What Is Melanotan II?

Melanotan II is a laboratory-made copy of alpha-MSH, the hormone that tells pigment cells in your skin to make more of the dark pigment behind a tan. It was designed in the 1980s to be stronger and longer-lasting than the natural hormone, and it was briefly tested in people in the 1990s. It has never been approved as a medicine anywhere in the world.

That short history hides a more interesting story. Melanotan II turned out to do a good deal more than darken skin, because it opens several related doors in the body rather than one. Two of its close relatives went on to become approved medicines for narrow purposes. Melanotan II itself never did. This page explains why, and then sets out the documented safety concerns in one plain paragraph.

What is the hormone it copies?

Your skin contains pigment cells called melanocytes. Their job is to make melanin, the pigment that gives skin, hair and eyes their colour. There are two main kinds: a brown-black one, which is better at soaking up ultraviolet light, and a red-yellow one, which is not.

Melanocytes do not decide by themselves how much of each to make. They listen for a hormone called alpha-melanocyte-stimulating hormone, usually shortened to alpha-MSH. A hormone is a chemical message that tells cells what to do. Alpha-MSH is a short peptide, meaning a small chain of amino acids, the building blocks of proteins. When it reaches a melanocyte, it fits a receptor, a structure on the cell's surface shaped to catch it, and the cell responds by making more of the brown-black pigment.

Where does alpha-MSH come from? It is cut out of a larger protein, a bit like a single word snipped out of a long sentence. That same long protein is also the source of a pituitary hormone that tells the adrenal glands to release cortisol, the body's stress hormone. Because the pigment hormone and the stress-signalling hormone come from the same parent and look alike, the receptors they fit are known together as the melanocortin receptors, a name stitched together from melanocyte and corticotropin. Keep that family name in mind. It becomes important in a moment, because melanotan II does not stay politely within one branch of the family.

A tan, then, is the skin reacting to a message. After sunlight damages skin cells, more alpha-MSH is made in the skin, and the melanocytes darken in response. It is the body's repair crew putting up shutters after the storm has already hit, not before.

Why build a copy?

In the 1980s, researchers at the University of Arizona had an appealing idea. If you could send the darkening message without the sun, you might give fair-skinned people a protective tan without the damage that normally causes it. The hope was to reduce sunburn and, in the long run, skin cancer.

The natural hormone was no good for this. Like most small peptides, it is cut apart by enzymes, proteins whose job is to break other molecules down, within minutes. So the team built tougher copies. The first was a straight chain with a couple of building blocks swapped. It later became known as afamelanotide. The second was smaller and ring-shaped. That one is melanotan II.

Ring-shaped, or cyclic, means the chain is joined back on itself to form a loop. Picture the difference between a loose piece of string and a bracelet. The string flops about and is easy to snip at an open end. The bracelet holds its shape and has no loose ends to grab. The ring made melanotan II far more potent and longer-lasting than the natural hormone. The researchers who first tested it in people called it "superpotent" 1.

One key, several doors

Here is the twist. The receptor on pigment cells belongs to a family of five related receptors called the melanocortin receptors. They are like five doors in the same building, with similar but not identical handles. One is the skin's pigment door. Others sit in the brain, where they help regulate appetite, energy use and sexual function.

A well-designed key opens one door. Melanotan II opens several. That lack of selectivity showed up the moment it was tested in people. In a small early study in the 1990s, it darkened skin, and the volunteers also reported nausea, flushing, a strong urge to stretch and yawn, and unprompted erections 1.

That last effect was noticed, and followed up. In 1998, the same group ran a small, carefully controlled study in ten men with erectile problems that had no physical cause. It was double-blind, meaning neither the men nor the researchers knew when they received melanotan II or a placebo, an inactive look-alike. Eight of the ten developed erections on melanotan II. Nausea, yawning and stretching, and reduced appetite were more common with it too 2.

So a compound designed for the skin turned out to act on the brain as well. That is not a moral failing of the molecule. It is what happens when one key fits several related locks.

Why was it never approved?

Approval means a medicines regulator has reviewed large trials of a specific product for a specific purpose and agreed it may be sold for that purpose. Melanotan II never reached that point. It was never taken through the large late-stage trials a regulator needs to see.

The simplest way to read what happened next is that each of its jobs was handed to a relative that did that job more cleanly. The skin idea went to afamelanotide, the straight-chain cousin. It was eventually approved in the European Union in 2014, not for cosmetic tanning, but for a rare genetic condition called erythropoietic protoporphyria, in which ordinary light causes severe pain in the skin. By increasing dark pigment, it helps those patients tolerate light 6.

The brain idea went to bremelanotide, a compound derived from melanotan II itself. In 2019 the US regulator approved it as a prescription treatment for a specific form of low sexual desire in women who have not reached menopause 7. Its approved labelling lists nausea, flushing and headache among its common side effects, which will sound familiar.

Melanotan II was left in between: too broad to be the skin medicine, too broad to be the brain medicine, and never tested at the scale that approval requires. No regulator has approved it for anything.

How do regulators treat it?

In the United Kingdom, the medicines regulator has said that products containing melanotan II count as medicines if they meet the legal definition of one, and that a medicine must be properly authorised before it can be sold. It has also said it has repeatedly acted to remove melanotan products from sale for more than ten years 8.

The same regulator was once asked how many suspected side-effect reports it had received for melanotan II over a decade. The answer was thirteen, and it came with an important caution: a report means someone suspected a link, not that the product caused the problem, and far fewer problems are reported than actually happen 8. That caution applies to every side-effect reporting system in the world, and it is worth remembering whenever you see a count of reports quoted as if it were a count of harms.

The documented safety signals

Dermatologists, doctors who specialise in skin, have published a series of reports on people who used unlicensed melanotan products. They describe moles appearing suddenly in large numbers, existing moles darkening or changing shape 4, and melanoma, the most serious form of skin cancer, found in people who had been using it 5. A review of this literature also lists the effects seen in the early studies, such as nausea and flushing, and points out that unregulated products may not contain what their labels claim 3. A safety signal is exactly what it sounds like: a warning light, not a verdict. Case reports cannot prove that melanotan II caused any of these problems, because users often also spend long periods in the sun and nobody tracked a comparison group. But changes to moles are precisely what doctors watch for as early signs of melanoma, and a compound that switches on pigment cells is exactly where you would expect such a warning to appear 3.

What melanotan II is not

• It is not afamelanotide. That is its straight-chain relative, approved in the EU for a rare light-sensitivity condition.
• It is not bremelanotide. That is a compound derived from it, approved in the US for one specific condition.
• It is not selective. It opens several melanocortin doors, not just the skin's.
• It is not a sunscreen. A tan follows skin damage; it does not undo it.
• It is not an approved medicine anywhere, and it never completed the trials that approval requires.

The short version

Melanotan II is a ring-shaped copy of the skin's darkening hormone. It was built to tan without the sun, but it fits several related receptors, so it also acts on the brain. Its relatives became medicines for narrow purposes. It did not, and the reports that have gathered around it since are about the very cells it was designed to switch on.