinuvel's program. ^{R10, R13}
• Other countries: Caution [UNVERIFIED: approvals in Australia, Switzerland, Israel or elsewhere not checked with those regulators]
• Compounding (503A/503B): no entry for afamelanotide or melanotan I in any category of the 503A nominations list (updated May 14, 2026), the 503B nominations list (updated Mar 21, 2025) or FDA's "significant safety risks" page (content current Apr 22, 2026). ^R18–R20
• Athletes: WADA's 2026 list does not name afamelanotide or melanotan I. Unknown The Open Peptide Project's reading (not a WADA ruling): because it is approved by health authorities, S0 ("non-approved substances") does not apply, and we found no other section covering it. Athletes should ask their anti-doping organization. ^R22

What's in the vial?

The approved product is the Scenesse implant. A gray-market "melanotan I" vial is not the approved product. It has no quality control and no guarantee of identity. It could contain the wrong compound (including melanotan II), the wrong amount, impurities or bacterial toxins, or be fake (counterfeit). The approval-trial results above don't transfer to it. We test retail vials blind under the Open Peptide Standard. See results at /tests/. A passing test covers one batch, tested on one date. It does not mean the compound itself is safe.

What do users report?

Self-report, not evidence.

We haven't summarized user reports for this peptide yet.

Study details

^{R1, R4, R7, R8, R14, R16, R17} Human Human studies

Study	People	Route	Dose used (study arm, not a recommendation)	Follow-up	Reported	Side effects / dropouts	Limitations	Citation
Dorr 2000	7 healthy volunteers (6 men, 1 woman), skin types III–IV	Subcutaneous injection	0.16 mg/kg/day, Monday–Friday, 10 injections over 2 weeks	~3 wk	Tanning at 3 of 8 sites; forearm eumelanin +98% (p=0.003)	Side effects and dropouts UNVERIFIED	No control; 7 people	PMID 11045725
Langendonk 2015, EU trial	74 with EPP	Subcutaneous implant	16 mg implant or placebo implant every 60 days, 5 implants	270 d	Pain-free sun 6.0 vs 0.8 h (P=0.005); light reactions 77 vs 146	Adverse events mostly mild; serious events not judged drug-related; dropouts by group UNVERIFIED	Clinuvel-funded	PMID 26132941; NCT00979745
Langendonk 2015, US trial	94 with EPP	Subcutaneous implant	16 mg implant or placebo implant every 60 days, 3 implants	180 d	Pain-free sun 69.4 vs 40.8 h (P=0.04)	As above; dropouts by group UNVERIFIED	Clinuvel-funded	PMID 26132941; NCT01605136
Biolcati 2015	115 with EPP, Rome and Zurich	Subcutaneous implant	16 mg implants, 1,023 in total over up to 8 years; interval per patient UNVERIFIED	Up to 8 yr	QoL 31% → 74% of max	Minor adverse events, mainly nausea; 23% stopped (mostly pregnancy, cost), 3 for lack of effect	No control group	PMID 25494545
Homey 2025 (post-approval safety study)	200 with EPP, Germany	Subcutaneous implant	16 mg implant, used as per the EU product information	Long-term	QoL improved vs baseline (p<0.0001)	Safety consistent with trials; 91% continued	No control; Clinuvel authors	PMID 40082741
Arisi 2021	15 with EPP, 103 moles	Subcutaneous implant	2 implants 50 days apart; amount UNVERIFIED (approved implant is 16 mg)	12 mo	Reversible mole changes; no melanoma features; no new moles	Dropouts UNVERIFIED	Small	PMID 33721252
Lim 2015	55 with vitiligo (28 combination, 27 light only)	Subcutaneous implant + narrowband UV-B	16 mg implant monthly for 4 months, starting after 1 month of light therapy, vs light therapy alone	168 d	Re-pigmentation 48.6% vs 33.3%	Redness in both groups; minor infections and nausea with combination; dropouts UNVERIFIED	No placebo implant	PMID 25230094
Stanislaus 2023	6 with acute stroke	Subcutaneous implant	16 mg implants on days 0 and 1, repeated on days 7 and 8 if not well recovered (4 people got 2, 2 got 4)	42 d	Median NIHSS 6 → 2 by day 7 in survivors	1 death (recurrent stroke) judged unrelated; no other local or major systemic adverse events	No control; Clinuvel-sponsored	PMID 37496004

^R10–R22 Regulatory sources (as of Oct 15, 2026)

• ^R10 Scenesse label, DailyMed (Clinuvel Inc.; label effective May 11, 2026): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48
• ^R11 EMA, Scenesse EPAR (authorised Dec 22, 2014): https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse
• ^R12 EMA orphan designations data (afamelanotide: EPP, expired; solar urticaria; Hailey-Hailey disease; xeroderma pigmentosum; variegate porphyria): https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json
• ^R13 Drugs@FDA: NDA 210797, SCENESSE, original approval Oct 8, 2019: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=210797
• ^R18 FDA 503A nominations list (May 14, 2026): https://www.fda.gov/media/94155/download
• ^R19 FDA 503B nominations list (Mar 21, 2025): https://www.fda.gov/media/94164/download
• ^R20 FDA, Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current Apr 22, 2026): https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
• ^R22 WADA 2026 Prohibited List: https://www.wada-ama.org/en/resources/world-anti-doping-code-and-international-standards/prohibited-list

Full reference list (PMIDs verified on PubMed, Oct 15, 2026)

• ^R1 Dorr RT, et al. Photochem Photobiol. 2000;72(4):526-32. doi:10.1562/0031-8655(2000)072<0526:ieeati>2.0.co;2. PMID 11045725. Funded by NIDDK and NCI.
• ^R2 Fabrikant J, et al. J Drugs Dermatol. 2013;12(7):775-9. PMID 23884489 (review).
• ^R3 Minder EI. Expert Rev Clin Pharmacol. 2015;8(1):43-53. doi:10.1586/17512433.2014.956089. PMID 25470471 (review).
• ^R4 Langendonk JG, et al. N Engl J Med. 2015;373(1):48-59. doi:10.1056/NEJMoa1411481. PMID 26132941. Funded by Clinuvel Pharmaceuticals; NHLBI and NIDDK grants listed on PubMed.
• ^R7 Biolcati G, et al. Br J Dermatol. 2015;172(6):1601-12. doi:10.1111/bjd.13598. PMID 25494545.
• ^R8 Homey B, et al. Photodermatol Photoimmunol Photomed. 2025;41(2):e13012. doi:10.1111/phpp.13012. PMID 40082741. Funded by Clinuvel; Clinuvel-salaried co-authors (one with stock).
• ^R14 Arisi M, et al. Photochem Photobiol Sci. 2021;20(2):315-320. doi:10.1007/s43630-021-00020-2. PMID 33721252.
• ^R15 Habbema L, et al. Int J Dermatol. 2017;56(10):975-980. doi:10.1111/ijd.13585. PMID 28266027 (review).
• ^R16 Lim HW, et al. JAMA Dermatol. 2015;151(1):42-50. doi:10.1001/jamadermatol.2014.1875. PMID 25230094.
• ^R17 Stanislaus V, et al. BMC Neurol. 2023;23(1):281. doi:10.1186/s12883-023-03338-9. PMID 37496004. Wolgen, Walker and Bilbao are Clinuvel employees.
• ^R21 Toh JJH, et al. J Am Acad Dermatol. 2020;82(6):1517-1519. doi:10.1016/j.jaad.2020.01.035. PMID 31987791 (letter).
• ^R23 Ericson MD, et al. Bench-top to clinical therapies: a review of melanocortin ligands from 1954 to 2016. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt A):2414-35. PMID 28363699.

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Disclaimer

This page is for education and harm reduction. It is not medical advice and not a recommendation to use melanotan I or afamelanotide. Please talk to a clinician you trust, especially if you have EPP or another light-sensitivity disorder, many or changing moles, a history of melanoma, or are pregnant, or are a tested athlete. Seek care right away for a serious reaction, and report it to FDA MedWatch (https://www.fda.gov/safety/medwatch) or your national regulator.