A different dosing strategy with bremelanotide (PT-141) yields dramatically better results

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Cataceous

Super Moderator
TL;DR: It may be possible to improve results with bremelanotide by taking multiple daily micro-doses.

Like many, I have experimented with bremelanotide at the recommended doses, which range from a few hundred micrograms up to a couple milligrams in one subcutaneous injection. And also like many, I found the results to be disappointing. Libido was not affected, spontaneous erections during the day were infrequent and random, and nighttime erections were prominent and disturbed sleep. Although the effects were not as desired, they seemed quite strong, leading me to question how bremelanotide compares to α-melanocyte-stimulating hormone, aka α-MSH, the hormone it augments. Some rudimentary calculations suggest that standard doses of bremelanotide could be comparable to an increase in α-MSH by as much as two orders of magnitude. That’s somewhat like giving a hypogonadal male 100 mg of testosterone propionate every couple weeks. He may experience some interesting effects, but there’s still some likelihood the overall experience would be poor, and certainly not comparable to TRT.

Credit to @Guided_by_Voices for also experimenting with and recommending lower doses of bremelanotide. I suspect these doses of 100-300 mcg could still be large relative to normal physiology — having very roughly estimated that multiple small daily doses on the order of 10 mcg would provide stimulation comparable to endogenous α-MSH. I set about testing this premise as follows:

Phase 1, days 1-4
Protocol: 20 mcg bremelanotide injected SC at 6 am, 9 am, 12 pm, 3 pm and 6 pm.
Results: Compared to a lackadaisical baseline, libido was high, even excessive and distracting. This began on the first day and continued for the entire phase. The “itch” was nearly constant, and erections came easily in response to sexual ideation or the presence of nubile females. This was again in marked contrast to baseline, where daytime erections were very uncommon without more substantial stimulation. The two negatives during this phase were a reduction in average sleep duration by 30-40 minutes and a slight feeling of overstimulation throughout. In fact these led to a dose reduction and the second phase. This was unfortunate from a data-gathering standpoint, because if the first phase was part of a honeymoon period then the period’s full duration was not established.

Phase 2, days 5-8
Protocol: 10 mcg bremelanotide injected SC at 6 am, 9 am, 12 pm, 3 pm and 6 pm.
Results: There was a rapid return to near-baseline conditions, though sleep still seemed degraded.

Phase 3, days 9-12
Protocol: 15 mcg bremelanotide injected SC at 6 am, 9 am, 12 pm, 3 pm and 6 pm.
Results: Libido improved a small amount. There was improvement in spontaneity of erections, but nothing like during the first phase. Sleep was modestly impaired compared to baseline.

Phase 4, days 13-15
Protocol: 20 mcg bremelanotide injected SC at 6 am, 9 am, 12 pm, 3 pm and 6 pm.
Results: This was an attempt to see if the results of the first phase would reappear after the prolonged exposure to slightly lower doses. They did not. Over these three days libido and sexual function dropped below baseline. Modest sleep impairment continued.

Phase 5, days 16-17
Protocol: no bremelanotide
Results: After this washout period things seemed to return to baseline.

Discussion: These results point to the need for further research. It’s intriguing to consider that it may be possible to obtain much better results with bremelanotide when it is dosed appropriately. While multiple daily injections are going to be unappealing to most, it seems likely that these protocols could be reproduced with correctly dosed troches and buccal delivery. It looks as though four days of the initial protocol was nearing the end of a possible honeymoon period, with most benefits dissipating soon thereafter. If so then the appropriate reset period is yet to be determined. If this period is only a week or two then the protocol is promising. My sense is that even 20 mcg taken five times a day is a pretty high level of stimulation relative to baseline α-MSH activity — thus caution is advised if long-term use is contemplated. It is concerning that prolonged continuous use in this trial seemed to degrade libido and sexual function below baseline, though at least recovery was rapid.

I continue to speculate that this is not the only case where overdosing a peptide obscures its full potential. For example, long-term micro-dosing of oxytocin may yield profound results that are dissimilar to what’s seen with occasional administration of much higher doses.
 
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Willyt

Well-Known Member
The “itch” was nearly constant, and erections came easily in response to sexual ideation or the presence of nubile females.
Quite possibly the best line I've ever read on this forum. A Cat classic. Hemmingway could not have said it better.

You mention a possible "reset" period. Do you think there is a reasonable dose that would provide on-demand libido similar to Viagra / Sildenafil? Let's say once per week. Hell, I would settle for that in a heartbeat. In fact, one could argue that on-demand would be preferable to the distraction of 24/7 libido.
 

Cataceous

Super Moderator
...
You mention a possible "reset" period. Do you think there is a reasonable dose that would provide on-demand libido similar to Viagra / Sildenafil? Let's say once per week. Hell, I would settle for that in a heartbeat. In fact, one could argue that on-demand would be preferable to the distraction of 24/7 libido.
I think there's a chance this would work. To test it one could take several of these small doses in the day or two preceding the event. If this was satisfactory then the next thing would be to try it again in a week. I may run this experiment in time. I'm currently trying to see if there's a discernible effect from isolated small doses, e.g. 20 mcg E3D.
 

Guided_by_Voices

Well-Known Member
Great work! That’s some fantastic citizen-science right there. I think reports like this give us a sense that much more is possible than what is commonly known and that we have only scratched the surface of what can be done. A few comments:

  • Anything that stimulates the sympathetic nervous system is likely to be anti-sexual and the reports of anxiety suggest that may be happening at larger doses.
  • From a practical perspective for others who want to try this, I assume you’re transferring the product to a larger vial and diluting it in order to get down to such small doses. This also argues for brewing a nasal delivery option. That was how it was originally envisioned by Palatin, but the nasal delivery apparently caused unacceptable blood pressure spikes, however those might not be present at smaller doses.
  • Stimulating the melanocortin system in this way seems like it can be thought of as injectable sunshine so it may not be possible to create a dawn-to-dusk affect without some form of down-regulation.
  • While I’m not in the camp that says nature has always done things the best way for our modern situation, nature got it right a very high percentage of the time and most males throughout history would have been hunting and gathering during the day while the nubile females were closer to the campsite, which could explain why the body seems to be optimized for nighttime/early morning sex, and hence why PT-141 seems to work better in that scenario.
  • It would be interesting to combine your approach with TNE or other short-acting forms of T, and/or something that mimics a low-epinephrine state (e.g. doxazosin).
Finally, while I fully support those who have sensibly arrived at an individual benefit from relatively high doses of hormone-related compounds, I think the pathological compulsion to default to high-doses in the body-building world has unfairly tainted some compounds that are considered “harsh” but which might be very net-beneficial at lower doses (and intermittent doses), so there is a lot of experimentation left to be done with both PT-141 other compounds and combinations.
 

Vince

Super Moderator
This is interesting so some men have a little sexual desire so they use bremelanotide to get their libido back. It makes me wonder what makes them to lose it in the first place. I would think it's anxiety. Maybe if you got rid of your anxiety your libido would stay strong?

 

nippy

Active Member
This is interesting so some men have a little sexual desire so they use bremelanotide to get their libido back. It makes me wonder what makes them to lose it in the first place. I would think it's anxiety. Maybe if you got rid of your anxiety your libido would stay strong?

Not anxiety in my case it was ssris
 

Willyt

Well-Known Member
This is interesting so some men have a little sexual desire so they use bremelanotide to get their libido back. It makes me wonder what makes them to lose it in the first place. I would think it's anxiety. Maybe if you got rid of your anxiety your libido would stay strong?

From much of the discussion around here, the problem is multi-faceted, but lack of dopamine is a major factor.
 

Vince

Super Moderator
I do all of those and makes no difference
 

electrify

Member
I think PT-141 (bremelanotide) is quite dangerous, years back in 2018 it sent me into a severe anhedonia episode at 200 mcg. Had to get ECT. I had symptoms basically resembling that of PSSD/PFS just from using it once.

Then I was fine for years until last year, when post covid an alcohol hangover made me relapse into some anhedonia suddenly. And I bet that the PT-141 incident way back somehow made my brain sensitized. I never ever had experienced any anhedonia before it.

And interestingly even today, MIF-1 the *opposite* peptide to PT-141 is actually helpful for my anhedonia issues when cycled.

I don't think melanocortin agonists are safe for dopamine either:


"Here we show that chronic stress decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons due to activation of melanocortin 4 receptors (MC4Rs)"

So literally PT-141 can *lower* dopamine signaling.

On the other hand MIF-1 enhances dopamine:

 

FunkOdyssey

Seeker of Wisdom
I think PT-141 (bremelanotide) is quite dangerous, years back in 2018 it sent me into a severe anhedonia episode at 200 mcg. Had to get ECT. I had symptoms basically resembling that of PSSD/PFS just from using it once.

Then I was fine for years until last year, when post covid an alcohol hangover made me relapse into some anhedonia suddenly. And I bet that the PT-141 incident way back somehow made my brain sensitized. I never ever had experienced any anhedonia before it.

And interestingly even today, MIF-1 the *opposite* peptide to PT-141 is actually helpful for my anhedonia issues when cycled.

I don't think melanocortin agonists are safe for dopamine either:


"Here we show that chronic stress decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons due to activation of melanocortin 4 receptors (MC4Rs)"

So literally PT-141 can *lower* dopamine signaling.

On the other hand MIF-1 enhances dopamine:

I have 60 mg MIF-1 at home and am super excited to try it. Any dosing tips or advice as to what to expect? Any side effects? I was going to try the 10 mg SC daily for five days described here:


What percent improvement with anhedonia do you see with MIF-1, how quick is the onset, and how long is it maintained? I find MIF-1 fascinating as a sort of anti-PT-141, as I had heard rumblings of anhedonic side effects with that compound.
 

brookseth

Member
I have 60 mg MIF-1 at home and am super excited to try it. Any dosing tips or advice as to what to expect? Any side effects? I was going to try the 10 mg SC daily for five days described here:


What percent improvement with anhedonia do you see with MIF-1, how quick is the onset, and how long is it maintained? I find MIF-1 fascinating as a sort of anti-PT-141, as I had heard rumblings of anhedonic side effects with that compound.
I don't think I've even seen MIF-1 on any of the peptide sources I've used before
 

electrify

Member
I have 60 mg MIF-1 at home and am super excited to try it. Any dosing tips or advice as to what to expect? Any side effects? I was going to try the 10 mg SC daily for five days described here:


What percent improvement with anhedonia do you see with MIF-1, how quick is the onset, and how long is it maintained? I find MIF-1 fascinating as a sort of anti-PT-141, as I had heard rumblings of anhedonic side effects with that compound.

Probably better for another thread specifically on MIF-1, I'll make one soon in the Mental Health forum.

But I've done multiple cycles of it and each one is kinda different. The 1st one I did back in May I didn't even feel anything until like the 4th day when suddenly while at an outdoor mall I could feel that "vibe" again. This peak effect subsided but I still felt like my baseline was higher for some time until crashing later on for unrelated reasons.

No side effects. Its an amazing peptide for me. When I first did it though I started the first day at a smaller dose like 5 mg just to make sure no adverse effects. One might think "Oh because PT141 improves libido then MIF1 will lower it" but this is absolutely not true and in fact its a little the opposite because if anhedonia improves, libido improves for me anyways and MIF is dopaminergic after all (But I wouldn't expect it to improve libido for a non-anhedonic/blunted person)

I was feeling horribly numb in late August, I had crashed badly and I was getting very worried and in a dark place. I took MIF-1 and then within 2 hours felt it this last cycle. Suddenly the world was brighter, I felt a huge motivation and hedonic tone boost, could anticipate the future again, feel the sun out. This peak effect went down but I still came out of the cycle "reset" back to a copable point. It has a great effect on lowering stress-too. And while on it, the morning dread of the day (when my symptoms are worst) gets so much better.

It seems like I feel the effects earlier with each cycle. Know that MIF-1 the effects can actually go backwards if you take too much too long (this is mentioned in a study on the oral form), which is why its important to keep the schedule/dosing in accordance with that study. The longest I've done it is 8 mg for 8 days and when I did it on the 8th day things kinda went backward slightly. 5-7 days at most seemed ok for me. 6 days for me is the sweet spot. I believe its because it inhibits alpha-MSH and some is needed.

I did do bloodwork on my alpha-MSH before and at the end of one of my cycles though and it didn't go down that much just from 13 to 9.

Also I think MIF-1 should be used like a 'reset' opportunity. So literally exercise intense every single day you are on a cycle of MIF to make use of that dopamine to try to make it stick. Another thing I found is taking Mucuna Pruriens L-dopa supplement synergises with it (this is also in studies, MIF potentiates L-dopa).

LDN I stop while on MIF to avoid any interactions with opiod system (MIF-1 is kind of like a super LDN, its an opiod antagonist in ways I don't really get) , but afterwards, I notice my LDN endorphin rebound is stronger too for like a few days.

These days Ketamine IV is presented as the 'hot' thing for anhedonia but MIF1 was way way better for me.
 
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