Men want (and need) amazing sexual intercourse. But erectile dysfunction and low libido are big sex killers.
2 peptides (lots of amino acids strung together) that can help with erectile dysfunction and low libido/desire include Melanotan II and PT-141. They both work via the melanocortin pathway in the brain and nervous system.
The melanocortin system and erectile function
It all starts with POMC (pro-opiomelanocortin), which is mostly synthesized in the anterior pituitary gland. It’s also created in the hypothalamus, brain stem and skin (you’ll see why this is important later on).
POMC is a polyhormone (a long chain of amino acids) that is cut (cleaved) to give rise to at least 8 distinct peptides. 3 important ones include:
- α-MSH, which is produced by neurons in the ventromedial nucleus. It plays am important role in satiety, sexual arousal (and promotes sexual activity) and melanin produced from melanocytes in the skin.
- ACTH, which stimulates the adrenal glands to release cortisol, DHEA and aldosterone.
- β-Endorphin and enkephalin, which are opioid peptides involved in pleasure and euphoria.
α-MSH then binds to melanocortin receptors of which there are 5. These receptors regulate many important physiological functions including food intake, energy homeostasis, and immune function. Melanocortin receptors 3 and 4 are the ones mainly involved in libido and erections.
Both α-MSH and ACTH, known as the melanocortins, play a role in penile erection and sex behavior in animals and humans (R).
α-MSH and ACTH are believed to act downstream from dopamine and oxytocin (R). Meaning, dopamine and oxytocin promote the release of POMC and the creation of α-MSH and ACTH.
Melanotan II, erections and libido
A number of melanocortin agonists have been synthesized to enhance skin pigmentation. Melanotan I is a linear peptide analog of a-MSH, causing tanning. However, it cannot cross the blood brain barrier (R).
Melanotan II, a cyclic non-selective melanocortin receptor agonist, promotes skin tanning and also initiates erections in rats, dogs, and humans (R). This is because it can cross the blood brain barrier.
Here you can see the different structures between melanocortin, α-MSH and ACTH.
The effectiveness of Melanotan II
Melanotan II injections are very effective at promoting erections. Based on 2 clinical trials in men with psychogenic and organic ED injected with Melanotan II at 0.025mg/kg (R):
- Between 63 and 85% of the men got proper erections.
- 63% of the men experienced a significant increase in sexual desire and sex drive.
- The average penile tip rigidity time greater than 80% was 41-45.3 min (R, R). 41 to 45.3 min of a long erection. That’s pretty good!
How to take Melanotan for erections
Melanotan 2 has a half-life of ~33 hours, this allows you to be very flexible with dosing.
According to ChemicalBook, the recommended starting dose is 250mcg every day to help your body acclimatize to the peptide and minimize the side effects. You can continue with this dose indefinitely if you are intending to do a low-dosage regimen (R).
If you want to use a higher dose, whenever you feel comfortable (minimal side effects), up the dose to 500mcg. 500mcg is the most common dosage amount administered by users (R).
In the 2 studies above, they use 0.025mg/kg (e.g. 2.5mg for 100kg guy) subcutaneous injection every 48 hours. The effects might be cumulative, meaning, the 6th dose will usually be better than the 1st (R). This dose is much higher than what is generally recommended (250mcg).
If 250 to 500mcg (0.25-0.5 mg dose) doesn’t do the trick for you, then increase the dose slowly by 250mcg. Don’t take large doses every day, but rather once or twice a week due to the long half-life.
The recommended dose for skin tanning is 0.1mg/kg (R).
Will Melanotan II work even if I have normal testosterone?
This study found that the effects of melanocortins on erection appear to be androgen-dependent because the erectile effect of ACTH was abolished by castration and restored by testosterone replacement (R). It might be that if you’re extremely hypogonadal, with testosterone below 300, then Melanotan II might potentially be less effective.
In this study, they gave 20 men with psychogenic (450ng/dl average testosterone) and organic (362ng/dl average testosterone) ED Melanotan II, and it was equally effective in both groups (R).
Positives that you can expect from Melanotan II
- Spontaneous erections
- Stronger erections (leading to better sexual performance and sexual satisfaction)
- Erections that last longer
- Enhanced orgasm pleasure
- Enhanced libido / sexual motivation
Adverse effects that you can expect from Melanotan II
- Facial flushing
- Reduced appetite (this can be a benefit for weight loss)
- Yawning (R).
- Stretching (R).
- Nausea: the occurrence of this is low (12.9%) at the recommended dose of 0.025mg/kg. In rare cases, vomiting (R).
- Priapism: painful erections for longer than 4 hours without sexual stimulation (R).
Downsides to Melanotan II
- You have to inject it.
- Irritation can take place at the injection site (as with all injections).
- The onset is about 2 hours (which is long especially if you want to do something soon).
- The effects can be a hit or miss (but works most of the time).
- It doesn’t work for everyone (but it works for a high percentage of people to give it a try).
PT-141 (AKA Bremelanotide)
PT-141 is a metabolite of Melanotan II and doesn’t have to be injected. It was originally designed in the United States and approved by the United States Food and Drug Administration for women with hypoactive sexual desire disorder. Later on, it was also marketed to men as an effective tool for ED treatments.
It’s mainly taken intranasally (via nasal spray) since oral absorption is very poor at around 14% (R). Also, the faster it can cross the blood-brain barrier, the faster it can give you results. Taking it intranasally is a good way to shorten the onset time.
Where Melanotan II is a non-selective melanocortin receptor agonist, PT-141 is an agonist at melanocortin receptors MC3-R and MC4-R, which are primarily expressed in the central nervous system (R).
The half-life of PT-141 is only around 2 hours so it can be taken more frequently (R).
The effectiveness (and side effects) of PT-141 is very similar to Melanotan II.
A good starting dose is 7mg and then you can work up from there. This study found that 4mg was ineffective, whereas the effective dose started at 7mg. The highest dose tested was 20mg.
The higher dose you use, the faster the onset and the stronger the effects will be. This counts for both the benefits (erection and desire) and side effects (flushing and nausea).
E.g. The average erection stronger than 60% (measured at the base) increased from 49.4 to 137.7 min for subjects receiving the 7 vs 20 mg PT-141 doses (R).
In short, PT-141 works!
Benefits of PT-141
- Faster onset: the onset of the first erection occurs in approximately 30 min (as opposed to 2 hours for Melanotan 2).
- Doesn’t have to be injected (it’s taken intranasally)
- The half-life is shorter. If you do get any side effects, they don’t last as long. For most people, it lasts 2-6 hours.
- It doesn’t affect nitric oxide or work via the vascular system or affect blood flow, thus it doesn’t affect blood pressure.
Can I take PT-141 with Viagra or Cialis?
Yes, they work synergistically together, and then you can take smaller doses of each.
This study found that the erectile boost induced by co-administration of PT-141 and sildenafil (25 mg sildenafil and 7.5 mg intranasal PT-141) was significantly greater than the improvement elicited by the sildenafil alone (R).
The benefit of combination therapy is that you can use smaller doses of each which limit the side effects. “Co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy.” (R).
Alternative to Melanotan II or PT-141
The dopamine and norepinephrine reuptake inhibitor anti-depressant Bupropion (Wellbutrin) + opioid antagonist naltrexone work via the POMC pathway to reduce appetite, increase energy expenditure and potentially promote sexual function (R).
Boosting POMC (and α-MSH) naturally
Sunlight and sunlight. Bright light acts on the skin and through the eyes into the hypothalamus to produce POMC.
Plus, in the summer, there is more sunlight and the days are longer. This enhances the conversion of thyroid pro-hormone T4 into the active hormone T3. T3 also enhances POMC production.
There are many ED medications and peptide treatments are one of them. Combining low-dose Cialis (5mg) with low-dose PT-141 peptide therapy (7-10mg) is likely best to eliminate most of the side effects.
Additionally, I’d focus on getting lots of sunlight and perhaps add a strong natural anti-oxidation that can also help with erections, namely pycnogenol. Pycnogenol with arginine has been shown to resolve 95% of ED cases in just 3 months. I prefer to use citrulline instead of pycnogenol, but you can use pycnogenol by itself as well.
Check out my ED article series: Erectile dysfunction part 1
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