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Melanotan II

Tier 1 · Human trials
Also known as MT-II · Melanotan-2 · MT2 peptide

Human efficacy data derive from small early-phase trials: a Phase I tanning study in 3 volunteers2, a placebo-controlled erection study in 20 men5, and an erectile dysfunction trial in 10 men1. These support Tier 1 evidence for tanning and erectile effects, though sample sizes are very small and no Phase III trials were completed (development discontinued ~2003). Mechanistic and receptor data are in-vitro/animal; serious harms (melanoma, priapism, rhabdomyolysis, renal failure, PRES) are documented only through case reports and anecdotal signals.

Half-life
~1 h
Routes
Subcutaneous injection · Intranasal (nasal spray) · Intravenous (in pharmacokinetic studies)
Goals
Cosmetic tanning / skin pigmentation · Sexual function / erectile support · Weight management / appetite suppression
Cost / mg
Not recorded

How it works

Melanotan II is a lab-made, ring-shaped copy of the natural hormone alpha-MSH that our bodies use to signal skin pigment cells. It switches on melanocortin receptors (MC1R, MC3R, MC4R and MC5R), which raises a cell-signaling molecule called cyclic AMP. In the skin this ramps up production of the dark pigment eumelanin, tanning the skin even without sunlight and offering some UV protection. Because it also hits receptors in the brain, it can trigger erections and sexual desire, suppress appetite, and affect glands — effects that cannot be separated from the tanning effect because the peptide is non-selective. It is far more potent than the natural hormone and its ring structure makes it last longer than natural alpha-MSH before being broken down.

Overview

Overview

Melanotan II (MT-II, Melanotan-2, MT2 peptide) is a synthetic cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH). Its structure is Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2), with molecular formula C50H69N15O9, a molecular weight of approximately 1024.18 g/mol, and CAS number 121062-08-6. It retains the 4-10 melanocortin receptor binding region shared by alpha-MSH and adrenocorticotropin (ACTH).

Development

Melanotan II was developed at the University of Arizona in the late 1980s/early 1990s (synthesized by Hadley and colleagues in 1989 by Victor Hruby and Mac Hadley) as a potential sunless tanning agent and skin cancer chemopreventive. It was conceived as a successor to afamelanotide (Melanotan I), a drug operating through a similar pathway. Reported synthesis proceeds in 12 steps with an overall yield of 2.6%, delivering product more than 90% pure without preparative chromatography.

How it works

Structural modifications — replacing methionine-4 with norleucine, substituting L-phenylalanine-7 with D-phenylalanine, and cyclization via a lactam bridge — stabilize the backbone against proteolysis. MT-II is a non-selective agonist of the Gs protein-coupled melanocortin receptors MC1R, MC3R, MC4R and MC5R, but does not significantly activate MC2R (the ACTH receptor). Receptor binding activates adenylyl cyclase and raises intracellular cAMP. In epidermal melanocytes, MC1R activation drives the cAMP-PKA-CREB cascade, upregulating tyrosinase and shifting melanin synthesis toward darker eumelanin — a process that occurs independently of ultraviolet exposure, with the resulting eumelanin providing genuine photoprotection. Centrally, MC4R activation in the hypothalamic paraventricular nucleus and spinal cord initiates erectile responses and sexual desire (thought to be dopaminergically mediated, possibly with MC3R involvement), while MC3R/MC4R activation in the hypothalamus suppresses food intake and MC5R modulates exocrine gland function. Because the peptide is non-selective, the desired MC1R-mediated tanning cannot be separated from the central sexual, appetite and autonomic effects.

MT-II is superpotent in vitro — roughly 1000-fold more potent than native alpha-MSH in the classic frog skin bioassay; its precursor [Nle4,D-Phe7]-alpha-MSH is about 26 times more potent than alpha-MSH in the mouse melanoma adenylate cyclase assay.

Human evidence

Tanning: Human tanning activity was established in 1996, with effect seen after only 5 low doses given every other day by subcutaneous injection. In a Phase I trial, three normal male volunteers received subcutaneous MT-II at escalating doses of 0.01-0.03 mg/kg on alternating days over two weeks; two of three showed measurable increases in facial pigmentation (with additional darkening of upper body and buttock) measured by quantitative reflectance and visual perception one week after dosing ended. MT-II produces robust cutaneous pigmentation and can cause dramatic skin darkening within days when injected or used as a nasal spray. Notably, it enhances the tanning response but does not eliminate the need for UV exposure; users typically combine it with 10-20 minutes of sun or sunbed exposure.

Erectile/sexual function: In a placebo-controlled trial, MT-II led to penile erection in 17 of 20 men in the absence of sexual stimulation, with a mean of 41 minutes of RigiScan tip rigidity >80% over a 6-hour monitoring period; increased sexual desire was reported after 68% of MT-II doses versus 19% of placebo doses (P<0.01). In 8 of 10 men with psychogenic erectile dysfunction (mean age 47.4 years), clinically apparent erections developed, with mean tip-rigidity-over-80% duration of 38.0 minutes versus 3.0 minutes on placebo (p=0.0045). No statistically significant change in testosterone or free testosterone occurred after the study. A stretching and yawning complex appeared to correlate with the onset of spontaneous erections, which were experienced intermittently for 1-5 hours (also reported 1-4 hours) depending on dose.

Appetite/weight: In obese rats, subcutaneous MT-II via minipump caused prompt suppression of food intake that moderately declined and returned to baseline within 8-12 days. MT-II can suppress appetite and lead to weight loss in humans (anecdotal). A single zebrafish study reported MT-II reversed high-fat-diet-induced impairments in recognition memory, anxiety and exploratory behavior — a finding not replicated elsewhere.

Uses and status

MT-II is mainly used for cosmetic tanning and, to a lesser degree, for weight loss, aphrodisiac effects, and to counter skin conditions such as rosacea. It has been patented and clinically tested for tanning and for diagnosis/treatment of male erectile dysfunction. It is unlicensed, unregulated and not approved by the FDA (which does not consider it a legal dietary or cosmetic ingredient), nor the Australian TGA; it is banned by WADA and can be purchased illicitly online. No completed Phase III safety or efficacy trials exist, and pharmaceutical development was discontinued around 2003 owing to the non-selective receptor profile and associated side effects. Illicit use has become prevalent among young people at fitness centres, often ahead of sun holidays or bodybuilding competitions. FDA-approved successor molecules include PT-141 (bremelanotide) and afamelanotide (Scenesse), both approved in 2019; bremelanotide was engineered for greater MC3R/MC4R selectivity without the melanogenic tanning effect and increases male erection rigidity/duration and female sexual desire in sexual arousal disorder.

What the research shows

126 findings extracted from the 23 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 10 human trial findings, 4 human study findings, 8 animal findings and 2 anecdotal findings.

  • human trialIn 8 of 10 men treated with Melanotan-II clinically apparent erections developed1

  • human trialMean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo1

  • human trialMean patient age was 47.4 years, mean serum testosterone 450 mg./ml., mean free testosterone 14.8 mg./ml. and mean serum cholesterol 201 mg./dl.1

  • human trialA stretching and yawning complex appeared to correlate with the onset of spontaneous, penile erections which were intermittently experienced for 1-5 hours after MT-II dosing, depending on the MT-II dose2

  • human trialTwo subjects had increased pigmentation in the face, upper body and buttock, as measured by quantitative reflectance and by visual perception 1 week after MT-II dosing ended2

  • human trialA stretching and yawning complex appeared to correlate with the onset of spontaneous, penile erections which were intermittently experienced for 1-5 hours after MT-II dosing, depending on the MT-II dose2

  • human trialTwo subjects had increased pigmentation in the face, upper body and buttock, as measured by quantitative reflectance and by visual perception 1 week after MT-II dosing ended2

  • human trialIn the absence of sexual stimulation, Melanotan II led to penile erection in 17 of 20 men5

Show 16 more findings

  • human trialIncreased sexual desire was reported after 13/19 (68%) doses of Melanotan II vs 4/21 (19%) of placebo (P<0.01)5

  • human trialMelanotan II is a potent initiator of penile erection in men with erectile dysfunction5

  • human studyTrials have shown that the tanning effect can occur within 5 doses13

  • human studyMelanotan II was found to be a potent stimulator of male erections during clinic trials13

  • human studyBremelanotide, a drug based on melanotan II, has been noted across several studies to increase rigidity and duration of male erection13

  • human studyBremelanotide has been shown to increase female sexual desire in patients with sexual arousal disorder13

  • animalMTII administered subcutaneously via minipump to obese rats caused prompt suppression of food intake, which moderately declined and returned to pretreatment levels within 8-12 days6

  • animalZebrafish fed a high-fat diet for three weeks showed impairment in recognition memory8

  • animalZebrafish fed a high-fat diet showed elevated anxiety levels8

  • animalZebrafish fed a high-fat diet showed reduced exploratory propensity8

  • animalMelanotan-II reversed high-fat diet-induced impairment in recognition memory in zebrafish8

  • animalMelanotan-II reversed elevated anxiety levels induced by high-fat diet in zebrafish8

  • animalMelanotan-II reversed reduced exploratory behavior induced by high-fat diet in zebrafish8

  • animalResearch in the early 1960s showed that in rats, administration of α-MSH caused sexual arousal10

  • anecdotalIf injected or used as a nasal spray, Melanotan-II can cause dramatic skin darkening in just days12

  • anecdotalMelanotan-II can suppress appetite and lead to weight loss12

How it works

Based on 6 human trial findings, 3 human study findings, 6 in vitro findings, 18 expert opinion findings and 2 theoretical findings.

  • human trialMelanotan-II is a synthetic cyclic heptapeptide, Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH21

  • human trialMelanotan-II contains the 4-10 melanocortin receptor binding region common to alpha-MSH and adrenocorticotropin1

  • human trialMelanotan-II is a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone with the structure Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH22

  • human trialMelanotan-II (MT-II) is a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH) with the structure Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH22

  • human trialMT-II has superpotent melanotropic activity in vitro2

  • human trialMelanotan II is a non-selective melanocortin receptor agonist5

  • human studyMelanotan II is a non-selective melanocortin-receptor agonist3

  • human studyMechanism of renal injury with Melanotan II involves thrombotic pharmacological influence3

Show 27 more findings

  • human studyMechanism of renal injury with Melanotan II involves possible direct toxic effect on renal parenchyma3

  • in vitroMelanotan-II has superpotent melanotropic activity in vitro2

  • in vitroStapled peptides derived from α-MSH using tryptathionine and 2,2'-bis-indole staples show nanomolar binding affinities (K values)7

  • in vitroOne stapled α-MSH peptide shows sub-nanomolar K value7

  • in vitroChemoselective stapling of α-MSH can be achieved using 5-hydroxypyrroloindoline condensation with cysteine-thiol or tryptophan-indole7

  • in vitroMelanotan II (MT-II) is a potent and unselective agonist of human MCRs (hMCRs)9

  • in vitroEnhanced sampling molecular dynamics simulations outlined how cyclization strategy affects peptides' conformational behavior and hMC1R affinity9

  • expert opinionMT-II is a cyclic α-melanocyte-stimulating hormone analogue4

  • expert opinionMelanotan II suppresses food intake by activation of melanocortin-4 receptors on brain neurons6

  • expert opinionMelanotan-II is quite potent at melanocortin MC1 receptors, but it is not particularly selective6

  • expert opinionMelanotan II is a synthetic analogue of the peptide hormone α-melanocyte-stimulating hormone (α-MSH) that stimulates melanogenesis to facilitate tanning10

  • expert opinionMelanotan II acts as a non-selective agonist of the melanocortin receptors MC1, MC3, MC4, and MC510

  • expert opinionMelanotan II produces melanogenesis by activation of the MC1 receptor10

  • expert opinionSexual effects are thought to be related to its ability to activate the MC4 receptor (though the MC3 is thought to also possibly be involved)10

  • expert opinionMelanotan is a peptide that tells your body to make more skin pigment (melanin)11

  • expert opinionMelanotan stimulates melanocytes, which are the cells in your body that provide pigment (melanin) to your skin11

  • expert opinionMelanotan-II is a synthetic version of α-Melanocyte-stimulating-hormone (α-MSH), which is produced in the pituitary gland of the brain and is naturally present in our bodies12

  • expert opinionMelanotan-II mimics the action of hormones and upregulates the activity of pigment cells, causing them to produce more melanin and resulting in a tan12

  • expert opinionStimulating pigment cells with Melanotan-II can cause abnormal proliferation of the cells and jumpstart progression to possible development of melanoma12

  • expert opinionMelanotan-II can bind to receptors in the brain and influence processes like appetite and sexual function12

  • expert opinionMelanotan II is an unlicensed and largely untested form of alpha-melanocyte-stimulating hormone, which causes pigmentation (tanning) of human skin13

  • expert opinionMelanotan II non-selectively mimics the action of melanocortin peptides13

  • expert opinionMelanotan II stimulates the production of eumelanin, causing the skin to go darker (tanning)13

  • expert opinionMelanotan II is a synthetic analogue of α-melanocyte-stimulating hormone that, via interaction with the melanocortin 1 receptor, induces skin hyperpigmentation14

  • expert opinionMelanotan-II is an alpha-melanocyte stimulating hormone (a-MSH) analogue15

  • theoreticalMelanotropins have been associated with diet-related disorders8

  • theoreticalMelanotan-II targets melanotropin receptors8

Dosing

Based on 3 human trial findings, 1 human study finding and 1 expert opinion finding.

  • human trialMelanotan-II is a potent initiator of erections in men with psychogenic erectile dysfunction and has manageable side effects at a dose of 0.025 mg./kg1

  • human trialThe recommended single MT-II dose for future Phase I studies is 0.025 mg/kg/day2

  • human trialThe recommended single MT-II dose for future Phase I studies is 0.025 mg/kg/day2

  • human studyPatient conducted a 3- to 4-week course of self-injections with MT-II prior to melanoma diagnosis4

  • expert opinionMelanotan II is usually administered as an injection of liquid underneath the skin, commonly every second day13

How the body handles it

Based on 1 in vitro finding.

  • in vitroNewly designed peptides displayed binding affinities toward MCRs ranging from the low nanomolar to the sub-micromolar range9

Safety and side effects

Based on 8 human trial findings, 4 human study findings, 23 expert opinion findings and 3 anecdotal findings.

  • human trialTransient side effects of nausea, stretching and yawning and decreased appetite were reported more frequently after injections of Melanotan-II than placebo but none required treatment1

  • human trialNo statistically significant change in testosterone or free testosterone level occurred after completion of the study1

  • human trialGrade II somnolence and fatigue occurred at the 0.03 mg/kg dose in one of two subjects2

  • human trialMild nausea, not requiring antiemetic treatment, was reported at most MT-II dose levels2

  • human trialSubcutaneous injections of MT-II at 0.03 mg/kg dose produced Grade II somnolence and fatigue in one of two subjects2

  • human trialMild nausea, not requiring antiemetic treatment, was reported at most MT-II dose levels2

  • human trialNausea and yawning were frequently reported side effects due to Melanotan II5

  • human trialAt a dose of 0.025 mg/kg, 12.9% of subjects had severe nausea5

Show 30 more findings

  • human studyMelanotan II inducing rhabdomyolysis and renal failure have been described previously3

  • human studyMelanotan II associated with renal infarction3

  • human studyMelanocyte stimulation of MT-II in combination with the use of sun tanning beds coincided with cutaneous melanoma in a 20-year-old woman4

  • human studyCase reports have described melanomas emerging from existing moles either during or shortly after the use of Melanotan-II, however evidence for causal associations is lacking12

  • expert opinionThe drug is unlicensed and incompletely tested, with unknown extent and types of adverse effects4

  • expert opinionMelanotan II may cause reversible darkening of moles and freckles10

  • expert opinionA 2013 scientific review found there was no conclusive evidence it causes melanoma10

  • expert opinionA 2021 review concluded the increased risk of melanoma in Melanotan users can probably be explained by more UV exposure10

  • expert opinionSide effects may include facial flushing, nausea and erection in males10

  • expert opinionOther effects including flushing, nausea, vomiting, stretching, yawning, and loss of appetite (via activation of MC4)10

  • expert opinionCommon side effects include brown or black lines on the nails (melanonychia), darker skin tone which may be uneven, facial redness or flushing, headache, nausea or vomiting, new moles or increased growth of existing moles, painful prolonged erection, and reduced appetite11

  • expert opinionLong-term use of melanotan can increase risk for skin cancer (melanoma)11

  • expert opinionMelanotan may cause allergic reactions including breathing problems, wheezing, racing heart, fever, swollen lymph nodes, swelling of face/lips/mouth/tongue/throat, trouble swallowing, itching, rash, hives, nausea, vomiting, dizziness, lightheadedness, fainting, stomach cramps, and joint pain11

  • expert opinionMelanotan-II has potential to induce melanoma, the deadliest form of skin cancer12

  • expert opinionDevelopment of Melanotan-II as a potential medicine was halted some years ago due to safety reasons12

  • expert opinionMelanotan II has been reported to cause a wide range of potentially serious side effects13

  • expert opinionShort term side effects after administration include facial flushing13

  • expert opinionShort term side effects include reduced appetite, nausea and vomiting13

  • expert opinionIn males, spontaneous erections 1-5 hours after administration (priapism), associated with yawning and stretching complex13

  • expert opinionLong term concern that melanotan II may increase the risk of melanoma13

  • expert opinionConcern about deepening of the colour of moles, new moles and atypical melanocytic naevi13

  • expert opinionConcern about melanonychia – brown to black discolouration of one or more nails13

  • expert opinionConcern about rhabdomyolysis – potentially fatal destruction of muscle cells13

  • expert opinionConcern about encephalopathy syndrome as a long term side effect13

  • expert opinionNo specific drug interactions have been identified with melanotan II13

  • expert opinionNo evidence exists for the use of melanotan II in pregnancy or breast feeding13

  • expert opinionMelanotan-II is an unregulated substance15

  • anecdotalNeurological effects reported with Melanotan-II include nausea, vomiting, facial flushing, priapism (prolonged erections), and yawning12

  • anecdotalPotential risks in relation to pigmented skin lesions are associated with MT II use14

  • anecdotalMedical hazards associated with MT II use include transmission of infectious diseases, use of potentially contaminated products, polypharmacy, and sunbed exposure14

What people use it for

Based on 2 human trial findings, 3 human study findings, 8 expert opinion findings, 4 anecdotal findings and 1 theoretical finding.

  • human trialMT-II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection2

  • human trialMT-II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection2

  • human studyMelanotan II effect on humans includes increasing of skin pigmentation3

  • human studyMelanotan II produces spontaneous penile erection and sexual stimulation3

  • human studyUnlicensed use of melanotan-II (MT-II) to promote skin pigmentation has become prevalent amongst young people attending fitness centres4

  • expert opinionMelanotan II is a cyclic truncated peptide analog of melanocortins that has been patented and clinically tested for its potential use in tanning of the skin and for the diagnosis and treatment of male erectile dysfunction6

  • expert opinionMelanotan II is mainly used for cosmetic reasons and to a lesser degree for weight loss, aphrodisiac and to counter skin conditions such as rosacea6

  • expert opinionIt may also increase sexual arousal10

Show 10 more findings

  • expert opinionMelanotan may be found in nasal sprays and products that are injected under the skin (subcutaneous)11

  • expert opinionMelanotan can increase sexual arousal in men and women11

  • expert opinionIn men, melanotan can cause an erection11

  • expert opinionMelanotan-II is not approved for use in Australia by the Therapeutics Goods Administration (TGA)12

  • expert opinionMelanotan II is not approved for the treatment of any medical conditions currently13

  • anecdotalMelanotan II has been acquired via the internet and other outlets for use as a tanning agent14

  • anecdotalMotivations for MT II use included the pursuit of a tanned appearance, often in anticipation of sun holidays and fitness/body building competitions14

  • anecdotalMelanotan-II can be purchased illicitly online with relative ease15

  • anecdotalMelanotan-II is injected subcutaneously to stimulate a tan15

  • theoreticalA high-fat diet increased the risk of neurological impairments and neurodegenerative disorders8

Other findings

Based on 5 expert opinion findings.

  • expert opinionMelanotan-II is a cyclic MSH analogue synthesized by Hadley et al. in 19896

  • expert opinionIt was developed as a successor to afamelanotide (Melanotan I), an FDA approved drug operating through a similar pathway10

  • expert opinionSynthesis can be accomplished in 12 steps with an overall yield of 2.6%, and the product is more than 90% pure without preparative chromatography10

  • expert opinionThe FDA has not reviewed melanotan for any use and does not consider melanotan to be a legal dietary or cosmetic ingredient in the U.S.11

  • expert opinionMelanotan-II was first developed at the University of Arizona in the 1990s12

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Contested

Sources disagree on whether Melanotan II causes melanoma

Several sources report melanoma case reports and concern that MT-II may increase melanoma risk (Melanotan II, Melanotan II: α-MSH Analog, FDA PCAC 2027 Review | Kalios, Melanotan: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews, What is Melanotan-II - the drug that the TGA urges consumers to avoid?, Melanoma associated with the use of melanotan-II.). However, Melanotan II notes a 2013 review found no conclusive evidence it causes melanoma, and a 2021 review concluded the increased risk in users can probably be explained by more UV exposure. What is Melanotan-II - the drug that the TGA urges consumers to avoid? explicitly states evidence for causal associations is lacking.

Limited evidence

Human efficacy data come from very small early-phase trials

The pivotal human tanning and erectile dysfunction findings derive from Phase I trials with very small samples (3 volunteers in Evaluation of melanotan-II, a superpotent cyclic melanotropic .../Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study - PubMed; 10 men in Clinical Urology: Original Articles SYNTHETIC MELANOTROPIC PEPTIDE INITIATES ERECTIONS IN MEN WITH PSYCHOGENIC ERECTILE DYSFUNCTION: DOUBLE-BLIND, PLACEBO CONTROLLED CROSSOVER STUDY; 20 men in Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II | International Journal of Impotence Research). Superpower notes there are no completed Phase III safety or efficacy trials, and development was discontinued around 2003 (Melanotan II (MT-II): Research Evidence & Safety Profile | PeptideInsight).

Limited evidence

Serious harms are documented only through case reports

Melanoma, priapism, rhabdomyolysis, renal infarction/failure, and posterior reversible encephalopathy syndrome are documented as case reports and anecdotal safety signals rather than controlled study outcomes (Melanotan II, Melanotan II: α-MSH Analog, FDA PCAC 2027 Review | Kalios, Superpower, Melanotan II: a possible cause of renal infarction: review of the literature and case report., Melanoma associated with the use of melanotan-II.).

Contested

Reported plasma half-life varies across sources

Half-life estimates range from approximately 30 minutes (Melanotan II: α-MSH Analog, FDA PCAC 2027 Review | Kalios), ~33 min IV (Melanotan II (MT-II): Research Evidence & Safety Profile | PeptideInsight), approximately one hour (Melanotan 2 (MT-II) — Evidence Review, Side Effects & Safety | PeptideGuide), to 1-2 hours (Melanotan II: The Synthetic Tanning Peptide and Its Risks | Peptidepedia), reflecting inconsistent low-tier and theoretical reporting.

Limited evidence

Circulated dosing protocols lack clinical validation

The loading/maintenance tanning protocols (0.1 mg initial, 0.25 mg daily, 0.5-1 mg maintenance) are anecdotal and, as Melanotan II: The Synthetic Tanning Peptide and Its Risks | Peptidepedia explicitly states, have no published clinical trial basis; only the 0.025 mg/kg Phase I dose is trial-derived.

Single source

Zebrafish cognitive/anxiety findings from a single animal study

The claim that MT-II reverses high-fat-diet-induced memory impairment, anxiety, and reduced exploration comes solely from one zebrafish study (Melanotan-II reverses memory impairment induced by a short-term HF diet.) and has not been replicated in the other sources.

Using it with other compounds

Check a stack
  • SemaglutideSame downstream effect

    Worth caution

    Semaglutide's satiety effect works partly by driving hypothalamic POMC/melanocortin (MC4R) signaling, and Melanotan II is a direct MC4R agonist that also suppresses appetite. They converge on the same anorexigenic circuit, so combining them can compound appetite loss and nausea rather than add distinct benefit.

    Tier 4Theoretical — not established
    What the research doesn't establish
    While both peptides suppress appetite, it is not established that they act through the same melanocortin (MC4R) circuit. Semaglutide's documented mechanism is GLP-1 receptor activation with downstream effects on insulin secretion, glucagon suppression and PI3K/AKT signaling; direct hypothalamic POMC/MC4R engagement is not shown, so shared downstream convergence with the MC4R agonist Melanotan II remains unconfirmed.

    Shares appetite regulation

  • TirzepatideSame downstream effect

    Worth caution

    Melanotan II is a melanocortin (MC4R) agonist whose known side effect is appetite suppression, and tirzepatide also strongly suppresses appetite through hypothalamic satiety signaling. These converge on the same downstream anorexigenic output, so combining them could produce excessive appetite loss and additive nausea.

    Tier 4Theoretical — not established

    Shares cAMP PKA · appetite regulation

  • OxytocinComplementary

    Worth caution

    Melanotan II and oxytocin both influence central dopaminergic arousal circuits and both act on appetite/satiety in the hypothalamus, but through completely different receptors (melanocortin MC3R/MC4R for MT2 versus OXTR for oxytocin). This means their effects on appetite suppression and sexual behavior can overlap and potentially compound, so users should be aware the two are pushing on the same physiological outputs by separate mechanisms.

    Tier 4Theoretical — not established

    Shares dopaminergic system · appetite regulation

  • RetatrutideSame downstream effect

    Worth caution

    Melanotan II activates central MC4R, which produces an anorexigenic (appetite-suppressing) effect on top of its pigmentation actions. Because retatrutide is already a powerful appetite suppressant, adding MC4R agonism converges on the same downstream satiety pathway and could over-suppress intake and worsen nausea. Worth understanding before combining.

    Tier 4Theoretical — not established

    Shares appetite regulation

  • BremelanotideSame mechanism

    Research does not support combining these

    Both are synthetic melanocortin agonists that switch on MC4R/MC3R and route through the same cAMP signaling and central dopaminergic arousal circuits — in fact bremelanotide is essentially the active fragment of melanotan II. Stacking them is redundant, not additive, and you would simply be doubling up on the same receptor activation. It also compounds the shared side effects (nausea, flushing, blood-pressure changes, and priapism-type over-activation), so combining them raises risk without new benefit.

    Tier 4Theoretical — not established

    Shares dopaminergic system · dopaminergic arousal · cAMP PKA

  • Alpha-MSHSame mechanism

    Worth caution

    Melanotan II is a synthetic cyclic copy of alpha-MSH that activates the same melanocortin receptors (MC1R/MC3R/MC4R/MC5R) through the identical cAMP pathway, producing the same tanning and appetite-suppressing effects. Combining the two is redundant and simply compounds melanocortin overactivation (nausea, flushing, blood-pressure and libido effects) — choose one, don't layer them.

    Tier 3Largely anecdotal — commonly discussed

    Shares cAMP PKA · appetite regulation

  • AfamelanotideSame mechanism

    Worth caution

    Both are alpha-MSH-derived melanocortin agonists that drive eumelanin synthesis and tanning through MC1R and the cAMP/PKA/CREB cascade. Afamelanotide is MC1R-selective while Melanotan II also hits MC3R/MC4R/MC5R (adding appetite suppression and sexual/erectile effects). Stacking them for pigmentation is redundant and would layer melanocortin over-activation; pick one for the pigment goal rather than combining.

    Tier 4Theoretical — not established

    Shares cAMP PKA

  • CagrilintideSame downstream effect

    Worth caution

    Melanotan II is anorexigenic through central melanocortin (MC4R) signaling, while cagrilintide reduces appetite via amylin signaling in the brainstem/area postrema — two different upstream routes into overlapping satiety circuits. Effects on appetite could be additive, but MT2 also carries unrelated pigmentation and cardiovascular effects, so combining is not a clean weight-loss stack.

    Tier 4Theoretical — not established

    Shares appetite regulation

Safety and side effects

Common / short-term side effects

Nausea, yawning, stretching, facial flushing/redness, reduced appetite, headache, somnolence and fatigue are frequently reported. In the tanning Phase I trial, mild nausea (not requiring antiemetic treatment) occurred at most dose levels, and Grade II somnolence and fatigue appeared at the 0.03 mg/kg dose in one of two subjects; nausea and fatigue appear to be dose-dependent class effects. In the erection trial, 12.9% of subjects experienced severe nausea at 0.025 mg/kg. Transient side effects — nausea, stretching, yawning and decreased appetite — occurred more frequently after MT-II than placebo but none required treatment. Spontaneous or prolonged painful erections (priapism) can occur in males.

Pigmentary effects

MT-II can cause reversible darkening of moles and freckles, deepening of existing moles, new moles, atypical melanocytic naevi, and melanonychia (brown-to-black nail discoloration).

Serious harms (case reports)

Published case reports link MT-II use to melanoma, ischemic priapism (sometimes requiring surgery), rhabdomyolysis, renal infarction/failure, dysplastic nevus eruption, and posterior reversible encephalopathy syndrome. Proposed mechanisms for renal injury include a thrombotic pharmacological influence and possible direct toxic effect on renal parenchyma. These serious harms are documented as case reports and anecdotal safety signals rather than controlled study outcomes.

Melanoma risk — contested

Whether MT-II causes melanoma is disputed. Several sources report melanoma case reports and concern that stimulating pigment cells may promote abnormal cell proliferation; one case described cutaneous melanoma in a 20-year-old woman (Fitzpatrick skin type II) who self-injected over 3-4 weeks alongside sunbed use. However, a 2013 review found no conclusive evidence of causation, a 2021 review concluded the increased risk in users can probably be explained by greater UV exposure, and other sources explicitly state evidence for causal associations is lacking.

Allergic and other reactions

Reported allergic reactions may include breathing problems, wheezing, racing heart, fever, swollen lymph nodes, facial/lip/mouth/tongue/throat swelling, trouble swallowing, itching, rash, hives, dizziness, fainting, stomach cramps and joint pain.

Additional considerations

No specific drug interactions have been identified, and there is no evidence supporting use in pregnancy or breastfeeding. Long-term concerns include melanoma/skin cancer risk and encephalopathy syndrome. Illicit-use hazards include transmission of infectious diseases, potentially contaminated products, polypharmacy and sunbed exposure. Product quality is a concern: one analysis (Breindahl and colleagues) found gray-market vials labeled 10 mg actually contained 4.32-8.84 mg of peptide. MT-II is largely untested, with no completed Phase III safety trials.

Reconstitution and handling

Administration

No dose has been established for this compound. No regulatory label exists for it, so the figures below are what sources report — not guidance.

Melanotan II is usually self-administered as a subcutaneous injection of reconstituted liquid, commonly every second day, and is also found in nasal sprays. Its cyclic structure confers significantly greater resistance to enzymatic breakdown than linear alpha-MSH, though plasma half-life remains relatively short (variously reported as ~30 minutes, ~33 minutes IV, ~1 hour, or ~1-2 hours), with peak plasma concentrations within 1-2 hours post-injection.

Trial-derived dosing

The only trial-derived dose is from Phase I studies: a recommended single dose of 0.025 mg/kg/day, escalated from a 0.01 mg/kg starting dose in 0.005 mg/kg increments to a 0.03 mg/kg maximum. For reference, 0.025 mg/kg corresponds to approximately 2 mg for an 80 kg individual. Tanning activity in humans was demonstrated with only 5 low doses given every other day subcutaneously.

Anecdotal (non-validated) protocols

A commonly circulated anecdotal tanning protocol involves an initial 0.1 mg dose for tolerance assessment, escalating to 0.25 mg daily for 2-4 weeks, then maintenance of 0.5-1 mg once or twice weekly. This loading/maintenance approach has no published clinical trial basis and should be regarded as unvalidated community practice, not clinical guidance.

Practical cautions

Because MT-II is unregulated and illicitly sourced, actual peptide content may differ substantially from label claims — one analysis found vials labeled 10 mg contained only 4.32-8.84 mg. Contaminated or mislabeled products, non-sterile injection practices, and combined sunbed exposure are documented hazards of illicit use.

Sources

Ordered by evidence quality — the strongest first.

  1. Clinical Urology: Original Articles SYNTHETIC MELANOTROPIC PEPTIDE INITIATES ERECTIONS IN MEN WITH PSYCHOGENIC ERECTILE DYSFUNCTION: DOUBLE-BLIND, PLACEBO CONTROLLED CROSSOVER STUDY(opens in a new tab)
    Tier 1Web · sciencedirect.com
  2. Evaluation of melanotan-II, a superpotent cyclic melanotropic ...(opens in a new tab)
    Tier 1Web · pubmed.ncbi.nlm.nih.gov
  3. Melanotan II: a possible cause of renal infarction: review of the literature and case report.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2020
  4. Melanoma associated with the use of melanotan-II.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2014
  5. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II | International Journal of Impotence Research(opens in a new tab)
    Tier 1Web · nature.com · 2000
  6. Melanotan II - an overview(opens in a new tab)
    Tier 2Web · sciencedirect.com
  7. 5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  8. Melanotan-II reverses memory impairment induced by a short-term HF diet.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  9. CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  10. Melanotan II(opens in a new tab)
    Tier 3Web · en.wikipedia.org
  11. Melanotan: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews(opens in a new tab)
    Tier 3Web · webmd.com
  12. What is Melanotan-II - the drug that the TGA urges consumers to avoid?(opens in a new tab)
    Tier 3Web · unsw.edu.au
  13. Melanotan II(opens in a new tab)
    Tier 3Web · dermnetnz.org · 2023
  14. Melanotan II User Experience: A Qualitative Study of Online Discussion Forums.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2021
  15. A glimpse into the underground market of melanotan.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2018
  16. Metallothionein in Brain Disorders.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2017
  17. A review of metallothionein isoforms and their role in pathophysiology.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2011
  18. Metallothioneins are multipurpose neuroprotectants during brain pathology.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2006
  19. Regulation of metallothionein gene expression.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 2001
  20. Induction of metallothionein by stress and its molecular mechanisms.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 1999
  21. [Metallothionein '96].(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 1997
  22. The functional significance of brain metallothioneins.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 1996
  23. Human metallothionein MT-I and MT-II processed genes.(opens in a new tab)
    Tier 4PubMed · pubmed.ncbi.nlm.nih.gov · 1984

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