Is Low Dose Naltrexone Stimulating Inflammation?

Naltrexone is usually used in 50mg doses as a drug to help heroin or opium addicts, by blocking the effect of such drugs.  By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones (endorphins) that the brain and adrenal glands produce.   Many body tissues have receptors for the endorphins, including virtually every cell of the body’s immune system.

FDA-approved naltrexone, in a low dose (only 3mg), can boost the immune system, helping those with HIV/AIDS, cancer, and autoimmune diseases.  LDN is currently under experimental use for many conditions.  Preliminary results in theory are very encouraging: Naltrexone increases the body’s production of the beta and metenkephalin endorphins and blood tests have indicated that it can double or even triple the activity of natural killer cellsNatural killer cells (also known as NK cells, K cells, and killer cells) are a type of lymphocyte (a white blood cell) and a component of innate immune system. NK cells play a major role in the host-tissue rejection of both tumours and damaged cells.

A wealth of experimental data suggest that T cells are self-restricted or self-regulated. Immune regulators of the NEI Supersystem cannot be too high or too low as the self-regulation is dose-dependent. Artificially suppressing or stimulating the levels has detrimental effects on the immune response.

LDN works by suppressing the immune system. Eventually, to quote, Dr. Ian Malcolm of Jurassic Park:

… the kind of control you’re attempting simply is… it’s not possible. If there is one thing the history of evolution has taught us it’s that life (the immune system) will not be contained. Life (the immune system) breaks free, it expands to new territories and crashes through barriers, painfully, maybe even dangerously, but, uh… well, there it is.

 

AI courseThere are three different methods by which the body fights infections.  While cellular immunity (Th1) directs Natural Killer T-cells and macrophages to attack abnormal cells and microorganisms at sites of infection inside the cells, humoral immunity (Th2) results in the production of antibodies used to neutralize foreign invaders and substances outside of the cells. T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17 (IL-17). They are developmentally distinct from Th1 and Th2 cells. Th17 cells are associated with autoimmune disease. The Th17 effector cells are triggered by IL-6 and TGF beta or IL-23 and IL-1β.

woman on fire

Are you on fire?

In many cases, all three arms of the immune system fight an infection.  At other times, only one is predominantly needed to control an infection.  A healthy immune system is both balanced and dynamic: it should be balanced between Th1 and Th2 and Th17 activity, switching back and forth between the three as needed.  This allows for a quick eradication of a threat and then a return to balance before responding to the next threat.  The inability to respond adequately with a Th1 response can result in chronic infection and cancer; an overactive Th2 response can contribute to allergies, various degenerative syndromes and autoimmune disease is a consequence of a Th17 response.  In autoimmune illnesses, all of the arms of the immune system are active, creating the inflammation and tissue injury in autoimmune disease.

A failure of the Th1 arm of the immune system and an overactive Th2 arm is implicated in a wide variety of chronic illnesses.  These include autoimmunity, CFS, candidiasis, multiple allergies, multiple chemical sensitivities (MCS), viral hepatitis, Hashimoto’s thyroiditis, cancer and other illnesses.  If these three arms of the immune system could be balanced by stimulating Th1 and decreasing Th2, then many of the symptoms associated with these chronic illnesses would diminish or disappear and we would have found the answer to immune restoration and balance or the equivalent of a cure. Unfortunately, where Th1 and Th2 leaves off, Th17 takes over and most treatments don’t take account of Th17. This is definitely the case for Low Dose Naltrexone (LDN).

While correct in theory, it is incorrect in terms of how the immune system functions. Most view the immune system only in terms of Th1, Th2 and rarely if ever include Th17. Cytokines, chemokines, neurotransmitters and hormones that control the Th1, Th2 and Th17 responses direct the immune response. Hormones are always thought of as only involved in sex and reproduction. However, progesterone, estriol and testosterone are immune suppressive. While two of the estrogens – estrone, and estradiol are immune stimulating. Not to mention the inflammatory hormone Etiocholanolone, which is rarely tested for and drives the Th17 response. Yes, Etiocholanolone is a hormone made from DHEA that drives Th17. All too often low DHEA is thought to be an adrenal problem, when it is actually being converted into etiocholanolone. Neurotransmitters work both to alert the immune system to an area of the body in distress and signal the immune system that the work is over. Again, rarely tested for. Collectively, this is known as the NEI Supersystem.

NEI supersystem

Th1 cells secrete INF-gamma and IL-2, which activate macrophages and cytotoxic T-cells to kill intracellular organisms; Type Th2 cells secrete IL-4, IL-5, and IL-10, which help B cells to secrete protective antibodies. Th17 cells are triggered by IL-6, IL-17, IL-1β, and IL-23 to clear out damaged tissue damaged by autoimmunity or the uterine lining during menstrual cycles or miscarriages.

I recommend calming and quieting the immune system so it can respond appropriately when needed.

Low Dose Naltrexone works by stimulating suppression of the immune response. When immune suppression occurs, those using LDN don’t feel the pain and discomfort with their immune system being suppressed. It’s a win/win situation. The patient isn’t feeling any pain and the Doctor isn’t getting asked by the patient isn’t feeling any better.

Low Dose Naltrexone works by Stimulating Suppression of the Immune system.

Parsing the Benefits of LDN

It’s worth mentioning LDN “stimulates” suppression. Proponents will parse it to “LDN works by stimulating an immune response.” Conveniently leaving off the end of the statement. “LDN works by stimulating an immune response to calm down or stop inflammatory immune responses (AKA – suppression).” Technically they are correct. By convention today, there is an agreement to only look at one aspect when publishing medical studies. They publish a study showing LDN works by stimulating a immune response. End of story. They assume those in the know reading this study would understand the consequences of this “stimulation.” However, the average person or Doctor(s)  (Don’t assume Doctors know much about the immune system) doesn’t know or care how it works. They only want to know will it give relief. Consequences be damned.

Fact: Inflammation is an immune response.

In answer to “a common anecdotal report is that people don’t get the common cold as much. Technically, they are correct. But??? They are equating not getting sick to a normal healthy immune system. After seeing the results from the Stimulated Cytokine lab test. I realized the reason they not getting sick is because their immune system is so fatigued or suppressed that no symptoms are generated. They come to my office reporting they feel like crap but they “never get sick”. “How can I be so healthy but feel so bad?”

Those using LDN usually report a blissful period where their inflammation (see fact above) subsides. Usually for a four to six month period; then other components of the immune system become overstimulated without the feedback control from the components that LDN suppressed. They have had half a year for smoldering inflammation doing further damage to their body. The good news is they will not feel it. The bad news is they will now seek help from a Doctor that will recommend immune stimulating supplements. Exacerbating the condition and the damage being done.

Alternative / Functional treatments focus on Stimulating the Immune Response.

Naltrexone Treatment by Immune Stimulation

A possible line of therapy being investigated by the medical community is to reintroduce some of these cytokines to people who have severe immune deficiencies.  This approach can be tricky because large amounts of any particular cytokine can have serious side-effects. This approach fails to recognize fatigued cells that are too exhausted to produce immune cells cause the deficiencies. How is stimulating the immune system beneficial?

The immune system by design provides your body with numerous layers of protection with a multiple backups. The system is set up so that if the responsible system is unable to handle the job and bigger, stronger system is recruited. Thus, if the basic Th1 or Th2 systems are fatigued to respond, the Th17 system is alerted to come in and take care of business.

Naltrexone t cell

 

Naltrexone Stimulation of the Immune System

Naltrexone treatment increases NK cell cytolytic activity and cytokine production in the spleen. Chronic naltrexone administration enhanced both basal and the cytokine-modulated NK cell cytolytic activity and IFN-γ production.

Naltrexone treatment increased the production of IL-2, IL-4, IL-6, and IL-18 and the basal and cytokine-activated NK cell cytolytic activity and IFN-γ production in the splenocytes. Chronic administration of naltrexone stimulates the production of cytokines and NK cell cytolytic activity in splenocytes. Naltrexone does not block IL-1β.,

Naltrexone Stimulation of NK cells

Natural killer cells are a T cells that share properties of both T cells and natural killer cells. NK cells can also produce many different cytokines as well as chemokines.  T cells are inherently cross-reactive, and this versatility and specificity is a hallmarks of adaptive immunity. T cells are prone to be autoreactive and thus able to induce autoimmunity.  Increasing the NK cell avtivity results in enhanced alloreactivity  and autoimmunity.

T-cell recognition is essential for protection against microbial pathogens, recognition of self-peptides by T cells that have escaped negative selection in the thymus can lead to autoimmune disease. A disregulated T cell interaction can initiate autoimmunity. Thus, antigen recognition by T cells must be tightly regulated in order to ensure protection against pathogens and tumors, avoiding activation of self-reactive T cells.

NK cell cytolytic activity has been shown to be activated by interferon-γ (IFN-γ), which has a number of opioid-like effects. Various other cytokines are also known to increase NK cell cytolytic activity and lymphocyte proliferation. Of these cytokines, interleukin (IL)-2, IL-12, and IL-18 stimulate NK cell cytolytic activity. Other cytokines like IL-4 and IL-6 are known to regulate NK cell proliferation and differentiation. Cytokines IFN-γ, IL-2, IL-4, IL-6, IL-12, and IL-18 have been shown to also affect the function of other immune cell populations in splenocytes.

Alcohol consumption is also known to suppress Lectin-induced production of various cytokines, including IL-2, IL-6, and IL-4 from splenocytes. Initially, Naltrexone therapy counteracts the suppressive effects of alcohol on NK cell cytolytic activity for the first couple of weeks allowing increase production of IL-2, IL-6, and IL-4 from splenocytes.

Naltrexone Stimulation of Chemokines

Naltrexone is an opioid antagonist when administered the first couple of weeks, but shows δ-opioid-like activity following chronic long-term administration. With constant use naltrexone selectively promotes the δ-opioid receptor activity and enhances NK cell cytolytic activity response to β-endorphin. Naltrexone disrupts the feedback control that results in enhanced NK cell cytolytic response.

Bone broth cytokinesThe chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, induce an intense fever. The central action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6), has been implicated in the mechanism underlying the pathogenesis of fever along with etiocholanolone. This is potentiated by the presence of lipopolysaccharide.

Naltrexone increases in neutrophil-associated myeloperoxidase activity and chemokine mRNA expression, including macrophage inflammatory protein-1 alpha (MIP-1α) and -2 (MIP-2).

LDN could enhance both morphological and functional maturation of bone marrow dendritic cells (BMDCs). Their main function is to process antigen material and present it to the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. LDN markedly up-regulates expression of key surface molecules, which will trigger a chain of cell mediated responses. In addition to this, LDN also markedly upregulate production of cytokines IL-12 and TNF-α, which will trigger Th1 cell response.

Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response.

Interleukin (IL-1), tumor necrosis factor α (TNFα), IL-3, and IL-6 collaborate with GM-CSF. β-endorphin increased the number of macrophage colonies when bone marrow cells were cultured in the presence of GM-CSF plus lipopolysaccharide (LPS). Naloxone and Naltrexone, an antagonist of endorphins for opioid-receptors, completely abolishes the effect of β-endorphin. Both Naloxone and Naltrexone stimulates suppression of the production of GM-CSF.

Naltrexone Stimulates Suppression of Cytokines

Naltrexone and naloxone stimulates suppression of microglia activation, reduces the production of re- active oxygen species and other potentially neuroexcitatory and neurotoxic chemicals.

Naltrexone causes a significant decrease of IL-12 and IL-10 production by macrophages. With chronic dosages, IL-12 remaines significantly suppressed. As for IL-10, naltrexone seems to partially prevent the IL-10 reduction. Naltrexone significantly inhibited the production of TNF-alpha induced by LPS.

Naltrexone Stimulates Suppression of Chemokines

The anti-inflammatory effect of opioid antagonists naltrexone and naloxone also extend to the periphery, as evidenced by stimulates suppression of TNF-alpha, MCP-1, and other inflammatory agents in peripheral macrophages.

Stimulated Cytokine Testing on LDN Patient

The lab results shown below are from a woman using Naltrexone therapy. Despite feeling better on the Autoimmune protocol recommended to her, she stopped doing the Autoimmune protocol after deciding to start Naltrexone.

After starting the Naltrexone, things changed drastically. A lot of the old symptoms reappeared and some got worse. She was experiencing severe pain on right side of body from neck and shoulder down to her hip and ankle. Her low back was really bad, and she could hardly walk being constantly achy and sore. She could not get out of bed, and had diarrhea a couple of times a week. When she gets a flair up – it can occur for no reason and they are lasting longer. Unfortunately, she failed to mention the LDN therapy.

Naltrexone Induced Ischemia

Ischemia is a restriction in blood supply to tissues causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue.

Neurons that demonstrate particular vulnerability to ischemic challenges have been termed “selectively vulnerable neurons”.  Of the entire brain, the neurons of the hippocampus are the most vulnerable.

This would result in problems with endocrine system, (thyroid, hormone, adrenal) as the blood-brain-barrier would be further compromised as a results of compromised (ischemic) blood flow to the pituitary, hypothalamus and hippocampus.

Exogenous ligands, i.e. naltrexone, that activate the δ receptors mimic the phenomenon known as ischemic preconditioning. Ischemia preconditioning/hypoxia preconditioning (IPC/HPC) is a phenomenon whereby brief ischemia/hypoxia “preconditions” cells and increases cellular resistance against subsequent lethal ischemia/hypoxia injury. Short periods of transient ischemia are induced the downstream tissues are robustly protected. This serves as a protective mechanism to restrict blood flow around an inflamed area of the body to prevent inflammation or microbes from spreading throughout the body. It is intended for short periods until the immune system is able to control the situation. If longer-duration interruption of the blood supply is then effected, ischemic damage from the lack of oxygen, glucose and elimination of cellular waste products occurs. Naltrexone and naloxone with δ activity mimic this effect.

Naltrexone Reduces Liver Enzymes

Naltrexone significantly reduces the elevation of serum glutamate-oxalacetate transaminase (SGOT) and glutamate-pyruvate transaminase (SGPT) (as index of hepatic function) induced by LPS.

Is LDN right for you?

The comments and posts you are reading saying how good they feel is because their immune status matches how LDN supports their imbalanced cytokines and chemokines. LDN works only for those with the correct immune status that Naltrexone or Naloxone supports.

If you do not match that cytokine or chemokine profile. LDN will only increase the damage and further disrupt your body’s ability to control the immune system. If you are using LDN and not satisfied with the way you are feeling. It is probably not right for you.

It is possible to get the immune system back under control. It is not a quick process but steady progress is experienced giving you the faith and confidence you need to know you did the right thing. One should never guess when it come to the immune system. Call today to have your Stimulated Cytokines and NEI Supersystem tested.

52 thoughts on “Is Low Dose Naltrexone Stimulating Inflammation?

  1. Hi David,
    Fascinating stuff. I have theorized the the low dose naltrexone functions as a means to limit endorphins (natural opioid type substances) and function as a negative feedback system to increase endorphin production and help with pain and joint healing. From your research is there any feasibility in this consideration?

    • In short, Low dose Naltrexone induces a negative feedback in other words – an Iatrogenic Acquired Immune Deficiency Syndrome (iAIDS). This does not suppress cytokines or chemokines while allowing the inflammation and damage to continue silently. The only tool the Medical community has is immune suppression. The Alternative and Function community recommend immune stimulation. I recommend quieting the immune system through supplements for the un-regulated Neuro-Endo-Immune Supersystem components.
      This was confusing until I applied Major’s 1930s publications on Vasomotor control and the NEI Supersystem.

      • Hello, nice to meet you; with all due respect, I would like you to attach the data source of the concepts you’ve commented on this page. I was trying to find them in PubMed, for example, and I do not see anything that you mention, including the issue of naltrexone inducing ischemia. Perhaps it’s still unclear the right dose to prevent the development of cancer stimulated by naltrexone, a possible terrible side effect, an issue to consider. Your concepts are theoretically interesting, but it’s essential to have a solid proof behind your statements, if not, they are minor compared with the results of Dr. Zagon with their experiments or Dr. Bihari, with their patients.
        I’d like to keep in touch with you and discuss, if you want, other topics related to health. I like your vision.

        Best regards
        Dr. Fridman

      • Hello Dr. Fridman, All of my blogs post are referenced to the point where I can defend them should they be questioned. In my early blogging, I did post the references supporting the post. Then I found the posts, graphics and references were being used by others without giving credit. The references will be a part of an instructional series I am currently writing. Dr. Dave

      • I had very bad experience with LDN. Started on it as a trial before giving it to autistic daughter. After a month since didn’t see any adverse effects I started it to my daughter as well.
        Within two months we both had such stimulated immune system, health just plummeted.
        This was in 2012. Still gastritis flares up with lots of substances. Asthma increased, caught every illness. Thyroid dysfunction. Still reeling from the effects in 2017.

      • Hi Kylie,
        I am sorry to learn of your LDN experience. They make it sound so wonderful. Your experience is not isolated.

        The immune system has a memory. Drugs like LDN or Methotrexate alter the control of the immune system memory. So instead of be Peaceful Warrior with a certain lifespan, immune cells become zombies that don’t die. Thus the constant immune over-stimulation. There is hope to get this reversed.

        It required rebalancing the NEI Supersystem. I would recommend specific lab tests depending on how your system is behaving. Then from the results, specific supplementation could be used to get your system reset. Give me a call 530-615-4083 or email me at dpeterson@stlwa.com.

        Dr. Dave

      • Dr. Peterson,

        Hello. I have started LDN last week for my ankylosing spondilytis and my health improved in a week. After reading your article, I stopped using it and some of my pain and inflammation came back. Would you recommend to take it again? You recommend taking supplements to regulate the immune system. Can you tell which one? and Where to get them? Thank you very much. Regards. Bertrand

      • Hi Bertrand,
        It depends on if you have real ankylosing spondylitis or someone needed a name for your back pain. I recently had someone diagnosed with ankylosing spondylitis because they had Klebsiella in a stool test. That is definitely NOT ankylosing spondylitis. I’ve recently been looking at epidural varices as a source of back pain. This would be congruent with Multiple Organ Dysfunction Syndrome (MODS).

        As I’m writing this, I let the frying pan get too hot. It set off the annoying Smoke Alarm, so I took out the batteries. The annoying alarm (pain and inflammation) stopped. But the smoke hadn’t cleared when I put the batteries back in. Guess what, The annoying alarm (pain and inflammation) started back up. Do I take the chance and take the batteries back out?

        LDN works by suppressing the immune system. Eventually, to quote, Dr. Ian Malcolm of Jurassic Park: … the kind of control you’re attempting simply is… it’s not possible. If there is one thing the history of evolution has taught us it’s that life (the immune system) will not be contained. Life (the immune system) breaks free, it expands to new territories and crashes through barriers, painfully, maybe even dangerously, but, uh… well, there it is.

        There is not a one size fits all regimen. I don’t know your unique circumstances, so I can not say which would be best for you. You can contact my office, where we can design a program specific to your needs.

  2. Pingback: What is the NEI Supersystem? | Living Wellness

  3. i found your article very confusing to read until i got to the end where you seemed to be saying that ‘the woman’ was hurt by taking ldn…but how could you have known it was the ldn that hurt her since she stopped her AIP diet just before starting ldn?

    if you have valid concerns about the safety of ldn, please write at least part of the piece in language that a lay person can understand. as for the scientific language, if you want that to be seen as credible, you HAVE to provide valid sources. saying that you have it as part of another post…or that it will be forthcoming with an instructional series you’re currently writing makes you look discreditable.

    since a year has passed since you originally wrote this, i wonder if you still stand by this. have you read the new ldn book that came out in february? published by chelsea green. the ldn book.

    • Of course this article was confusing because it was not the typical pro-LDN info posted on the internet.
      I wrote this with out any agenda or preconceived notion following the social media meme. I wrote this after looking at both sides of the LDN scientific literature plus Stimulated Cytokine and NEI Supersystem lab tests.
      I would have to ask if Chelsea Green has read my article. I would also have to ask if she has done any of the lab testing mentioned above. You can prove anything with science as long as you do not quote too much of it.

      • Dr. Peterson,
        Wanted to let you know that Chelsea Green is not a person — this is the name of the publishing co.
        You might find “The LDN Book” very interesting, as it is not (in my opinion) written as much for the layperson, more for scientists, and dr.s who are studying LDN for various ailments. (There are 30 pages of footnotes at the end of the book). The various sections are written by many doctors and/or researchers based on their own studies and experience in the use of low-dose naltrexone.
        As a layperson, I can only say that LDN is the only thing that has ended my long-term agonizing arthritic pain (e.g. inflammation). I don’t know why it works, only that it does in my case.

  4. I found your article very difficult to follow. I confess that it is partly because I lack your scientific training. However your title says it is about LDN and yet you often refer to Naltrexone which generally refers to the full dose of 50mg. This seems to be confirmed by your at times mentioning Naloxone side by side. 50mg and LDN have very different effects and it’s hard to see the point of switching back and forth in your article.

    I agree that without footnotes your article is basically a series of opinions with no backing and it would require the reader to research each point. References are standard practice in scientific writing and it’s odd that they produced a problem for you.

    I’m sorry that these issues have clouded for me what might have been an interesting article. It is certainly true based on my experience that LDN benefits some people a lot, some just enough to be worth taking and others do not benefit. We do need to understand why that is and I hope you will consider re-working the article and backing up your statements.

    • As you wrote, “LDN benefits some people a lot, some just enough to be worth taking and others do not benefit.” What defines ‘benefits’.
      I have to chuckle at the splitting of hairs in your comments. I refer to the effects of “Naloxone and Naltrexone” in the post because I have had patients doing both. The point is they induce an Iatrogenic Acquired Immune Deficiency Syndrome (iAIDS). Suppress the immune system – Suppress the symptoms and woohoo! People claim they feel better. Really? If an acquired immune deficiency would make those with AIDS the healthiest people alive.
      It wouldn’t surprise me to see someone take this to the next level like those inoculating themselves with parasites or fecal transplants. Why not suppress the immune system naturally by swapping spit with someone with AIDS since suppressing the immune system is such a good thing.
      Why do some people feel worse? Because the Naltrexone suppresses the part of the immune system, leaving other parts unchecked.
      A lot of time was put into this. How would you propose I re-work this. Maybe by parroting all the proponents of LDN? It seems people want a Doctor that is an independent thinker as long as they think like everybody else. How dare I come up with my own opinion. You can buy my book when it is published for the references.

      • OK please just clarify what dosage or range of dosage of Naltrexone you were using. I have never heard of using Naloxone in a low dose like LDN which is why I wondered if you were using 50mg Naltrexone.

      • I’m not using or recommending Naltrexone or Naloxone. Unfortunately, many patients have drank the koolaid and are using these drugs. You can dance around this six ways from Sunday. But the bottom line is that these drugs work by inducing an iatrogenic Acquired Immune Deficiency Syndrome (iAIDS). The same as cortisone shots. I drank the “progesterone koolaid” years ago screwing up my health. Read a book by Dr. Lee. Said it was good for men too. Fell into the Autoimmune Pitfalls listed in my autoimmune course. http://masteringthegut.com/home-page/free-autoimmune-disease-online-education-seriesu/

  5. Thank you for your response and I apologize for saying you were using Naltrexone and Naloxone. My question should have been “please just clarify what dosage or range of dosage of Naltrexone you are talking about in your article. I have never heard of using Naloxone in a low dose like LDN which is why I wondered if you were talking about 50mg Naltrexone.”

    • Only aficionados of drugs would know the proper vernacular. When people say they are taking “armour” or “lipitor” there is no hidden meaning of dosage. Drugs work through certain mechanisms regardless of the dosages. These mechanisms cause an effect in the body. These effects are more pronounced in high dosages and less pronounced in low dosages. Regardless of the dosage, the mechanisms are the same. We have been taught to call adverse effects of drugs – “Side Effects”. However, there is no such thing as “Side Effects” There are only desired and undesired effects. Many drugs are misused by playing around with the dosages. My post was discussing the mechanisms of the Naltrexone. Not the dosages.

  6. Excuse my bluntness David Peterson, but it’s my observation that you have absolutely no idea what you are talking about concerning the mechanism of LDN – Low Dose Naltrexone.
    A little knowledge is a dangerous thing and so are articles like this one that are filled with misinformation!
    What a detriment this could be to many patients who need to know there is an alternative out there for them.
    If you asked me the question: “How would you propose I re-work this.” My reply would be: Don’t! Just deposit it in the trash where it belongs!
    I don’t see that happening with this comment from you: “You can buy my book when it is published for the references.” No thanks – I’ll pass!
    http://www.ldnresearchtrust.org/sites/default/files/LDN_Mechanism_Of_Action_Pradeep_Chopra_MD.pdf
    Information from Medical Experts WITH references – It’s a BOOK – not a person!
    http://www.ldn2016.com/ldn-book
    http://www.lowdosenaltrexone.org/

    • page from Pradeep Chopra, MD pdf One should read the pages used to support their position.
      “LDN blocks release of proinflammatory cytokines including Interleukins IL6 and IL12, TNFα, NF-ĸB.” Blocking release of pro-inflammatory cytokines would suppress the immune response. The kicker is that chronic use of “LDN” has the reverse effect. Most patients coming to my office are chronic users wondering why it isn’t working anymore. They exhausted from looking for something else to blame because it couldn’t be the LDN. Combine it with bone broth stimulating TH17 and they are a mess.
      “Shift of immune response from TH2 to TH1” Th1-type cytokines tend to produce the proinflammatory responses responsible for killing microbes, intracellular parasites and for perpetuating autoimmune responses. http://www.bmj.com/content/321/7258/424.1

      No mention what so ever of TH17 by Dr. Chopra. No mention of how bacterial toxins from bacteria like staph are impervious to the effects of LDN. Oh by the way Brian, Dr. Chopra does not use the preferred designation of LDN and mentions Naloxone. Yes, Phyllis a little knowledge is a dangerous thing. If you are reading articles on the immune system and they are not mentioning TH17 in the mix, look for another article.

  7. Hello,

    Interesting article, although very confusing and without supporting citations. And no, it’s not because it ia not a pro-LDN article. It’s just very poorly written.

    “Blocking release of pro-inflammatory cytokines would suppress the immune response. The kicker is that chronic use of “LDN” has the reverse effect.” Any reference to this statement?

    You seem quite confused. First you say it stimulates immune system, then you say it suppresses it. Then you say it first stimulates, then suppresses. There’s no basis for any of those claims.

    There’s some evidence that it enhances immune system in HIV patients
    http://www.lowdosenaltrexone.org/ldn_and_hiv.htm

    https://www.google.lt/url?sa=t&source=web&rct=j&url=http://www.academicjournals.org/journal/JAHR/article-full-text-pdf/8728EFA2976&ved=0ahUKEwjTwaC-7anNAhUDJpoKHVxRAm8QFgg1MAc&usg=AFQjCNEa28TROOZtJg3c1zcqL9ZveXmr6Q&sig2=NRvJ2v6FBuiB7FQlSoayvQ

    In the end, i think it’s way more complicated than you think.
    Blocking release of proinflammatory cytokines does not necessarily mean it suppresses immune system, and it certainly is not the case with LDN since we see lower infection rates in HIV patients.

    I would be really interested to read your ideas in a new, well referenced and backed up article, without statements out of nowhere.

  8. Thank you – I found this a really interesting article. Am I right then that people with auto-immune illnesses should not supplement with either LDN or DHEA? I have celiac disease but also late stage Lyme, so it is very difficult to know how best to try to balance things. I find a very small dose of DHEA tremendously helpful and develop joint pains quite severely if I stop taking it. I had been considering LDN but am now not entirely clear whether it is likely to help or hinder an over-active Th17 response. Best wishes, Carolyn

    • If you are feeling better with DHEA, I have to ask why. To understand this, it requires understanding the complete hormone picture. Unlike the current memes in healthcare where hormones and the immune system are compartmentalized and individualized. DHEA stands alone in their view. The immune system is viewed in terms of Th1 and Th2. When I view hormones, the immune system and neurotransmitter, I do so through the lens of the Neuro-Endo-Immune Supersystem. Knowing no part of the body can be understood separate from the whole. I started off in the low DHEA meme. Then I looked at a hormone chart. What are these other hormones? We don’t look at them because the author of the course doesn’t. It’s not advised to stray from the cliche, because if it was important the author would have covered it.
      DHEA converts into either a pro-inflammatory hormone or androgens which are immunosuppressive. The pro-inflammatory hormone stimulates Th1/Th17 pathways. Since you feel better with this, I would suspect a Th2 dominance. The only way to know your immune status is to do a Stimulated Cytokine panel. Test don’t guess.
      The Lyme Disease diagnosis has become a catchall diagnosis. I would say you are suffering from Cytokine-Induced Sickness Disease. Read this article for more information. http://www.wellnessalternatives-stl.com/confused-lyme-disease/ Please contact my office for more information. Dr. Dave

  9. hello, is it possible that naltrexone at 50mg doses, can cause permanent receptor blockage? or permanent brain damage? im very worried at what it may have done to me, thanks for any help

    • I’ve always question about the receptor blockage whether it is permanent or temporary. Temporary is not the usual, it’ll go away in a couple of weeks. It’s more a matter years because of the immune memory cells. They have a minimum of a two year lifespan. Certain bacteria have the ability to make them immortal.
      Think how sensitive the immune system is. Those with peanut allergies have only to touch a peanut to have a reaction. We don’t know what we’re doing when it comes to immune system modulation as is the case with LDN. Yes, most do feel better initially on LDN. It usually take about three to six months for the persons immune system to adjust to the modulation. Then because it was artificially chemically altered; all the feedback controls are obliterated. The only way to know what your immune system is doing is to do a Stimulated Cytokine Profile and Neurotransmitter lab test.

      • this scares me, let me explain my issue. i used naltrexone 50mg’s for a few weeks because of my pain pill addiction. during this time i was having ongoing steroid (prednisone) treatment for Autoimmune hepatitis – liver desease. once i stopped the naltrexone i noticed prednisone stopped working! im worried naltrexone has permanently damaged me or boosted my immune system and no treatment will work and ill need a liver transplant? what if i do, and no pain meds work? i will be in agony!

      • thank you,i understand you cant recommend anything, however i have seen doctors who have told me it cannot permanently blockade. even so, if i had to have pain relief are there alternatives to opiates in hospital? many thanks

  10. I have no actual diagnosis..had the “usual suspects” ruled out by numerous GP’s so was left to self diagnose ChronicFatigue..my main symptom being mostly morning exhaustion and exercise intolerance. Used LDN for six months with great results, then slowly started sliding back to almost pre LDN currently. Stopped LDN altogether about 4 weeks ago. No worse or better. How does one know what condition one has if GP’s just say “exercise more “etc?..I now am again pre diabetic and hypertensive because I cannot exercise enough.

    • Rhonda, The first thins is to stop chasing for the Savior Diagnosis. Secondly, “pre-diabetic” is insulin resistance and is very reversible. The “pre-diabetic” meme is conditioning your mind to accept their cash cow diagnosis, making you a life-long source of revenue. Plus, they get to up-sell you to addition conditions, which you have already been conditioned to accept. The same goes for the hypertensive, which just happens to occur with the “insulin resistance”.
      The reason you cannot exercise is because your red blood cells get sticky with “insulin resistance” making them unable to deliver oxygen to your muscles. Watch this video: https://youtu.be/YRmmFn5BrCY

    • Rhonda, Unfortunately the LDN is a Milgram’s Law treatment.
      Milligram’s Law * The Market place will blindly believe the words of an expert even if it is detrimental to themselves. I have personal experience with this as you can see on my website. http://www.stlwa.com
      As stated in the blog post. You felt better because it suppressed your immune system. To paraphrase Dr. Ian Malcolm (Jurassic Park): Rhonda, the kind of control LDN proponents are attempting simply is… it’s not possible. If there is one thing the history of evolution has taught us it’s that the immune system will not be contained. The immune system breaks free, it expands to new territories and crashes through barriers, painfully, maybe even dangerously, but, uh… well, there it is.
      LDN crashed your immune system. The only way to know how is through a Stimulated Cytokine and Neurotransmitter test. https://youtu.be/xlbpT4_CBhU
      Call my office for more information. Dr. Dave

  11. Dr. Peterson, I actually appreciate your dissenting opinion. My question is… if LDN is in fact immune suppression, then why do a lot of people report increased resistance to infection? For instance, a common anecdotal report is that people don’t get the common cold as much.

    My impression of the anecdotal reporting is that people have bad reactions to LDN when it triggers an up-regulated attack against latent pathogens, like EBV or parasitic infections.

    What makes me consider what you’re proposing is that almost all people with auto-immune have relapses as soon as they stop the LDN protocol. If it were truly up-regulatory and modulatory, you’d think that it would create a lasting benefit, rather than a drug dependency. For this reason I am not overly worried about permanently altering the immune system with LDN. Its effects seem transitory. Even a period of increased emotional stress can impede its usefulness.

    • I recommend calming and quieting the immune system so it can respond appropriately when needed. When that occurs they don’t feel the pain and discomfort with their immune system under control. It’s a win / win situation. It is possible to get the immune system back under control. It is not a quick process but steady progress is experienced giving you the faith and confidence you need to know you did the right thing.

      It’s worth mentioning LDN “stimulates” suppression. Proponents will parse it to “LDN works by stimulating an immune response.” Conveniently leaving off the end of the statement. “LDN works by stimulating an immune response to calm down or stop (AKA – suppression).” Technically they are correct. By convention today, there is an agreement to only look at one aspect when publishing medical studies. They publish a study showing LDN works by stimulating a immune response. End of story. They assume those in the know reading this study would understand the consequences of this “stimulation.” However, the average person or Doctor (Don’t assume Doctors know much about the immune system) on the street doesn’t know or care how it works. They only want to know will it give relief. Consequences be damned.

      Fact: Inflammation is an immune response.

      In answer to “a common anecdotal report is that people don’t get the common cold as much.” You are equating not getting sick to a normal healthy immune system. After seeing the results from the Stimulated Cytokine lab test. I realized the reason they not getting sick is because their immune system is so fatigued or suppressed that no symptoms are generated. They come to my office reporting they feel like crap but they “never get sick”. “How can I be so healthy but feel so bad.”

      Those using LDN usually report a blissful period where their inflammation (see fact above) subsides. Usually for a four to six month period; then other components of the immune system become overstimulated without the feedback control from the components the LDN suppressed. They have had half a year for smoldering inflammation to further damage their body. The good news is they will not feel it. The bad news is they will now seek help from a Doctor that will recommend immune stimulating supplements. Exacerbating the condition and the damage being done.

      Naltrexone Stimulates Suppression of Cytokines

      Naltrexone and naloxone stimulates suppression of microglia activation, reduces the production of re- active oxygen species and other potentially neuroexcitatory and neurotoxic chemicals.

      Naltrexone causes a significant decrease of IL-12 and IL-10 production by macrophages. With chronic dosages, IL-12 remaines significantly suppressed. As for IL-10, naltrexone seems to partially prevent the IL-10 reduction. Naltrexone significantly inhibited the production of TNF-alpha induced by LPS.

      Naltrexone Stimulates Suppression of Chemokines

      The anti-inflammatory effect of opioid antagonists naltrexone and naloxone also extend to the periphery, as evidenced by stimulates suppression of TNF-alpha, MCP-1, and other inflammatory agents in peripheral macrophages.

      • Dr Peterson,
        I’m taking LDN for pain. I was given Cipro for a bacteria infection a year ago. The Ciproflaxon caused me to have severe Neroplacey in the feet, so bad I couldn’t walk without severe stabbing pain to the bottoms and tops of my feet, imbalance when Id get up many times falling. Since being put on LDN the pain went away after the first 6 weeks of use, cleared my brain fog and I can walk and work in my massive garden. I have what I call flare ups. The flare ups can last anywhere from a day to two weeks, I realise they happen when I eat glutin or to much sugar.

      • Hi Barbara,
        Was it ever considered that you experienced Oxygen Deprivation Neuropathy?
        The antibiotic damaged the blood cells and vascular system so much so that by the time the Red Blood Cells get the distant parts of the body there is no oxygen available for delivery.

        Of course, you noticed a difference in the pain after the LDN. Just like the other night, I let a pan get too hot and it started smoking, setting off the smoke detector. What did I do? Took the battery out of the smoke detector. No more annoying painful sound. Unfortunately, it didn’t clear the smoke out. Which is how LDN works.

        Flare ups are your immune system trying to compensate for the suppression. Like when I put the battery back in the smoke detector, it was chirping. There is a way to reset and restore the immune system without suppressing it. We do need a properly functioning immune system for health. Contact my office for more information.

  12. Hi Dr. Peterson,
    I have had Hashimotos for 20 years. My TPO antibodies have never been higher than 79 thruout this auto-immune journey. Thru diet and awareness I was able to bring my antibodies down to 16…. And then, 14 months ago, I started seeing a naturopathic doctor who thought I would benefit from LDN. Over the course of the past 13 months, my antibodies have climbed up to 250. My naturopath doesn’t think the LDN has anything to do with the increased antibodies, but LDN is the only thing I’ve done differently at this point…. Oh — and she has me taking Progesterone as well. Any thoughts? (I need to add that I have felt absolutely no different on LDN… no improvement in symptoms. She tested my Killer Cell activity 13 months ago and then again two weeks ago. The numbers are the same!)
    I also have Rosacea… and before I completely write off LDN as being potentially problematic, I have noticed that my skin is improved…
    Thank you for your article…. it’s the first I’ve read that maybe LDN is hurting rather than helping…
    Best, Sharon

    • Hi Sharon,
      As you read in my LDN article; LDN work by “stimulating a part of the immune system” to suppress other parts of the immune system. The part it stimulates is the part associated with antibody production. Thus the increase in antibody production. Rosacea may be improved but underlying that one has to ask what is the state of your immune system. A low grade smoldering response throughout your body.
      As to the progesterone. This is how I screwed my health. I assumed like your Naturopath that progesterone stays as progesterone. Assuming the body would get rid of whatever it does not need. It doesn’t. It converts to some downstream hormone further upsetting the feed-back control of entire hormone system. http://www.wellnessalternatives-stl.com/progesterone-answer-estrogen-dominance-hypothyroid/

  13. hi Dr Peterson, Your article is AMAZING!, and way beyond my ability to fully comprehend. I have an immune deficiency, so by default I am th2 low. I also have been taking ldn for years, but just recently began to wonder if I am benefiting from it or not. What I don’t want to do is stimulate th1 since I’m already high due to the immune deficiency. I know in some cases, ldn works wonders. I give it to my 20 year old cat for irritable bowel and he has no symptoms when I have him on it. In my case, I wonder if it is what has kicked me into lupus with lots of difficult symptoms. Many health care people don’t understand fully how ldn works. Hopefully one day that will change, but until then lay people/patients have to figure things out for themselves. Am I correct in interpreting your article that ldn does cause a shift from th2 to th1? If that’s the case, I am making things worse by taking it.
    I really need to boost my th2 instead. Thanks for the depth of your article. I appreciate it so much.

    • Hi Anna, Thanks for commenting. However, it is a gross error to focus only on Th1 and Th2 as well as assuming you have an immune deficiency. You should read my post: Am I Th1, Th2 or Th17?
      Your immune system can be fatigued but still respond inappropriately when exposed to lectins or bacterial LPS. By doing LDN you are inadvertently stimulating Th17 and that is bad. Bad because Th17 takes no prisoners.
      Naming diseases is like the old game show, “Name that Tune”. If the only answers one has is Elvis, Elton John or Foghat. Eventually, you will hit on a correct answer.
      My answer is Cytokine-Induced Sickness. Never, ever, ever stimulate the immune system. You really should read the “Am I Th1, Th2 or Th17” post.
      Dr. Dave

      • So nice of you to reply! After I posted my question, I saw your other articles. Some of them go beyond my comprehension, but what I did understand is never stimulate the immune system but focus on ‘calming it’, and supporting my t cells and inhibitory cytokines and neurotransmitters. I have not eaten sugars, simple carbs and lectins for several years. Not sure about the bacterial LPS. I will read up on that. It’s my desire and goal to have a consultation with you one of these days, but until then I will study your posts and do my best to take of myself. Thanks so much.

      • BTW, I don’t assume that I have an immune deficiency, I was diagnosed with CVID using the titer response to a vaccination. Unless the doctors are all wrong on this, which is a possibility, then I most likely do have an immune deficiency. I get sub q infusions weekly of immunoglobulin.

      • I was one of five Doctors across the country that was given carte’ blanc lab testing. I ran a lot of stimulated cytokine tests. It gave me a totally different perspective on the immune system.

        Common variable immunodeficiency (CVID) is a disorder that involves the following:
        – Low levels of most or all of the immunoglobulin (Ig) classes. (There entirely too much focus on immunoglobulins. Th17 does not need immunoglobulins to provoke an immune response.)
        – Lack of B lymphocytes or plasma cells that are capable of producing antibodies. (The Question should be “Why is there a lack of B lymphocytes producing antibodies?” Bacteria are known to hijack immune cells altering their behavior and ability to produce immunoglobulins. So, will IV immunoglobulins know how to respond appropriately?)
        – Frequent bacterial infections. (See note above. Bacterial LPS provoke inflammatory responses.)
        – A diagnosis of CVID is reserved for persons with an “undefined” B-cell dysfunction.

        Variable is the key word with immunodeficiency. It is “deficiency” as in – an inability to respond appropriately. Not a deficiency as in – lack thereof. Variable means the immune system can respond aggressively or collapse when exposed to different stimuli. If it was a immunodeficiency without variability, there would be no need for “variable” in the name.

  14. I saw you mention in the comments that bone broth stimulates Th17. Does this mean bone broth is harmful for Hashimoto’s?

    I am in the AIP diet and am now further removing remaining lectins, after reading your research. Will that help to calm and quiet the immune system?

    Thank you!

    • Hi Jen,

      If you have an Autoimmune condition, for example Hashimoto’s, it is an uncontrolled immune response. Stimulatory immune messengers concentrated in bone broth provokes an immune response, which in Autoimmunity is uncontrolled. Th17 is responsible for organ rejection, miscarriages and massive tissue damage. Does that sound like something that should be stimulated? Did you know Immune cells produce TSH? Read More

      Avoiding the lectins will help stop the provocation of an immune response. Did you know Th17 does not need antibodies for food or otherwise to be stimulated. Lectins provoke a direct inflammatory response from Th17.

      The next thing to do is to stop treating the thyroid like it is the only organ in the body. More often than not. “Thyroid” symptoms are due to dysfunction somewhere else in the body. But thyroid gets all the blame, making it impossible to reverse. Because the wrong thing is being treated. Read More

      Contact my office if you want more information.
      Dr. Dave

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