Melanocortin receptor desensitization with chronic melanotan 2 use?

[JohnBoy2000]

I wanted to experiment with different means of using this based on the benefits I'd experienced with it.

So over a period of 18 months I microdosed 50 mcg daily, no breaks. I was also using it for its effect on oxytocin and behavioral associated effects.

When the summer came and I increased my dose to 500 mcg again, it did still work but I noticed I would go red first before tanning.
I NEVER burned using mt2 before; in addition to it no longer turning my hair as dark.

I thought perhaps the mt2 I used was weaker but then having shopped around and tried the most potent mt2 imaginable at high dose, no change.

Eventually it was suggested that with the possibility persistent use, no breaks, had caused a downregulation of melanocortin receptors.

So at the moment for the first time in a couple years, I'm taking a break from its use, backing off to a dose of 250 mcg occasionally for maintenance, but cessation of daily dosing.

Any thoughts on how long restoration of melanocortin receptor sensitivity may take?

i.e. how long do I need to not use it, to begin to experience its full effect again?

 

[Serotonin101]

Honestly I've never experienced this and that was with regular heavy use. Hair still turns black. I still tanned easily. Just no nausea/hot flashes. Now I only use it for like 4-6 weeks a year to get dark for summer. No nausea or hot flashing, only the positives

 

[JohnBoy2000]

Honestly I've never experienced this and that was with regular heavy use. Hair still turns black. I still tanned easily. Just no nausea/hot flashes. Now I only use it for like 4-6 weeks a year to get dark for summer. No nausea or hot flashing, only the positives

Regular heavy use would be, daily for 18 months straight?

I used it daily for 2 or 3 months at a time and no problems but over a year or more (significantly more), I'm assuming that's what happened;

A local user used some vials from the same batch I ordered and his hair turned completely black where it had little to no effect on mine.

Sounds unusual but I suspect most people don't micro-dose it without missing a single day for a period of years.

 

[Serotonin101]

Regular heavy use would be, daily for 18 months straight?

I used it daily for 2 or 3 months at a time and no problems but over a year or more (significantly more), I'm assuming that's what happened;

A local user used some vials from the same batch I ordered and his hair turned completely black where it had little to no effect on mine.

Sounds unusual but I suspect most people don't micro-dose it without missing a single day for a period of years.

My first rodeo was about 1 year or so straight, first like 4 months at 1mg/day until I turned grey/purple, then dropped to 250-500mcg/day. I still have some scar tissue on my abdomen from being a pin cushion back then as I was also using ghrp-2 multiple times a day for months on end too.

 

[Phobos]

Honestly I've never experienced this and that was with regular heavy use. Hair still turns black. I still tanned easily. Just no nausea/hot flashes. Now I only use it for like 4-6 weeks a year to get dark for summer. No nausea or hot flashing, only the positives

I didn't know Melanotan affected hairs.
Does it make white hair go black again? Or is it something else?

 

[Serotonin101]

I didn't know Melanotan affected hairs.
Does it make white hair go black again? Or is it something else?

I don't think it can darken pigment of hair that is lacking pigment. For me, my natural hair color is like a medium brown (level 3 I believe color level wise) and it'll turn like ashy first (charcoal hue), and eventually it'll turn straight charcoal in color. My facial hair as a variety of light to dark brown with some red. But will turn charcoal as well with prolonged mt2 usage. I have some white hairs that show through but I don't have a lot of grey/white yet at 31 yrs old. Facial hair is more noticeable for me because I shave frequently and it grows quickly (can have a full face of hair in a month). Scalp hair requires me to maintain some mt2 usage for months as my hair grows maybe 3/4 inch per month so usually 8-10 weeks my scalp hair will noticeably dark.

 

[JohnBoy2000]

 

[JohnBoy2000]

A dude pm'd me some thoughts on this:

That’s interesting as I would have thought that low of a dose would have no discernible affect even when the blood half life is three days. The a-msh antagonist is always present in blood but in minuscule amounts so there is definitely a threshold for how it affects people. I find that the negative sides like sleep interference and weight loss tell me when I’ve had too much. The sweet spot is 150-300mcg for me. Discovered through three years of using it and monitoring tanning affect.

You’ll find that down and up regulation of receptors is a normal bodily process and as soon as you abstain from a particular antagonist they will immediately regulate to where they were prior in response to other feedback systems that those receptors affect unless you’ve ingested something neurotoxic or carcinogenic that’s how receptors work they are constantly being produced as they are inherently part of your body’s cells. If your body was not producing adequate MCR’s in response to an antagonist you’d have bigger problems than not tanning.

Further to this too the a-msh antagonist which MT2 is a synthetic version of, does not have a direct feedback mechanism controlling its release. Meaning it’s presence in the system alone will not affect the body’s ability to produce it. It’s cleaved from the POMC hormone which is regulated by the hypothalamus and pituitary gland and influenced by a number of hormones including insulin. MT2 does not interact directly with insulin and especially not in any way that affected your body’s ability to produce pre-POMC hormone. There is plenty of literature on this. If that was the case there wouldn’t be regular users who have used it for over a decade with no waning affect and if they did this would align with other serious side affects. The MCR system does interact with other systems but it’s a very “hardy” mechanism of the body that peptides are not going to destroy or permanently affect in any other way hence why MT2 is so widely used now with less adverse affects reported than off the shelf medications.

It could be the fact it’s a synthetic and your body is finding a way to fight it perhaps.. Are you normally pale and red or light haired? I read a forum a few years back where a user was saying the same thing and he was also using it to keep his hair dark. It may also not be the peptide itself necessarily but some sequence of the amino triggering an immune response or the process of it mimicking another amino targeted by the body. Or perhaps being lighter skinned your body has evolved to do away with the MCR1 in skin cells without adverse affect hence the natural lack of melanin to start with. All guesses though as it’s not been studied. Did you notice when taking it your libido Increased even though the melanin affects weren’t working? Reason being that different MCR receptors are responsible but a-msh is an antagonist of both. If your libido did not increase either then it’s more likely to be the product itself.

Instead of those low doses have you ever tried just dosing say 150mcg every second day for a week or so to get your body used to it then just 300mcg on tan days then say 300 a week spread over 2 x 150 doses thereafter?. I tan naturally and only use MT to avoid too much sun exposure. I can lay off it for a couple of weeks then one dose of 150mcg without any sun and I will be noticeably darker the next day. I usually only dose on weekends before going out or before going on holiday. My hair and beard are already very dark brown but go almost jet black on it. However, I’ve never taken a dose as low as 50mcg except in the very beginning just to gauge my reaction. I’m careful to never go too big though like you read some people doing. Never gone over 400mcg and never will.

Uses some advanced enough rationale but unsure of its merit.

 

[JohnBoy2000]

I assume this poster did some reading around the issue, I'm unsure how valid these scientific claims are but being melanotan and not sufficiently clinically studied, I'm always curious to at least examine such claims.

I personally hadn't ever experienced effects on arousal/libido from melanotan, in response to this the following rationale seems to have been applied?

The receptor that interacts with oxytocin is MCR4 which is also the same receptor involved in regulating sexual behavior. It’s extremely unlikely that an a-msh analogue is going to affect your oxytocin to a noticeable degree and not affect your libido / sexual behavior. That’s like saying glucose only affects your brains left hemisphere. Unless you have zero sexual arousal mechanism to start, it’s impossible that this is the causation. MT2 is systemic when administered in the blood through injection and crosses the blood brain barrier and affects MCR’s 1,3,4 & 5 and almost in that order by degree of affect. 1 is pigment fyi.

There is no place in your body this hormone won’t reach even inside your bone tissue. If you were dosing to a level that caused degeneration / down-regulation of these receptors to inhibit oxytocin in your body you would have to have had equal libido affects prior. It doesn’t make any sense in causing your condition. MCR system is also heavily involved in inflammation processes you would have serious health consequences alongside your oxytocin inhibition if the peptide was causing degeneration of any of these receptors. a-msh cannot selectively antagonize receptors. That’s why it’s the alpha hormone which is what the ‘a’ stands for.

It definitely feels like some overblown and poorly understood bro-science.

 

[JohnBoy2000]

You can’t noticeably down-regulate a receptor and only notice an inhibition of a single process it’s involved in when it’s involved in so much more than interacting with oxytocin mechanisms and the receptor that MT2 interacts with associated with oxytocin (MC4) only plays a small part in this. You’d have to affect your pituitary gland or hypothalamus to have any noticeable affect on your oxytocin function and again you’d notice severe system wide issues. You’re oversimplifying the role of hormones and their associate receptors. Hormones don’t target single processes involved in associated receptor binding it’s literally impossible. They are merely on / off switches that only respond to specific hormones like keys in a lock.

This I find interesting, same poster.

I suppose it's also the danger of reddit bro-science.

Pretty dramatic claims as to the nature of endocrinology without any scientific/laboratory based validation.

Of course they may be valid none the less? Claim being if receptor downregulation via chronic mt2 use happened, it would precipitate evident systemic wide issues, and would not be evident exclusively in reduction of the peptides effect.

Which sounds like total horse shit to me; I've never read an iota of even anecdotal evidence to support such a dramatic claim.

To say that you identified your receptors down-regulating by noticing an inhibition of a single involved process is like someone saying their eyes only went blind to seeing poodles. It doesn’t make sense from a biochemistry perspective.

Oxytocin has its own receptors OXTR not related to the MCR receptors that are not affected by a-msh and has a positive feedback mechanism which means more oxytocin detected in the blood leads to more being released. a-msh or MT2 cannot affect this system for you to notice. Likely a placebo or increased pleasure from your improved appearance. The waning tan affect was more than likely bunk gear and as said before the only way to know is to get legitimate purity tested produced. Can pay for HPLC testing or locate a credible vendor like I was buying from the last three years. The Chinese stuff is not a reliable enough variable for you to diagnose your health on man believe me.

More of the same.

Anyone follow the chain of logic in those quotations, is there any merit to it?

 

[JohnBoy2000]

Quote from reddit:

"
Biophysics major pre med.

Yes correct. Key word is correlation. Meaning the systems interact. Just as insulin a principally hunger hormone interacts with sleep. That doesn’t mean much though when quantifying causality for a peptide not working.

You don’t know your receptors were down-regulated. That’s been your own diagnosis and without any other systemwide issues in your body this isn’t possible which is what I’m trying to say to put your mind at ease. Peptides don’t stop working either, hormones aren’t drugs. That’s why they’re so effective at what they do. If your body stopped responding then it’s not a peptide or it’s a dud amino chain.

Best analogy I can give is imagine an enormous house (the body) full of switches that all do different things like turn lights on, turn heaters, activate toasters etc but the switches are all genetically linked by finger print to one power circuit that can only be activated by one specific person per circuit and if one switch on that circuit fails in response to its antagonist then they all fail. The person who can activate these has infinite identical clones (the hormone). The person is allowed to go into the house for a specific amount of time and hit as many switches as they can within that time they are present in the house (the MT2 dose).

What you’re suggesting is that there has been too much activation of this switch over a given time duration and only a single bathroom light has stopped working in the whole house (oxytocin inhibition) which given all the other switches on that circuit doing different things is not possible unless you had many other issues going on. If this switch stopped working, there’d be no heating, no computers, no tv and any other things not responding by this switch not working. This is how receptors work. They cannot selective stop activating their process. While their function mechanism are related to different bodily processes, their activation is all the same and they cannot selectively down regulate single processes within the body. Hopefully that makes sense.

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