Melanotan I is the original research name for afamelanotide, a synthetic copy of the skin-darkening hormone alpha-melanocyte-stimulating hormone (α-MSH). It was first described in 1980 and first tested in people at the University of Arizona as a “sunless tanning” agent. Today it is sold as Scenesse, a small implant placed under the skin every two months.
Scenesse is approved in the EU (2014) and the US (2019) for one use only: adults with erythropoietic protoporphyria (EPP), a rare inherited disorder in which light exposure causes severe skin pain. It is not approved for cosmetic tanning. Vials sold online and in salons as “Melanotan I” tanning injections are unregulated products with no quality control, and regulators and dermatologists have warned about them since at least 2010.
This page summarizes what the FDA and EMA labels, clinical trials and published case reports describe. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Synthetic α-MSH analog; melanocortin 1 receptor (MC1R) agonist |
| Other names | Afamelanotide (INN), MT-I, NDP-α-MSH |
| Brand / approval | Scenesse (Clinuvel); EU December 22, 2014; FDA October 8, 2019 (NDA 210797) |
| Approved use | Adults with erythropoietic protoporphyria (EPP) |
| Approved form and dose | One 16 mg bioresorbable implant under the skin every 2 months, inserted by a trained clinician |
| Half-life | ≈30 min for the peptide itself (EMA); apparent ≈15 h when released from the implant (FDA) |
| Main effect | Raises eumelanin (brown-black pigment) in skin without UV exposure |
| “Tanning injection” products | Not approved anywhere; unregulated content, purity and sterility |
| WADA status | Not named on the WADA 2026 Prohibited List |
What it is
Afamelanotide is a 13-amino-acid peptide (a tridecapeptide) built on the sequence of natural α-MSH. Two positions are changed: methionine at position 4 is replaced by norleucine, and the L-phenylalanine at position 7 is replaced by its mirror-image D-form (Sawyer et al., PNAS 1980). Its formula is C₇₈H₁₁₁N₂₁O₁₉ and its molecular weight is 1,646.85 g/mol as the free base (FDA label).
These changes make the peptide resist breakdown by enzymes in serum. In the 1980 lab work (frog skin and mouse melanoma cells), it was about 26 times as potent as natural α-MSH in one assay and had a much longer-lasting effect (Sawyer et al., PNAS 1980).
How it works
Afamelanotide binds mainly to MC1R, the receptor on pigment cells (melanocytes) that natural α-MSH uses to switch on melanin production. This increases eumelanin, the brown-black pigment, in the skin, and it does so without sunlight or UV light (FDA label). The EMA product information describes eumelanin as protective in several ways (EMA SmPC):
- it absorbs a broad range of UV and visible light, acting as a filter;
- it scavenges free radicals (antioxidant activity);
- it inactivates the superoxide anion, reducing oxidative stress.
The darkening fades gradually unless another implant is given.
In EPP, a light-sensitive molecule called protoporphyrin IX builds up in the body. Light striking it in the skin causes painful phototoxic reactions. Extra eumelanin reduces how much light reaches it (EMA EPAR).
Related melanocortin peptides
Melanotan I is often confused with two related compounds that have their own pages:
- Melanotan II is a different, cyclic α-MSH analog (Hjuler and Lorentzen, Dermatology 2014). Besides darkening skin, it causes spontaneous erections and sexual stimulation (Nelson et al., Clin Toxicol 2012). Many published harm reports from tanning injections involve products labeled melanotan II.
- PT-141 (bremelanotide) is a variation of melanotan II developed for sexual stimulation rather than tanning (Nelson et al., Clin Toxicol 2012).
Pharmacokinetics
The peptide itself is cleared quickly. The implant exists to stretch out a short-lived peptide over days.
| Measure | Finding | Source |
|---|---|---|
| Half-life of the peptide | ≈30 minutes | EMA SmPC |
| Half-life after injection of a solution under the skin | 0.8–1.7 h (elimination phase), in 3 men | Ugwu et al., 1997 |
| Bioavailability | Complete under the skin vs IV; no measurable blood levels when taken by mouth | Ugwu et al., 1997 |
| Release from the 16 mg implant | Most released in the first 48 h, over 90% by day 5 | EMA SmPC |
| Peak level after one implant (12 healthy adults) | Median Tmax 36 h; mean Cmax 3.7 ± 1.3 ng/mL | FDA label |
| Apparent half-life from the implant | ≈15 h | FDA label |
| Time to undetectable levels | Last measurable level at 96 h in 9 of 12 subjects (FDA); below quantitation by day 10 in most studies (EMA) | FDA label; EMA SmPC |
| Implant resorption | The rod is absorbed within 50–60 days | EMA SmPC |
The skin effect lasts much longer than the drug stays in the blood. In the early Arizona studies, tanning peaked about 1 week after a 10-dose course and was still present 3 weeks later (Ugwu et al., 1997). Metabolism has not been fully characterized; the peptide is expected to be broken down into smaller fragments and amino acids (EMA SmPC).
Approved medical use
The Scenesse implant
Scenesse is a solid rod about 1.7 cm long and 1.45 mm wide. It contains 16 mg of afamelanotide mixed into a bioresorbable polymer, poly(DL-lactide-co-glycolide) (FDA label). It is not a self-injected product.
| Feature | US (FDA) | EU (EMA) |
|---|---|---|
| Indication | To increase pain-free light exposure in adults with a history of phototoxic reactions from EPP | Prevention of phototoxicity in adults with EPP |
| Dose | One 16 mg implant every 2 months | One implant every 2 months before expected and during increased sunlight exposure |
| Who gives it | A healthcare professional who has completed the manufacturer’s training | Specialist physicians in recognized porphyria centers; a physician trained and accredited by the manufacturer |
| Approval | October 8, 2019; orphan drug, priority review, new molecular entity | December 22, 2014, under “exceptional circumstances” |
| Children | Not established | Not established |
Sources: FDA label; Drugs@FDA; EMA SmPC; EMA EPAR.
“Exceptional circumstances” means the EMA accepted that complete data could not be collected because the disease is so rare. As a condition, the company must provide longer-term data from an EU patient registry, and the EMA reviews new information every year (EMA EPAR). Both labels say patients must keep using their usual sun and light protection while on treatment.
What the research shows
Erythropoietic protoporphyria: the pivotal trials
Two multicenter, randomized, double-blind, placebo-controlled trials supported approval. Patients received a 16 mg implant or a placebo implant every 60 days and kept daily diaries of sun exposure and pain (Langendonk et al., NEJM 2015):
| Trial | Patients | Implants / follow-up | Primary endpoint | Afamelanotide | Placebo |
|---|---|---|---|---|---|
| US (CUV039) | 94 randomized | 3 implants / 180 days | Median hours in direct sunlight on pain-free days | 69.4 h | 40.8 h (p = 0.04) |
| EU (CUV029) | 74 randomized | 5 implants / 270 days | Median hours in direct sunlight on pain-free days | 6.0 h | 0.8 h (p = 0.005) |
In the EU trial, the total number of phototoxic reactions was also lower with afamelanotide: 77 vs 146 (p = 0.04). Quality of life improved in both trials (Langendonk et al., NEJM 2015).
The FDA’s own analysis of the same trials gives slightly different medians: 64.1 vs 40.5 hours over 180 days in CUV039, and 6.0 vs 0.75 hours over 270 days in CUV029 (FDA label). In CUV039, the mean was 115.6 vs 60.6 hours (EMA SmPC).
The absolute gains are modest. The EMA noted that “the additional time spent in sunlight was small,” but approved the drug because of quality-of-life gains, the lack of any other treatment, and mild side effects in short-term use (EMA EPAR).
Erythropoietic protoporphyria: long-term and real-world data
Observational studies, several funded in part by the manufacturer, have followed patients on routine treatment:
| Study | Patients | Follow-up | Main findings |
|---|---|---|---|
| Rome and Zurich centers (Biolcati et al., BJD 2015) | 115 (1,023 implants) | Up to 8 years | EPP quality-of-life score rose from 31% to 74% of maximum and stayed there; adverse events minor, mostly nausea |
| Rotterdam, EMA-directed cohort (Wensink et al., JAMA Dermatol 2020) | 117 | Median 2.0 years | +6.1 h/week outdoors (95% CI 3.62–8.67); quality of life +14.0% (95% CI 4.53–23.50); reactions less painful but not fewer; 98% stayed on treatment |
| German post-authorization safety study (Homey et al., 2025) | 200 | Ongoing | Safety consistent with trials; 91.0% of starters continued treatment |
These studies were not randomized, so they cannot separate the drug’s effect from patient expectations or behavior.
Vitiligo (not an approved use)
In a randomized trial, 55 adults with nonsegmental vitiligo and skin types III–VI received narrowband UV-B light therapy alone or combined with a 16 mg afamelanotide implant monthly for 4 months (Lim et al., JAMA Dermatol 2015):
| Arm | n | Repigmentation at day 168 (95% CI) |
|---|---|---|
| UV-B + afamelanotide | 28 | 48.6% (39.5–57.8) |
| UV-B alone | 27 | 33.3% (24.2–42.3) |
Repigmentation also started sooner on the face and arms with the combination. The benefit was clearer in skin types IV–VI than in type III.
Other light-sensitivity disorders
Small pilot studies have tested the implant in other conditions. In 5 patients with solar urticaria (hives triggered by light), one implant raised skin melanin from day 7, peaking at day 15, and reduced the hive response to light testing at day 60 (Haylett et al., BJD 2011). These are not approved uses.
Tanning in healthy volunteers
The original Arizona studies used daily injections of a dissolved peptide, not the implant:
- First tanning trial. In a randomized, double-blind trial, 28 healthy white men received 10 injections of Melanotan I or saline over 12 days. Skin darkened in both poor tanners (skin types I–II) and good tanners (types III–IV), with peak changes 1–3 weeks after the last dose. Placebo caused no darkening (Levine et al., JAMA 1991).
- Eumelanin, not just color. In 7 volunteers, a 10-dose course increased the eumelanin content of skin biopsies (Dorr et al., Photochem Photobiol 2000).
- Combined with sunlight. In three small open-label phase 1 studies, Melanotan I plus sunlight produced more tanning than sunlight alone, which lasted at least 3 weeks longer. The sunlight-only group needed 50% more sun time for an equal tan (Dorr et al., Arch Dermatol 2004).
These studies were very small and short. They measured skin color, not protection against skin cancer, and they did not lead to approval of any cosmetic tanning product.
Side effects and risks of the approved implant
Common side effects
The FDA label pools three vehicle-controlled EPP trials (125 patients on Scenesse, 119 on vehicle) through month 6 (FDA label):
| Adverse reaction | Scenesse | Vehicle |
|---|---|---|
| Implant site reaction | 21% | 10% |
| Nausea | 19% | 14% |
| Oropharyngeal (throat) pain | 7% | 5% |
| Cough | 6% | 3% |
| Fatigue | 6% | 3% |
| Skin hyperpigmentation | 4% | 0% |
| Dizziness | 4% | 3% |
| Melanocytic nevus (mole) | 4% | 2% |
| Somnolence (drowsiness) | 2% | 1% |
In a larger EU pooled dataset of 425 patients, headache was reported in about 20% (EMA SmPC). The EU label also warns that somnolence, fatigue, dizziness and nausea can affect driving, especially within 72 hours of an implant.
Hypersensitivity
Serious allergic reactions, including anaphylaxis, have been reported since approval. Patients are observed for 30 minutes after each implant. If a serious reaction occurs, the implant may be removed and treatment stopped for good (FDA label).
Moles and skin cancer monitoring
Because it stimulates pigment cells, afamelanotide can darken the whole skin as well as existing moles and freckles. Both labels recommend a full-body skin examination twice a year (FDA label). The EU label explains that the exams are meant to catch melanoma early and to catch UV-related skin cancers in patients who now spend more time in the sun. It advises special caution in people with a personal or family history of melanoma, or a history of other skin cancers (EMA SmPC).
Who should not use it
The labels differ in how strict they are:
- US: contraindicated only after a severe allergic reaction to afamelanotide or the implant material.
- EU: also contraindicated in severe liver disease, liver impairment and kidney impairment. It should not be used in pregnancy or breastfeeding, and women who could become pregnant must use effective contraception during treatment and for 3 months after. It should not be used in people over 70.
- Long-term safety: the EU label states that safety has not been studied in clinical trials longer than 2 years.
Interactions
No formal drug interaction studies have been done. The EU label warns that people taking anticoagulants such as warfarin, aspirin or NSAIDs may have more bruising or bleeding at the implant site (EMA SmPC).
Unregulated “Melanotan I” tanning injections
Outside the Scenesse program, products labeled “melanotan I” or “melanotan II” are obtained through the internet, tanning salons and gyms and self-injected under the skin to get a tan (Langan et al., BJD 2010). These products are not Scenesse.
A 2017 dermatology review described afamelanotide as the only α-MSH analog approved for medical use. It concluded that, although afamelanotide has been thoroughly tested, the illegal melanotans are likely risky, with open questions about their preparation, administration and dosage (Habbema et al., Int J Dermatol 2017).
Documented harms
Most case reports describe products sold as melanotan II or as unspecified “melanotan.” Because illicit labels cannot be checked, it is often unclear which peptide a person actually injected.
| Harm | What has been documented |
|---|---|
| New and changing moles | Case reports of new atypical or “eruptive” moles and changes in existing moles after melanotan injections, including multiple new atypical moles within one week of two melanotan injections (Reid et al., Ir Med J 2013; Burian and Burian, Lakartidningen 2013; Habbema et al., 2017) |
| Melanoma | By 2017, four case reports described melanoma arising from existing moles during or shortly after melanotan use. A causal link has not been proven (Habbema et al., 2017). One case involved a 20-year-old woman who had used melanotan II with sunbeds (Hjuler and Lorentzen, Dermatology 2014) |
| Wrong dose and impurities | Vials from three online shops, each sold as 10 mg of melanotan II, contained 4.32–8.84 mg, and vials from two shops had 4.1–5.9% unidentified impurities (Breindahl et al., Drug Test Anal 2015) |
| Infection from injecting | The UK medicines regulator (MHRA) warned of blood-borne virus transmission through needle sharing and of possible product impurity (Langan et al., BJD 2010) |
| Systemic toxicity | A man who injected an internet product confirmed as melanotan II developed rapid heart rate, muscle breakdown (rhabdomyolysis) and kidney injury needing intensive care (Nelson et al., Clin Toxicol 2012) |
| Harder mole assessment | Dermatologists note that these agents can complicate the assessment of pigmented lesions, which may darken quickly (Langan et al., 2010) |
Multiple national health agencies have issued safety warnings about melanotan I and II (Habbema et al., 2017).
About “safe tanning.” Online sellers often present melanotan as a way to tan without sun damage. The approved implant was only shown to increase pain-free light exposure in EPP. No study has shown that injected melanotan products prevent skin cancer, and case reports link them to changing moles and melanoma, in some cases alongside sunbed use.
Key takeaways
- Melanotan I is afamelanotide. It is a stabilized copy of α-MSH that darkens skin by raising eumelanin, independent of sunlight.
- One approved product, one approved use. Scenesse is a 16 mg implant given every 2 months by a trained clinician to adults with erythropoietic protoporphyria. It is not approved for tanning.
- Modest but real benefit in EPP. In the US trial, median pain-free time in direct sunlight over 6 months was 69.4 hours vs 40.8 hours on placebo, with better quality of life.
- Mostly mild side effects, with skin checks required. Implant site reactions, nausea and headache are the most common. Serious allergic reactions can occur, and twice-yearly full-body skin exams are recommended.
- Tanning injections are a different matter. Unregulated “melanotan” vials have shown wrong doses and impurities, and case reports link them to new or changing moles, melanoma and serious systemic toxicity.
Sources
- Clinuvel Inc. Scenesse (afamelanotide) implant, for subcutaneous use, prescribing information. DailyMed.
- Food and Drug Administration. Drugs@FDA: NDA 210797, Scenesse (afamelanotide) implant, approved October 8, 2019. FDA.
- European Medicines Agency. Scenesse: summary of product characteristics. EMA.
- European Medicines Agency. Scenesse (afamelanotide): European public assessment report (EPAR) overview. EMA.
- Sawyer TK, Sanfilippo PJ, Hruby VJ, et al. 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci U S A. 1980;77(10):5754–5758. PubMed.
- Levine N, Sheftel SN, Eytan T, et al. Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin. JAMA. 1991;266(19):2730–2736. PubMed.
- Ugwu SO, Blanchard J, Dorr RT, et al. Skin pigmentation and pharmacokinetics of melanotan-I in humans. Biopharm Drug Dispos. 1997;18(3):259–269. PubMed.
- Dorr RT, Dvorakova K, Brooks C, et al. Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-alpha-MSH in humans. Photochem Photobiol. 2000;72(4):526–532. PubMed.
- Dorr RT, Ertl G, Levine N, 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;140(7):827–835. PubMed.
- Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015;373(1):48–59. PubMed.
- Biolcati G, Marchesini E, Sorge F, et al. Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Br J Dermatol. 2015;172(6):1601–1612. PubMed.
- Wensink D, Wagenmakers MAEM, Barman-Aksözen J, et al. Association of afamelanotide with improved outcomes in patients with erythropoietic protoporphyria in clinical practice. JAMA Dermatol. 2020;156(5):570–575. PubMed.
- Homey B, Schelonke K, Schlegel CM, et al. German cohort observational study to investigate the short- and long-term safety and clinical effectiveness of afamelanotide 16 mg (SCENESSE) in patients with erythropoietic protoporphyria (EPP). Photodermatol Photoimmunol Photomed. 2025;41(2):e13012. PubMed.
- Lim HW, Grimes PE, Agbai O, et al. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. JAMA Dermatol. 2015;151(1):42–50. PubMed.
- Haylett AK, Nie Z, Brownrigg M, et al. Systemic photoprotection in solar urticaria with α-melanocyte-stimulating hormone analogue [Nle4-D-Phe7]-α-MSH. Br J Dermatol. 2011;164(2):407–414. PubMed.
- Langan EA, Nie Z, Rhodes LE. Melanotropic peptides: more than just ‘Barbie drugs’ and ‘sun-tan jabs’? Br J Dermatol. 2010;163(3):451–455. PubMed.
- Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017;56(10):975–980. PubMed.
- Reid C, Fitzgerald T, Fabre A, Kirby B. Atypical melanocytic naevi following melanotan injection. Ir Med J. 2013;106(5):148–149. PubMed.
- Burian E, Burian E. Eruptive nevi after injection of drugs marketed as melanotan II. The first two Swedish cases described [in Swedish]. Lakartidningen. 2013;110(5):208–210. PubMed.
- Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34–36. PubMed.
- Breindahl T, Evans-Brown M, Hindersson P, et al. Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet. Drug Test Anal. 2015;7(2):164–172. PubMed.
- Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169–1173. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.