Multiple sclerosis: low endorphin research and the amino acid DPA (d-phenylalanine) for pain, depression, comfort and trauma support

The research on the role of low endorphins in multiple sclerosis (MS) is exciting because it creates more awareness about a powerful way to offer pain and mood support if you have been diagnosed with this condition. Typically, I ignore the diagnosis when assessing for low levels of neurotransmitters (via a symptoms questionnaire) and have clients do a trial of the amino acid DPA (d-phenylalanine) if they have physical pain symptoms, experience emotional pain symptoms with excessive weepiness/crying and seek comfort via treats/rewarding foods or the numbing effects of alcohol. However, we now know low endorphins play a role in MS (via the endogenous opioid system). By addressing low levels with DPA, you can find some relief of the above pain/depression symptoms and a need for comfort and numbing. DPA may also offer some trauma support if past trauma is a contributing factor (more on all of this below).

Low endorphins play a role in multiple sclerosis: the research

This 2021 paper, Multiple Sclerosis and the Endogenous Opioid System describes MS and the fact that current therapies have limited efficacy: “Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation, neuronal degeneration and demyelinating lesions within the central nervous system. The mechanisms that underlie the pathogenesis and progression of MS are not fully known and current therapies have limited efficacy.”

What is exciting is the identification of the role of the endogenous opioid system and specific opioid peptides in MS:

Preclinical investigations using the murine experimental autoimmune encephalomyelitis (EAE) model of MS, as well as clinical observations in patients with MS, provide converging lines of evidence implicating the endogenous opioid system in the pathogenesis of this disease.

In recent years, it has become increasingly clear that endogenous opioid peptides, binding μ- (MOR), κ- (KOR) and δ-opioid receptors (DOR), function as immunomodulatory molecules within both the immune and nervous systems.

The endogenous opioid system is also well known to play a role in the development of chronic pain and negative affect [i.e. depression], both of which are common comorbidities in MS. As such, dysregulation of the opioid system may be a mechanism that contributes to the pathogenesis of MS and associated symptoms.

Endogenous means internal i.e natural compounds produced by the body and involved in pain relief and mood improvement. This article, Opioid Peptides, describes peptides as compounds that “produce the same effects as the chemicals known as classic alkaloid opiates, which include morphine and heroin.”

It also mentions three major categories of opioid receptors – mu, delta, and kappa – referred to as MOR, DOR and KOR above.

D-phenylalanine for human “endorphin deficiency diseases”

Unfortunately neither of these papers mentions the amino acid DPA (d-phenylalanine) and the fact that it supports endorphin production (by inhibiting the breakdown of endorphins), reducing pain and improving mood – quickly (as in 5-10 minutes).

The use of DPA is not new information as you can read in this paper from 1982 – D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application

A number of compounds have been shown to inhibit the degradation of enkephalins. As expected, these compounds produce naloxone reversible analgesia and potentiate the analgesia produced by enkephalins and by acupuncture.

One of these, D-phenylalanine, is also anti-inflammatory.

D-phenylalanine has proven to be beneficial in many human patients with chronic, intractable pain. It is proposed the enkephalinase inhibitors may be effective in a number of human “endorphin deficiency diseases” such as depression, schizophrenia, convulsive disorders and arthritis.

Such compounds may alleviate other conditions associated with decreased endorphin levels such as opiate withdrawal symptoms.

Prevalence of anxiety/depression and alcohol abuse in MS

As I shared in the recent post addressing low GABA symptoms (anxiety, muscle stiffness, swallowing/voice issues and pain) in multiple sclerosis, anxiety and depression is common in this condition. Alcohol abuse is also high. I shared this paper, The incidence and prevalence of psychiatric disorders in multiple sclerosis: A systematic Review, with the following results:

Among population-based studies, the prevalence of anxiety was 21.9% (and up to 35.0% in some papers), 23.7% for depression …and 14.8% for alcohol abuse.

The above Opioid Peptides paper highlights that the endogenous opioid system may be related to excessive alcohol-drinking behavior. In the work I do with amino acids, I see alcohol used as a way to numb out.

All this supports the fact that the amino acid DPA may help ease symptoms of depression and weepiness seen in MS, and self-medicating with alcohol.

The goal is to use these amino acids instead of needing to use benzodiazepines (covered in the above GABA blog), antidepressants and pain medications.

DPA may help trauma in MS, and the freeze response

This paper, Childhood Trauma in Multiple Sclerosis: A Case-Control Study, suggests an association between childhood trauma and early-life stress and MS:

Although childhood trauma was not associated with the degree of current MS-related disability, patients with MS with histories of physical and/or sexual abuse had significantly higher relapse rates than patients without early-life stress.

DPA may also offer some trauma support if past trauma is a contributing factor. I learned about trauma and the low energy freeze state (a survival mechanism) from Dr. Aimie Apigian, MD, MS, MPH. There is the feeling of numbness and being disconnected when in the freeze state and this eventually becomes the default pattern that the nervous system has been wired into.

Individuals with low endorphins are often in the freeze state and are more emotionally sensitive to everything and because of this they experience much more stress. They also experience a feeling of numbness and feel disconnected. The encouraging news is that the amino acid DPA helps ease the low endorphin symptoms while they are addressing their trauma in other ways, like with somatic work and addressing other biological underpinnings of trauma.

DPA is comforting, helps you feel safe and is often described as feeling like someone just hugged you.

Endorphins and the amino acid DPA (d-phenylalanine) and DLPA (dl-phenylalanine)

If you’re new to endorphins and the amino acid DPA and DLPA here are some blog posts:

• When using the amino acid DPA (d-phenylalanine) I have more resilience and more buffer in the caregiving work I do, and just the oops’s of life
• What is the difference between DPA and DLPA (amino acids) and which one do I use for weepiness, heart-ache, pain and energy?
• Wean off prescription pain medication, improve sleep and reduce emotional eating with DPA (an endorphin-boosting amino acid)
• DPA for weepiness, pain and comfort and reward eating
• How best to use the amino acid DPA for easing heart-ache, weepiness, comfort eating and a compulsive desire for food

Low GABA and low serotonin are common in multiple sclerosis too

Low endorphins are just the tip of the iceberg when it comes to the underlying neurotransmitter imbalances in MS. Low GABA and low serotonin are common too.

As mentioned, I recently blogged about the GABA research and applications of GABA when it comes to multiple sclerosis. Here is that link.

When that blog was published I had a number of questions (see the comments in the above link) from folks asking if GABA could help with similar symptoms in Parkinson’s: swallowing and voice problems, pain and hand spasms. I said yes – if GABA is low, the amino acid GABA will help. As important as your diagnosis is, it’s always the questionnaire/symptoms that help you figure out if it’s worth trialing GABA, DPA or one of the other amino acids.

Both GABA and DPA can help pain symptoms via different mechanisms, so it’s a matter of doing a trial of each amino acid, one at a time and monitoring your response.

Tryptophan and/or 5-HTP may help ease some of the low serotonin worry-type of anxiety, fear, panic attacks, obsessing, low mood and MS-specific pain issues and insomnia.

If you do have more than one imbalance (which is not unusual), you need to figure out which imbalance you have and address that with the relevant amino acids, one at a time. I have clients pick the area that is more problematic for them and start there.

I gathered some of this research while preparing for an interview with the wonderful Dr. Terry Wahls, MD and author of “The Wahls Protocol.” We were both pleasantly surprised to see these endorphin/MS and other neurotransmitter connections.

I really look forward to seeing future research on the use of the amino acids DPA, GABA and tryptophan in MS. And I’d love to be involved in some studies if you are associated with a research facility or do research.

Resources if you are new to using amino acids as supplements

If you are new to using amino acids as supplements, here is the Amino Acids Mood Questionnaire from The Antianxiety Food Solution (you can see all the symptoms of neurotransmitter imbalances, including low GABA, low serotonin and low endorphins).

If you suspect low levels of any of the neurotransmitters and do not yet have my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and using amino acids on your own so you are knowledgeable. And be sure to share it with the practitioner/health team you or your loved one is working with.

There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control, sugar cravings, anxiety and mood issues.

The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the amino acids that I use with my individual clients and those in my group programs. You can find them all in my online store.

If, after reading this blog and my book, you don’t feel comfortable figuring things out on your own (i.e. doing the symptoms questionnaire and respective amino acids trials), a good place to get help is the GABA QuickStart Program (if you have low GABA symptoms too). This is a paid online/virtual group program where you get my guidance and community support.

If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids.

Do you have multiple sclerosis and has the amino acid DPA helped with your low endorphin symptoms: pain, depression, alcohol addiction, comfort and trauma support?

How much has helped and which product do you use?

Do you find opening a capsule of DPA helps more than swallowing the DPA capsule?

Were you surprised that DPA would help so much?

What else has helped your multiple sclerosis symptoms? And have you also addressed low GABA and serotonin with amino acids GABA and tryptophan?

If you have questions and other feedback please share it here too.