Natural Treatment for Chronic Pain: A Supplement Stronger than Morphine?

“5.3 million adults (11.2 percent) experience chronic pain—that is, they had pain every day for the preceding 3 months. Nearly 40 million adults (17.6 percent) experience severe levels of pain.”  – U.S. Department of Health and Human Services, 2015

Those numbers are horrific, and they are most likely a gross underestimation.  Chronic pain can be debilitating, and is the leading cause of disability in America.  If you are reading this and sitting there in pain, hang in there. Keep reading.

Before we get into the amino acids, I am going to mention that it is monumentally important that chronic pain sufferers make sure they are eating a healthy diet filled with nutrient rich and anti-inflammatory foods — and not just on Sundays.  Garbage in isn’t garbage out, garbage in is inflammation, illness and pain. Start there. I personally do my best to maintain a cross between paleo and ketogenic dietary lifestyle. It has worked well my family.

So, what the heck is enkephalinase?  You could skip this entire paragraph, but I am a huge proponent of people understanding how something works before they decide to take it, so I encourage you to do your best with this complicated information.  You will need to understand this first to understand how and why the amino acid d-phenylalanine works to alleviate chronic pain.

Enkephalinases are enzymes that break down our endogenous enkephalin opioid peptides.  Huh? Ok, let’s break it down a bit. Enkephalins are essentially one of the natural opioids found in the human body, and their receptor sites are opioid receptors. Opioid peptides are short chains of amino acids that actually bind to those opioid receptors on the sensory nerve endings, thereby inhibiting painful sensations.  This means that enkephalins are your natural morphine, except better.  They have an affinity for two (out of the three) main opioid receptors: the mu-opioid receptors (MORs) and the delta-opioid receptors (DORs). 

This is important because the affinity (definition of affinity here is the enkephalin’s ability to bind to the intended target site)  of enkephalins for MORs is nearly identical to morphine, whereas their affinity for DORs is about ten times higher (Fournié-Zaluski, Roques, & Wurm (2012).

That’s right, I said TEN TIMES HIGHER than morphine.  So basically, enkephalinases are the enzymes that break down enkephalins, preventing the human body from benefiting from one of its primary internal pain relief systems that are potentially stronger than drugs like morphine (which of course has many undesirable side effects, as do other narcotics).  

If you need further explanation, feel free to comment below and I will do my best to clarify for you. I try to do my best to be a good science communicator. It’s not easy, but sometimes having the right question helps me provide a clear answer, so feel free to help me out.

Now that we understand enkephalinases, we can look further into how d-phenylalanine works.  D-phenylalanine is an enkephalinase enzyme inhibitor.  Therefore, it helps you to KEEP your enkephalins (those feel-good natural opioids) working in your brain and spinal cord where those pesky pain impulses are transmitted.  You might be concerned that enkephalinase inhibitors might cause all the same side effects of exogenous opioids like morphine, but studies show that their major advantage is that they deliver pain relief that is better than morphine, but without any of the opioid side effects (Ghosh, R., Kadum, V., & Thanawala, V., 2008).  

There are many drugs being developed by pharmaceutical companies that are enkephalinase inhibitors as well that are being termed “DENKIs.” For example, in a study on mice, the enkephalinase inhibitor drug PL265 was highly effective for cancer related bone pain (they also studied its use in combination with drugs that act on cannabinoid receptors and found that the results were even better) (Baamonde et al., 2017).  You can follow more here:  

As a nurse, I am deeply concerned about the current opioid epidemic.  I have high hopes for the development of these drugs and the role they will play in helping people who are suffering from chronic pain that led to opioid dependence.

The bottom line is that enkephalinase inhibitors work so well that it is only a matter of time before the painkiller industry capitalizes on it.  After all, about $300 billion per year is spent on painkillers, and that’s just here in America.

Now, obviously, chronic pain comes in all shapes and sizes.  There are different types of pain. No one person’s pain experience is the same as another’s.  And chronic pain can be caused by a variety of issues. Further, chronic pain leads to a multitude of other issues affecting both mental and physical health.  Even if d-phenylalanine works for you, it is essential not to ignore other problems that may have resulted from suffering for so long. And of course there is the possibility that it will not work for you at all.  There could be issues with absorption, other hormone issues, contraindicative medical history, medication interactions, etc. For instance, people who have been diagnosed with Phenylketonuria (PKU) should never, ever take d-phenylalanine.  That is why I always advise people to speak with their health care provider before taking any supplement or adding any form of therapy into their health regimen. There are many brands of d-phenylalanine (DPA) available for purchase online.  One brand I generally trust is Doctor’s Best. We use many of their supplements in our home.

You can also take DL-Phenylalanine, which is both the D form and the L form of the amino acid phenylalanine.  I will go into more detail on this in the future, but to be brief: L-phenylalanine improves mood, and D-phenylalanine alleviates pain.  Many people experience great benefits with DLPA because chronic pain and depression often go hand in hand.  We like the DLPA made by Life Extension.

I hope this article helped you.  If DPA does not work for you, keep your eyes open for the advancements in other enkephalinase inhibitor drugs.   

Another option for natural pain relief is CBD oil. I will be posting on the use of CBD oil for the treatment of chronic pain in the future.

If you have any questions or comments, or if you feel it is necessary to correct something that you read here, feel free to do so below.  I appreciate any and all of your contributions. If you think this post could help a friend, share it. You might change their life.

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Baamonde, A., González-Rodríguez, S., Fournié-Zaluski, M., Lastraa, A., Menéndez, L., Ouimet, T., Poras, H., & Roques, B. (2017). Synergistic combinations of the dual enkephalinase inhibitor PL265 given orally with various analgesic compounds acting on different targets, in a murine model of cancer-induced bone pain. Scandinavian Journal of Pain. Retrieved from

Fournié-Zaluski, M., Roques, B., & Wurm, M. (2012). Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nature Reviews Drug Discovery, 11, 292-310. Retrieved from

Ghosh, R., Kadum, V., & Thanawala, V. (2008).
Enkephalinase inhibitors: potential agents for the management of pain. Retrieved from

U.S. Department of Health and Human Services. (2015). NIH Analysis Shows Americans are in Pain.  Retrieved from