MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Melanotan II Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Melanotan II (MT-II) is a synthetic cyclic heptapeptide analog of alpha-MSH developed by Victor Hruby and colleagues at the University of Arizona in the 1980s as a non-selective melanocortin receptor agonist. It activates MC1R on cutaneous melanocytes to stimulate eumelanin synthesis and tanning, and engages MC3R and MC4R in central pathways governing sexual arousal and appetite suppression. The original libido work by Dorr and Hadley demonstrated spontaneous erections in male volunteers receiving subcutaneous MT-II, an observation that later led to the development of MC4R-selective bremelanotide (PT-141) [PMID: 8951738]. MT-II is studied for darkening of skin tone, photoprotection in fair-skinned individuals, and as an aphrodisiac. It is not approved by the FDA or EMA, and its non-selective melanocortin activity drives the bulk of its adverse effects, including nausea, flushing, blood pressure changes, and atypical or rapidly changing nevi.
Reconstitute: Add 3 mL bacteriostatic water → 3.33 mg/mL concentration.
Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL = 0.0333 mg (33 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen at −20 °C; reconstituted refrigerated at 2–8 °C; use within 1–2 weeks[7].
Non-selective MC agonism: MT-II activates MC1R, MC3R, MC4R, and MC5R. The MC4R activity drives nausea, libido, and appetite suppression; non-selectivity is the main reason PT-141 was developed as a cleaner MC4R-selective agent.
Melanoma and nevus concern: Case reports describe darkening, enlargement, and dysplastic change in pre-existing nevi during MT-II use, and rare melanoma cases have been described. Skin surveillance by a dermatologist is strongly recommended.
No approved formulation: MT-II is sold only as research chemical or grey-market product; no pharmaceutical-grade formulation exists. Unregulated peptide purity, endotoxin, and dosing have been linked to systemic reactions and hospitalizations.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall to avoid foaming; do not shake vigorously.
Gently roll or swirl the vial until the powder is fully dissolved.
Inject slowly and steadily; wait a few seconds before withdrawing the needle.
Do not aspirate for subcutaneous injections; inject slowly and steadily[11].
Interactive Melanotan II Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 3mL water yields 3.33 mg/mL. To evaluate a 250mcg dose, pull to 7.5 units (8 syringe ticks).
U-100 Syringe Representation
7.5 Units (8 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week / Phase | Daily Dose | Units (per injection) (mL) |
|---|---|---|
| Week 1 | 250 mcg (0.25 mg) | 7.5 units (0.075 mL) |
| Week 2 | 500 mcg (0.5 mg) | 15 units (0.15 mL) |
| Week 3 | 750 mcg (0.75 mg) | 22.5 units (0.225 mL) |
| Weeks 4–8 | 1000 mcg (1 mg) | 30 units (0.30 mL) |
| Maintenance(after Week 8) | 500–1000 mcg(1–2× weekly) | 15–30 units(0.15–0.30 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (Melanotan II, 10 mg each):
- check8 weeks ≈ 5 vials (~45–50 mg total)
- check12 weeks ≈ 8 vials (~70–75 mg total)
- check16 weeks ≈ 10 vials (~95–100 mg total)
Insulin Syringes (U-100, 1 mL):
- checkPer week (daily dosing): 7 syringes
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
- check16 weeks: 112 syringes
Bacteriostatic Water (10 mL bottles): Use 3.0 mL per vial for reconstitution.
- check8 weeks (5 vials): 15 mL → 2 × 10 mL bottles
- check12 weeks (8 vials): 24 mL → 3 × 10 mL bottles
- check16 weeks (10 vials): 30 mL → 3 × 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs → recommend 2 × 100-count boxes
- check12 weeks: 168 swabs → recommend 2 × 100-count boxes
- check16 weeks: 224 swabs → recommend 3 × 100-count boxes
Mechanism of Action (MOA)
Melanotan II (MT-II) is a synthetic cyclic heptapeptide with the structure Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 and a molecular weight of 1,024 Da. The cyclic lactam constraint and substitution of unnatural amino acids confer remarkable metabolic stability and dramatically increased potency at the melanocortin receptors compared with the native linear hormone alpha-MSH. MT-II was developed at the University of Arizona by Hadley, Hruby, Dorr, Levine, and colleagues during the 1980s and characterized in a Phase I clinical evaluation published by Dorr and colleagues in Life Sciences in 1996 [1]. The melanocortin system consists of five G protein-coupled receptors (MC1R–MC5R) coupled primarily to Gs and the cAMP/protein kinase A pathway. MT-II is a non-selective agonist that activates MC1R on cutaneous melanocytes (driving eumelanin synthesis and tanning), MC3R and MC4R in hypothalamic and limbic neurons (controlling appetite, energy expenditure, sexual function, and autonomic tone), and MC5R on exocrine glands. It does not significantly bind MC2R, the adrenocortical receptor for ACTH, which is selective for the longer ACTH peptide [2]. At cutaneous melanocytes, MT-II binding activates adenylyl cyclase, elevates cAMP, and triggers downstream activation of microphthalmia-associated transcription factor (MITF), driving expression of tyrosinase, TRP-1, and TRP-2. The result is a shift from the lighter, sulfur-containing pheomelanin pathway to the darker, photoprotective eumelanin pathway. Visible tanning develops over one to two weeks of subcutaneous dosing and may persist for several weeks after discontinuation, depending on individual MC1R genotype and skin phototype. In the central nervous system, MC4R activation in the paraventricular hypothalamus and limbic structures triggers two well-documented effects relevant to MT-II use. First, MT-II produces a centrally mediated penile erection independent of direct sexual stimulation; Wessells and colleagues demonstrated in a double-blind, placebo-controlled study of men with erectile dysfunction that subcutaneous MT-II produced erection in seventeen of twenty subjects and significantly increased sexual desire scores [3]. This finding led to the development of the MT-II metabolite bremelanotide (PT-141), which the FDA approved in 2019 for hypoactive sexual desire disorder in premenopausal women. Second, MC4R activation suppresses appetite and increases energy expenditure. MT-II reduces food intake in animal and human studies and can produce modest weight loss with chronic dosing, although nausea and other side effects typically limit titration. MC3R and MC4R activation also influences autonomic tone, blood pressure, and inflammation. Activation of MC5R contributes to sebaceous gland activity and may underlie reports of increased skin oiliness or acne in some users. Research subcutaneous dosing typically begins at 0.10–0.25 mg per administration to assess tolerance, given that MC3R/MC4R activation commonly produces nausea, flushing, and yawning at higher doses. After gradual desensitization, doses may be titrated to 0.5–1 mg administered every one to several days during a loading phase, followed by less frequent maintenance dosing once the desired pigmentation is achieved. Sun or controlled ultraviolet exposure is required to translate melanocyte stimulation into visible tanning [4].
Clinical Trial Efficacy Highlights
- starDorr and colleagues conducted the first Phase I clinical safety study of subcutaneous Melanotan II in healthy subjects, documenting dose-dependent skin darkening, transient nausea, flushing, and absence of serious laboratory or cardiovascular adverse events at investigational doses, establishing the foundational pharmacology that underpins subsequent off-label use [1].
- starWessells and colleagues performed double-blind, placebo-controlled crossover studies in men with psychogenic and organic erectile dysfunction and reported that subcutaneous Melanotan II produced penile erection in seventeen of twenty subjects in the absence of erotic stimulation and significantly increased self-reported sexual desire, providing the human proof-of-concept for melanocortin agonism in sexual medicine [3].
- starRosen and colleagues confirmed the pro-erectile effects of Melanotan II in additional double-blind trials and characterized the dose-response relationship with nausea, supporting the subsequent development of the MC3R/MC4R-selective analog bremelanotide (PT-141), which the FDA approved in 2019 for hypoactive sexual desire disorder in premenopausal women [2].
- starOpen-label observational studies and dermatological case series document robust, dose-dependent cutaneous pigmentation in fair-skinned individuals (Fitzpatrick skin types I–III) using subcutaneous Melanotan II in combination with intermittent ultraviolet exposure, with tanning persisting for several weeks after discontinuation due to the cyclic peptide's metabolic stability and durable transcriptional effects on melanocytes [4].
- starCase reports and series have documented eruption of new pigmented nevi, darkening of pre-existing nevi, and several instances of melanoma developing in young Melanotan II users, particularly in those with fair skin, multiple nevi, family history of melanoma, or concurrent ultraviolet exposure, raising significant concerns about long-term oncologic safety [5].
- starAnimal and human studies indicate that Melanotan II reduces food intake, modestly elevates blood pressure, and may have anti-inflammatory effects through MC3R and MC4R activation, but the magnitude and clinical relevance of these effects vary widely and are typically overshadowed by dose-limiting nausea and yawning [2].
- starTolerability profiling consistently identifies nausea (50–80%), facial flushing (40–60%), yawning, spontaneous erections in men, and transient blood pressure changes as the most common adverse effects, with intensity strongly dose-dependent and partially attenuated by gradual titration over the first one to two weeks of use [4].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningNausea, occasionally accompanied by vomiting, is reported by 50–80% of Melanotan II users, typically within thirty to ninety minutes of injection, and reflects central MC4R activation in brainstem nuclei controlling emesis; gradual dose titration partially attenuates this effect.
- warningFacial flushing, yawning, fatigue, and dose-dependent transient elevations in blood pressure and heart rate are common, reflecting melanocortin-mediated effects on the autonomic nervous system and cutaneous vasculature.
- warningSpontaneous penile erections in men and increased sexual arousal in both sexes occur due to MC4R activation in central reward and erectile circuits and can be inconvenient, embarrassing, or in rare cases prolonged.
- warningDermatologically, Melanotan II can cause the appearance of new pigmented melanocytic nevi, darkening and enlargement of pre-existing nevi, and irregularity of pigmentation; multiple case reports document melanoma emerging in users, although causality cannot be definitively established and confounding ultraviolet exposure is usually present.
- warningLong-term safety, including cardiovascular, neuropsychiatric, and oncologic risk, is not characterized; concerns include theoretical risks of melanoma promotion, hypertension, and adverse effects on glucose metabolism.
- warningAcute hyperpigmentation can be uneven, producing dark macules on the lips, gingiva, areolae, axillae, and palms; pigmentary changes may be permanent or only slowly reversible.
- warningSterile injection technique is essential because subcutaneous self-administration of unregulated, often grey-market lyophilized peptide carries risks of cutaneous abscess, cellulitis, and bloodborne infection transmission.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Melanotan II dosage?expand_more
Research subcutaneous protocols start with 0.10–0.25 mg per dose to assess tolerance. After gradual desensitization to nausea, doses may rise to 0.5–1 mg every one to several days during a loading phase, followed by less frequent maintenance dosing. Melanotan II is not approved for human use.
How is Melanotan II administered?expand_more
Melanotan II is administered by small-volume subcutaneous injection, usually into the abdomen, using an insulin syringe after reconstitution of lyophilized peptide with bacteriostatic water. Sun or controlled UV exposure is required to translate melanocyte stimulation into visible tanning. No oral or transdermal route is effective.
Can Melanotan II be combined with other compounds?expand_more
Melanotan II is sometimes stacked with PT-141 for sexual function, although safety of combined melanocortin agonists has not been studied. Combination with ultraviolet exposure is standard for tanning. It should not be combined with other sympathomimetics or stimulants due to potential cardiovascular effects.
What are the side effects of Melanotan II?expand_more
Common effects include nausea, flushing, yawning, fatigue, spontaneous erections, transient blood pressure increase, and appetite suppression. Dermatologic concerns include new pigmented nevi, darkening of existing nevi, and isolated case reports of melanoma. Long-term safety is not established.
Is Melanotan II FDA approved?expand_more
No. Melanotan II is not approved by the FDA or any major regulatory agency for any indication. Regulators in the UK, EU, Australia, and elsewhere have issued warnings against its use as a tanning agent. The related analog bremelanotide (PT-141) is FDA-approved for hypoactive sexual desire disorder.
Academic References & Study Citations
Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-1784. View Scientific Paper →
Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-930. View Scientific Paper →
Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000;12 Suppl 4:S74-S79. View Scientific Paper →
Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Int J Impot Res. 2004;16(2):135-142. View Scientific Paper →
Cardones AR, Grichnik JM. Alpha-melanocyte-stimulating hormone-induced eruptive nevi. Arch Dermatol. 2009;145(4):441-444. View Scientific Paper →
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. View Scientific Paper →
Paurobally D, Jason F, Dezfoulian B, Nikkels AF. Melanotan-associated transformation of a melanocytic nevus. Dermatology. 2011;222(4):373-374. View Scientific Paper →
Cousen P, Colver G, Helbling I. Eruptive melanocytic naevi following melanotan injection. Br J Dermatol. 2009;161(3):707-708. View Scientific Paper →
Ellis R, Kirkham N, Seukeran D. Malignant melanoma in a user of melanotan I. BMJ. 2009;338:b566. View Scientific Paper →
Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34-36. View Scientific Paper →