Melanotan II
A synthetic, non-selective melanocortin receptor agonist best known for UV-independent skin tanning, with bundled effects on sexual arousal and appetite.
Melanotan II is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (alpha-MSH) engineered at the University of Arizona in the late 1980s as a potential skin-cancer prophylactic. It activates all four druggable melanocortin receptors (MC1R, MC3R, MC4R, MC5R), driving eumelanin synthesis (tanning) via MC1R and central sexual arousal plus appetite suppression via MC4R. It has never been approved as a pharmaceutical in any country and persists as a grey-market tanning and libido compound; its MC4R-selective spin-off, bremelanotide (PT-141/Vyleesi), reached FDA approval for hypoactive sexual desire disorder.
Class
Synthetic cyclic heptapeptide (non-selective melanocortin receptor agonist)
Half-life
~30-60 minutes; subjective effects last 4-8 hours after injection
Routes
Subcutaneous injection, Intranasal (poor, inconsistent bioavailability)
Category
Sexual Health & Melanocortin
Researched benefits
What it's studied for
UV-independent skin tanning
MC1R activation on melanocytes drives cAMP-PKA-CREB signaling that upregulates MITF and downstream tyrosinase, TRP-1 and DCT, shifting the pigment ratio toward photoprotective eumelanin. Pigmentation is dose-dependent and reproducible, typically appearing within 10-14 days, and even fair Fitzpatrick I-II users can develop deep tans.
Central sexual arousal and erectile function
MC4R activation in spinal cord and brainstem sexual-response circuits drives centrally mediated arousal, distinct from the peripheral vasodilatory mechanism of PDE5 inhibitors. An early randomized crossover trial in men with organic erectile dysfunction reported significantly more subjectively rated erections and higher post-injection sexual desire than placebo — the same mechanism that spawned PT-141.
Appetite suppression
MC4R activation in the paraventricular and ventromedial hypothalamic nuclei produces dose-dependent appetite suppression, with users frequently reporting 20-40% reductions in food intake during active dosing. This effect is real but inconsistent and sometimes overlaps with nausea.
Modest energy-balance and fat effects
MC3R contributes to energy homeostasis and appears to promote lipolysis and modest fat-mass reduction independent of appetite effects, though this pathway is less well-characterized than MC4R.
Mechanism
How it works
Melanotan II is a synthetic cyclic analog of alpha-melanocyte-stimulating hormone (alpha-MSH), the 13-amino-acid POMC-derived neuropeptide. Hruby's team cyclized the molecule with a lactam bridge (between Asp5 and Lys10) and substituted D-phenylalanine at position 7, producing a non-selective melanocortin agonist roughly 1,000-fold more potent than alpha-MSH at MC1R with a dramatically extended half-life. The result is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2.
MT-II binds and activates the four melanocortin receptors expressed in mammalian tissue (MC1R, MC3R, MC4R, MC5R; MC2R responds only to ACTH), with high affinity at MC1R, MC3R and MC4R. These receptors couple primarily to Gas, so binding increases adenylyl cyclase activity, raises intracellular cAMP, and activates protein kinase A and the CREB transcription factor. The downstream effect depends on which tissue expresses the receptor.
At MC1R on skin and follicular melanocytes, cAMP-PKA-CREB signaling upregulates MITF, the master melanocyte regulator, which drives tyrosinase, TRP-1 and DCT to convert tyrosine into photoprotective eumelanin (the tan). At MC4R in the hypothalamus and sexual-response circuits, activation suppresses appetite and drives central sexual arousal, while also elevating sympathetic outflow and blood pressure (typically 5-10 mmHg systolic). MC3R contributes to energy balance and lipolysis, and MC5R stimulation on sebaceous glands increases sebum, explaining oilier skin and acne flares.
Because MT-II is a pan-agonist, its effects and side effects are an inseparable package: tanning cannot be obtained without also accepting MC4R-mediated nausea, appetite suppression, sexual activation and pressor effects, plus MC5R seborrhea. This trade-off motivated the development of receptor-selective successors — the MC4R-selective bremelanotide (PT-141) for sexual function and the MC1R-selective afamelanotide (Scenesse) for photoprotection. The cyclic lactam structure resists peptidase degradation, giving a half-life of roughly 30-60 minutes with peak plasma levels 1-2 hours after subcutaneous injection; because pigmentation is cumulative, users dose daily or every other day rather than for continuous plasma coverage.
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
Supplied as lyophilized powder in 5 mg or 10 mg vials; a proper pellet should be a fluffy white or pale-yellow cake, and the reconstituted solution should be perfectly clear and colorless. Reconstitute with bacteriostatic water and store the reconstituted solution refrigerated.
Beginner
- Dose
- 100 mcg test dose, then 250 mcg
- Frequency
- Daily during loading
- Timing
- Before bed to sleep through the nausea peak; inject before UV exposure for maximal tanning
- Duration
- 2-week loading phase
- Route
- Subcutaneous
Start with a 100 mcg test injection to assess nausea tolerance before ramping to 250 mcg daily. Tolerance to nausea builds over the first week.
Intermediate
- Dose
- 500 mcg
- Frequency
- Daily during loading, then 1-2x per week maintenance
- Timing
- Evening dosing; pair loading with controlled UV exposure
- Duration
- 2-week loading, then maintenance as desired
- Route
- Subcutaneous
500 mcg daily for two weeks of loading, dropping to 500 mcg once or twice weekly to maintain pigmentation.
Advanced
- Dose
- 500-1,000 mcg
- Frequency
- Daily during loading, then 1,000 mcg once weekly maintenance
- Timing
- Evening; combine with controlled UV exposure
- Duration
- Loading to desired depth, then weekly maintenance
- Route
- Subcutaneous
Higher loading doses accelerate tanning but amplify nausea, flushing and pressor effects. Typical overall dose range is 250-1,000 mcg per injection.
- There is no FDA-approved product, label or medically supervised protocol for Melanotan II; community regimens are not a use guide and product quality on the grey market varies widely.
- Nausea is the most common and dose-limiting effect — start low, ramp slowly, dose in the evening 1-2 hours before sleep, and avoid alcohol and fatty meals during loading.
- Tanning is cumulative and builds over weeks; the pigmentation response is amplified by UV exposure but MT-II is not a sunscreen and does not protect against UV-induced DNA damage.
- Obtain a full-body dermatologic mole map before the first cycle and monitor existing moles for darkening or architectural change throughout; new or changing pigmented lesions warrant prompt evaluation.
- Check blood pressure at baseline and within the first week of each cycle given MC4R-mediated pressor effects.
- Intranasal bioavailability is poor and inconsistent, and a 2025 case report links the nasal route to mucosal melanoma; most reliable effects come from subcutaneous injection.
Evidence
Research & clinical studies (3)
Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction
In a double-blind crossover trial of 10 men with organic erectile dysfunction, subcutaneous Melanotan II (0.025 mg/kg) initiated erections in 12 of 19 injections versus 1 of 21 placebo doses, with mean tip rigidity >80% lasting 45.3 versus 1.9 minutes (p=0.047) and significantly higher sexual desire scores.
PMID 11018622Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies
Summarizes the clinical development of melanocortin receptor agonists including Melanotan II and bremelanotide, documenting that central melanocortinergic activation modulates both peripheral genital vascular responses and central arousal circuitry as a therapeutic class for sexual dysfunction.
PMID 25096243Mucosal melanoma of the anterior maxilla following melanotan II nasal-spray use
Documents an anterior-maxilla mucosal melanoma arising after intranasal Melanotan II use, implicating the nasal route specifically and adding to the cutaneous-melanoma case-report literature associated with the compound.
PMID 40210573Combinations
Stacking & blends
Melanotan II + Gonadorelin: Central & Hormonal Sexual Health
Support sexual health through combined central arousal signaling and hormonal baseline support
Melanotan II acts as a melanocortin receptor agonist with centrally mediated effects on arousal and sexual motivation through MC3R and MC4R, while Gonadorelin (a synthetic GnRH analog) stimulates pulsatile LH and FSH release to support the hypothalamic-pituitary-gonadal axis. The combination pairs central arousal drive with hormonal baseline support (preclinical rationale).
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Personal or family history of melanoma or skin cancer
- Dysplastic nevus syndrome or numerous atypical moles
- Fitzpatrick skin type I (always burns, never tans)
- Uncontrolled or severe hypertension and recent cardiovascular events
- Cardiovascular disease or significant cardiac risk factors
- Pregnancy, attempting to conceive, or breastfeeding
- History of priapism
- Concurrent PDE5 inhibitor use (highest priapism risk)
- Known hypersensitivity to melanocortin peptides
The side-effect profile is a package deal driven by pan-agonism at melanocortin receptors and is dose-dependent, with nausea the most common adverse event and more pronounced than the selective successor PT-141. The most important harm-reduction step is dermatologic mole mapping before and after any cycle: multiple case reports document mole darkening, eruptive nevi, and melanoma diagnoses during or after use, though most cases are attributed to elevated baseline risk and sun-seeking behavior rather than proven direct carcinogenesis. Stop immediately and seek care for any ABCD mole changes, a new irregular pigmented lesion, an erection lasting over 4 hours, chest pain or blood pressure persistently over 160/100, or a positive pregnancy test. Grey-market product purity varies widely and can include substitution with related compounds such as PT-141.
FAQ
Melanotan II — common questions
How is Melanotan II different from PT-141 (bremelanotide)?
Both are synthetic melanocortin agonists, but MT-II is a cyclic 7-amino-acid peptide that binds MC1R, MC3R, MC4R and MC5R roughly equally, producing tanning (MC1R), appetite suppression and sexual arousal (MC4R), and increased sebum (MC5R). PT-141 is a linear derivative designed for MC4R selectivity, producing primarily sexual effects with minimal tanning, and it is FDA-approved as Vyleesi. Users who want tanning choose MT-II; users who want sexual-function effects without pigmentation choose PT-141.
Does MT-II replace sunscreen or protect against UV damage?
No. MT-II amplifies the tanning response to UV but does not protect against UV-induced DNA damage, sunburn or photoaging. The extra eumelanin adds only modest UV absorption compared with daily SPF 50+ sunscreen. A deep MT-II tan can coexist with ongoing UV damage, so rigorous sunscreen use should continue throughout any cycle.
Will MT-II cause melanoma?
It is not established. Multiple dermatology case reports document melanoma diagnoses and eruptive nevi during or after use, but MT-II users skew young, fair-skinned and heavily tanning — a population with elevated baseline risk. MT-II clearly darkens existing moles and can drive new pigmented lesions; whether it initiates melanoma or merely changes the visible behavior of lesions is uncertain. Anyone with elevated baseline melanoma risk should not use it, and everyone using it should have pre- and post-cycle mole mapping.
Why does MT-II cause nausea and how do I minimize it?
Nausea is mediated by MC4R activation in the brainstem and area postrema, is dose-dependent, and is nearly universal at full doses. The most effective steps are to start with very small doses (around 100 mcg) and ramp slowly as tolerance builds, dose in the evening 1-2 hours before sleep so the nausea peak occurs during sleep, and avoid alcohol and fatty meals during loading.
How long does the tan last after stopping MT-II?
MT-II-driven pigmentation fades over roughly 4-6 weeks as melanin-containing keratinocytes are shed during normal epidermal turnover. Darkened moles, freckles and age spots may persist longer, and some users report semi-permanent darkening of lips, nipples and genital skin after repeated cycles.
Is Melanotan II legal and FDA-approved?
It is not FDA-approved for any indication and is not approved anywhere in the world. In the US it is commonly sold as a research chemical in a regulatory grey zone; the UK MHRA has warned against it and Australia's TGA has prosecuted sellers. It was removed from the FDA Category 2 503A bulk substances list in April 2026 and is scheduled for PCAC review in early 2027, though removal does not authorize compounding.
Can women use MT-II?
Women use MT-II with outcomes similar to men — pigmentation, appetite suppression and increased libido — but it is contraindicated in pregnancy and while trying to conceive, so reliable contraception is essential during a cycle. Women are also more prone to facial hyperpigmentation (melasma-like patterns), which can be stubborn and outlast the cycle, so strict facial sunscreen is advised.
How do I know if my MT-II product is real?
Without third-party HPLC and mass-spectrometry testing you largely can't. Practical signals: the lyophilized powder should be a structured fluffy white or pale-yellow cake, the reconstituted solution should be perfectly clear and colorless, and effects (tanning, nausea, mole darkening) should emerge within the expected dose response. Grey-market vials should be assumed to be only approximately what they claim, and mislabeling — including substitution with PT-141 — has been documented.
