Melanotan II

1. Overview  

Melanotan II (MT-II) is a synthetic, cyclic analog of α-MSH that acts as a non-selective melanocortin receptor agonist (primarily MC1R for pigmentation; MC3R/MC4R in the CNS for appetite/sexual effects). By activating MC1R in melanocytes, it promotes eumelanin production and can deepen tanning with less UV exposure than baseline. Centrally, MT-II’s MC3R/MC4R activity is linked to decreased appetite and pro-erectile effects observed in trials. MT-II is not approved for therapeutic use and is typically obtained from unregulated sources. 

In early human work, subcutaneous MT-II led to measurable skin darkening and characteristic transient effects (nausea, yawning/stretching, spontaneous erections). 

2. Key Clinical Findings

Pilot Phase I (tanning/PK-like observations).

A single-blind, alternating-day, placebo-controlled Phase I in three healthy men escalated MT-II from 0.01 to 0.025–0.03 mg/kg SC over two weeks. Two participants developed visible/quantified increased pigmentation after only five doses (given every other day). Common transient effects included nausea and a yawning/stretching complex temporally associated with spontaneous erections. Authors proposed 0.025 mg/kg/day as a workable single dose for future studies. 

Double-blind, placebo-controlled crossover in psychogenic ED (erectogenic effect).

Ten men with psychogenic erectile dysfunction received MT-II (0.025 mg/kg SC) or placebo with RigiScan monitoring over 6 hours. Clinically apparent erections occurred in 8/10 on MT-II. Mean duration of tip rigidity >80% was 38.0 minutes on MT-II vs 3.0 minutes on placebo (p=0.0045). Transient adverse effects (nausea, stretching/yawning, decreased appetite) were more frequent with MT-II, none requiring treatment. 

Additional clinical/observational context.

Early human work consistently reports tanning activity with low, intermittent doses and the same transient side-effect pattern. Later case literature (outside controlled trials) describes priapism and other systemic toxicities after non-medical use, underscoring the risks of unregulated supply. 

3. Mechanisms & Effects

Pigmentation (MC1R). MT-II directly activates MC1R on melanocytes to increase eumelanin synthesis and augment UV-mediated tanning. 

Central effects (MC3R/MC4R). In the CNS, MC3R/MC4R signaling modulates appetite and sexual function, aligning with decreased appetite and pro-erectile responses seen in human trials. MT-II is non-selective and crosses the blood–brain barrier, which explains systemic/central side effects (fatigue, reduced appetite, erections). 

Broader melanocortin biology (review context). Comprehensive receptor-ligand reviews support these receptor assignments and downstream physiological roles across pigmentation, energy homeostasis, and sexual function. 

4. Safety & Considerations

Regulatory status. MT-II is not approved for any indication; products sold online/gym settings are unregulated and may contain impurities or variable concentrations. 

Short-term adverse effects (most common in studies). Nausea, flushing, fatigue, stretching/yawning, decreased appetite; spontaneous erections in males. 

Serious events reported outside trials. Case reports describe priapism and systemic toxicity; rare reports link use with renal infarction. Causality is hard to establish given dosing unknowns and co-factors (e.g., dehydration, stimulants). 

Pigmented lesion changes and melanoma signal. Multiple case reports document darkening or eruption of melanocytic nevi and occasional melanomas temporally associated with MT-II use—often alongside sunbed/UV exposure. While these reports raise concern, causality remains uncertain; confounding by increased UV exposure is likely. Regardless, any mole changes warrant medical evaluation, and unregulated use poses added risk. 

References

1. Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84.
2. Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998;160(2):389-393. 
3. Laiho L, et al. The Multifaceted Melanocortin Receptors. Endocrinology. 2022;163(7):bqac083. (MC1R/MC3R/MC4R roles). 
4. Yuan XC, et al. Ligands for Melanocortin Receptors: Beyond Melanocyte Stimulation. Front Endocrinol. 2022. (Receptor-ligand landscape). 
5. Böhm M, et al. Benefits and risks of chronic MC1R activation. Exp Dermatol. 2024. (Regulatory status; adverse events overview).
6. Mallory CW, et al. Melanotan Tanning Injection: A Rare Cause of Priapism. Cureus. 2021. (Case report).
7. Peters B, et al. Melanotan II: a possible cause of renal infarction. Clin Toxicol (Phila). 2020. (Case report). 
8. Sivyer GW, et al. Changes of melanocytic lesions induced by Melanotan 2 and UV tanning. Case Rep Dermatol Med. 2012. (Pigmented lesion changes). 
9. Hjuler KF, et al. Melanoma associated with the use of melanotan-II. Clin Exp Dermatol. 2014. (Case report with concurrent sunbed use). 
10. DermNet NZ. Melanotan II—side effects and risks. (Clinical dermatology perspective).