Neuropeptide Y: The Eternal Enemy of Substance P

Neuropeptides are a class of molecules that allow neurons in the brain to communicate with each other. Many types of neuropeptides, such as dopamine and endorphins, are associated with happiness, pain relief, and reduced stress.

However, not all neuropeptides produced within the human body have such pleasant effects. Some neuropeptides increase stress levels, harm both mental and physical health, and cause inflammation of the skin. One neuropeptide, named Substance P, has been identified as an active cause of the signs of skin aging.

This article will discuss:

What is Substance P?

Substance P is a neuropeptide that transmits signals of pain to the central nervous system. Because the human brain does not contain pain receptors, the release of Substance P into the brain does not cause actual physical pain in the brain. Instead, when substance P enters the brain, it can have a negative impact on a person’s mental state and even trigger depression.

Substance P  has a similarly detrimental relationship with skin. When skin is traumatized, for example by a small cut, Substance P is  released, and pain signals are transmitted. Along with these pain signals, Substance P activates inflammatory triggers throughout the body. Studies have shown that when Substance P is reduced, stress linked to pain also subsides. Thus, when you reduce stress, inflammation also decreases, which in turn slows down the aspects of the aging process caused by inflammation.

Neuropeptide Y is a great weapon against Substance P because they have opposite effects on the body. Neuropeptide Y increases appetite, improves memory, and most importantly, blocks the production of Substance P and thus its inflammatory side-effects.

Substance P and Brain Cells

Substance P is released simultaneously with several amino acids including glutamate and aspartate. Glutamate is a neurotransmitter, present in very small amounts, that aids the brain in learning as well as short and long term memory.

Neurons begin to fire across the synapse in an abnormal way when the amount of glutamate increases. In other words, the release of Substance P, which is accompanied by glutamate, is implicated in a process that can actively disrupts normal brain cell function. At very high concentrations, glutamate can cause excitotoxicity, or cell death. This damaging process can lead to several diseases including Alzheimer’s and ALS. This neuron response to glutamate upon the release of Substance P not only causes the death of cells, but researchers believe it may lead to shrinkage of the brain.

Since any type of common mental stress, whether work, family, or emotional, can trigger the release of Substance P in the brain, there is a great deal of interest in protecting against it. Researchers have found a few possible combatants against Substance P damage:

  1. Excitotoxicity Reducers

    Traditional anti-depressants prescribed by doctors can aid in the reduction of excitotoxicity caused by Substance P. However, other fields of research have found that nutrients like  pycnogenol and acetyl-L carnitine can also help protect the brain.

    Pycnogenol is a natural plant extract that comes from the bark of the Maritime pine found along the southwestern coast of France.


    • Is a powerful antioxidant.
    • Acts as a natural anti-inflammatory.
    • Binds to collagen and elastin.
    • Aids in the production of endothelial nitric oxide, which helps to dilate blood vessels.


    • Helps delay the progression of Alzheimer’s disease.
    • Relieves depression related to senility.
    • Improves memory.
    • Maintains cellular energy and metabolism by assisting in the transport of fat through the cell membrane and into the mitochondria.
  2. Substance P Blockers
    Ongoing research is searching for possible treatments that that will help block Substance P entirely. One possible solution is capsaicin, the ingredient in hot peppers that gives them their spicy taste. It is a natural Substance P blocker that can be taken as a supplement or applied to the skin and is already in commercial use as a topical pain reliever. Capsaicin is also used for inflammatory skin ailments such as eczema, shingles, and acne.
  3. Stress Relievers
    In today’s fast-paced world, everyone is looking for a way to reduce their stress level. Since stress leads to Substance P, inflammation, and possible cell death, this goal takes on additional urgency. While it is nearly impossible to avoid stress completely, steps can be taken to minimize and manage it. A moderate daily or weekly exercise routine is a particularly effective means to reduce stress. It relieves tension and even has the power to achieve an anti-inflammatory effect for skin. Other excellent stress relievers include setting aside time for a regular period of calm and meditation. Many people also find that owning and caring for a pet significantly reduces their stress.

Neuropeptide Y

Many researchers, including Dr. Perricone, believe that Neuropeptide Y the best treatment for reversing the effects of Substance P on both the skin and mind. Dr. Perricone has developed an exclusive line of neuropeptide skin care products, and a Perricone code to go with it, designed to keep Substance P to a minimum and promote more youthful appearance of the skin.

Although Neuropeptide Y is the most abundant neuropeptide in the brain, researchers are looking for ways to boost production because of its wide range treatment possibilities. Neuropeptide Y promotes appetite, regulates body temperature, and controls the release of sex hormones.

In his book The Perricone Promise, Dr. Perricone calls attention to a study of Post Traumatic Stress Disorder (PTSD) that illuminates a particularly fascinating use for Neuropeptide Y. According to the study, U.S. Special Forces soldiers, who are known to experience a higher stress level than regular soldiers, also have a higher level of Neuropeptide Y in their central nervous system.

Even though stress has been proved to significantly reduce levels of Neuropeptide Y, the Special Forces soldiers have shown an amazing bounce back to normal levels post-combat. Regular soldiers, however, showed no such rapid return to normal level and were at a greater risk of developing PTSD. It has also been theorized that their high levels of Neuropeptide Y may allow for a Special Forces soldier’s extreme courage and calmness in combat, leading to Neuropeptide Y’s nickname the “calm and courageous peptide.”

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26 Comments • Please comment below


  1. This insanely ridiculous. Substance P is a critical modulator or various critical processes in the body. It has nothing whatsoever to do with aging or brain function.

    If you decimate levels of substance P, your digestive system will slow down significantly and you will can develop diabetes.

    Substance P is part of the puzzle, but simply supressing it is massively dumb.

  2. pleeeeeeeeeeeeease help me…
    is there anybody knows from where may i buy Neuropeptide Y ? Melanocortin Hormone (MSH) and Leptin ? please if you know any phone number or Email ..please send it to me

  3. Neuropeptide Y has been found by researchers to stimulate the growth of belly fat. There is ongoing research to find a way to BLOCK NEUROPEPTIDE Y in order to reduce belly fat.

  4. [...] Neuropeptides are small protein-like molecules in the body that communicate with other molecules. They play a number of roles within the body. Neuropeptides are released by brain cells acting as either neurotransmitters, chemicals which allow the transmission of signals from one neuron to the next, or hormones, which affect the functions of organs and tissue. [...]

  5. [...] Neuropeptide Y, on the other hand, has the opposite effect of Substance P. When it is released into the brain, it lessens anxiety and depression while increasing appetite and memory ability. Neuropeptide Y also constricts blood vessels and regulates body temperature, blood pressure, and the release of sex hormones. [...]

  6. I read your book and would love to test your products!

  7. I started using Perricone the day I was diagnosed with Inflammatory Breast Cancer. I left the doctors office and went to Nordstroms to buy something to lift my spirits. I passed the Perricone and decided to try it since I would be bald and at least wanted my face to look good. Ha. i loved the products that the rep recommended, and got several complements on my skin. i thought people were just being nice or it was the flush and skin tightening from all the steroids. As my products ran out, I did not repurchase them because of the cost. So now after trying all the “cheaper” skin care products, I am sure that Perricone made a difference. I just bought the Neuropeptide Conformer, Neck cream and Amine face lift. I would love to try the weight management system now to shed the extra pounds I gained during treatment.

  8. I would love to try the neopetide eye contour. I am so desperate to get my eyes to look good. I have dark circles,wrinkles, puffiness and lines. Please help me I cant afford to get surgery. I am 60 years old and would love to look better than I do.

  9. I’m in my 50′s and use the entire neuropeptide line. I once got a severe
    face/eye sunburn,-shortly after I had
    switched to Perricone and you can barely see a wrinkle. I know it was
    Perricone that saved my skin and is keeping those wrinkles from showing up.

    I haven’t tried the new serum and would
    like to try that.

  10. Am using alot of your products-am noticing great results-Who says getting older isn’t beautiful-would love to test YOUR PRODUCTS-Dr. you’re wonderful

  11. I have osteoma cutis. Can your products help me?

  12. Since I first read The Perricone Promise about four years ago,I’ve been using it as something of a skin care reference book both for myself and my conulting clients and friends. I was reading it again last night to gather information for a friend and realized I’d like to understand the positive skin impact of Neuropeptides better…and, frankly, I’d like to see “real-life” comparison of skin WITH neuropeptide application and without it. Please respond. Thank you!

  13. I would love to try this product. My skin gets inflammed easily, and I want to calm down the inflammation while preventing wrinkles.

  14. I would love to try anything that makes my skin better at age 50!

  15. You think everything sounds like existentialism.

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  18. Just wanted to say HI. I found your blog a few days ago on Technorati and have been reading it over the past few days.

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  22. Thanks for posting about this, I would like to read more about this topic.

  23. Sun damage has made my skin look very old, and I am always looking for products that really work.

  24. I love the reseach behind all the products! Since I’m busy I don’t have the time to.

  25. I need to get my skin back in shape!