What is Melanotan II?

Melanotan II, also known as Melanotan 2, is a synthetic peptide with similar structure and function to melanocortin. Melanotan II has the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, molar mass of 1024.18 g/mol and the CAS number is 121062-08-6. Melanocortin is a hormone and signaling peptide that plays roles in stimulating the production of melanin (dark skin pigment) and in increasing libido. The side effects associated with Melanotan II have resulted in its production and sale for human use being made illegal in several countries for human use. As it stands, the Melanotan II is only available for research use in the UK, USA and most of Europe. Purchasing the product, owning it, and using it are not illegal.

Melanocortin Peptide Hormones

Melanocortin is not one molecule, but rather a family of peptide hormones that includes adrenocorticotropic hormone (ACTH). It is accurate to refer to a single member of the group as "a melanocortin" or to refer to the entire group as the "melanocortins." There is no molecule called melanocortin at present. In the past, ACTH was referred to as melanocortin, but that was before the other molecules in the group were discovered. Having cleared up the naming, it is important to note that what draws the melanocortins into a single family of peptide hormones is the fact that they bind to and activate melanocortin receptors throughout the body. Most melanocortins are derived from the proopimelanocortin pre-hormone in the pituitary gland.

Effects of Melanocortins (Melancortin Receptors)

Melanocortin (MC) receptors are G protein-coupled receptors found on cells throughout the body. Currently, the receptors are numbered 1 through 5. Each receptor has a different function for the particular cell it is found on. Cells that contain melanocortin receptors range from skin cells to kidney cells.

MC(1) is found on melanocytes, skill cells that are responsible for the production of melanin, the molecule that imparts a dark color to the skin. MC(1) is also found in hair cells, where it also controls the production of melanin. More melanin leads to darker skin and less melanin leads to lighter skin. MC(2) is also referred to as the adrenocorticotropic hormone receptor (ACTH). MC(2) is specific for ACTH, which means that other melanocortins do not bind to it. ACTH regulates the secretion of glucocorticoid steroid hormones from the adrenal glands and can also bind to and activate the MC(1) receptor. Excess ACTH, which leads to excess stimulation of MC(2), can lead to Cushing's syndrome. MC(3) is sensitive to several different members of the melaocortin family. It is thought to play a role in appetite control and homeostasis. It is not found in the adrenal glands or in the melanocytes. MC(4) plays a role in feeding, sexual behavior, and male erectile function. Mutations in MC(4) are associated with inherited obesity and are thought to play a role weight gain in about 2.5% of people who have BMIs greater than 30. MC(5) is the newest member of the melanocortin receptor family to be discovered. Its effects are localized to the exocrine glands (such as sweat glands). An absence of MC(5) function can lead to a decrease in the production of sebum (oil).

The effects of the melanocortins depend on which receptors they activate. ACTH, for instance, is capable of activating MC(1), MC(2), MC(3), and MC(4). That means that excess ACTH causes darkening of the skin, increased levels of cortisol (stress hormone), increased appetite, and increased erectile activity. Melanotan II is thought to bind to MC(1), MC(2), and MC(4). It may also bind to MC(5).

Melanotan II Development

Melanotan II was synthesized by scientists at the University of Arizona who thought that it could provide protection against skin cancer by activating melanocytes in the skin. They hypothesized that boosting the body's natural pigment, which offers protection from the harmful effects of ultraviolet (UV) radiation, could reduce rates of skin cancer. It is, in essence, a sunless tanner. Shortly after Melanotan's development, it was licensed to several biotechnology companies to be converted into a practical drug. There are two other drugs associated with Melanotan 2: Melanotan I and bremelanotide. Melanotan I increases pigmentation, but is not associated with spontaneous penile erections, presumably because the majority of its binding occurs at MC(1). Bremelanotide is a metabolite of Melanotan II. Its development has been directed primarily at sexual dysfunction. It interacts with MC(4), almost exclusively, to improve erectile function. It is currently in phase I testing.

Melanotan II Testing

Early clinical trials of Melanotan II were carried out in 1996. Results indicated that just five doses of the molecule could result in significant tanning activity. Reported side effects included fatigue as well as spontaneous penile erection. Further testing, in 1998, confirmed the side effects of Melanotan II when the drug was tested on men who suffered from psychogenic erectile dysfunction. A more recent test of Melanotan II, in 2000, found that it is a potent initiator of penile erection in men with erectile dysfunction. In 2012, the journal of Clinical Toxicology reported systemic toxicity and rhabdomyolysis (severe muscle damage) in an individual who injected Melanotan II. The patient took six times the recommended dose of the product he had purchased. He suffered kidney damage and spent three days in the ICU.

Uses of Melanotan II

The original impetus for developing Melanotan II was to reduce the incidence of skin cancer. Because the peptide leads to skin-darkening, it was thought that it could be used as a sunless tanner to help protect the skin from harmful UV radiation. Recent research indicates that Melanotan II can up-regulate melanocyte activity, leading to reduced incidence of sunburn and improved levels of tanning. In fact, Melanotan II can improve tanning by up to 50%, which means that people can get the same tan after being exposed to only half as much sunlight. Taken at the right doses, research indicates that Melanotan II is not only safe, but that it may actually be beneficial in terms of overall skin health.

Though not an original use of the product, Melanotan II has become a potent aphrodisiac and libido-enhancer. Research supports the claims that Melanotan II can improve rates of penile erection and lead to spontaneous penile erection in some individuals. The drug has been of particular interest for the treatment of psychogenic erectile dysfunction (PED). PED is not amenable to current mainstays of erectile dysfunction (ED) treatment, like Viagra, and has proven exceptionally resistant to most forms of treatment. The advent of Melanotan II has provided hope that a drug, with few side effects, can be developed to treat PED.

Melanotan II has also become popular as a performance enhancer, though there has been no connection between Melanotan II and increased strength, flexibility, or stamina. The drug is popular among bodybuilders, who use it to darken their skin for competition.

Autism

There is preliminary interest in the use of Melanotan 2 to treat autism and other "social anxiety" disorders. This interest arises form the fact that Melanotan II has been shown to reduce the time required for the prairie vole to remember its lifelong companion and resume mating. Some have interpreted this to mean that the drug is improving social conditioning and that it might therefore be useful in the treatment of autism. Psychologists have also speculated that the drug may be useful in certain types of behavioral therapy.

The effects of Melanotan II on social behavior appear to be mediated through the release of oxytocin, a brain chemical associated with reduce anxiety, improved social behavior, and increased bonding. The results are very preliminary, however, and there is a great deal of skepticism about the drug's potential uses for treating autism and other social anxiety disorders. New research is currently testing the effects of Melanotan II on primates.

Side Effects of Melanotan II

The most common side effects of Melanotan II are nausea, vomiting, and upset stomach. Unfortunately, other side effects of injecting Melanotan II are more severe. The side effects are directly linked to the drug's melanocortin receptor activity and are dose-dependent.

By activating MC(1), Melanotan II not only leads to improved tanning and darker skin tones, it directly affects the replication of melanocytes. Increased replications of melanocytes, the cells from which melanoma arises, is a clear risk-factor for the development of skin cancer. In fact, reports of melanoma that has arisen due to Melanotan II use have cropped up in the medical literature. The risk of skin cancer appears to be increased when Melanotan II is used in conjunction with exposure to UV light (tanning beds, the sun, etc.) to enhance tanning.

The research regarding Melanotan II and skin health is conflicting. Several studies have found benefits and several have linked Melanotan II to the development of skin cancer, including melanoma. There is no general consensus as to whether the benefits of this drug outweigh its risks. Most scientists appear to be leaning toward the risks outweighing the benefits.

Activating MC(2) Melanotan II increases the excretion cortisol from the adrenal glands, which, in turn, can lead to weight gain, fat deposition, and loss of water through the kidneys. The latter is the most acute and significant effect. Too much Melanotan II can lead to dehydration and subsequent heart and kidney damage.

The MC(3) receptor appears to be relatively unaffected by Melanotan 2, but the MC(4) receptor is clearly activated. Though low doses of Melanotan II can be helpful in treating certain types of erectile dysfunction, too much of drug can lead to prolonged erections and damage to the tissue of the penis. Reports of erections that last six to eight hours, well above the maximum of four hours that requires medical attention, have been reported.

Melanotan II has also been shown to interact relatively strongly with MC(5), though the exact consequences of this interaction are not clear. Because MC(5) is associated with exocrine gland function, it is possible the Melanotan II could lead to decreased sweating and thus decreased evaporative cooling. The net effect might be hyperthermia, particularly during exercise.

"The stretch and yawn" phenomenon is one side effect of Melanotan II that has yet to be explained. People who have taken the drug indicate that it "feels great" to stretch and yawn after taking it, particularly after waking up. There is no clear reason for this particular effect, but it has not been linked to any damage or harm.

Regulation

The regulation of Melanotan II is quite complex. It is not currently approved for human use by the Food and Drug Administration (FDA) or any other major body that governs the use of medications. In fact, the FDA has issued several warnings to vendors of Melanotan II regarding how they market products that contain the drug. The Danish Medicines Agency (DMA), Medicines and Healthcare Products Regulator Agency in the UK, and the Irish Medicines Board (IMB) have all issued warnings to companies who market Melanotan II. Many of these agencies have published precautionary statements about Melanotan II use.

Despite the warnings from major drug regulatory agencies, it is not illegal to import or to take Melanotan II. It is illegal to market the product for human use, however, and that is often where companies that sell Melanotan II run afoul of the law. In short, people can own it and people can inject it, but companies that make Melanotan II cannot market it for human use. The only legally-permissible uses of Melanotan II in people are in government-sanctioned trials.

Melanotan II Moving Forward

It is impossible to predict what regulations, if any, will be put on Melanotan 2 in the future. As it stands, the drugs shows significant promise in treating a handful of conditions. It is likely that it will be approved for limited use in treating these conditions, but that approval will be contingent on research that will take years to complete.

Melanotan II may or may not have significant positive effect in terms of reducing the incidence of skin cancer. The jury remains out on that verdict, so to speak, and the evidence that does exist is quite contradictory. Given the potential for serious side effects, like cancer, most people would do well to steer clear of Melanotan II until more is known about the drug and its long-term side effects.

In short, Melanotan II shows a great deal of promise in the treatment of previously untreatable conditions. It may turn out to be a boon for dermatologists as well, reducing rates of skin cancer and improving the body's natural protection against the sun. Right now, however, there is simply too little data and there are too many potential risks to justify the use of Melanotan II outside of clinical trials and research.