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Is Low-Dose Naltrexone a New Treatment Option for Fibromyalgia?

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Do you have patients suffering from fibromyalgia who have had very little luck with conventional treatments? Read on to learn what low-dose naltrexone might have to offer for this complex disorder.

Fibromyalgia is the second most common rheumatological disorder, behind only osteoarthritis, affecting around 5 percent of women and 1.6 percent of men (1). Instead of having a true diagnostic test, it is diagnosed based on symptoms and only after excluding other conditions like rheumatoid arthritis, major depressive disorder, multiple sclerosis, and other autoimmune diseases. Common symptoms include:

  • Muscle pain and fatigue
  • Tenderness at certain points on the body when pressure is applied
  • Sleep disturbances
  • Headaches
  • Numbness/tingling in the hands and feet
  • Brain fog

In 2010, the American College of Rheumatology revised its diagnosis criteria to include either:

  1. Widespread pain index ≥ 7 and a severity score ≥ 5, OR
  2. A widespread pain index of 3 to 6 and a severity score ≥ 9,

AND symptoms persisting for at least three months.

Conventional Treatments Fall Short

Fibromyalgia can be a debilitating condition that impacts mood, personal life, and professional life. Conventional treatment may include a combination of pregabalin, duloxetine, and milnacipran, the three drugs currently FDA-approved for fibromyalgia. However, recent reviews report that these medications are either accompanied by intolerable side effects or don’t offer substantial symptomatic relief (2, 3, 4).

Doctors may also prescribe analgesics, antidepressants, antiseizure drugs, or muscle relaxants, but again, these drugs attempt only to alleviate symptoms, with widely varying success rates.

Enter Low-Dose Naltrexone

Naltrexone was initially approved back in 1984 at a higher 50mg dose to treat opioid and heroin addiction. An opioid antagonist, naltrexone blocks endorphin action, preventing a patient from getting high on any dose of a drug.

As early as 1985, Dr. Bernard Bihari discovered that naltrexone in a lower 3mg dose enhanced patients’ response to HIV infection (5). By the 1990s, low-dose naltrexone (LDN) was being used in cancer patients and in patients with autoimmune diseases for its observed positive effects on the immune system. Recently, small studies have shown promising benefits of LDN for patients with fibromyalgia as well (6, 7, 8).

In fibromyalgia patients, something is off in the opioid system. Beta-endorphin levels tend to be lower compared to the general population, while met-enkephalin and dynorphin levels tend to be elevated. Although not proven, one hypothesis is that opioid resistance is an aspect of fibromyalgia, much like the insulin resistance observed in type 2 diabetes.

A low dose of naltrexone, when taken at bedtime, blocks opioid receptors for a short time in the middle of the night (9, 10). In response, the body thinks it needs more opioids, and so more are produced. By the time these opioids reach their receptors, LDN is out of the system, and the receptors are free to receive the opioids. Therefore, the major therapeutic action of LDN is probably a net increase in opioid production.

LDN Regulates the Immune System and Reduces Inflammation

Opioid-related receptors are present on all immune cells, from T cells and B cells to macrophages and natural killer cells. Opioids have the ability to alter the development, differentiation, and function of immune cells (11, 12), and therefore blocking their activities via LDN affects the immune system. LDN appears to work in two ways:

  1. By regulating the immune system, and
  2. By reducing inflammation in the central nervous system.

Fibromyalgia isn’t generally classified as an autoimmune disease per se, but it shares many traits with Hashimoto’s, rheumatoid arthritis, Crohn’s disease, and other autoimmune-like diseases. In an autoimmune disease, the body is attacking itself, often as a result of chronic overproduction of inflammatory cytokines. T regulatory cells are responsible for turning inflammation on and off and can help prevent an immune system from becoming overactive and eventually leading to autoimmune dysfunction (13). LDN promotes T regulatory cell function, keeping the immune system in check.

LDN’s second major role is reducing inflammation in the central nervous system, a common attribute of fibromyalgia, chronic pain, and depression. The key cells here are white blood cells called microglia, the resident macrophages of the CNS. Normally, they are inactive, but they can be triggered by cell death, peripheral inflammation, and infection (14). Once activated, they release proinflammatory factors that interact with neurons to induce hyperalgesia, fatigue, and other symptoms (15, 16).

LDN blocks toll-like receptor 4, a protein found on microglia (17) that essentially blocks the cascade of inflammation. LDN has been shown to reduce erythrocyte sedimentation rate, or ESR, an inflammatory marker often elevated in fibromyalgia patients. In fact, the success of treating fibromyalgia with LDN correlated well with baseline ESR levels in two studies (6, 8). Evidence suggests that LDN may also reduce peripheral inflammation by suppressing TNF-alpha, IL-6, MCP-1, and others (18).

LDN Treatment for Fibromyalgia Shows Promising Results

LDN as a treatment has been studied most extensively for Crohn’s disease (19, 20, 21) and multiple sclerosis (22, 23) in the past decade with fantastic results. One study showed complete mucosal healing for Crohn’s disease patients (20). Small trials and case studies have shown success using LDN to treat a variety of autoimmune diseases, neurodegenerative disorders, and chronic pain disorders like fibromyalgia.

In 2009, a small pilot study observed LDN for the treatment of 10 women with fibromyalgia. The crossover trial showed that 4.5mg of LDN daily reduced fibromyalgia symptoms 30 percent more than placebo (6). The drug showed the greatest improvements in daily pain, highest pain, and stress levels, but it did not significantly impact sleep quality, headaches, concentration, or sadness. The patients were on LDN for eight weeks, and the peak effect occurred after approximately one month of treatment.

A randomized, double-blind, placebo-controlled trial of 31 women with fibromyalgia demonstrated a greater reduction of pain with LDN treatment (29 percent) versus placebo (18 percent) (7). Almost a third of patients had a significant reduction in both pain and either fatigue or sleep with LDN, versus only 11 percent with placebo.

Another small crossover trial just published in 2017 showed that eight weeks of LDN treatment reduced proinflammatory cytokines in eight fibromyalgia patients (8). The women also reported a 15 percent reduction in pain.

In all three of the above studies that explored LDN as a treatment for fibromyalgia, side effects were rare, mild, and usually temporary, a huge advantage over conventional treatments. Because its patent expired many years ago, LDN is also relatively cheap, at $40 per month or less.

Pharmaceuticals are not usually my first choice. However, in this case, LDN might be doing more than merely treating symptoms. LDN has been shown to restore normal endorphin levels, regulate the immune system, and reduce inflammation in the CNS, all of which seem to play a role in fibromyalgia etiology.

Contraindications and Alternatives

LDN has few known contraindications. Because it blocks opioid receptors, LDN shouldn’t be taken together with narcotics like Percocet, morphine, or tramadol. Patients who are already taking medication for Graves’ or Hashimoto’s need to be closely monitored when beginning LDN treatment. Often, LDN treatment also improves thyroid function, and therefore whatever dose of thyroid medication the patient is taking can become too high or too low, which can trigger a hyperthyroid or hypothyroid episode, respectively.

Make sure your patients obtain LDN from a reliable compounding pharmacy by consulting the list found at LDN should not be administered in the slow-release form, and filler type is especially important for this drug.

Before prescribing LDN, alternatives for promoting T regulatory cell function and reducing CNS inflammation can be explored. Vitamin D, vitamin A, glutathione, and probiotics all promote T regulatory cells. Selenium, zinc, and iodine are important for immune function in general. Some options for treating inflammation are curcumin, boswellia, stinging nettle, reishi mushroom (24), high-quality fish oil, and an anti-inflammatory diet.

Furthermore, additional benefits may be found in other alternative treatments, including:

  • Meditation (2526)
  • Cannabinoids (27, 28)
  • Exercise (29, 30)
  • Tai chi (31)
  • Massage (32)
  • Acupuncture (33)

The Bottom Line

Although LDN has few known side effects and downsides, before recommending it to fibromyalgia patients, I would first make sure everything else was in check. I would test for nutrient deficiencies, see that the patient had been on an anti-inflammatory diet, and maybe see if the patient had considered some of the alternative treatments from above. Given the debilitating nature of fibromyalgia and suboptimal conventional treatments, LDN is worth considering as a promising treatment.

Chris Kresser
Chris Kresser is the founder of the Kresser Institute and a health detective specializing in investigative medicine. He is a blogger, podcaster, teacher, and Paleo diet and lifestyle enthusiast.

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  1. Hi Chris,
    I have fibromyalgia and my doctor prescribed LDN for me about 4-5 years ago I guess. I didn’t notice any earth shattering changes at first. But I did stop taking it and noticed a big difference. I think one reason I didn’t notice a huge difference at first is that I still had some other issues going on. I have Lyme, IBS, fibromyalgia. And I struggled with these things for a long time. My PCP had actually recommended I try to see you. But I live in the Boulder, CO area, so….not super convenient. I have been receiving acupuncture which has been hugely helpful. And earlier this year I was diagnosed with ideopathic hypersomnia/borderline narcolepsy without cataplexie. My sleep doc started me on Provigil. And it’s made a huge difference. Not only does it help with my daytime sleepiness, but it helps my fibromyalgia pain as well. I had to go off it for a week this spring to do a MSLT and I noticed that my fibromyalgia pain came back.

    On a professional note, I am also a Physical Therapist and a Rolfer so I frequently suggest my patients with fibromyalgia and other auto immune issues ask their doctor about LDN.

    I enjoy reading your posts. Thank you.

  2. I think I need to reassess where I am right now?
    I’d be really interested to hear what gets found about LDN. I’ve been on it for 15 or so years. I was diagnosed with MS in 94 and found out about LDN in the early noughties.

    I have high-ish TPO (around 200) but rest of thyroid numbers are ‘normal’.
    I think LDN has kept a lid on Hashimoto’s for me? My gp eventually decided to give me 50mg of levothyroxine which I think has helped my body function a little better. I still use a walking stick and I drive an adapted car but life is feeling richer, nowadays.

  3. As an Osteopathic/Naturopathic Physician, I frequently prescribe LDN. It is a very powerful immune-modulator. However, I never prescribe it in a “vacuum”; I always promote vitamin and mineral optimization, along with lifestyle-modification medicine before I prescribe LDN.

  4. This is good to hear. I purchased a book call Good Medicine and it is all about LDN, which also appears to help MS, Liver disease, etc. It goes over the history of LDN, Dr. Bihari, etc., It’s worth a read

  5. I have had fms/cfs since 1999 but wasn’t dxd ’til 2004 because I was told it didn’t exist and then when I was dxd, I told there was nothing to do about it anyway so go home and learn to live with the pain by my then doc and rheumatologist, both of whom I never went back to. I found a new doc in 2008 and was dxd in 2010 with Hashimoto’s and I feel there is more wrong inside me too but anyway, I had read about some folks’ success using LDN on some of the online Fibromyalgia and Hashimoto’s forums to which I belong. So I asked my next doc if I could try LDN as I got sick so easily and was sick more than I wasn’t, always upper respiratory and sometimes bronchial involvement. He agreed to prescribe LDN for me but unfortunately, he didn’t follow Dr. Bihari’s protocol of beginning very low like 1.5 mg @ hs and slowly working upwards to a maximum dose of 4.5 mg so instead he prescribed me the full dose of 4.5 mg @ hs right off the bat. I tolerated it okay though insofar as I can recall and I felt that it did help me feel better but it lasted only for a few months when it no longer seemed to work anymore and I was getting sick again as often as before the LDN. Apparently from what I’ve read about when LDN doesn’t work for someone, it’s because there is a problem with their cortisol levels (either too low/too high) &/or they have some undiagnsosed chronic infection going on which I believe is my case (suspect SIBO, candida overgrowth, possibly lyme as I’ve been bitten twice that I know of, possibly more) but I haven’t the money to find out as for reasons I do not understand, testing has to be paid for out of pocket but I lack the necessary funds. I live in Ontario, Canada and these tests aren’t covered by our provincial gov’t (OHIP) nor by our extended coverage (Green Shield). I’ve been sick for so long now (since 1999) that my memories of feeling good are now distant ones:-(

  6. LDN was suggested by our Doc, too.
    We both tried it, and found some amount of relief. BUT….
    1. It must be compounded. Finding a truly accurate, reliable compounding pharmacy, can be a frustrating process.
    2. Now that LDN has gained some popularity for some years as helping FMS, etc. pain problems, the prices on those tiny 3mg doses, has skyrocketed.
    3. There’s now a full-blown witch-hunt against opiates [again]. Naltrexone is in the same class. Not only are patients forced to have a Doc. appt. and new script every 6 months, but pharmacists in some places get really weird/wigged-out when explaining that to patients. And, State regulators are coming down on ALL practitioners who can prescribe controlled substances, and routinely tell Docs when the regulators think the Docs have written too many scripts for controlled substances….doesn’t matter if the Doc specializes in pain issues [most of their patients], and doesn’t matter how tiny the dose.
    …..That’s been our experience. Cost: Benefit + Risk: Benefit ratios just don’t work for us.
    Maybe other’s experiences are better. But for those in WA State….it seems a poor solution.

    • I’m sorry you’ve had a negative experience. I’ve had a good one and want to share a couple of things.
      There is a list of compounding pharmacies on the lowdosenaltrexone website that are reliable. I use Belmar in Colorado. I live in TN and they ship, no problem. Their pricing is not bad. For me, what I pay is absolutely worth the benefit of the medication.
      Naltrexone is not in the same class as narcotics. Opiates/narcotics are very different from opiate antagonists which is the class of drugs to which naltrexone belongs.
      Hope this is helpful!

  7. Hi folks

    Does anyone know of any doctors in Australia that have experience prescribing this medication?

    many thanks, Milly

  8. I was prescribed LDN for Crohn’s. However, I saw the most benefit with my Fibro/CFS symptoms. I have been taking 4.5mgs for over 3 years. It has been a game changer for me. Anyone with FIBRO or CFS should give it a try.

  9. Hello,

    Iv been reading quite a lot on forums of patients taking LDN, and complaining of huge fatigue, probably linked to adrenal exhaustion with low cortisol.
    Anyone heard of this contraindication?
    Adrenal fatigue/ LDN sideeffects of fatigue.
    Should i be careful to prescribe it to patients with Adrenal fatigue?
    Best wishes,
    Dr. Denef Liesbeth
    Integrativ emedicine/functional medicine