Melanotan II Side Effects: Moles, Nausea and Why It Is Not Approved

The melanotan 2 side effects described in the medical literature run from nausea, yawning, drowsiness and unwanted erections in small early trials, to case reports of new and darkening moles, melanoma, painful erections that needed surgery, muscle breakdown and kidney injury in people who injected products bought online. Melanotan II has never been approved by the FDA, so none of these products has been checked for what it contains or how it was made. If a mole is new, changing or darkening after use, a dermatologist is the person to see.

What melanotan II is, and what was approved instead

Melanotan II is a small, ring-shaped synthetic copy of alpha-melanocyte stimulating hormone (alpha-MSH), the hormone that tells pigment cells to make melanin. It was developed by researchers at the University of Arizona College of Medicine, who reported the first small human study in 1996 (Dorr et al., Life Sciences). It does not act only on skin: it is a non-selective melanocortin-receptor agonist, which means it also switches on receptors involved in appetite, sexual response and other body systems (Peters et al., CEN Case Reports, 2020).

Two related drugs did go through full FDA review. Afamelanotide (Scenesse), an implant for adults with the rare light-sensitivity disorder erythropoietic protoporphyria, was approved on October 8, 2019 (FDA approval letter, NDA 210797). Bremelanotide (Vyleesi), an injection for low sexual desire in premenopausal women, was approved on June 21, 2019 (FDA approval letter, NDA 210557). They are different molecules, tested in controlled trials and made to drug-manufacturing standards. Their approval says nothing about the safety of melanotan II.

Melanotan II itself has no FDA approval. The FDA lists it among bulk substances that were nominated for use in compounding, placed in category 2 because of safety concerns, and later withdrawn by the people who nominated them (FDA, bulk drug substances that may present significant safety risks, content current as of April 22, 2026). For what that category means legally, see Are Peptides Legal?

Melanotan 2 side effects in the early human studies

Only two small controlled studies of melanotan II in people were published by its developers.

• 1996 pilot study, 3 healthy men. Mild nausea was reported at most dose levels. At the highest level tested, one of two men had moderate drowsiness and fatigue. A stretching and yawning pattern came with spontaneous erections lasting one to five hours. Two of the three men had measurably darker skin a week after the injections ended (Dorr et al., 1996).
• 1998 erectile dysfunction study, 10 men. Eight of ten developed erections. Nausea, stretching and yawning, and reduced appetite were reported more often than with placebo; none needed treatment (Wessells et al., Journal of Urology).

That is 13 people in total, given a known, pharmaceutical-grade compound under supervision for a short time. Nothing in those studies tells you what happens with months of use, with tanning beds, or with an unlabelled vial.

The approved relatives give a sense of what this receptor family does. In the phase 3 trials for Vyleesi, nausea was reported by 40% of patients. Focal darkening of the face, gums and breasts was reported in 1% of patients in those trials, but in another study 38% developed it after eight consecutive daily doses, and the label says it did not clear in every patient after stopping (Vyleesi prescribing information, 2019). The Scenesse label lists melanocytic nevus (a mole) in 4% of treated patients versus 2% on vehicle, and recommends a full body skin examination twice a year to watch moles (Scenesse prescribing information, 2019).

Side effects reported, and what to do about each

Moles, new moles and melanoma

Changes to moles are the side effect dermatologists report most. A 2017 review by Dutch dermatologists found growing numbers of case reports linking unregulated melanotan I and II to changes in existing moles and newly appearing, sometimes atypical, moles. Four case reports described melanomas arising from existing moles during or shortly after use. The authors were clear that conclusive evidence of cause is lacking (Habbema et al., International Journal of Dermatology, 2017).

Individual reports show how quickly it can happen. German dermatologists described eruptive moles and darkening of existing moles 24 hours after a single injection (Schulze et al., European Journal of Dermatology, 2014). A Danish team reported melanoma in a 20-year-old woman with fair skin who had injected melanotan II for three to four weeks, three months before the lesion was removed; she was also using sunbeds (Hjuler and Lorentzen, Dermatology, 2014). A UK case described melanoma in situ in a melanotan user (Ong and Bowling, Australasian Journal of Dermatology, 2012).

Case reports cannot show that melanotan II causes melanoma. Many users also tan in the sun or on sunbeds, which is a known risk on its own. The practical problem is different: a drug that darkens every mole makes it harder for you, and for a doctor, to spot the one that is changing for a worse reason.

Serious reactions reported after injection

Priapism. A Glasgow team reported a man with a low-flow priapism after injecting melanotan; it was treated with aspiration and medication, and he had not recovered erectile function four weeks later (Dreyer et al., BMJ Case Reports, 2019). A Miami case did not respond to those treatments and needed surgery (Mallory et al., Sexual Medicine, 2021).

Sympathomimetic toxicity and muscle breakdown. A 39-year-old man injected far more than the amount he believed to be a starting dose. Within two hours he had a racing heart, sweating, tremor and agitation, and he went on to develop rhabdomyolysis (muscle breakdown) and kidney dysfunction, spending three days in intensive care. Laboratory testing confirmed the product was melanotan II (Nelson et al., Clinical Toxicology, 2012).

Kidney infarction. Swedish nephrologists reported a renal infarction, a blocked blood supply to part of the kidney, that they judged most likely related to melanotan II (Peters et al., 2020).

The FDA’s safety summary adds posterior reversible encephalopathy syndrome, a brain-swelling condition, to the list of serious events in published case reports, alongside melanoma, sympathomimetic toxicity and priapism (FDA).

What is actually in a melanotan vial

When Danish and UK researchers bought melanotan II vials from three online shops and analyzed them, every vial held less than the label claimed, between roughly 43% and 88% of the stated amount. Vials from two of the shops also contained unknown impurities making up 4.1% to 5.9% of the content (Breindahl et al., Drug Testing and Analysis, 2015). The FDA notes that melanotan II products may also provoke immune reactions because of clumping (aggregation) and peptide-related impurities.

Unknown strength means the person injecting cannot know how much they are taking, and unknown impurities cannot be tested for in advance. Purity numbers on paperwork do not settle this either; see what a certificate of analysis can and cannot prove and why products carry a “research use only” label. Any injected product that was not made sterile also carries the risks covered in injection-site infections and abscesses.

Checklist: when to get medical help

• Call emergency services or go to an emergency department for an erection that will not subside, chest pain, a racing heart with agitation, a sudden severe headache, confusion, seizure, or vision loss.
• Same-day care for severe muscle pain or weakness with dark urine, sudden pain in the side or back, or a hot, spreading, painful injection site.
• Book a dermatologist for any new mole, a mole that has darkened, grown, changed shape or started to itch or bleed, or a mole that looks different from your others.
• Tell the clinician exactly what you injected, for how long, and whether you also use sunbeds. Bring the vial or packaging if you still have it.

Even for afamelanotide, the one tanning-pathway drug the FDA approved after controlled trials, the label recommends a full body skin examination twice a year to check moles. If you have used melanotan II, telling a dermatologist so that your moles can be mapped and photographed gives you a baseline to compare against later.

Sources

• U.S. Food and Drug Administration: Certain bulk drug substances for use in compounding that may present significant safety risks
• FDA: Scenesse (afamelanotide) NDA 210797 approval letter, October 8, 2019
• FDA: Vyleesi (bremelanotide) NDA 210557 approval letter, June 21, 2019
• FDA: Vyleesi (bremelanotide) prescribing information, 2019
• FDA: Scenesse (afamelanotide) prescribing information, 2019
• Dorr RT et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci, 1996.
• Wessells H et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction. J Urol, 1998.
• Habbema L et al. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol, 2017.
• Schulze F et al. Eruptive naevi and darkening of pre-existing naevi 24 h after a single mono-dose injection of melanotan II. Eur J Dermatol, 2014.
• Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology, 2014.
• Ong S, Bowling J. Melanotan-associated melanoma in situ. Australas J Dermatol, 2012.
• Dreyer BA et al. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep, 2019.
• Mallory CW et al. Melanotan tanning injection: a rare cause of priapism. Sex Med, 2021.
• Nelson ME et al. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol, 2012.
• Peters B et al. Melanotan II: a possible cause of renal infarction. CEN Case Rep, 2020.
• Breindahl T et al. Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet. Drug Test Anal, 2015.