Melanotan I
A linear, MC1R-selective alpha-MSH analog (afamelanotide) that drives UV-independent skin tanning and is FDA-approved as Scenesse for the rare photosensitivity disorder EPP.
Melanotan I (afamelanotide) is a synthetic 13-amino-acid linear analog of alpha-melanocyte-stimulating hormone (alpha-MSH), stabilized against enzymatic breakdown by a norleucine substitution at position 4 and a D-phenylalanine at position 7. It is highly selective for the melanocortin-1 receptor (MC1R), stimulating eumelanin production and skin darkening without the libido and appetite effects seen with the broader-acting Melanotan II. Afamelanotide is FDA-approved (2019) and EU-approved (2014) as the Scenesse controlled-release implant for erythropoietic protoporphyria (EPP), while grey-market injectable versions are used off-label for cosmetic tanning with no long-term safety data.
Class
Synthetic linear tridecapeptide (alpha-MSH analog)
Half-life
~30 minutes serum for the free peptide; subcutaneous afamelanotide data cited around ~25 hours; the approved Scenesse implant provides roughly 2 months of sustained effect per dose.
Routes
Subcutaneous, Intramuscular, Controlled-release subcutaneous implant (Scenesse)
Category
Sexual Health & Melanocortin
Researched benefits
What it's studied for
Photoprotection in EPP (approved indication)
In erythropoietic protoporphyria, the MC1R-driven boost in melanin lets patients tolerate sunlight without porphyrin-mediated burning pain. Phase 3 registration trials showed significant increases in pain-free sun-exposure time and quality of life, supporting FDA and EU approval of the Scenesse implant.
UV-independent skin tanning
Activating MC1R upregulates tyrosinase and stimulates eumelanin synthesis, producing visible skin darkening over roughly 2 to 6 weeks without sun exposure. This is the core established pharmacology and the basis for cosmetic tanning interest.
High MC1R selectivity vs Melanotan II
As a linear peptide, MT-1 is substantially more selective for MC1R over MC3R/MC4R/MC5R than the cyclic Melanotan II. This yields a cleaner acute side-effect profile with less nausea, milder flushing, and essentially no sexual-arousal or appetite-suppression effects.
Reduced UV-induced erythema
By increasing protective pigmentation, Melanotan I reduces UV-induced skin reddening in photosensitivity research models, which underpins its role in UV-sensitive populations.
Potential vitiligo application (investigational)
The CUV105 Phase 3 trial pairing Scenesse with NB-UVB phototherapy in vitiligo finished enrollment in May 2025, with topline results expected in H2 2026. A positive result would extend afamelanotide beyond its EPP orphan indication.
Mechanism
How it works
Melanotan I binds and activates the melanocortin-1 receptor (MC1R) on melanocytes with high selectivity. MC1R is a Gs-coupled receptor, so activation stimulates adenylyl cyclase and raises intracellular cAMP, which activates protein kinase A (PKA) and ultimately upregulates tyrosinase, the rate-limiting enzyme in melanin synthesis. Tyrosinase converts tyrosine into melanin precursors, driving increased production of eumelanin, the protective dark pigment, and visible skin darkening.
Because this pigmentation occurs through direct receptor stimulation rather than sun exposure, Melanotan I produces UV-independent tanning. In erythropoietic protoporphyria, that increased melanin allows patients to tolerate light without the severe porphyrin-mediated pain that normally follows even brief sun exposure.
The molecule is a linear 13-amino-acid analog of alpha-MSH engineered for stability: a norleucine substitution at position 4 and a D-phenylalanine at position 7 block enzymatic degradation, extending the peptide's activity relative to native alpha-MSH. Its linear structure gives it markedly greater MC1R selectivity than the smaller cyclic Melanotan II, which also engages MC3R, MC4R, and MC5R and thereby produces sexual and appetite effects that MT-1 largely lacks.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Reconstitute with bacteriostatic water. A 10 mg vial plus 5 mL BAC water yields 2000 mcg/mL, so 25 units on a U-100 insulin syringe delivers 500 mcg. Refrigerate and use within 28 days.
Beginner
- Dose
- 500 mcg
- Frequency
- Daily during loading, then weekly
- Timing
- Loading phase paired with mild UV exposure to drive tanning
- Duration
- 2 weeks loading, then weekly maintenance
- Route
- Subcutaneous
Lowest-dose community tanning protocol; drop to 500 mcg weekly once desired pigmentation is reached.
Intermediate
- Dose
- 750-1000 mcg
- Frequency
- Daily during loading, then weekly
- Timing
- Loading phase, tapering to maintenance
- Duration
- 2-3 weeks loading, then weekly maintenance
- Route
- Subcutaneous
Maintenance held at 500 mcg weekly.
Advanced
- Dose
- 1000 mcg
- Frequency
- Daily during loading, then weekly
- Timing
- Loading phase, then ongoing maintenance
- Duration
- 4 weeks loading, then weekly maintenance
- Route
- Subcutaneous
Maintenance at 1000 mcg weekly. Monitor for new naevi or darkening of existing moles; an annual dermatology check is recommended.
Approved (Scenesse, EPP)
- Dose
- 16 mg implant
- Frequency
- Every 2 months
- Timing
- Placed under dermatologist supervision
- Duration
- Ongoing per EPP treatment plan
- Route
- Controlled-release subcutaneous implant
The FDA/EU-approved protocol; approximately $49,000 per implant at orphan-drug pricing. This is a fundamentally different administration from grey-market injectable use.
- Community tanning protocols typically use a daily loading phase (2-4 weeks) to build pigmentation, followed by weekly maintenance dosing.
- The approved Scenesse regimen (a dermatologist-placed controlled-release implant every 2 months) is not the same as the self-injected vials sold for cosmetic tanning, and its safety record does not transfer to repeated off-label cycling.
- Monitor moles and nevi throughout use; new or darkening lesions warrant dermatological evaluation.
Evidence
Research & clinical studies (5)
CUV039 Phase 3 registration trial in erythropoietic protoporphyria
Afamelanotide implant increased pain-free sun-exposure time and improved quality of life in EPP patients, supporting FDA and EU approval.
CUV029 Phase 3 registration trial in erythropoietic protoporphyria
One of the pivotal EPP registration studies demonstrating photoprotective benefit that underpinned Scenesse approval.
CUV010 Phase 3 study in erythropoietic protoporphyria
Additional Phase 3 evidence supporting efficacy of afamelanotide in EPP.
CUV105 Phase 3 trial of Scenesse plus NB-UVB phototherapy in vitiligo
Enrollment completed May 2025 with topline results expected H2 2026; investigating afamelanotide as a repigmentation therapy in vitiligo.
Afamelanotide degradation and stability study
Mapped the peptide's degradation pathways, characterizing it as a formulated drug product.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Personal history of melanoma or dysplastic naevi syndrome
- Pregnancy and breastfeeding
- Active liver disease
- Pediatric use outside specialist EPP protocols
New or darkening moles require dermatology follow-up; case literature documents new nevus formation, darkening of existing nevi, and dysplastic changes in melanotan users. There is a theoretical melanoma concern in predisposed individuals given melanocyte stimulation, though EMA post-market surveillance in approved EPP use has not surfaced increased melanoma incidence. Sexual and cardiovascular side effects are minimal because MC4R agonism is low at therapeutic doses. Long-term safety of repeated cosmetic tanning cycles in healthy users is not established.
FAQ
Melanotan I — common questions
What is Melanotan I?
Melanotan I is afamelanotide, a synthetic 13-amino-acid linear analog of alpha-melanocyte-stimulating hormone (alpha-MSH) designed at the University of Arizona in the 1980s. It is FDA-approved as Scenesse (2019) and EU-approved (2014) for erythropoietic protoporphyria, a rare photosensitivity disorder.
How is Melanotan I different from Melanotan II?
Melanotan I is a longer linear peptide that is selective for MC1R, so it mainly produces pigmentation. Melanotan II is a smaller cyclic analog with broad melanocortin activity (MC1R + MC3R + MC4R + MC5R), adding significant sexual-arousal and appetite-suppression effects. MT-1 also has a cleaner acute side-effect profile with less nausea and milder flushing.
How is Melanotan I administered?
The approved Scenesse product is a 16 mg controlled-release subcutaneous implant placed by a dermatologist every 2 months for EPP patients. Grey-market cosmetic use is self-administered subcutaneous injection, commonly a daily loading phase for 2-4 weeks followed by weekly maintenance.
Is Melanotan I FDA-approved?
Yes, but narrowly. Afamelanotide was FDA-approved as Scenesse in October 2019 specifically for erythropoietic protoporphyria (EU approval 2014). It is not approved for cosmetic tanning anywhere in the world.
What are the side effects of Melanotan I?
Common effects include nausea (mostly at first doses), facial flushing, fatigue during loading, headache, and darkening of existing moles and freckles. Sexual and cardiovascular effects are minimal versus MT-II. Long-term safety in healthy cosmetic users is not well established, and new or changing moles warrant dermatological monitoring.
Does Melanotan I cause melanoma?
The melanocortin pathway is theoretically implicated in melanoma because it stimulates melanocytes, and dermatology case reports document new mole formation and nevus changes in users. However, EMA post-market surveillance in approved EPP use has not surfaced increased melanoma incidence. Long-term cosmetic-use safety is less characterized.
How much does Melanotan I cost?
Branded Scenesse is roughly $49,000 per 16 mg implant at orphan-drug pricing for EPP patients. Research-grade injectable Melanotan I sold for cosmetic use is inexpensive on the research-chemical market, with vials commonly around $19-$35.
