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

April 28, 2023 By Trudy Scott 8 Comments

MS 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.

Filed Under: Addiction, Amino Acids, DPA/DLPA, Endorphins, Multiple sclerosis Tagged With: alcohol, alcohol addiction, comfort, crying, d-phenylalanine, depression, dl-phenylalanine, DLPA, DPA, emotional pain, endogenous opioid system, endorphin, endorphins, freeze response, GABA, GABA Quickstart online program; Balancing Neurotransmitters: the Fundamentals program for practitioners, multiple sclerosis, numbing, pain, reward, serotonin, trauma, treats, weepiness

What if rewarding, comforting, numbing or distracting behaviors (caused by low endorphins) are causing low motivation, instead of low dopamine?

June 17, 2022 By Trudy Scott 21 Comments

behaviors and low motivation

One of the first things that comes to mind when someone is stuck and not able to get things done is low motivation caused by low catecholamines/low dopamine. But what if numbing, rewarding, comforting and/or distracting behaviors (caused by low endorphins) are holding you back and preventing you from getting things done instead? It may be low endorphins only or may be in conjunction with other neurotransmitter imbalances. The following question and stories from women in the community (and my insights and some of the research) may help you figure it out if any of this applies to you.

I posted a question to this effect on Facebook and there was a great deal of interest. Many folks shared examples of what their distractions are and how they fit into being rewarding and comforting for them. Here is what I posted:

I’m digging into the research connecting low endorphins and low motivation i.e. not being able to get stuff done! We associate low endorphins with physical pain, emotional pain and comfort/reward eating. But in a similar way that emotional eating /comfort food is used to numb us out and reward and comfort us, certain behaviors can do this too. Here are some examples you may relate to:

  • mindless scrolling through Facebook or other social media platforms instead of working on your new project
  • binge watching hours of Netflix shows instead of getting to bed early so you’re productive and motivated (and not distracted)
  • playing video games for days (and not going outdoors, eating proper meals and even bathing)

All of these are also an addiction and we know low endorphins are a factor when it comes to addictions too. There is also an endorphin/dopamine connection hence the motivation aspect I’m looking into.

Can you relate to any of this and has endorphin support (with the amino acid DPA/d-phenylalanine as a supplement) or exercise or LDN (low dose naltrexone) helped with your low endorphin symptoms, your lack of motivation and the distractions you almost create for yourself?

I’d expect the amino acid DLPA (dl-phenylalanine) to help since it works on boosting both low endorphins and low dopamine. I am really curious about DPA because some folks can’t tolerate DLPA or it’s contraindicated.

What are some examples of your distractions and what has helped you?

Sarah: finds looking for split ends and cutting them off very rewarding. Is this a low endorphin behavior?

Omgosh this is so me. I often wonder what the heck is wrong with me. I look around at everything that needs to be done but just get overwhelmed and have no motivation to get it done. I don’t know where to start and then get anxious about it. I will immerse myself looking for split ends in my hair instead, I can spend easily over an hour at a time just sitting there looking for split ends and cutting them off. I find it very rewarding and it’s become such a habit now that if I’m out publicly and see a pesky split end l can’t ignore it and as Í don’t typically carry scissors with me (because that would be weird right?!) so I bite them off. I often think I must look like a nutter! I am always thinking what is wrong with me???!!

Sarah describes a rewarding activity perfectly and I’d suspect endorphin support – using the amino acid DPA (d-phenylalanine) – will likely help her. This behavior is her distraction from getting things done. It’s such a distraction that she cannot ignore it even when in public.

Since she also mentions overwhelm and anxiety I’d also want to explore low GABA physical-type anxiety and low serotonin worry-type anxiety and consider trials of both GABA and tryptophan (or 5-HTP).

There may also be an obsessive element to her distracting behavior and serotonin support (with the above, inositol and possibly NAC) has been shown to help with trichotillomania (recurring habit of pulling one’s hair).

Bonnie: low motivation almost feels physical or like something is missing in my brain. Low endorphins and low dopamine?

I relate to this very much – low motivation almost feels physical or like something is missing in my brain, also an almost inability to focus or organize how to do something or get through the day. I have low motivation with poor focus … but I am also constantly craving reward, comfort, or some kind of boost in energy or pleasure to motivate or energize me – this used to be things like sweets or chocolate but I have been lowering sugar/attempting to quit.

I haven’t tried any supplements mentioned but I’m very interested to learn more as this significantly affects my life.

She says her low motivation feels physical or like something is missing. It’s great she has that awareness and she is spot on – she is missing the specific action of certain neurotransmitters (which can be resolved with amino acid supplementation).

We address neurotransmitter imbalances, one at a time:

  • DPA for low endorphin support to help with the comfort/distraction/reward
  • And tyrosine for dopamine support to help with the inability to focus and needing something to energize her
  • Her inability to focus or organize could be due to the spinning we see with the low GABA type of physical anxiety too

She also shares that she has “feelings of anxiety, hopelessness and self judgment” so low serotonin worry-type anxiety is also likely in the mix.

As always it’s best to trial one at a time and find the ideal dose before trialing the next one. I recommend trialing in the area that causes the most distress. What is great is that addressing all this will make quitting sweets and chocolate easy and with no feelings of deprivation.

Jennifer: video games are hard to break free of / switches to learning languages. Could it be low GABA and an inability to prioritize?

All of the above but video games are especially hard to break free from. Luckily I decided to use those dopamine hits to my advantage and am closing in on a 1000 day Duolingo streak, having made it to the end of the French, Norwegian, and Japanese courses.  Yes I neglect other things, but it’s better than wasting time on video games. I do worry a bit that I would lose interest if my chemistry was fully balanced, but then again there are more important things that I could be doing.

I congratulated her on her language learning and shared that it’s common to switch one addiction for another. For example alcoholics quit drinking and then get addicted to sugar or caffeine unless they address their neurotransmitter imbalances.

Jennifer has been using GABA without much success yet and once she finds the ideal dose it may be the solution or part of the solution for her spinning and inability to prioritize (which she “chalked up to ADHD, but also only became a problem when I got sick.”

Initially I would focus on GABA support (for physical anxiety) more than endorphin support, because she shares she also has all these other low GABA symptoms:

  • acrophobia (which started when she got sick)
  • proctalgia fugax/rectal spasms (recently developed
  • and burning mouth (which was a big part of her mold symptoms)

Keep in mind mold can deplete GABA and other brain chemicals so this does need to be addressed (home/office remediation and healing from the mycotoxin effects), in addition to using amino acid support.

She does check all the boxes on the symptoms questionnaire and it’ll be interesting to see which other amino acids help her with this gaming/language learning challenge. There may well be a low endorphin distraction and reward aspect too.

As always it’s best to trial one amino acid at a time and find the ideal dose before moving on to the next one.

Some of the research

I actually went looking for the research to support what I was seeing in terms of these struggles folks are experiencing i.e. another type of low motivation that is driven by low endorphins and has a numbing, rewarding and addiction aspect.

As mentioned above there is an endorphin/dopamine connection. This paper, Opioids for hedonic experience and dopamine to get ready for it, summarizes it well:

Brain dopamine has been suggested to rather code for the preparatory aspects of behavior, while brain opioids [endorphins] seem to mediate the perception of the hedonic [or pleasant] properties of rewards.

There is an addiction/cravings aspect with each of the neurotransmitter imbalances, including low endorphins.  As mentioned above, these distracting behaviors can also be addicting. And we know low endorphins are a factor when it comes to addictions to drugs, carbs/sweets and behaviors.

DPA destroys the enzyme that breaks down/inhibits endorphins and in essence raises endorphin levels, This paper discusses beta-endorphins and the reward mechanism and how they can induce euphoria, reduce pain and ease addictions and distress: “Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties.” You can read more about DPA here.

With regards to DLPA (which supports low endorphins and low dopamine), a really interesting study identified low endorphins and low catecholamines as a probable cause of PMS (premenstrual syndrome) or PMDD (premenstrual dysphoric disorder) in some women. I blogged about this study and the use of DLPA here.

When it comes to exercise, this study, Opioid Release after High-Intensity Interval Training in Healthy Human Subjects, highlights the effects of different exercise intensities on opioid release, with moderate-intensity exercise being more beneficial for endorphin support. You can read about the impacts of exercise on pain, reward, and emotional processing and “the most commonly adopted theory on physical exercise induced euphoria …the ‘endorphin hypothesis’.”

LDN (low dose naltrexone) is often used in autoimmune conditions and to help with inflammation. This article, The Uses of Low-Dose Naltrexone in Clinical Practice, provides a good overview, and states that “unlike higher doses of naltrexone, LDN acts on β-endorphin receptors to stimulate the release of endorphins in the body.”  I’m not advocating the use of LDN instead of DPA or DLPA, but if you’ve been prescribed LDN you may have observed the endorphin boosting effects.

Brain chemical imbalances to consider when you experience low motivation and can’t get things done

Here is a short summary of brain chemical/neurotransmitter imbalances to consider when you have low motivation and can’t get things done:

  • Low endorphins – the less recognized low endorphin/comfort/distraction type as discussed in this blog
  • Low dopamine/low catecholamines – this is what we think of as the classic low motivation trigger where there is also poor focus, low energy and sometimes curl-up-in bed kind of depression
  • Low serotonin is another less recognized kind of low motivation I’ve blogged about: What if overthinking, fear, anxiety and worry (caused by low serotonin) is holding you back instead of low motivation/low dopamine?
  • Low GABA is also not recognized as a trigger of low motivation but since anxiety can cause inability to prioritize and spinning, this could be a factor too
  • Low blood sugar could also be a factor since it affects focus and energy

Resources if you are new to using the amino acids as supplements

If you are new to using any of the 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).

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, blood sugar control, sugar cravings, self-medicating with alcohol and more.

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.

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). This is a paid online/virtual group program where you get my guidance and community support. There are many moms in the program who are having much success with their kids.

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.

With much appreciation for these women for sharing their stories and allowing me to provide my insights for them and you. We all have much to learn from each other.

Can you relate to any of this and has endorphin support with the amino acid DPA (d-phenylalanine) used as a supplement) helped?

What about exercise or LDN (low dose naltrexone) or DLPA (dl-phenylalanine)?

What are some examples of your distractions or rewarding/comforting/numbing behaviors?

And do you have a mix of neurotransmitter imbalances to address? Which is the most troubling area for you?

If you have questions please share them here too.

Filed Under: Anxiety, Endorphins, GABA, serotonin Tagged With: addiction, binge watching Netflix, catecholamines, comforting, d-phenylalanine, distracting behaviors, dl-phenylalanine, DLPA, DPA, exercise, LDN, low dopamine, low dose naltrexone, low endorphins, low motivation, mindless scrolling, neurotransmitter imbalances, numbing, playing video games, rewarding

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