The Melanotan Masterclass

Happy Tuesday!

Depending on where you live, you've probably got three or four good weeks of summer left.

Which is why I wanted to make sure I released the Melanotan masterclass today.

▶️ Watch on YouTube

🎧 Listen on Spotify

I put both compounds in the same class because you really can't talk about one without talking about the other.

And most of the bad experiences I hear about come from people mixing the two up.

Here's what I covered in the masterclass.

Background

Melanotan 1 was synthesized in 1980 at the University of Arizona.

Researchers took alpha melanocyte stimulating hormone, which is the natural signal your body uses to make pigment, and swapped two amino acids. That made it resistant to enzymatic breakdown and locked it into the shape the receptor prefers.

The result was roughly 26 times more potent than the natural version, with activity that lasts days instead of minutes.

You'll see it called MT1, afamelanotide, Scenesse, or NDP-MSH. All the same molecule.

Melanotan 2 came out of the same program. The original paper was published in the Journal of Medicinal Chemistry in 1995. They took the seven-amino-acid core that fires the receptor and stitched it into a ring.

Think of MT1 as a long straight chain and MT2 as a small tight ring.

Same parent molecule, two very different drugs.

MT1 went the pharmaceutical route. Licensed by the University of Arizona, developed by Clinuvel as a 16mg implant, approved in Europe in 2014 and by the FDA in 2019. The only approved indication anywhere is a rare light sensitivity condition called EPP.

MT2 never got approved anywhere. They took it into early testing for erectile dysfunction, and PT-141 came out of that work instead.

MT1 vs. MT2

Both work through the MC1R receptor, which is the pigmentation switch sitting on your melanocytes, the cells in your skin that make pigment.

Flip that switch, and you get more cyclic AMP, more tyrosinase, and more melanin. More melanin means visible color.

Both also shift you toward eumelanin, the brown pigment that absorbs UV broadly and scavenges free radicals. That's the protective one. Pheomelanin is the red and yellow pigment of fair skin, and it shields UV poorly.

The cosmetic mechanism and the protective mechanism are the same mechanism.

Now here's where they split.

MT1 is selective. It hits MC1R and mostly leaves everything else alone.

MT2 walks down the hallway flipping the other switches too. It hits MC3R and MC4R, which is where you get spontaneous erections, a real jump in libido, appetite suppression, more nausea, more flushing, and heart rate changes.

MT2 is stronger for tanning. It's also stronger at everything you didn't ask for.

Benefits

Melanotan 1 is for the person who lives outside.

Hikers, athletes, guys working construction, anyone who wants durable pigment without reapplying sunscreen all day. I'm in that camp. I try to get two to three hours of sunlight a day.

I've been running MT1 for years now, and I don't use sunscreen anymore.

It also does things that have nothing to do with looking tan. MC1R activation improves repair of UV-damaged DNA. It brings reactive oxygen species down independently of pigment. It calms inflammation through the same pathway that makes everyone love KPV.

I'm not going to sit here and tell you MT1 prevents skin cancer. We can't say that. But we do know burning is what drives the damage, and MT1 keeps me from burning.

Melanotan 2 is for speed.

If you're very pale and MT1 isn't moving your pigmentation much, MT2 will.

If you have a wedding, a photo shoot, a bodybuilding show, or a January trip to the Bahamas with no time to build a base, MT2 gets you there faster.

MT2 is not for appetite suppression or sexual function. It does both, and people chase it for that reason.

Use a GLP-1 for appetite. Use PT-141 for erections. You’ll thank me later.

Dosing

MT1 should be first for almost everyone.

Starting out, 250mcg (0.25mg) subcutaneously twice per week. Run that for two weeks and see how you respond.

From there, 0.5 to 1mg two to three times weekly for four to six weeks while you're actually getting sun.

Then maintain at 0.25 to 0.5mg once or twice weekly through the summer.

I rarely see anyone need more than 1mg.

For MT2, low and slow. 100 to 250mcg in the evening, daily for one to two weeks as a loading phase. Evening dosing so you sleep through the nausea.

Once you have the color you want, drop to 250mcg once or twice weekly, or transition over to MT1 for maintenance.

Do not jump straight in at 1mg of MT2. You'll shift your color way too fast and probably spend the night hovered over the toilet.

Remember, these peptides are synergists with sunlight, not replacements for it.

You still have to go outside!

Final Thoughts

Melanotan 1 for almost everybody.

It has the pedigree, the human safety data, and in most cases it's all you need. MT1 is your sunscreen, the background player that's always there.

Melanotan 2 is the tanning bed. Great for a very specific purpose in a very short window. Not something I'd run long term or year-round.

If you're going to use both, do MT1 first.

Most people do it backward because MT2 has more name recognition in the fitness world, and then the side effects blindside them.

Skip both if you have an active melanoma or a lot of atypical moles. Never run MT1 or MT2 on the same day as PT-141.

Get a skin check twice a year. And avoid tanning beds, because almost every melanoma case report tied to MT2 involves someone who was using a bed too.

As I always say, have a goal when you use peptides.

"I want to be tan for the summer" is a perfectly fine goal, but just be smart about how you get there.

The full masterclass goes a lot deeper on cycling, stacking, troubleshooting, and the melanoma question.

Have a fantastic week!

Best,

Hunter Williams