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Melanocyte-stimulating hormone (MSH)

July 16, 2019

The melanocyte-stimulating hormone (MSH) is the body’s peptide hormone that regulates the function of the melanocytes (i.e. skin pigment cells) [1]. MSH also affects other types of cells [2, 3] and it has been manufactured into various synthetic forms [4], which are analogous to the body’s MSH. Melanotan I and melanotan II, which are also referred to as “Barbie drugs”, are examples of synthetic forms that simulate the body’s MSH. These substances come as either injections or nasal sprays and they are often used to obtain a tan. Melanotan I is the slightly more expensive one of the two products and it produces a tan that is more natural in appearance. Melanotan II is cheaper and produces a dark tan and reduces the appetite [5].

The term “melanotan I” and the status of the substance may cause some confusion because on the markets there is a peptide, which used to be known by the same name. Nowadays, however, this substance is referred to by the term “afamelanotide”. Afamelanotide was granted a sales permit at the end of 2014 and there are medical purposes for its use. The terms “melanotan I” and “melanotan II” are used nowadays in reference to the tanning substances sold on the black market. By comparison, afamelanotide has been the subject of more research and it has been found to be relatively safe. The same cannot be said of the melanotan I and II products because their manufacture and sale are not regulated or monitored [6].

MSH affects the skin functions in particular. The skin is the body’s largest sense organ, which senses pressure, touch, the temperature, and pain [7]. Its structure is multilayered [7]. The outermost layer is the stratum corneum, which is formed of dead cells and corneocytes. Under the stratum corneum, there is the epidermis, the bottom layer of which has special pigment cells: the melanocytes, which produce melanin. Located under the epidermis is the dermis, which turns into hydrous and fatty subcutaneous tissue without an exact boundary.

MHS also affects nutrient intake [8, 9]. If the body absorbs more nutrients than the cells need at that moment, the surplus is stored as glycogen or adipose tissue [7]. Between meals, the body releases energy from these reserves. The body hormonally regulates the release and storing of nutrients. The α-melanocyte-stimulating hormone reduces the quantity of the nutriments ingested [8, 9], which can lead to slimming.

Medical purpose of use

In the body, MSH has many points of action. These are the receptors, which may enable its use for a number of different medical purposes [3]. The α-MSH analogue (afamelanotide) has been studied, for example, in the treatment of erythropoietic protoporphyria (EPP) [8]. EPP is a disease with symptoms, such as skin hypersensitivity to the effect of sunlight. The α-MSH analogues have also been studied in the treatment of erectile disorders.

Properties and mechanism of action

MSH affects the body through the melanocortin receptors (MCRs) [3]. MCRs are located in several different parts of the body, which explains the manifold effects of MSH on body functions. For the individual, those effects may be desired or they may be experienced as harmful. In addition to the pigmentation of the skin, MSH has been found to affect sexual functions and the regulation of ingestion.

The melanin of the epidermis plays an important role in protecting the skin cells from harmful ultraviolet rays (UV-radiation) [2, 7]. When the skin is exposed to ultraviolet rays, the melanin binds the rays to it. As a result, the melanocytes are activated and begin to produce more melanin [7]. As the amount of melanin grows, the colour of the skin becomes darker: in other words, the skin tans. Thus, the melanin pigment of the skin protects the skin from damage caused by ultraviolet rays [2].

Research has found that synthetic α-MSH increases skin pigmentation [11, 4]: α-MSH has been found to significantly increase the amount of melanin in the skin and, at the same time, the number of skin injuries caused by UV-radiation decreases [4].

α-MSH reduces the quantity of nutriments ingested [8, 9]. The reported adverse effects of melanotan II include nausea and diminished appetite [11], which may explain the possible occurrence of slimming in conjunction with MSH use.

Synthetic α-MSH is used because of its skin-tanning effect. Other reasons for using α-MSH analogues include weight loss and increased libido. Unsurprisingly, this is why melanotan II is also called the “Barbie drug”.

Adverse effects

Studies on synthetic α-MSH analogues report several adverse effects, such as nausea and the flushing of the face [4, 10, 11], fatigue, [11, 4], vomiting [4], arrhythmias, perspiration, increased aggression, as well as spontaneous erections and priapisms. A priapism is a painful, prolonged erection, which may require surgical treatment [13]. Users have also been found to have melanomas, which have formed quickly, but the causal relationship has not been established [14].

MSH and its analogues have many kinds of effects on the body. When using MSH analogs, there is no way of knowing whether only the desired effects of the hormone will appear; rather, some adverse effects may appear as well. In particular, melanotan II has comparatively more potential adverse effects [6].

This is due to the fact that the target receptors of MSH are in many parts of the body. Injected MSH or its synthetic analogue can affect all these receptors and cause undesired effects. Furthermore, the composition of analogues, such as melanotan II, which are purchased online, is not known. Therefore, the safety of its use is difficult to assess.


Salla Ruuska
Master of Philosophy (MPhil), Pharmacist

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[1] Tirri R, Lehtonen J, Lemmetyinen R, Pihakaski S & Portin P (2001): Biologian sanakirja. Kustannusosakeyhtiö Otava, Keuruu

[2] Thody AJ & Graham A (1998): Does α-MSH Have a Role in Regulating Skin Pigmentation in Humans? Pigment Cell Research. 1998; 11:265-274

[3] Bertolini A, Tacchi R & Vergoni AV. Brain effects of melanocortins. Review. Pharmacological Research. 2009; 59:13-47

[4] Barnetson R, Ooi TKT, Zhuang L, Halliday GM, Reid CM, Walker PC, Humphrey SM & Kleinig MJ. [Nle4-D-Phe7]-α-Melanocyte-Stimulating Hormone Significantly Increased Pigmentation and Decreased UV Damage in Fair-Skinned Caucasian Volunteers. Journal of Investigative Dermatology. 2006; 126:1869-1878

[5] Brennan R, Wells JSG, Van Hout MC. The Injecting use of Image and Performance-Enhancing (IPED) in the General Population. A Systematic Review. Health Soc Care Community. 2017;25(5):1459–1531

[6] Callaghan Lii DJ. A glimpse into the underground market of melanotan. Dermatol Online J. 2018;24(5)

[7] Haug E, Sand O, Sjaastad ØV & Toverud KC (1999): Ihmisen fysiologia. s. 147-154, 323-327, 371-410, 411-422. WSOY, Porvoo

[8] Smith GP. The Controls of Eating: A Shift from Nutritional Homeostasis to Behavioral Neuroscience. Nutrition. 2000; 16:814-820

[9] Williams G, Bing C, Cai XJ, Harrold JA, King PJ & Liu XH. The hypothalamus and the control of energy homeostasis. Different circuits, different purposes. Physiology & Behavior. 2001; 74:683-701

[10] Harms JH, Lautenschlager S, Minder CE & Minder EI. Mitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of α-Melanocyte Stimulating Hormone. Photochemistry and Photobiology. 2009; 85:1434-1439

[11] Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ & Hadley ME. Evaluation of Melanotan-II, a Superpotent Cyclic Melanotropic Peptide in a Pilot Phase-I Clinical Study. Life Sciences. 1996; 58:1777-1784.

[12] Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S & Alberts DS. Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers. Archives of Dermatology. 2004; 140:827-835

[13] Dreyer B, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep. 2019;12(2)

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

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