Melanotan II: pigment in gums and cheeks

The oral-pigmentation case

Brown pigmentation appeared on the attached gingiva of both jaws and on the buccal mucosa: the gums and the lining of the cheeks. The 2026 report by Bonchev describes a man who had self-administered Melanotan II. By 28 days after cessation the cheek pigmentation was beginning to fade. At 3 months the gum pigmentation remained at reduced intensity.

“Reversible” sounds tidy until those observations are put next to one another. I read them as a record of uneven fading, with pigment still visible at follow-up. This case gives no frequency estimate and no standard timetable for returning to a previous appearance.

Inside the mouth is a remarkably specific place for a supposedly cosmetic change to announce itself.

Community accounts also describe patchy tanning, darkened lips, freckles, moles, scars and other areas, as well as fading that is slow or uneven. These are anecdotal accounts, not clinical evidence. Some people report cosmetic satisfaction or believe that darker skin protects them from burning; the reported belief supplies no demonstrated protection, and burning appears in the accounts too.

Melanocortin receptors

Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone, or alpha-MSH. Its ring structure and other modifications make it resistant to the enzymes that break down the natural signal. The history of melanocortin therapeutics follows the development of linear Melanotan I alongside cyclic Melanotan II into different clinical programmes.

At MC1R on a melanocyte, the cell that makes pigment, activation raises cyclic AMP. Through PKA, CREB and MITF, that signal increases the pigment-making enzyme tyrosinase and shifts synthesis toward eumelanin. It can therefore produce pigmentation without ultraviolet exposure. Copper, from the other side of this site, is a helper metal for tyrosinase.

Melanotan II acts broadly across the melanocortin receptor family. MC3R and MC4R are involved in appetite, energy balance and sexual motivation; MC5R has roles in exocrine and sebaceous glands. I regard that breadth as central to the subject. The tan is merely the easiest effect to see.

Appetite and sexual-function experiments

In male C57BL/6J mice given Melanotan II into the nucleus accumbens, food consumption and responding to obtain food decreased. The investigators found neither conditioned taste aversion nor a change in metabolic rate. The experiment addressed a brain region involved in reward and motivation. Its route and animal model make it an appetite-circuit finding rather than evidence for human weight management.

The double-blind crossover study in 10 men with psychogenic erectile dysfunction found clinically apparent erections in 8 of 10 men. Mean duration of greater-than-80% tip rigidity was 38.0 minutes with Melanotan II versus 3.0 minutes with placebo. Transient nausea, stretching and yawning required no treatment in that study.

That is a measured human response, and a useful explanation for why sexual effects recur in user accounts. Nausea, flushing, appetite loss, fatigue, yawning and spontaneous erections in those accounts remain anecdotal reports. A small controlled experiment on erectile function leaves the safety of unsupervised tanning use unresolved.

Serious adverse events

The renal-infarction case and literature review describes an association considered most likely attributable to Melanotan II. Its authors discuss a possible thrombotic influence and direct toxicity to kidney tissue, and note earlier reports of rhabdomyolysis and renal failure. Rhabdomyolysis means severe muscle breakdown, which can in turn injure the kidneys. The proposed mechanisms remain proposals.

The safety record also includes reports of new or changing melanocytic lesions, melanoma, prolonged painful erections and posterior reversible encephalopathy syndrome, a neurological condition involving brain swelling. Case reports do not establish the size of a risk or prove that Melanotan II caused every event. For me, those cases demand a safety discussion that reaches well beyond the visible tan.

A new or changing mole warrants prompt dermatological assessment. Priapism is a medical emergency because prolonged erections can damage erectile tissue. Those clinical concerns require medical care; a page about pigment cannot assess an individual's symptoms.

Preclinical work also raises blood-pressure concerns, while unregulated preparations add uncertainty about identity, content, purity and sterility. The early controlled human study and the kidney case review answer different questions; neither constitutes a long-term safety programme for products circulating outside it.

Regulation and related medicines

Melanotan II has no approved use anywhere. No Phase II or Phase III trial has been completed for the compound, and long-term human safety remains unknown. The FDA, TGA, MHRA and HPRA have warned against melanotan tanning products.

Afamelanotide is separately approved for erythropoietic protoporphyria, a rare light-sensitivity disorder. Bremelanotide, derived from the Melanotan II family, has a separate sexual-desire indication. The historical review explains the relationship among these compounds; the approvals described in the current source record apply to those specific medicines. Chemical kinship supplies no approval for Melanotan II.

Melanotan II falls under WADA's S0 category of non-approved substances and is prohibited in sport at all times. That regulatory position, the broad receptor activity and the case literature all matter alongside the pigment response.