Summary:

LDN (Low Dose Naltrexone) has gotten much attention in recent years because many people report resolution or improvement of significant problems like chronic pain, fibromyalgia, fatigue, and autoimmune problems.

Fibromyalgia

Fibromyalgia is an important syndrome because it shares underlying biological issues with so many problems.  There is overlap of the underlying biological imbalances in fibromyalgia, chronic fatigue, CFS/ME, chronic pain, neuropathy, and other diseases. That’s why this video is important for almost anyone suffering from pain, fatigue, neurologic dysfunction, psychiatric illness, or other chronic issues that your doctor can’t fix.

LDN

LDN is an off-label use of a very well-used and safe drug. It stimulates the body’s natural production of endorphins and enkephalins. These are signalling molecules that do two very important things.

• First, endorphins and enkephalins activate your opioid receptors, which can have all sorts of benefits including blocking pain, improving mood, increasing energy, reducing irritability of the intestines, and so on.
• Second, endorphins and enkephalins gently turn down your body’s production of inflammatory chemicals. Those inflammatory chemicals are involved in chronic pain, fatigue, fibromyalgia, neurologic degeneration, irritable bladder, depression, anxiety, and auto-immune disease.

There are good reasons why LDN can help pain, fatigue, and fibromyalgia. And a few small controlled trials show that it reduces pain and reduces inflammatory chemicals in people with fibromalgia. To my thinking after a couple of decades of experience, it makes more sense to start with LDN before Lyrica or Cymbalta, which are commonly-prescribed first-line drugs. But fibromyalgia is a complex illness with many factors. It’s important to take a broad understanding of the things that can drive fibromyalgia, so you can do what can be done about them. LDN can be part of the picture, but in my experience, it works better as part of an integrative approach. If you have fibromyalgia, chronic pain, or chronic fatigue, it’s also important to address stress, trauma, negative emotions, insomnia, hormonal and nutritional issues, low-grade infections, intestinal permeability, mindful movement, mitochondrial function, and so-on.

Not for Everyone

LDN is not for everyone. It’s important to find a competent prescriber who understands your illness, to see whether it has a good chance of being effective for you. But there is no incentive for a drug company to do large controlled trials. So LDN is likely to be an “off-label” use. I hope you enjoy the video.  Just click above to see it.

Did You Know:

Dr Shiller is responding to the chaos and overwhelm of the corona pandemic by offering regular free stress-busting mind-body training sessions on zoom. You can get the schedule and register at www.mindbodygroove.com

•  https://www.drshiller.com/interview-ldn-pain-auto-immunity/
• https://www.drshiller.com/healing-chronic-pain-illness-ldn-low-dose-naltrexone-part-1/
• https://www.drshiller.com/healing-neuropathy-ldn-functional-medicine/

Full Transcript:

This talk was given as a scientific presentation and includes slides to illustrate the points.  If you prefer to read the transcript, you can also download the slides. 2019 conference fms ldn FINAL slides Is LDN a magic bullet in fibromyalgia? As we know LDN has got unique immune-modulating and analgesic effects, and in my experience is great synergy with other aspects of an integrative approach to pain and inflammatory conditions. I find it especially relevant and helpful in fibromyalgia. As you probably know, most of the meds that doctors give for fibromyalgia do not work. There are 10 million people in America with fibromyalgia, 3% to 6% of the world population. It is a huge problem, very disabling, and a lot of people who are really believing the kind of mainstream view that, “Hey there is nothing we can do for you to help you. These medications might control your symptoms.”

LDN

That is not my experience, and when I think about medication choices, it seems to me like LDN is probably a better first-line agent than Lyrica or Cymbalta because of the difficult side-effect profiles, and because they don’t have such compelling evidence for the effectiveness. We do have some small studies with LDN in fibro that seems to show that it helps, and to me, it seems like it gets more at the root of the issue than the antiepileptic drugs. Some people think it seems like a magic bullet, but in my experience, it is not the case. It is important to put things in the context of a systems biology approach, and it is a functional approach, and we will talk together about LDN’s place in that, and then look at a couple of case studies. –Next Slide– I think we all know the picture of fibromyalgia that people suffer with widespread pain, fatigue, unrestorative sleep, gastrointestinal problems like irritable bowel, cognitive issues, affective problems, neuropathic pain, environmental sensitivity, pelvic pain, cystitis, postural orthostatic tachycardia syndrome, which is when people stand up and they get dizzy and their heart is racing. It can be really disabling, and like we said, affecting 7 to 10 million people just in the U.S. –Next Slide–

Case Study

Let us start with a case study. Naomi, she is 42, a mother of 6, exhausted, widespread pain, insomnia, irritable bowel, kind of a classic presentation. Her husband works and studies all day. He is emotionally supportive, but he is not really around, he is a busy guy. She is alone at home with the kids, cannot keep up, has minimal social support, they live in a small town in the mountains. She has a diagnosis of fibromyalgia. She was seen by a rheumatologist. They worked her up for the normal things, and you know, it is really important to rule out things like thyroid problems and neuropathy and frank inflammatory disorders. She had an elevated sed rate, but she did not have any other markers, and so the rheumatologists were not very interested in doing anything for her. The typical meds did not work. She was overwhelmed and had no knowledge of inclination towards self-care. I asked her what she knew about diet and fibromyalgia, and she said, “Oh, healthy eating…you mean eating whole wheat bread? That’s a pretty simplistic and outdated view, and maybe we will have time to get into that later. This is not someone who really has the resources to do lifestyle approaches towards fibro. So, we started LDN, and did a typical titration of 1.5 mg to 3 mg to 4.5 mg, five to seven days between doses, recommending for night time use if possible. I tell my patients its okay to use it in the day if you have persistent insomnia or vivid dreams that keep you awake. That is kind of my standard approach to prescribing LDN for people with chronic pain. Cautions about sleep disturbance, like I said, some people get more pain, some people get headaches, some people get GI symptoms. It is important just to let patients know about that in advance, and I typically write people for an eight-week script that gives them a bunch of 1.5 mg caps and then a month’s worth of 4.5 mg, because some people do not get the 4 mg right away, some people have to stop at 3 for a few weeks until they kind of accustom themselves to it.

What happened with her?

She followed up three to four months after starting LDN. She said, “Doctor, I’m in horrible pain.” I am thinking “oh no it didn’t work or she had side effects and stopped instead of letting me know”. I asked her, “Did you take the medicine?” She says, “yeah.” “And then what happened?” I asked. “Well, after two weeks on it, I felt normal again, and I didn’t have fibromyalgia.” So, I am like “Great!, what happened? Why are you in pain now?” She said, “Well, I ran out of meds, and I had to wait to see you to come back in.” Okay, so we can look at this case, and this happens sometimes but not usually. –Next Slide–

Is LDN a magic bullet for fibromyalgia?

In my experience, not always! In my experience, most people are not cured with LDN alone. Naomi was an unusual case, but it happens sometimes. It is wonderful and gratifying when someone feels so well with such a simple intervention, and for sure, that can be part of the picture, but in my experience, there are other issues, and we will get into that in a little bit. We know the main mechanisms of LDN are improving opioid function, both sensitivity and production of endorphins and enkephalins, and that because of the enkephalins, there is this immune shift and reduction in inflammatory chemicals called cytokines, which in certain populations seems to have a big impact on chronic pain. What I want to talk about now is fibromyalgia as a model of functional systems illness, where there are multiple systems with different things going on. And the systems all work together to create the illness That scenario is typical of things that I see a lot of: chronic pain, irritable bowl, headache, fatigue, even inflammatory disorders. In many of these syndromes, LDN has a powerful influence on certain aspects and pathways. It can even result it complete ending of the symptoms. But is it really a magic bullet? No. Not in the old sense of it, but there is a new kind of magic bullet out there, and that is more like a blender that brings different aspects together, that has different sizes and different caps and is individualized towards patients, and let us talk about that kind of magic bullet because to me that is what the functional approach is like for fibromyalgia. –Next Slide–

Systems Biology

Let us start just thinking about systems biology. It is an integrative approach to try to address complex multisystem illness, and the academic buzzword is systems biology. A lot of the big universities in America have Departments Of Systems Biology, where they are trying to look at how everything works together. They are looking at complexity in a relationship. They are looking at all the reductionist details that modern medicine has developed and looking at them in biological context, how the systems relate? Because on a certain level, we have subsystems, but we have one system, and on a personal level, intrapersonal, cardiovascular, pulmonary, GI, immune, neuro, all of that. Then environmentally, our interpersonal relationships, relationships with society, with the natural world, exposures, and all of that. Really systems biology is about looking at the whole picture. The way that I have been taught in a more functional medicine context is understanding how these variables relate to each other over time. We talk about antecedents, triggers, and mediators, and let us just unpack that, although many of you may have heard about this idea. –Next Slide– Here is the picture of fibromyalgia, and we are going to look at that in terms of system biology. Antecedents, those are foundational issues or principles of the individual’s life and function, things like genetics, early life trauma, early illness or exposure, lifestyle issues. And then there are triggers which are transient events or things that happen; they are states that occur, and they shift the system; they can modify gene expression and metabolism; they can instil new beliefs in a person or emotions or behavior. You know, in the course of a person’s life, the things we go through, and for sure, a lot of us have heard of many people with fibromyalgia have some sort of traumatic trigger or inflammatory immune trigger, and then they develop the illness. So, we will unpack that a little bit. Mediators are more enduring states or even traits that perpetuate or feed the phenotype. These are the things that keep a person sick, and so there can be metabolic things, like inflammation or lung disease or anemia or chronic distress or adrenal dysregulation. There can be mental emotional things, like anxiety or depression, social issues like isolation or discrimination or poverty; and behavioral issues like substance abuse, diet, insomnia. These are mediators. Exercise regularly, good health habits. These are mediators, things that could keep a person sick or keep them healthy, and then we study the flow of information in the system over time. Fibromyalgia can get overwhelming and confusing when we just start looking at the details of what modern science is telling us, because mainstream medical science does not really have a clear picture of what is going on, and that is why there is so much confusion. The mainstream view is fibromyalgia is incurable, it is just all about central sensitization, and sure we know there are connections with early trauma and genetics and that people get disabled and deconditioned. The neuromedical literature talks about other issues that seem to show up in people with fibromyalgia. For instance, oxidative stress and inflammation, both peripheral inflammation and central inflammation, and of course, we are talking about low-grade inflammation with altered inflammatory cytokine profiles and activation of glial cells in the brain. Glial cells are like the support cells of your brain. Somewhat like macrophages, and they get hot and bothered in fibro and other central pain states and they secrete abundant inflammatory cytokines, and that seems to be part of what generates central pain sensitivity. Which we know is one of the issues in fibromyalgia, but you do not need to have an elevated sed rate or a C-reactive protein to have these things going on. We do not really have ways of clinically measuring them, they measure them in research. I think an unenlightened way, and so we go further and we have hypothalamic-pituitary-adrenal axis, and I put the T there for thyroid, because the whole hormonal system is all interrelated and connected, and these are some of the hormonal issues that we see in people with fibro that seem to fit into the whole picture. There is mitochondrial dysfunction. As with a lot of chronic degenerative diseases, mitochondria, the cellular energy production warehouses that actually are power plants for our cells. They get dysfunctional. Our cells do not produce energy, and that is part of why people with fibro probably get their fatigue and chronic pain. They do a little bit of activity, and they go beyond their aerobic threshold, and their body starts producing lactic acid. And they get all this pain, and they flare up from that. Then, of course, sleep disturbance and gastrointestinal dysfunction, which tend to get thought of as symptoms in mainstream medicine, but in a functional model, we understand that they are part of what perpetuates fibro. I think an enlightened medical approach would look at all this and say: Okay so what do I do about that? How do I fix those things? Is there a single cause that we can treat or can I give a pill for each one of those things? My sense is that in the medical press and the popular press about fibro, you see this persistent search for what is the single cause? So, a researcher finds a physiologic change in fibromyalgia and wants to say, “Here’s the cause.” You know, for instance, recently, there has been some research showing that combining an NSAID and anti-inflammatory along with an antiviral helps a lot of people with fibromyalgia and people are running around and saying, “Oh, this is the cure, because fibromyalgia is caused by herpes simplex virus. We have found the cure and the cause,” and to me, that seems kind of silly. I do not know if anyone has ever proven this premise that there needs to be one cause, that is something that we developed out of the modern bacteria, antibiotic era with one disease has one cause and one treatment. But the picture that seems to be emerging in the literature to me is that we have got multiple different physiologic dysfunctions in fibromyalgia that can come about through various triggers, various genetic predispositions, various moderating factors that are going on in that person’s life. My sense is that we will be further along towards improving diagnosis and treatment. We stopped looking for one cause and started looking at it as a complex systems dysfunction. –Next Slide–

How does mainstream medicine think about fibro in what to do?

This is just from the Mayo Clinic on their website, great place, amazing, obviously one of the best institutions in the world, but basically researchers believe that fibromyalgia amplifies painful sensations by affecting the way your brain processes pain signals. Okay, we know that we call that central sensitization creating widespread pain. The question is why? What creates central sensitization? Research has progressed. I do not know why they are not talking about this so much, but it is pretty clear that there is glial activation, that there is inflammation, both central and peripheral that is driving changes in brain function, and that is not just in fibromyalgia. It is also in complex regional pain syndrome, we see that in chronic peripheral neuropathy. We even see it I think starting in osteoarthritis. I am not sure if we have got research to show that, but clearly, there is a central pain component there, and the common threat is that we have got activation of central inflammatory responses in the brain, that part of what sensitizes the brain. There is more to it though, because we have also got research showing hypothalamic-pituitary-adrenal axis, stress overdrive. We will unpack this more in a moment, but that is part of what seems to create central sensitization, as we know from the fact that so many people who have got early life stressors and adverse childhood events tend to have chronic pain syndromes in a much higher percentage than other populations.

Sleep Disturbance

Sleep disturbance is an intimate bed partner so to speak with chronic stress response. They feed into each other, and as any medical doctor could probably tell you after working a 36-hour shift in the ICU or in the ER or wherever it is. I do not know about the rest of you, but I always felt like a wreck, and if I miss a night’s sleep, I am aching the next day, and so it is not so hard to see a connection between sleep disturbance and central sensitization. Finally, mitochondrial dysfunction is part of this picture too. –Next Slide– Let us unpack things a little bit more, right, and let us start with the stress axis, the overall stress response, because to me it seems like that is a really key issue. I say that in part because it seems to be part of the presentation of every one of my patients with fibromyalgia, and part because it is so clearly feeds into these vicious cycles of physiologic changes. We understand that genetics and early life trauma can be part of the picture. People with fibromyalgia have a higher incidence of genetic polymorphisms that are involved in breakdown of stress hormones and catecholamines. So it seems like there is a predisposition there to having an overabundant stress response that does not shut off, because the body does not break down the epinephrine and norepinephrine so quickly. That feeds into this constellation of things, and so I am just drawing a picture that is connecting mental-emotional stress, adrenal dysfunction, and sleep disturbance. You know, I want to just say one quick thing, because we have all heard the term ‘adrenal fatigue,’ and I think that is a very misleading term, and I think it is unproductive term, because the adrenals are not really broken. We do understand that there is this normally in health, there is a feedback system between the hypothalamus, pituitary, and adrenal glands and that feedback gets altered in people with fibromyalgia. There can be distortions in the normal pattern of diurnal cortisol secretion. Cortisol is being one of our main stress hormones for chronic stress. Again it is not adrenal fatigue, but it is more of a distorted feedback system, and that is got huge implications for thyroid hormones, sex hormones, and other signaling systems. It is also interesting because we are starting to see rich connection among hormonal systems and mitochondria. It turns out that mitochondria, and here is a reference, that I get a lot of this from Bruce McEwen, who is really kind of one of the big guys in stress physiology for decades and decades at Rockefeller. He wrote a beautiful interesting review, it is really worth looking at. Focus on Mitochondria, an energetic view of stress. He is pointing out that our stress hormones and sex hormones for the most part are actually synthesized in our mitochondria, and it seems like there is a two-way street, where dysfunction of our hormonal axes is associated with mitochondrial dysfunction and vice versa. His view is that stress is an energy-dependent function. A person who has got overabundant stress and allostatic load as he calls it, meaning a need to adapt to some sort of thing going on in person’s environment, whether internal or external. Naturally, you need energy for that, and so energy production in our mitochondria are intimately connected with our hormonal axis, and so let us not forget how these things are connected to behavioral dysregulation. Research is showing over and over that the desire for fatty, sugary, comfort foods is physiologically integrated with stress and mitochondrial dysfunction, and other behaviors, like smoking and other substance abuse can also be part of the picture, and so finally in just acknowledging that pain itself and the other symptoms of fibro are part of the cycle. Because pain is a distress signal and pain is something that stimulates parts of our limbic system that tell us that there is danger that we need to get up and go and do something, and we know that the stress system, when it is activated, worsens and intensifies pain transmission. –Next Slide– Let us look at this in other contexts too, like here again is the same hypothalamic-pituitary-adrenal axis with our genetic and early trauma influences on it, and we think about it in terms of a mitochondria. We have got what seems like to me a relevant connection to one of the common clinical observations in fibro, because what I have heard from so many patients over the years is, “Okay, I am living my busy, busy go-go life. I had some difficult early life experiences, but I was tough and strong, and I was a perfectionist, and I worked hard, and I went to nursing school or medical school or I got a business degree, and I was working, working, working. They described kind of a go-go-go energizer bunny lifestyle, and life gets more complicated, and the stress load increases, and most people are not paying attention to the level of stress, it is happening, they are habituating to it, and they are just living a stressed out life and going and going. Here is adrenal stress over time, and there is this gradual crescendo adrenal hyperfunction, and then there is a trigger event, and that could be a car accident or a surgery or falling down and hitting their head or some kind of stressful life event or a really bad illness, and then there is this pulse of stress followed by a crash, and in that crash. There is what looks like adrenal hypofunction, and that is where this whole adrenal fatigue language seems to have come out of, but we really understand it to be like I said before is dysregulation of the hypothalamic-pituitary-adrenal axis, which I am just going to call HPA going forward, because it is a mouthful, and if we put this together with our staining of mitochondria, we are adding a level of dynamism to this whole system, right? When systems get more complicated, they get more susceptible to having extreme shifts in function when there are big perturbations in that system. Just picturing someone who has got an increased HPA axis in adrenal function over time and then suddenly there is a huge boost of it, which potentially, I am proposing, creates a breakdown in mitochondrial function. Which creates a further breakdown in HPA axis function and you get this vicious cycle and boom. Maybe that is part of what causes people’s crash. It is hard to know. We are going to have to do more measurement. Let us keep going and look a bit more and a little bit more detail about some of the other aspects of these vicious cycles of what seems to be giving rise to and perpetuating fibromyalgia syndrome. –Next Slide– This is kind of an overall picture of our gut brain axis from a 2017 article about the influence of the microbiome on neurotransmitters and affective disorders, and most of you have seen this, but just to briefly explain what is going on here. Here is your brain. Here is your vagus nerve. Your vagus nerve is this big nerve that comes out of the base of your skull and goes and feeds all of your viscera. Your vagus nerve is a huge aspect of the relaxation response. It is your big parasympathetic nerve, and so when there is vagal dysfunction, when there is a decrease in vagal tone, there is actually an increase or overactive stress response. Vagal tones connected so profoundly to what is going on in your intestine. This is the lumen, the barrier of the intestine. This is what is inside your intestine. Gazillions or actually trillions of bacteria, more than human cells. We have learned that the biome of all of these bacteria has a huge impact, not only on what is going on in your gut in terms of producing neurotransmitters and various other chemicals that can be involved with gut inflammation and the health of this mucous and cellular barrier. It creates a barrier between that and the immune system, and all the vasculature that surrounds your intestines. There is also feedback from the vagus, a sensory feedback that goes up to the brain, that affects mood, that affects behavior, that affects so many aspects of our functioning, and yes our hypothalamic-pituitary-axis also. Basically, there are three main things that go on when we get dysregulation of our vagal function when we get overactive stress response. We get a change in our biome. We get breakdown in that intestinal barrier, and we get changes in our intestinal motility. Irritable bowel syndrome is a change in intestinal motility. –Next Slide–

Mind-Body Disfunction

Let us plug this back into our mind-body dysfunction, because it is so deeply interconnected, and just unpack it a little bit. We saw, okay, HPA axis, stress response, and gut-brain access changes. Yeah, we know about that, but let us unpack that. There is motility issues, barrier issues, biome issues. We understand that the biome feeds back into your brain and affects mood and affects behavior and a lot of other things. We understand that when the barrier breaks down and we get leaky gut or intestinal permeability, it can generate systemic inflammation, and systemic inflammation can generate central inflammation, and that can generate glial activation and pain syndromes, like we talked about before. Systemic inflammation obviously feeding back not only into pain but into mood and affect and behaviour, and then irritable bowel, motility issues, changing people’s diets, inability to absorb nutrients when a person eats food and has to run to the bathroom in 10 minutes, their gut motilities, and so they cannot absorb nutrients. There is potential for malabsorption there, though I have not seen any studies showing that yet. –Next Slide– Let us look at the big picture here again, and let us try to put the whole picture together and think about, well where is LDN likely to be helpful in fibromyalgia, and we are almost done with all these complex physiology slides. Bear with me, this is the most important one. Try to bring your attention to this one, okay. We start with this foundation of genetics and early life experiences and trauma, which can affect our overall inclination towards inflammation and oxidative stress through various pathways, and a key aspect to that is their relation, both directioned with mitochondrial dysfunction, oxidative stress, and inflammation. They feed into each other. Oxidative stress and inflammation generates mitochondrial dysfunction. When the mitochondria are dysfunctional, they generate reactive oxygen species, and that is a vicious cycle, and that itself could start to stimulate a lot of the symptoms we see in fibromyalgia, pain, brain fog, affective disturbances, fatigue, and these are all associated with mitochondrial dysfunction. Going forward, we understand we talked about central sensitization, glial activation, which are related to inflammation systemically and related to mitochondrial dysfunction, because when the mitochondria in the brain get dysfunctional, the glia get activated, and when the glia get dysfunctional, it is part of the vicious cycle here. Then we are looking at here stealth infections and our biome and GI issues. We did not really talk about the stealth infection thing, very controversial topic, but some people seem to have low-grade infections that may be contributing to low-grade systemic inflammation that feed into all of these other changes in fibro. Let us not forget about biochemistry and toxicity. Things like heavy metal exposure, chemotherapy exposure. These are massive oxidative stressors; they put a huge load on the system, and putting back in and plugging in our HPA axis and thyroid dysfunction, and like we talked about that feeds into the whole system. We are coming to the main point of this slide. What is the role of LDN? If we think about our main understanding of LDN, we have got shifting in our pain transmission because it enhances opioid production, and there is also an aspect of effect on our inflammatory pathways. I am sorry, I forgot to talk about or just put in this last connection of our stress response as it affects central sensitization and the stress responses. It affects our GI function, and so what I am trying to clarify here is just that we have got multiple different systems that are affected and get dysfunctional in people with fibromyalgia, and LDN at least in its putative effects, tends to work the most in terms of on our inflammation, glial activation, and central sensitization. I want to suggest that the picture might be a little bit more complex than that, because LDN enhances opioid function, and our opioid systems are endorphins and our enkephalins, affect all the systems of our body, and so just an example, we talked about sleep dysfunction, as it relates to HPA axis. I had somebody come to me about five months ago, I guess, with horrible fibromyalgia, chronic widespread pain, a little bit of sleep dysfunction. She was not really saying that was a huge issue. Again, this was someone who did not have a lot of interest or pre-education about doing positive lifestyle things. We started with LDN, and then also some osteopathy, because she had some structural issues, especially around some mild head trauma, and she came back to me two weeks later for an osteopathic treatment after starting LDN. She said, “Doctor, I’m sleeping 15 hours a day. I can’t wake up in the morning,” and my response was, “Can you work that into your life,” and she said, “Yeah, I can work around it. I’m self-employed.” I said, you know, maybe you just need to sleep 15 hours a day for a while, and she slept 15 hours a day for like two months, and then her sleep came back to a normal rhythm, and that was associated with such a profound improvement. There may be issues with LDN affecting other aspects of our system, our HPA axis. There may be aspects of it shifting things, like oxidative stress and even for sure we know that there are implications for our gastrointestinal symptoms and improvements in GI motility, and a lot of people with IBS improve when they get to the end. There is broad, broad application, but the system is broader and more complex. –Next Slide– Okay, so that was a lot of information, and just changing gears, I want to introduce to one of my friends. I was just sitting next to this wall up above the dead sea, eating some salad, and this character just showed up. It is kind of like he blinked himself into existence, he just popped up, it is an ibex, and these things do these incredible, like acrobatic, running up and down hillsides, and seems they can jump 15 feet in a single bound, and he just kind of popped up, and they are so calm these creatures. They just sit there and look at you, and when they figure out that you are not a tree they can eat, they seem to turn their heads and walk in a different direction and look for something to eat, cute right? –Next Slide– Okay, so, let us just one more time visit the complex physiology, and I want to just express why and how we think about this whole thing in terms of antecedents, triggers, and mediators because that whole map of physiology can be very overwhelming. When I first started thinking that way years and years ago before I started formally studying functional medicine, my brain was just exploding with every patient I saw, and the antecedents, triggers, and mediators approach is really helpful, because it lets us think about each patient and try to see what is driving the issue. So, here is what is going on. I have some with fibromyalgia, they have got some combination of the usual symptoms of pain, sleep disturbance, fatigue, GI, cognitive, affective, other, and I am going to make a map, and I am going to think about antecedents, triggers, and mediators. Antecedents are things like genetics and early trauma or illness or exposures or lifestyle, and triggers are things like trauma, illness, viral, toxic, infectious, and my suspect that any anyone out there who sees a bunch of people with fibromyalgia, if you start asking the question, you are going to hear that there is a trigger in a large number of patients, where they had some sort of this is when it happened, right, and it could be a trauma, and it could be a viral disease or some sort of toxic or chemical exposure. It could be an emotional or mental stress, loss of a loved one, and people will report, “Yeah, that is when it all started. My life hasn’t been the same since then,” and that often gives us a clue in terms of where to focus on what we are doing, because if that insult was infectious, then we want to think about immune, we want to think about whether that infectious agent is still around. I had a patient who came to me who got really sick with some sort of parasite in Asia and comes back to me five years later with horrible widespread fatigue and all kinds of symptoms, and we did a workup, and she still had a parasite. She had a worm, and so that was generating chronic inflammation. Antecedents, people who have asthma, and they take their adenoids out, and they take their tonsils out, and you know there is clearly like an immune infectious thing going on early on in life, and frequently you check their biome with some sort of gastrointestinal check, testing, and they are all out of whack with dysbiosis, and so that is a focal point of treatment. Finally mediators, things that are going on now that may be perpetuating the problem, and that is where the antecedents and triggers lead you to look to ask, well what might be perpetuating in keeping this person sick, is it profound ongoing stress and interpersonal abuse or trauma? Is there some sort of inflammatory driver? Is it just the central sensitization feeding into their stress? Are their mitochondria tanked out? Do they have really bad cortisol axis, and they are not producing any cortisol or their cortisol response is flipped over and they are producing too much at night and not enough during the day, so they are exhausted the day, but cannot wake up at night? And these are things that are treatable with appropriate approaches, which we do not have time to go into right now, but the point I am trying to make is that, we create a flow chart and we try to see and determine what might be contributory, and in addition to LDN, if I elect to use that in a given patient, what else do I need to be thinking about? So, looking at those vicious cycles. –Next Slide– Okay, so let us change gears now, and we are going to run through for a few cases just that have been illustrated to me about some of the issues of using LDN in this population. Another case here, Angela. I am subtitling it, can I please have my brain back. So, Angela is a lovely person. She comes in, she is 55. She has got severe fibromyalgia with high disability scores, widespread pain, sleep disturbance, IBS, the usual. She had chronic pain for years, but it really got worse in the last four years after she had a family tragedy. Now, she went and saw a naturopath and got a really complex diet and supplement regimen with all the things that you might think are relevant to fibromyalgia, but she did not do any of it, and when I was talking with Angela, one of the main things that that struck it from the exam was she seemed kind of tired and floaty and had trouble paying attention. I sort of did a little intervention, and I discussed fibromyalgia pathophysiology and how to treat it in the context of her history for about 15 minutes, and I asked her what she understood from the conversation, and she was not retaining anything at all, and so her brain was so dysfunctional, and her attention was so dysfunctional that she could not comply with a treatment plan, and my concern was that maybe she would not even be able to know how to take the LDN. With Angela, I encouraged her to enrol in an online mind-body skills course that I give relaxation, mindfulness, emotional self-awareness, mind retraining according to a particular map that I share based on my own spiritual tradition, and group support, and just to show what happened just from that intervention. I have started getting an FIQ of fibromyalgia impact questionnaire revised on all of my patients. It is got three scores. The first one is about function, the second one is about overall dysfunction, and the third one is about subjective symptoms, about a bunch of different symptoms, and high score is bad, low score is good. Here is how Angela showed up before the course, where she had dysfunction level of 72/90, meaning like she could not prepare a meal and clean herself and take a shower and do things around the house, described herself as profoundly disabled and profoundly overwhelmed, and had really severe symptoms severity scores. She spent eight weeks in the course and met with me about three weeks afterwards and redid the FIQ, and look what happened to her dysfunction score, she still had really high symptom severity. So, still a lot of pain, a lot of stiffness, a lot of fatigue, but she got her brain back from retraining her HPA axis, from retraining her stress response, and for developing skills for coping with the challenging things. Part of what we do in the course is not just going to a calm place inside, which is vastly important and powerful for many people, but it is also about noticing what are the triggers in one’s own experience in the course of the days and weeks that take me out of that calm place? What are the places in my experience in my life personally, interpersonally that create stress and take me off of my groove? –Next Slide– That had a profound impact on her, and she loved her new brain, and then we started on fibromyalgia, and here is her scores before fibro. She was doing a lot better.So I did standard dosing, and then after she was on fibro for I think it was about eight weeks, she came back, and her symptom severity cut in half. So, kind of a double whammy we did here. I looked at her and I said, “Look, there is a huge brain dysfunction, brain fog, sympathetic overdrive thing going on. Let’s try to address that first,” and I think she is going to get a bigger impact from everything else we do, and after this, we went on to do some of the things around exercise, and diet, nutrition. –Next Slide– Just a slight sort of going back into pathophysiology. The degree to which the mind-body issue and overactive stress response and hypothalamic-pituitary-adrenal/thyroid dysfunction feeds into all these other issues, like gut-brain axis and immune activation, mitochondrial dysfunction, and pain pathway sensitization. My sense is that it is so vital with this population to really get the mind-body axis healthier, to take an approach and do some kind of intervention that is empowering, that gives some freedom of choice, some degree of self-efficacy, a sense of coherence and understanding, and the capacity for transformation for meeting difficult circumstances that might have once been overwhelming, and giving skills and confidence for dealing with them effectively. –Next Slide– And so, my goal in the course that I give is giving people a calm and clear mind, teaching them to be compassionate and forgiving of themselves, but also discerning and aware, and giving them a map of consciousness, so they can kind of understand what is going on inside of them, teaching them to be responsive rather than reactive. Reactive is the automatic stress response. Responsive is choosing how to be in response to a difficult situation, and sometimes for some people, spiritual connection is profoundly important. –Next Slide– And then fostering healing attitudes like joy, generosity, focused desire. In my tradition, desire, when we connect to our core and we know what we really want and we are actually living purpose, that is resilience. You may have heard of Victor Frankl who survived the concentration camps. I think he was in Auschwitz, and he chronicled the people who were successful in dealing with such unbelievably challenging situations, and it is the ones who had purpose, the ones who decided that despite being in hell, they were going to be human. Those are the ones who seem to survive better, and so giving people back their humanity. They have got a disease, they have got hopelessness, they have been shamed and blamed by their doctors and family members, it is so challenging, and giving them back a capacity to connect to who they are and what they care about, it is profound what it does for them; gratitude, trust, life skills. –Next Slide– These are obviously all very experiential things we can talk about them to blue in the face, but feeling it and knowing is really the thing, and that is what I try to give over to people when I do that training, and there is lots of different ways to do that. –Next Slide– Let us change the gear and go back to cases a little bit, right. I could talk all day about mindfulness and practical and spiritual development, and why it is helpful, but this is the LDN conference, so let us focus on that.

A Case of Fatigue

Richard, because this was a great case for me, this is when I first started using LDN. He comes in with a lot of fatigue and a little bit of pain, mainly it was fatigue, and he had numerous immune and biome issues. He was premature infant, got a lot antibiotics, asthma. He got fibro after a bad flu, and I put him on standard dosing, 1.5, 3, 4.5 mg, every five days increased the dose, and he calls me four days into it, and he says, “I am so wiped out, I can’t function. The pain is killing me. What have you done to me?” So, humbling, I just fell on my face on this one, poor guy. I learned to do something differently, and when I see someone who is really dysfunctional in terms of fatigue or really sensitive in terms of pain symptoms. This is not just about fatigue. I saw someone recently with a really bad kind of migraine equivalent, where when he gets overstimulated, he gets these attacks where he cannot speak and he just gets brain dysfunction, has to lie down and kind of close his eyes, put in ear plugs, dark room, turn off all the electronics, cannot stand electromagnetic fields.

Dosages

For that kind of situation as well environmental sensitivity, I tend to start on 0.5 mg and then go in 0.5 mg increments every week, and I give them very careful instructions about waiting at “your best dose,” because some people find that they go up to, in his case, he went to 2.5 mg, and he started feeling a bit better. When he went to 3, he started getting overwhelmed and fatigued and having pain again. So, we stopped at 2.5 for a couple of months, and then after that, he was able to increase and went up to 4 mg and had continued benefit, and I think from my understanding is that is often the case with people who have chronic fatigue, people who have really bad fatigue with multiple sclerosis, they need to find the right dose. I actually had someone who came in, who I started on 0.5 mg, and that was too much. So, we went down to a quarter, and that is what worked for her and helped her start to kind of climb out of the hole that she was in so to speak in terms of her physiologic dysfunction. –Next Slide– Next case is Faith, and I am speaking about this one. She has really kind of a complex multiple medical issue thing going on here. Yes, 47 years old, severe fibromyalgia with a high pain and disability scores, and I am sorry I wrote psoriatic arthritis here without active joints. She actually had a lupus diagnosis, this was my mistake, sorry about that. In any event, obesity, hypertension, on two meds, elevated inflammatory markers. She had a DVT. She was hypercoagulable with an MHTFR and was on anticoagulant, and anxiety and depression, long medication list. One of the first things we did was fibro, I mean LDN at standard doses, and that helped her a lot. She had a significantly more energy after just about eight weeks, and she was able to stop her antihypertensive medications and stop her antidepressants. So, really improving medically, but still with a lot of pain and really disabled from it.

Gut Dysfunction

What now? That is when we got biochemical and tried to address some of the issues in terms of her significant gut dysfunction as well as what I saw to be both central sensitization and mitochondrial dysfunction. She did mind-body program, and then we did supplements for mitochondrial function, methyl donors, because people who have MHTFR dysfunctions can often have issues with neurotransmitter synthesis. They can have issues with detoxification. These are some of the things we did for her, and I often work with a health coach in complex patients like this, because even when they have a good brain that functions well, it is really hard to make change, and especially this person who had a little bit of OCD, it was really helpful to put her in touch with the coach, who helped her gradually, gently, compassionately make changes and support her practice, and in kind of workable chunks of her lifestyle plan.

Movement and Mindfulness

That was associated with some improvement, and she was feeling better and had more mobility, and then we started working on movement in a mindful context, and mindful context means within threshold, because when mitochondria are not functioning, when I do not have enough cortisol to drive my system, I have got a low threshold, and that to me seems to be the issue with the normal exercise recommendations. You know, a person with fibro, who goes out and tries to do what they used to do and run a mile is going to be wiped out and fatigued or even trying to clean their house or whatever it is. They have got to find what is their threshold, and they have got to have the compassion and the presence to know when they are getting to it, and walk half a block, and if that feels a good, do it again, and then after doing that every day, walk a block and a half. We know exercise improves mitochondrial function, but you got to do it at the right rate. I am a big fan of Yoga, Tai Chi, Feldenkrais, Pilates, because there is an instructional methodology there. If it is done with the right teacher, where it is gradual, and it is gentle, and it is mindful, and you can start slow and build. –Next Slide– That is it for me today. Thank you so much for listening. Thanks for being here, and I wish you all lots of success working with your patients with LDN with fibromyalgia and wishing you all the best.