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Melanotan I13 residues (approx.)SYSMEHFRWGKPVEach bubble = one amino acid. Size = residue mass. Color = chemical class.Uses closest standard amino acids for non-standard residues.Also known as: MT-I, afamelanotide, Scenesse
Median pain-free sun exposure jumped from 0.8 hours to 6.0 hours in the important Phase 3 trial (168 EPP patients)[1]. Melanotan I (afamelanotide) is a 13-amino-acid synthetic analog of alpha-MSH that selectively activates MC1R to drive eumelanin production. It's the only FDA-approved melanocortin receptor agonist, sold as Scenesse for erythropoietic protoporphyria. All randomized trial data covers EPP, not cosmetic tanning. In the research peptide community, injectable MT-I is used at lower doses (500 to 1,500 mcg daily) for UV-free pigmentation, though no dose-finding RCT exists for that use case.
Median sun exposure went from 48 minutes to 6 hours. That's the headline from the Phase 3 EPP trials (Langendonk et al., NEJM 2015, n=168)[1] that earned afamelanotide its FDA approval in October 2019. Melanotan I (also called afamelanotide, brand name Scenesse, CAS 75921-69-6) is a 13-amino-acid synthetic analog of alpha-melanocyte stimulating hormone. It carries a norleucine substitution at position 4 and a D-phenylalanine at position 7, giving it resistance to enzymatic breakdown and an apparent half-life around 15 hours. The mechanism is straightforward. Afamelanotide binds MC1R on melanocytes, triggering a cAMP cascade that upregulates tyrosinase and shifts pigment production from pheomelanin (red-yellow, photosensitizing) toward eumelanin (brown-black, photoprotective). The result is real melanin that absorbs UV radiation and dissipates it as heat. In EPP patients, that translates to fewer phototoxic reactions (77 vs 146 episodes, p=0.04) and dramatically longer time outdoors. A 200-patient German real-world cohort confirmed 91% treatment continuation and up to 245% improvement in quality of life scores by season (2025)[2]. A separate 2024 safety review found zero melanoma events in over 1,000 afamelanotide-exposed patients [3]. Outside the clinic, injectable research-grade MT-I is used at 500 to 1,500 mcg daily for cosmetic tanning. Its MC1R selectivity means no spontaneous erections, no appetite suppression, and milder nausea compared to Melanotan II. The tradeoff: slower onset (4 to 8 weeks vs 2 to 3 weeks with MT-II) and higher cost per tan.
Afamelanotide selectively binds the melanocortin-1 receptor (MC1R) on melanocytes. That receptor sits on the cell surface coupled to a Gs protein. Binding triggers adenylyl cyclase activation, raising intracellular cAMP levels. From there, the signal runs through protein kinase A (PKA), which phosphorylates CREB. Phosphorylated CREB turns on MITF, the master transcription factor for melanogenesis. MITF drives expression of three enzymes: tyrosinase, TYRP1, and DCT. Those three are the full enzymatic machinery required for eumelanin synthesis. The practical outcome is a shift in melanin type. Human melanocytes can produce two pigments: pheomelanin (red-yellow, photosensitizing, generates reactive oxygen species under UV) and eumelanin (brown-black, photoprotective, absorbs UV and converts it to heat). MC1R activation pushes the ratio toward eumelanin. Two structural modifications make afamelanotide more useful than native alpha-MSH. A norleucine at position 4 and D-phenylalanine at position 7 protect the peptide from rapid enzymatic degradation. Native alpha-MSH is cleared in minutes; afamelanotide has an apparent half-life of approximately 15 hours from the subcutaneous implant (Scenesse FDA label, Section 12.3).
Afamelanotide is the only FDA-approved synthetic alpha-MSH analog. Phase 3 trials [1] demonstrated significant increase in pain-free sun exposure in EPP patients (median 6.0 h vs 0.8 h placebo, p=0.005). A 200-patient German real-world cohort (2025)[2] confirmed 91% treatment continuation and 55–245% EPP-QoL improvement by season. A 2024 safety review [3] found zero melanoma events in >1,000 afamelanotide-exposed patients despite prolonged MC1R activation. Evidence base for EPP indication is strong; evidence for cosmetic tanning is extrapolated from mechanism, not clinical trials.
Langendonk et al. NEJM 2015 (PMID 26132941): Phase 3 EU/US EPP trials; 168 patients; primary endpoint met in both studies
All RCT data is in EPP patients, not healthy volunteers seeking cosmetic tanning. Injectable research-grade MT-I has no published dose-finding RCT. EMA approved year-round use September 2025, but FDA label still specifies EPP indication only. No published head-to-head trial vs. Melanotan II.
Community uses injectable research-grade MT-I primarily for cosmetic tanning, often as a "clean" alternative to Melanotan II due to absence of sexual arousal and appetite suppression. General satisfaction for tanning is positive but MT-I is viewed as slower and more expensive per tan than MT-II.
Science and community agree on the mechanism (MC1R → eumelanin → photoprotection) and general dose range. Science evidence base is for EPP, not cosmetic tanning. Community extrapolates from mechanism and anecdote, not from RCTs in healthy volunteers. Both agree on SC injection route, loading-then-maintenance structure, and lack of sexual side effects.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 500mcg | Daily |
| Moderate | 1mg | Daily |
| Aggressive | 1,500mcg | Daily |
Reconstitution math for the standard 10 mg vial: add 2 mL of bacteriostatic water. That gives you 5,000 mcg per mL, or 50 mcg per unit on a U-100 insulin syringe. So 100 mcg equals 2 units, 250 mcg equals 5 units, 500 mcg equals 10 units, and 1,000 mcg equals 20 units. MT-I is slower than MT-II. Expect 4 to 8 weeks to reach your desired pigmentation, compared to 2 to 3 weeks with MT-II. You need UV activation; the peptide stimulates melanin production, but melanin has to be activated by sunlight or a tanning bed to transfer to keratinocytes. Plan for 10 to 20 minutes of UV exposure after each injection during loading. If you get unexpected sexual side effects (spontaneous erections, flushing beyond the first few doses), test whether your vial contains MT-II instead. MT-I is 13 amino acids, MT-II is a 7-amino-acid ring structure. Contamination happens in the gray market. Start any new vendor's product at 100 mcg and assess before loading. Store reconstituted vials at 2 to 8 degrees Celsius; use within 3 to 4 weeks. Discard any solution that's cloudy or amber.
Scenesse implant is administered every 60 days continuously throughout seasons of sun exposure. For injectable melanotan I, a common research protocol is daily injections for 2-3 weeks as a loading phase, then 2-3x/week for maintenance.
Continuous MC1R agonism theoretically leads to receptor downregulation and reduced signaling efficiency over time. Clinically, this is most relevant for research injectable use: the EMA now permits year-round Scenesse implant use in EPP patients without breaks, so desensitization is not considered a clinical problem at implant doses. For the research community, cycling (8 weeks on / 8 weeks off) is used to maintain skin monitoring windows, manage pigmentation levels, and avoid prolonged continuous melanocyte stimulation. There is no published data specifically on MT-I tachyphylaxis in humans.
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Expected: Significant increase in pain-free sun exposure (median 6.0 h vs 0.8 h placebo in Phase 3); reduced frequency of phototoxic reactions
Monitor: Full-body skin exam twice yearly. Monitor pre-existing nevi and new pigmentary lesions. Women of childbearing age must use effective contraception during treatment and for 3 months after last implant.
Gather supplies: 10 mg lyophilized MT-I vial, bacteriostatic water, alcohol swabs, 29 or 30 gauge insulin syringe (U-100, 0.5 mL or 1 mL).
Draw 2 mL of bacteriostatic water into a syringe. Inject it slowly down the inside wall of the vial. Don't shake. Swirl gently until the powder dissolves completely. The solution should be clear and colorless.
At 2 mL reconstitution, the concentration is 50 mcg per unit. For a 250 mcg dose, draw to the 5-unit mark. For 500 mcg, draw to the 10-unit mark.
Clean the abdomen or outer thigh with an alcohol swab. Rotate injection sites with each dose.
Pinch a fold of skin, insert the needle at a 45-degree angle, push the plunger slowly, hold for 5 seconds, then withdraw.
Inject in the evening to minimize any daytime nausea. During the loading phase, get 10 to 20 minutes of UV exposure (sunlight or tanning bed) within a few hours of injection to activate melanin transfer.
Keep it at 2 to 8 degrees Celsius, protected from light. Use within 3 to 4 weeks.
Community "kickstart + switch" protocol: MT-II used for first 1–2 weeks for rapid pigmentation onset (faster tan due to multi-receptor activation), then transition to MT-I for long-term maintenance (cleaner profile, no sexual side effects). Not recommended on the same day.
MT-II loading 100–250 mcg daily ×7–14 days → switch to MT-I 500 mcg daily ×14 days → MT-I maintenance 500 mcg 2–3×/week
Skin quality synergy: GHK-Cu stimulates collagen/elastin while MT-I increases protective eumelanin. Community "skin health" stack for improved skin texture, firmness, and even pigmentation alongside tanning. No pharmacological interaction concern.
Additive MC receptor stimulation on the same day increases risk of nausea, flushing, spontaneous erection, and excessive pigmentation. Sequential use is acceptable; same-day co-administration is not recommended.
PT-141 is also a melanocortin agonist (MC4R primary). Same-day use with MT-I adds to overall melanocortin load; risk of synergistic nausea, flushing, and cardiovascular effects. Sequential use (different days) is lower risk.
MT-I increases sun tolerance, which may mask early signs of drug-induced photosensitivity reactions. Patients on photosensitizing drugs should exercise heightened caution about UV exposure even if the normal phototoxic signal is blunted.
Relevant for the Scenesse implant procedure: subcutaneous insertion carries increased bleeding risk at the insertion site. Not a pharmacokinetic interaction; procedural concern only.
Pricing updated 2026-04-09
The most important safety consideration with Melanotan I is mole and freckle darkening. All existing pigmented lesions will darken during use. That's a pharmacological certainty, not a side effect to dismiss. Rapid asymmetric changes in any mole warrant immediate dermatological evaluation and discontinuation. The FDA label mandates full-body skin exams twice yearly during Scenesse treatment, and the same standard applies to research injectable use. No melanoma cases have been confirmed in over 1,000 afamelanotide-exposed patients (2024 safety review)[3]. The published melanoma reports in the literature all involve unlicensed Melanotan II products, not pharmaceutical afamelanotide. That said, the FDA label contraindication for patients with melanoma history is precautionary and appropriate; MC1R stimulation could theoretically promote subclinical melanocyte proliferation. Implant site reactions are the most common adverse event with Scenesse. Discoloration at the insertion site occurs in roughly 10% of patients, along with bruising, pain, and swelling. These resolve without intervention. Nausea and headache each affect more than 10% of patients but are typically mild. Both tend to resolve within 1 to 2 days. For injectable users, nausea is worst at doses of 500 mcg or higher on an empty stomach. Evening dosing with food reduces this considerably. Community reports confirm that MT-I causes significantly less nausea than MT-II at comparable tanning doses. Other reported effects include fatigue, dizziness, and back pain. Skin darkening beyond the desired tanning effect is expected rather than pathological. Allergic reactions, including anaphylaxis, are rare but documented. The Scenesse FDA label was updated in 2024 to include an anaphylaxis signal. Anyone experiencing difficulty breathing, throat tightness, or severe flushing after an injection should seek emergency medical attention. Contraindications are clear: pregnancy (no adequate safety data; discontinue immediately if pregnancy occurs), personal history of melanoma or dysplastic nevi, severe hepatic impairment, breastfeeding (excretion in human milk unknown), and children under 18 (safety not established). Women of childbearing age should use effective contraception during treatment and for 3 months after the last dose. A vitamin D monitoring note: a German cohort study [2] found vitamin D deficiency in 29% of EPP patients on afamelanotide. Paradoxically, users who reduce UV exposure while tanned may become vitamin D deficient. Baseline and periodic 25-OH vitamin D testing is reasonable during extended use.
Verify Melanotan I dosing and safety with a second opinion
Research-grade injectable MT-I has no FDA-approved injectable form: all gray-market sourcing. The pharmaceutical (Scenesse) is an implant administered by healthcare providers. Injectable peptide purity is entirely vendor-dependent with no regulatory oversight. Impurities, incorrect sequence, or cross-contamination with MT-II (which has different receptor profile) are documented risks in the research peptide market.
| Test | When | Target |
|---|---|---|
| Full-body dermatological skin exam | Twice yearly during extended use; before starting and after cessation | No new atypical/changing lesions; pre-existing lesions stable in size, symmetry, color |
| Serum vitamin D (25-OH) | Baseline and every 3–6 months with extended use | 30–80 ng/mL (50–200 nmol/L) |
| Blood pressure check | Before starting if on antihypertensives; at week 2 | — |
MT-I darkens all existing pigmented lesions (moles, freckles, seborrheic keratoses), which can mask early melanocytic changes. FDA/EMA mandate biannual monitoring during Scenesse treatment; same prudence applies to research injectable use.
German cohort study (PMID 40082741) found vitamin D deficiency in 29% of EPP patients on afamelanotide: likely due to reduced UV-seeking behavior. Paradoxically, MT-I users who continue sun avoidance may become vitamin D deficient even while tanned.
Melanocortin receptor activation can cause transient cardiovascular effects. Scenesse FDA label updated 2024 to note anaphylaxis signal; monitor first implant/loading doses closely.
Implant releases the majority of the 16 mg dose. Plasma levels peak around 36 hours. MC1R signaling activates eumelanin synthesis. Mild nausea or headache may occur within the first 1-2 days.
Visible skin darkening begins as eumelanin accumulates in keratinocytes. Implant drug release is essentially complete by day 10.
Peak pigmentation achieved. Patients report increased tolerance to sun exposure and fewer phototoxic episodes.
Pigmentation begins to gradually fade as melanin-loaded keratinocytes are shed through normal skin turnover. Next implant due at the 60-day mark.
Days 1 through 7 (Tolerance establishment): MC1R activation starts within hours of the first injection. Intracellular cAMP rises, MITF and tyrosinase gene expression ramps up. You won't see visible changes yet. Nausea and mild flushing are common in the first 1 to 3 days, especially at doses of 500 mcg or higher. Moles may begin darkening subtly. Some users report fatigue and a mild headache that clears within 48 hours. Weeks 2 through 3 (Early pigmentation): Eumelanin accumulates in melanocytes and transfers to keratinocytes through melanocyte dendrites. Visible tanning appears, most noticeably in areas that get sun exposure. Freckles and moles darken more obviously now. Side effects from the first week typically fade. Weeks 3 through 6 (Peak pigmentation): Eumelanin density reaches its maximum. Photoprotection is functional at this point. UV absorption thresholds are measurably higher. Community users typically report reaching their desired tan level during this window and transition to maintenance dosing. Overall satisfaction is high at this stage. Weeks 6 through 12 (Maintenance): Pigmentation holds steady with periodic dosing. Skin turns over on a 28-day keratinocyte cycle, so the tan fades naturally without continued injections. Maintenance at 250 to 500 mcg two to three times per week offsets this turnover. Long-term users report stable year-round tanning with minimal side effects at well-tolerated doses. Post-cessation, weeks 1 through 8 (Fade phase): Eumelanin production stops once MC1R stimulation ceases. Normal keratinocyte turnover removes melanin-loaded cells gradually. The tan fades evenly over 4 to 8 weeks. Moles and freckles return to their baseline pigmentation over the same window. No rebound effects or withdrawal symptoms are reported.
MC1R activation begins within hours of injection; cAMP upregulates MITF/tyrosinase. Pharmacokinetic peak at ~2h (injectable form). Subclinical eumelanin synthesis starts immediately.
Most users notice no visible change in week 1. Nausea and mild flushing common in first 1–3 days. Moles may begin to subtly darken. Some users report fatigue and mild headache.
Eumelanin accumulates in melanocytes and transfers to keratinocytes via dendrites. Pigmentation becomes macroscopically visible as melanin-loaded keratinocytes migrate to the upper epidermis.
Visible tan begins to appear, most notably in sun-exposed areas. Freckles and moles darken noticeably. Side effects typically diminish after week 1.
Maximal eumelanin density achieved. Photoprotection is functional: elevated UV absorption threshold reduces erythema and phototoxic reactions (clinically demonstrated in EPP trials).
Users report desired tan level reached. UV activation sessions reduce or stop. Switch to maintenance dosing. Overall satisfaction high at this stage.
Pigmentation maintained with periodic dosing. Skin turnover (28-day cycle) naturally fades tan; maintenance dosing counteracts this. No data on receptor desensitization with intermittent maintenance dosing.
Stable tan at 250–500 mcg 2–3×/week. Some users drop to 1×/week. Long-term users report sustained tan year-round with minimal side effects.
Eumelanin production stops without continued MC1R stimulation. Normal keratinocyte turnover (~28 days) removes melanin-loaded cells; tan fades gradually over 4–8 weeks.
Tan fades evenly. Users report no rebound or withdrawal. Moles and freckles return to baseline pigmentation over same 4–8 week window.
Source: Scenesse FDA Prescribing Information, Section 12.3 Pharmacokinetics. Apparent terminal half-life ~15 hours from 16 mg SC implant.
Loading the interactive decay curve.
Melanotan I (afamelanotide) received FDA approval in October 2019 under the brand name Scenesse for erythropoietic protoporphyria (EPP). It is a 16 mg subcutaneous implant administered every 60 days by a healthcare provider. The EMA updated its approval in September 2025 to permit year-round use. Scenesse is available through specialty pharmacies with manufacturer patient assistance programs. No FDA-approved injectable form of Melanotan I exists. Research-grade injectable MT-I is sold for laboratory research purposes only. Purchasing, possessing, or self-administering research peptides occupies a legal gray area that varies by jurisdiction. It is not scheduled as a controlled substance in the United States. Melanotan I is prohibited by WADA under section S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics). Athletes subject to anti-doping testing should not use this peptide in any form. This content is for informational purposes only and does not constitute medical advice. Consult a licensed healthcare provider before using any peptide product.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
