Melanotan 2 Nasal Spray

Melanotan 2, usually written Melanotan-II or MT-II in the literature, is a synthetic copy of the body's own hormone alpha-MSH, but heavily shortened and closed into a ring. Only a stretch of seven amino acids of the original remains (positions 4 to 10), six of which are closed into a ring by a bridge between aspartic acid and lysine. On top of that come the same tricks as in Melanotan 1: norleucine instead of methionine and a D-phenylalanine that slows breakdown by enzymes. The molecule was developed at the University of Arizona. The first human study appeared in 1996 (Dorr 1996). Melanotan 2 is not approved anywhere, but its close derivative bremelanotide (PT-141), which lacks only an amide group at the end of the chain, is.

This variant is the finished nasal spray: 10mg of Melanotan 2 dissolved in 5ml of saline (NaCl) plus 0.4ml of bacteriostatic water, 5.4ml in total, which gives 1.85mg per ml. The pump delivers 0.1ml per spray, so about 185mcg (0.19mg). On paper the bottle holds 54 sprays; after priming the pump about 50 remain. Mixing, needles and unit maths all fall away; the spray is filled fresh once you place your order and ships as an express item. If you prefer to work with the vial, the Melanotan II entry has the calculator.

Two things up front. First, Melanotan 2 is considerably more potent and broader than Melanotan 1: in the trials it tans at a fraction of the dose, but it also acts in the brain, with nausea, flushing and spontaneous erections as typical companions. Second, every human study of Melanotan 2 used injections under the skin. There is no measurement of nasal dosing, only data on the closely related PT-141 and one case report. This entry therefore separates what carries over from the injection trials from what remains experience with the spray.

This information is for research and educational purposes only. No medical advice.

Melanotan 2 is a non-selective melanocortin agonist that binds to the MC1R, MC3R, MC4R and MC5R receptors. For tanning, what counts is MC1R on melanocytes, the pigment cells of the skin. Via the messenger cAMP the receptor switches on tyrosinase, the key enzyme of melanin production; the cell makes more brown-black eumelanin and passes it on to the surrounding skin cells. The skin darkens, with less UV than would otherwise be needed. In the first human study, 5 low doses two days apart were enough (Dorr 1996), whereas the Melanotan 1 trials needed several times as much per kg of body weight.

The difference from Melanotan 1 lies in the brain. Through MC4R and MC3R in the hypothalamus, Melanotan 2 taps into pathways that control sexual arousal, appetite and nausea. That is where the effects Melanotan 1 barely has come from: spontaneous erections, often preceded by yawning and stretching, more sexual desire, less appetite and a wave of nausea after dosing (Dorr 1996, Wessells 1998 and 2000). For tanning these effects are a side show; for tolerability they are the main issue.

How long Melanotan 2 stays in the blood has not been published for humans. Its close relative PT-141 has a half-life of about 2 hours after nasal dosing (Diamond 2004). In the phase 1 study the erections after Melanotan 2 came and went for 1 to 5 hours after the injection, depending on the dose. So the compound is largely gone within hours, but the tan is not: the melanocytes keep working after the signal. The extra pigmentation was still measurable a week after the last dose. What you spray today, you only see with a delay.

The nasal lining is thin and richly supplied with blood. Whatever crosses it into the bloodstream bypasses the stomach and liver. At roughly 1,024 daltons, Melanotan 2 is a small peptide and in principle a candidate for this route. Part of every dose is still lost: peptidases in the mucosa break it down. Whatever drains with the secretions into the throat is swallowed and largely digested in the stomach.

There is no human nasal measurement for Melanotan 2 itself, but there is one for PT-141. The two molecules differ only in one end group. Nasal PT-141 reached its peak level after about 30 minutes, yet a statistically significant erectile response appeared only above 7mg (Diamond 2004). Subcutaneously, Melanotan 2 triggered the same response at 0.025mg per kg, roughly 1.75mg at 70kg (Wessells 2000). That is a rough comparison between two related compounds, but it suggests that only a fraction of a nasal dose arrives in active form. So expect one spray of nominally 185mcg to do clearly less than 185mcg from a syringe. More sprays at once help little: one side of the nose holds only about one spray of liquid. Anything beyond that runs down the back of the throat.

In practice: before first use, pump 2 to 3 times into the air until a fine mist appears. Gently clear your nose first, keep your head upright, aim the nozzle slightly outward toward the nasal wall rather than at the septum, breathe in calmly, do not sniff hard. Avoid blowing your nose for 10 to 15 minutes afterwards. With two sprays use one per nostril, not both on the same side. With a cold or an irritated lining, uptake is unpredictable, so pause rather than push through.

The evidence on Melanotan 2 is small and old. Nearly all of it comes from one research group in Arizona. The first human study (Dorr 1996, Life Sciences) was a pilot in 3 healthy men: Melanotan 2 and saline were injected subcutaneously on alternating days, starting at 0.01mg per kg and escalating to 0.025 or 0.03mg per kg. After only 5 low doses, two of the three had more pigment on the face, upper body and buttocks, measured a week after the last dose. Mild nausea occurred at most dose levels, a stretching and yawning complex came with spontaneous erections over 1 to 5 hours. At 0.03mg per kg one subject became markedly tired and drowsy. The authors recommended 0.025mg per kg for further studies.

After that the focus shifted to erections. In a crossover study in 10 men with psychogenic erectile dysfunction, 8 developed a visible erection on Melanotan 2 (Wessells 1998). The follow-up study in 10 men with organic risk factors (Wessells 2000, Urology) gave 0.025mg per kg subcutaneously twice: 12 of 19 injections triggered an erection versus 1 of 21 placebo doses, the phase with more than 80 percent tip rigidity lasted 45 minutes on average versus just under 2. Sexual desire was clearly higher afterwards. The price was nausea, severe after 4 of the 19 injections. In the end it was not Melanotan 2 that was developed further but its derivative PT-141, which was also tested nasally in men (Diamond 2004) and is now approved subcutaneously in the US.

No further controlled tanning studies with Melanotan 2 have been published since that pilot. There are no long-term data. What does exist are dermatology case reports, summarised in a review by Habbema and colleagues (International Journal of Dermatology 2017): changed moles, newly emerging and partly dysplastic naevi as well as four cases in which a melanoma arose from a mole during or shortly after melanotan use. These reports do not prove a causal link, but several national health authorities have issued warnings anyway. For the spray itself there is not a single controlled human measurement.

Melanotan 2 has a clearly broader side-effect profile than Melanotan 1, because it also acts in the brain. Most common in the trials: nausea, especially at the start, plus yawning and stretching, reduced appetite and spontaneous erections that can keep coming back for hours (Dorr 1996, Wessells 1998 and 2000). Facial flushing with a feeling of warmth is common too; in its close relative PT-141 it was the most frequent adverse event alongside nausea (Diamond 2004). At 0.03mg per kg, marked tiredness and drowsiness were added. These data come from doses of roughly 0.7 to 2.1mg subcutaneously; with a nominal 185mcg per spray and weaker nasal uptake the effects are likely to be milder. They do not disappear entirely, which is why you start with one spray in the evening. How much the dose matters is shown by a case report from the US: after injecting 6mg of Melanotan 2 in one go, a man developed a racing heart, agitation, muscle breakdown and temporarily impaired kidney function. He spent three days in intensive care.

Pigment is the most important safety point. Melanotan 2 darkens not only the skin but also existing moles and freckles. Newly appearing, sometimes atypical moles have also been described, in one case report from Lübeck as early as 24 hours after a single injection. Four melanomas arising from existing moles during or shortly after use have been published; a causal link is not proven, but not ruled out either (Habbema 2017).

What follows from this: photograph your skin and moles before you start or have them checked by a doctor, keep an eye on them during use and have anything new, or anything that changes in shape, colour or size, looked at by a dermatologist. The same goes for dark spots on the gums, the palate or inside the nose. Anyone with a history of melanoma, many atypical moles or melanoma in the family should leave Melanotan 2 alone, as should anyone pregnant or breastfeeding, for which there are no data. Take care with cardiovascular disease or high blood pressure: there are no measurements for Melanotan 2, while a brief rise in blood pressure has been documented for its derivative PT-141. An erection lasting longer than 4 hours is an emergency.

Nasal use adds local effects: burning or tingling in the nose, sneezing, a runny nose, a bitter aftertaste and with frequent use a dry lining or slight nosebleeds. If you notice these, pause for a few days instead of pushing on. And as with every tanning peptide: the tan is not reliable sun protection, sunburn and UV damage remain possible. Sunscreen stays mandatory.

The spray belongs in the fridge (2 to 8 degrees), not in the freezer and not in the door compartment where the temperature swings every time it opens. Keep it out of the light, for example in a small box. Store it upright so the dip tube stays in the solution. A few hours or a day or two at room temperature, in the post or in a bag, do the solution no harm, but it should not sit warm for long.

Once opened, the solution keeps for several months in the fridge. Melanotan 2 is sturdily built: the ring protects the chain from enzymes, the oxidation-prone methionine of natural alpha-MSH is replaced by norleucine. There is no cysteine. Saline is a stable medium. The most light-sensitive part is the tryptophan in the chain, hence the dark storage. The real weak spot is germs: only 0.4ml of the 5.4ml is bacteriostatic water, so its benzyl alcohol is heavily diluted and protects the solution only to a limited extent. That is why cleanliness counts for more than cold alone. During loading the bottle is empty after 3 to 7 weeks anyway; in maintenance, use it up within about 3 months, even if sprays are left over.

Wipe the nozzle with a clean tissue after each use and put the cap back on so nothing dries in and no germs migrate into the bottle. A bottle is personal, do not share it. If the solution turns gel-like, lumpy or smells different, stop using it. Slight cloudiness on its own is not a reason.