Melanotan II

01 · What it is

The published human literature on Melanotan II is, overwhelmingly, a record of harm.

Not a record of trials with adverse events in the safety table — a record made almost entirely of case reports, written by clinicians describing what arrived in their emergency departments and dermatology clinics. Melanoma ^5,7,9. Eruptive melanocytic nevi ^4,13. Systemic toxicity with sympathomimetic excess and rhabdomyolysis ⁸. Renal infarction, in a patient where rhabdomyolysis and renal failure had already been described for the compound ¹⁵. Acute ischaemic priapism, twice ^12,16. Oral mucosal changes ²⁰, and a possible oral mucosal malignant melanoma after use of a nasal spray formulation ¹⁹.

Why this compound behaves differently from Melanotan I. Melanotan II is a cyclic truncated analogue of α-melanocyte-stimulating hormone ². Where afamelanotide is a selective melanocortin-1 receptor agonist, Melanotan II is not selective — and the melanocortin receptor family governs pigmentation, sexual function, cardiovascular tone, inflammation and appetite. The clinical consequences of that breadth are visible in the case reports above: the priapism and the sympathomimetic toxicity are not off-target surprises, they are the pharmacology.

The compound was tested clinically and then superseded. Both melanotan I and melanotan II were patented and tested clinically — melanotan I for skin tanning and melanotan II for the diagnosis and treatment of male erectile dysfunction ². The erectile-function work led to bremelanotide, covered separately in this family. Melanotan II itself was never approved anywhere identified here.

What is sold is not a characterised product. Melanotan II appears in a review of falsified biotechnology drugs alongside human growth hormone ¹¹, and a 2024 forensic paper describes the analytical difficulty of confirming its identity in seized vials ¹⁸. A 2025 report states that the compound is unlicensed and its sale illegal in the United Kingdom and many other countries ¹⁹.

This is the compound in the project with the clearest documented harm profile and the weakest evidence of benefit, and the two facts are connected: nobody ran the trials that would have found the harms first.

02 · Evidence at a glance

Evidence grade

Early Clinical — historical clinical testing is attested ², but see the note below

What it is

A cyclic, truncated synthetic analogue of α-MSH ²

Receptor selectivity

Non-selective across the melanocortin receptor family — the origin of its adverse-effect profile

Historical clinical testing

Tanning (melanotan I) and male erectile dysfunction (melanotan II) ²

What it became

The erectile-function programme led to bremelanotide, an approved drug

Approval status

None anywhere identified. Unlicensed; sale illegal in the UK and many other countries ¹⁹

Documented: melanoma

Case reports ^5,7,9; five associated melanomas in an eruptive-nevi review ¹³

Documented: dysplastic and eruptive nevi

^4,10,13; 16% of eruptive-nevi cases had ≥1 histologically confirmed dysplastic nevus ¹³

Documented: rhabdomyolysis and systemic toxicity

⁸, with renal failure previously described ¹⁵

Documented: renal infarction

¹⁵

Documented: priapism

^12,16

Documented: oral mucosal changes and possible mucosal melanoma

^19,20

Product integrity

Listed among falsified biotechnology drugs ¹¹; analytically difficult to confirm ¹⁸

Efficacy trials located

None for tanning

Contrary animal finding

Topical MTII suppressed melanoma via PTEN upregulation in a mouse model ¹⁴

Negative animal finding

Did not protect against cisplatin ototoxicity, unlike related peptides ¹

On the grade. Early Clinical requires at least one published human trial, and a 2006 review of melanocortin peptide therapeutics states that melanotan II was patented and tested clinically for erectile dysfunction ². This guide did not locate those individual trial reports, and the human literature it did find consists almost entirely of adverse-event case reports rather than efficacy studies. The grade reflects the historical record; it should not be read as indicating that controlled evidence of benefit exists for the use the compound is actually sold for.

03 · Mechanism of action

Non-selectivity is the whole story

Melanotan II is a cyclic truncated α-MSH analogue ². The melanocortin receptor family spans five subtypes with distinct roles across pigmentation, sexual function, cardiovascular regulation, inflammation and energy balance. A ligand that does not discriminate among them produces effects across all of those domains at once.

The comparison that makes this concrete sits in the same family. Afamelanotide is described in its literature as a first-in-class MC1R agonist and is an approved photoprotective drug. Melanotan II is the non-selective sibling, and it is the one generating priapism reports ^12,16 and sympathomimetic toxicity ⁸.

The pigmentation effect, and why it is not obviously protective

Melanotan II has been applied for skin tanning in humans ¹⁴. The intuition that increased melanin should protect against melanoma has been questioned directly in this literature: a 2009 report on α-MSH-induced eruptive nevi notes the postulate that synthetic α-MSH peptides might protect against melanoma because of their melanogenic activity, and observes that their ultimate biological effect — especially in people with dysplastic nevi — is a different question ⁴.

Stimulating melanocytes and protecting against melanocyte cancer are not the same intervention, and the case reports ^5,7,9 are what the difference looks like.

A genuinely contrary finding, reported here for completeness

A 2020 mouse study found that topical MTII suppressed melanoma progression through PTEN upregulation via MC1R and cyclooxygenase-2 inhibition ¹⁴.

This points the opposite way to the human case reports and it is included because leaving it out would be selective. It is topical, in mice, in an induced tumour model, and it does not bear on systemic self-administration in people. But it is real, and a reader deserves to know the picture is not uniform at the mechanistic level.

A negative animal result

Co-treatment with melanotan II did not protect against cisplatin ototoxicity in guinea pigs, although the related peptides ORG 2766 and α-MSH had reduced it in the same group’s earlier work ¹.

A specific, well-controlled negative, and one of very few genuine efficacy experiments on this compound in the file.

04 · Key research findings

Historical development, 2006. A review of melanocortin peptide therapeutics recording that melanotan I and melanotan II were patented and clinically tested — the linear peptide for skin tanning, the cyclic truncated peptide for diagnosis and treatment of male erectile dysfunction ².

This is the compound’s legitimate origin, and the point at which the regulated path and the informal one separate. One branch became afamelanotide and bremelanotide. The other became a product sold over the internet.

The public-health alarm, 2009. A BMJ piece on use of melanotan I and II in the general population ³.

Published seventeen years ago. The harm reports that follow accumulate after this warning, not before it.

Eruptive nevi, 2009 and 2019. A report of α-MSH-induced eruptive nevi questioning whether melanogenic activity is protective ⁴, and a systematic review of eruptive melanocytic nevi finding that 16% of cases had at least one histologically confirmed dysplastic nevus, with five cases of associated melanoma across the reviewed literature ¹³.

Melanoma case reports, 2011–2014. Melanotan-associated melanoma ⁵; melanotan-associated melanoma in situ, noting prior reports of dysplastic naevi and melanoma with melanotropic peptides ⁷; and melanoma associated with melanotan-II use, in a case combining the compound with sun-bed exposure, in a population described as young people attending fitness centres ⁹.

Three independent reports, in three countries, in mainstream dermatology journals. Case reports cannot establish causation. A cluster of them in a young, otherwise low-risk population, all sharing one exposure, is the signal that would ordinarily trigger a formal safety investigation.

Systemic toxicity, 2012. A case of systemic toxicity with sympathomimetic excess and rhabdomyolysis following melanotan II injection, in a paper noting that melanotan products are purchased over the internet and used both for sunless tanning and as sexual stimulants ⁸.

The risk review, 2017. A review of the risks of unregulated use of α-MSH analogues, reporting increasing numbers of case reports of cutaneous complications with both melanotan I and II — particularly melanocytic changes in existing moles and newly emerging dysplastic nevi ¹⁰.

The most systematic treatment of the harm literature located here, and its conclusion is that the reports are increasing.

Falsification, 2018. Melanotan II appears in a review of falsified biotechnology drugs, grouped with image-enhancing polypeptides such as human growth hormone ¹¹.

Priapism, 2019 and 2021. Acute priapism described as an unreported side effect of melanocortin analogue use, managed without surgery, with the authors noting that future therapeutic application of these agents will need to account for this potentially life-altering complication ¹²; and acute ischaemic priapism after subcutaneous injection ¹⁶.

Ischaemic priapism is a urological emergency. Two independent reports, in a compound whose sibling molecule was developed specifically for its effect on sexual function.

Renal injury, 2020. A case of renal infarction attributed to melanotan II, in a review noting that melanotan II inducing rhabdomyolysis and renal failure had already been described ¹⁵.

Forensic identification, 2024. A study of “Barbie drug” identification, in which vials labelled as melanotan II required mass spectrometric analysis that the authors describe as challenging, the compound being a small peptide of 1024 Da ¹⁸.

The people whose job is identifying seized substances describe this one as difficult. That is the sourcing problem stated by someone with no commercial interest in it.

Mucosal findings, 2025 and 2026. A report raising melanotan II nasal spray as a possible risk factor for oral mucosal malignant melanoma, noting the compound is unlicensed and its sale illegal in the United Kingdom and many other countries ¹⁹; and a three-month follow-up of oral mucosal changes in a patient who self-administered injections over 64 days ²⁰.

The most recent entries in this literature are still case reports of harm, twenty years after the compound entered informal circulation.

05 · Evidence overview

06 · Safety profile

This section is the guide. For most compounds in this project the safety section records an absence of data. Here there is data, it is human, it is independently replicated across countries, and it is uniformly unfavourable.

Dermatological. Melanoma ^5,7,9 and melanoma in situ ⁷. Eruptive melanocytic nevi, with 16% of reviewed cases showing at least one histologically confirmed dysplastic nevus and five associated melanomas ¹³. Melanocytic changes in existing moles and newly emerging dysplastic nevi, described as increasing in frequency across the case literature ¹⁰.

Systemic and emergency. Systemic toxicity with sympathomimetic excess and rhabdomyolysis ⁸. Renal infarction, with rhabdomyolysis and renal failure previously described ¹⁵. Acute ischaemic priapism in two independent reports, one describing it as a potentially life-altering complication ^12,16.

Mucosal. Oral mucosal changes following a 64-day course of self-administration ²⁰, and a possible link to oral mucosal malignant melanoma raised in a patient using a nasal spray formulation ¹⁹.

Product-level. Documented falsification ¹¹ and analytically difficult identification ¹⁸ mean that what a given vial contains is not established, which compounds every hazard above.

What is genuinely unknown. The denominator. Every harm listed here is a numerator without one: case reports establish that these events occur in people using this compound and cannot establish how often. No cohort study, registry or controlled trial exists in this file to put a rate on any of it. That is a limitation on estimating risk — it is not a reason to discount the reports, because the consistency and severity of what has been published is itself the finding.

Also unknown: whether the melanoma cases reflect causation, confounding by sun-bed and UV exposure ⁹, or detection bias; long-term effects of repeated use at any dose; and the composition of any particular product.

07 · US regulatory status

Current as of 7 September 2026. Melanotan II is not an approved drug in the United States and is not a lawful dietary supplement ingredient. It is not a controlled substance. No marketing authorisation in any jurisdiction was identified for this guide, and a 2025 clinical report states that the compound is unlicensed and its sale illegal in the United Kingdom and in many other countries around the world ¹⁹.

This guide has not consulted regulatory or enforcement records in any jurisdiction and reports the legal characterisation above as it appears in the cited clinical literature.

Under the World Anti-Doping Code, melanotan II does not appear as a named prohibited substance in the classes reviewed for this guide. Competitors should consult the current Prohibited List directly rather than rely on secondary summaries, including this one.

08 · Limitations of the evidence

1. There is no controlled efficacy evidence for the use this compound is sold for. No trial of melanotan II for cosmetic tanning was located. The historical clinical testing recorded in the literature concerns erectile dysfunction ², and that programme produced a different, approved molecule.
2. The harm literature is case reports, which cannot establish incidence. Each report ^{4,5,7,8,9,12,15,16,19,20} describes an association in one person. What they collectively establish is that these events occur; what they cannot establish is how often, or in whom.
3. Confounding is real and acknowledged in the sources. At least one melanoma case involved concurrent sun-bed use ⁹. Populations using this compound may differ systematically in UV exposure and skin surveillance from those who do not.
4. Publication bias runs in the opposite direction here, and that cuts both ways. Clinicians publish unusual harms, not uneventful use. The case series therefore over-represents severe outcomes — and it is also the only human evidence that exists, because nobody ran the trials.
5. One preclinical finding contradicts the human picture ¹⁴: topical MTII suppressed melanoma in a mouse model. Topical, murine, and induced-tumour; it does not resolve the human reports, and it is reported here rather than omitted.
6. The compound’s identity in circulation is not established. Falsification is documented ¹¹ and identification is analytically challenging ¹⁸, so harms attributed to melanotan II may in some cases involve something else in the vial.
7. No dose-response information exists for any outcome, beneficial or harmful.
8. Two sources are non-English and were read on their English abstracts and titles alone ^6,17.
9. Receptor selectivity is asserted from the compound’s structural class and its clinical effects rather than from a binding study cited here. The inference is well supported by the pattern of adverse effects but is not sourced to a receptor-pharmacology paper in this file.
10. This guide has read abstracts, not full texts, for every source cited.
11. No regulatory or enforcement record was consulted; legal status is reported as characterised in the clinical literature ¹⁹.

09 · References

1. Wolters FL, de Vocht TF, Klis SF, Hamers FP, Smoorenburg GF. Co-treatment with melanotan-II, a potent melanocortin, does not protect against cisplatin ototoxicity. Hear Res. 2002 Oct;172(1–2):110–117.

   PMID 12361873 ↗

2. Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006 Apr;27(4):921–930. Review.

   PMID 16412534 ↗

3. Evans-Brown M, Dawson RT, Chandler M, McVeigh J. Use of melanotan I and II in the general population. BMJ. 2009 Feb 17;338:b566. No abstract available..

   PMID 19224885 ↗

4. Cardones AR, Grichnik JM. α-Melanocyte-stimulating hormone-induced eruptive nevi. Arch Dermatol. 2009 Apr;145(4):441–444.

   PMID 19380666 ↗

5. Paurobally D, Jason F, Dezfoulian B, Nikkels AF. Melanotan-associated melanoma. Br J Dermatol. 2011 Jun;164(6):1403–1405. No abstract available..

   PMID 21564053 ↗

6. Mahiques-Santos L. [Melanotan]. Actas Dermosifiliogr. 2012 May;103(4):257–259. Spanish. No abstract available..

   PMID 22051769 ↗

7. Ong S, Bowling J. Melanotan-associated melanoma in situ. Australas J Dermatol. 2012 Nov;53(4):301–302.

   PMID 22724573 ↗

8. Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012 Dec;50(10):1169–1173.

   PMID 23121206 ↗

9. Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34–36.

   PMID 24355990 ↗

10. Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017 Oct;56(10):975–980. Review.

    PMID 28266027 ↗

11. Janvier S, De Spiegeleer B, Vanhee C, Deconinck E. Falsification of biotechnology drugs: current dangers and/or future disasters? J Pharm Biomed Anal. 2018 Nov 30;161:175–191. Review.

    PMID 30165334 ↗

12. Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep. 2019 Feb 21;12(2):e227644. Review.

    PMID 30796078 ↗

13. Burian EA, Jemec GBE. Eruptive melanocytic nevi: a review. Am J Clin Dermatol. 2019 Oct;20(5):669–682. Review.

    PMID 31119650 ↗

14. Wu JC, Tsai HE, Hsiao YH, Wu JS, Wu CS, Tai MH. Topical MTII therapy suppresses melanoma through PTEN upregulation and cyclooxygenase II inhibition. Int J Mol Sci. 2020 Jan 20;21(2):681.

    PMID 31968661 ↗

15. Peters B, Hadimeri H, Wahlberg R, Afghahi H. Melanotan II: a possible cause of renal infarction — review of the literature and case report. CEN Case Rep. 2020 May;9(2):159–161. Review.

    PMID 31953620 ↗

16. Mallory CW, Lopategui DM, Cordon BH. Melanotan tanning injection: a rare cause of priapism. Sex Med. 2021 Feb;9(1):100298.

    PMID 33460908 ↗

17. Eijmael MJPM, Janmaat CJ, Briët-Schipper EMN. [The risks of tanning with the Barbie drug]. Ned Tijdschr Geneeskd. 2022 May 19;166:D6578. Dutch.

    PMID 35736369 ↗

18. Deville M, Charlier C. Barbie drug identification: not a child’s play. J Forensic Sci. 2024 Nov;69(6):2331–2338.

    PMID 39302005 ↗

19. Yassin Alsabbagh A, Bhujel N, Singh RP. Melanotan II nasal spray: a possible risk factor for oral mucosal malignant melanoma? Int J Oral Maxillofac Surg. 2025 Sep;54(9):806–808.

    PMID 40210573 ↗

20. Bonchev A. Changes in oral mucosa associated with Melanotan II injections: a case report. Life (Basel). 2026 Feb 3;16(2):265.

    PMID 41752902 ↗