Low Dose Naltrexone For Chronic Pain And Autoimmunity
Low Dose Naltrexone is currently under study in patients with various types of chronic pain including migraines, fibromyalgia, and neuropathy. Other chronic pain states, various types of cancers, and autoimmune related disorders are also being studied. While these studies are underway, it is used widely in the U.S. for a variety of pain related disorders and autoimmune conditions.
Use In Chronic Fatigue Syndrome
So far, LDN has not been studied for chronic fatigue syndrome. However, some healthcare providers and patients say they’ve used it successfully.
With recent evidence pointing to the possibility of neuroinflammation in chronic fatigue syndrome and LDN’s possible impact on inflammation in the nervous system, we may be seeing why this is an effective treatment for some.
As with fibromyalgia, LDN is sometimes prescribed off-label for chronic fatigue syndrome.
An Alternate Explanation Of Ldn Mechanism
While we believe much data is consistent with that claim that LDN works via novel anti-inflammatory channels, there are alternative compelling explanatory models of the LDN mechanism. The most prevalent hypothesis, advanced by Dr. Ian Zagon and colleagues, states that inducing a small and transient opioid blockade will prompt the body to compensate by upregulating both endogenous opioids and opioid receptors . The opioid upregulation effect of temporary naltrexone or naloxone blockade has been demonstrated multiple times previously . This opioid rebound effect could have multiple impacts on health and quality of life, including enhanced endogenous analgesia and repression of critical immune factors .
Further research is needed with naltrexone and naloxone stereoisomers to determine the true mechanism of clinical action. In the meantime, we note that both the TLR4 and opioid receptor mechanisms may play a role in LDN action, as the hypotheses are not mutually exclusive.
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Research For Ldn And Graves Disease
Currently, there is not a lot of research in terms of the benefits of low dose naltrexone. However, a small study has observed that the compound may be used for helping patients with active Graves disease. There are no studies that show LDN to be ineffective in helping manage the symptoms of thyroid.
The limited research is not an indication that LDN should not be considered. There are several reports of patients doing well after taking LDN. Healthcare professionals working with patients of Graves disease and other autoimmune thyroid patients have also reported significant benefits.
Use Of Ldn In Research Studies
It is important to note that there are currently no guidelines for the clinical use of LDN. There is no FDA-approved use for naltrexone at any dosage for the treatment of chronic pain and inflammatory diseases. There is also no FDA-approved use of LDN for the treatment of any medical condition. Researchers using LDN must do so under an FDA Investigational New Drug application. While physicians have developed varying strategies for the use of LDN, none have been empirically validated. Therefore, in this section, we cover the use of LDN in published research trials and do not intend this discussion to be viewed as guidelines for the clinical use of LDN.
The typical dosage of LDN in published research is 4.5 mg. The medication is commonly given approximately an hour before bedtime, though some individuals reporting insomnia as a side effect are moved to a morning dosing. Individuals with side effects also have their dosage reduced to 3.0 mg. At the time of writing, naltrexone is commercially available only in a 50-mg tablet form, although one US-based company appears to be gathering regulatory approvals to market the 4.5 mg formulation. Because there is no commercial formulation of LDN, research studies obtain the medication via compounding pharmacies. Standard gelatin capsules and microcrystalline cellulose filler are commonly used.
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How Do You Know If Its A Herx And Not An Adverse Drug Reaction
It is important to distinguish between a herx and an adverse drug reaction . The onset of a Herxheimer reaction is somewhat diagnostic of a spirochetal infection. So, if youre being treated for Lyme based on a clinical diagnosis, the herx can actually be a good sign that you are killing the right bacteria.
Ive talked to patients whove had Herxheimer reactions and almost all of them tell me it is a very intense experience. One patient described it as an altered state. Said one: Every cell in my body feels like its being crippled. Its mentally overwhelming and physically exhausting. I usually have a pulsing feeling in my body which distinguishes it from a medication side effect.
Adverse drug reactions, on the other hand, can range from mild to severe and can be mistaken for a herx. So how do you tell the difference?
Another patient distinguishes the two reactions as follows: Herxes for me seem to be more all over and include psych symptoms. Drug reactions seem to be more in line with what is described in the drug manufacturers papers. With antimicrobials, you can have both simultaneously, of course.
Mild ADRs will typically resolve shortly after the medication is stopped. On the other hand, a severe allergic reaction, called anaphylaxis, causes swelling of the airways, and can be fatal if not treated immediately .
Emerging Treatment Shows Promise
Naltrexone is a drug that, at a normal dose of 50 to 100 milligrams , blocks the effects of opioids. At very low doses, however, some researchers believe the drug may be beneficial to people with fibromyalgia and chronic fatigue syndrome.
Low-dose naltrexone is an inexpensive drug that’s already on the market, which has fueled excitement about its possible uses. Research is moving slowly, though, likely because there’s not a big financial incentive.
Other conditions where low-dose naltrexone is being explored include autoimmune/inflammatory diseases including multiple sclerosis, complex regional pain syndrome, and Crohn’s disease and other immune-related diseases, like HIV/AIDS.
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Patients Creating Their Own Dosages
At the time of writing, LDN is not available at the 4.5-mg dosage that would be typical for the management of chronic pain. As such, many individuals may try to create their own dosing by subdividing 50-mg tablets. Internet resources that explain the process of splitting 50-mg tablets or creating a solution and dividing out liquid doses have been found. Such approaches will likely lead to unintended variability in the day-to-day dosing. The harm of such inconsistency is mitigated by the fact that it is very unlikely that someone could dangerously overdose on naltrexone. Still, patients taking responsibility for creating doses is far from optimal.
Thyroid Medication Vs Low Dose Naltrexone
Most medical professionals will recommend thyroid hormone medication when patients are dealing with hypothyroidism. It is common for endocrinologists as well to recommend anti-thyroid medication for treating patients with Graves disease and hyperthyroidism. It is important to manage the symptoms while addressing the root cause of the issue.
However, it makes sense if a patient wants to take low dose naltrexone and not thyroid medication. The reason for this is that if LDN seems to work, then the person taking anti-thyroid medication or thyroid hormone medication may be able to stop taking the medications. This is important because many people suffering from Gravess Disease or hyperthyroidism are unable to take antithyroid medications, such as Methimazole.
Endocrinologists tend to pressure patients into getting radioactive iodine and thyroid surgery if they cannot take antithyroid medications because of many reasons. LDN can modulate the immune system in a natural way and help people avoid radioactive iodine and thyroid surgery.
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Studies Show Low Dose Naltrexone Is Safe
Current studies show that Low Dose Naltrexone is a safe, cost effective yet effective treatment for chronic pain and autoimmunity. It is believed that LDN works in the brain by reducing pro-inflammatory chemicals called cytokines, which are known to inflame and sensitize various tissues that can cause pain.
How Does Low Dose Naltrexone Work
Low Dose Naltrexone works on two areas:
Since it blocks opioid receptors, the body is tricked into thinking endorphin levels are low which results in an increase in endorphin production. Endorphins enhance the bodys immune function and reduces pain.
It also binds and blocks Toll-like Receptors, which release inflammatory cytokines, thereby reducing inflammation.
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How Is Low Dose Naltrexone Taken
Naltrexone is manufactured in 50mg tablets, so it must be compounded by a compounding pharmacy to get lower doses. I typically start patients on 0.5mg-1mg once per day at night. Then they increase the dose each week by one capsule at night until they reach 4mg at night. If a patients symptoms are better on a dose lower than 4 mg, they should stay on the lower dose for a more extended period of time.
It may take 3-6 months to notice the benefits of LDN. In my experience, this medication is one of the most effective treatments for a majority of my patients with symptoms rooted in chronic inflammation and immune dysregulation. It is necessary to give LDN some time to work on these underlying causes.
Association With General Markers Of Inflammation
As clinical research of LDN is still in its infancy, we do not have studies in humans that parallel the work performed in animal models. However, some indirect evidence supports the concept of LDN as a novel anti-inflammatory. In the initial pilot study of LDN in fibromyalgia , baseline erythrocyte sedimentation rate was a significant predictor of clinical response to LDN. ESR is a commonly employed clinical test that is sensitive to both chronic and acute inflammatory processes . In our study, individuals with greater ESR at baseline experienced a greater drop in pain when taking LDN, despite that fact that FM is not considered to be a classic inflammatory disorder, and ESR values were in the normal to high-normal range.
Relationship between baseline erythrocyte sedimentation rate and change in pain during administration of LDN and placebo . The figure uses data from earlier clinical trials and has not been previously published
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Why Has My Doctor Not Suggested Low Dose Naltrexone
Most doctors in traditional medicine only know about the use of naltrexone for opioid addiction. They are unaware mainly because Low Dose Naltrexone is an inexpensive, generic medication, so no drug company is interested in funding research or promoting it due to the low revenue. There has been a lot of independent research, however, and you can find information on research and other general information on: https://www.ldnresearchtrust.org
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Test Ldn In Other Inflammatory Conditions
Our findings that baseline ESR may be associated with LDN response suggest that other inflammatory conditions, such as rheumatoid arthritis, polymyalgia rheumatica, and lupus, may benefit from LDN. LDN may serve as a concomitant medication when immunomodulatory therapies are not effective or not well tolerated by the patient. We propose that pilot trials could be carried out to test LDN in inflammatory and autoimmune conditions.
What Is Low Dose Naltrexone
Naltrexone is an opioid receptor blocker. Narcotics, like oxycodone found in Percocet and hydrocodone found in Vicodin, are opioids. When they bind to an opioid receptor, narcotics regulate pain. Humans make natural narcotics called endorphins. These endorphins regulate pain and the immune system.
Low dose naltrexone is “low” because it is used at much lower doses than physicians use to treat people with narcotic addictions and alcoholism. It is manufactured only as a 50 mg pill. When it is used to regulate the immune system, it is dosed at 1.5 to 4.5 mg a day.
Compounding pharmacies that make medicines in house are able to produce naltrexone in low doses by crushing the 50 mg pill and dividing it into to “low” dose 1.5 to 4.5 mg pills.
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Better Tracking Of Inflammatory Markers During Ldn Treatment
Future studies examining LDN should determine if positive response is associated with a reduction of ESR or other measures of inflammation . Such information would help provide mechanistic information about the treatment. Examination of intracellular immune processes may further shed light on the mechanism of LDN treatment. Measurements of immune activity should be collected at least immediately before and after treatment or when the primary outcomes are assessed.
Side Effects Of Low Dose Naltrexone
The FDA approved naltrexone in the 1980s, so it has a long track record with an excellent safety profile. At much lower doses than the manufactured 50mg dose of naltrexone, compounded low-dose naltrexone has very few adverse effects.
To coincide with the bodys natural nighttime increase in endorphin production, LDN is typically taken at bedtime. For some people, LDN can contribute to insomnia. Often insomnia can be prevented if the dose of LDN is started lower than the target dose and titrated up as described above. If insomnia continues after titrating the dose, some people benefit from taking LDN in the morning instead of at night.
Since naltrexone partially blocks opioid receptors, LDN cannot be taken with opioid pain medications. The exception to this is the use of ultra low dose naltrexone to improve the effect of opioid pain medications.
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Low Dose Naltrexone Therapy
Accumulating evidence suggests that Low Dose Naltrexone can promote health supporting immune-modulation which may reduce various cancer-causing and inflammatory autoimmune processes. LDN may also play a role in healing and repair of tissues, as well as promoting stress resilience, social bonding, and emotional well-being and helping with psychiatric problems such as autism and depression.
Ldn Has Efficacy In Treating Known Inflammatory Disorders
A third piece of evidence that suggests LDN may have anti-inflammatory properties in humans is found in the nature of the chronic conditions that appear to respond to LDN treatment. The condition with the most scientific support for LDN efficacy is Crohns disease . CD is an inflammatory bowel disease that exerts gastrointestinal tract and systemic effects. LDN has been reported to reduce not only self-reported pain in that condition but also objective markers of inflammation and disease severity . The response rate of LDN in Crohns disease may be even higher than that seen in fibromyalgia, with over 80 % of the study participants exhibiting significant improvement .
Naltrexone has also shown some promise in improving disease severity in multiple sclerosis , an inflammatory, demyelinating condition of the central nervous system. The evidence of LDN efficacy is not as robust as in the previously mentioned conditions. There is some evidence of reduced spasticity and improved mental health, but many clinical endpoints fail to show difference from placebo, and one study did not find improvements in any of the clinical endpoints.
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Possibly The Least Expensive Most Effective Therapy For Immune Dysfunction And Inflammation
There are few medications available that are safe, inexpensive, and effective for chronic inflammation and immune-related conditions. When properly prescribed, LDN has the potential to improve the quality of life for people suffering from symptoms from Lyme disease, mold illness, and other chronic inflammatory states.
What Can Ldn Treat
Aside from autoimmune diseases, LDN is also used in the treatment of the following conditions. Bear in mind this is not a complete list. Some of these conditions have been featured in various documentaries5 produced by the LDN Research Trust. You can find links to those documentaries in the references.
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Cancer6 Research by professor Angus George Dalgleish and his colleague Dr. Wei Lou showed LDN could bring cancer cells into remission using pulse dosing.7 LDN also works synergistically with cannabidiol , and works well for cancer, autoimmunity and pain conditions |
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Opioid addiction, dependence and recovery8 Using microdoses of 0.001 milligrams , long-term users of opioids who have developed a tolerance to the drug are able to, over time, lower their opioid dose and avoid withdrawal symptoms as the LDN makes the opioid more effective. For opioid dependence, the typical starting dose is 1 microgram twice a day, which will allow them to lower their opioid dose by about 60%. When the opioid is taken for pain, the LDN must be taken four to six hours apart from the opioid in order to not displace the opioids effects |
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Lyme disease and its coinfections9 |
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Fibromyalgia |
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Infertility |
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What Are The Side Effects Of Low Dose Naltrexone
- Low Dose Naltrexone is generally very well tolerated and has very few side effects.
- Some of the possible side effects include fatigue, insomnia, vivid dreams, loss of appetite, nausea, headaches, mood swings.
- To lessen or eliminate possible side effects, the dose is gradually increased. It is also recommended to take in the morning to eliminate the side effect of insomnia and vivid dreams.
Ldn Decreases Inflammation In The Brain
The primary immune cells that protect the brain and spinal cord are called microglia. The microglia survey the central nervous system for foreign invaders such as bacteria, viruses, and toxins such as mold. When the microglia encounter one of these threatening invaders, an inflammatory response is triggered.
Microglia possess toll-like receptor 4 , which are part of this inflammatory cascade. LDN binds to TLR4 and blocks downstream neurological inflammation. I have found LDN to be one of the most effective therapies for my patients who have immune dysregulation and inflammation-causing symptoms of the brain, including headaches, anxiety, depression, and brain fog.
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