LDN: Sensible Treatment for Chronic Fatigue Syndrome and Fibromyaglia

Low dose naltrexone reduces neuroinflammation and may help symptoms of chronic fatigue syndrome and fibromyalgia

First synthesized in 1963, naltrexone is an opioid antagonist meaning it blocks the body’s opioid receptors. Naltrexone has been used for decades to combat opioid overdose and addiction due to these mechanisms. For this purpose, the drug is sold at 50 mg doses.

In the late 1980’s, low doses of the drug were proposed to treat immune disorders. Low dose naltrexone (LDN) is defined as any dose range from 1 to 5 mg.

Naltrexone was patented in 1967, and therein lies the rub. The expiry of the patent limits the drugs ability to garner interest in pharmaceutical companies. Instead it must rely on non-business driven funding to achieve wider recognition. To date, LDN is not FDA-approved to treat any condition. That may soon change…

LDN in Fibromyalgia

A small pilot study from 2009, of 10 women with fibromyalgia, showed that LDN significantly improved pain in 6 out of 10 of the participants after 8 week of 4.5 mg. The intervention was started after a 2 week placebo. This study was followed up in 2013 with a double-blind, crossover study of 30 women with fibromyalgia. As much as 57% of the participants were observed to exhibit a significant reduction in pain and overall sense of improvement. The same group measured what was causing these improvements in 2018, and found that inflammatory cytokines were reduced in 10 women with fibromyalgia following 8 weeks of LDN. They reported a 15% reduction of fibromyalgia-associated pain and an 18% reduction in overall symptoms. This last study is vitally important as it may show that indeed inflammatory cytokines are the main contributor to symptom and symptom severity.

An interesting caveat of the 2013 study was that individuals with greater ESR at baseline experienced a greater drop in pain when taking LDN. However, ESR was still within normal range, but at the high end of normal. ESR, or erythrocyte sedimentation rate, is a basic laboratory marker of systemic inflammation.


LDN in Other Conditions

The best studied condition using LDN as a treatment option is Crohn’s disease. Some studies suggest up to 80% of those with Crohn’s respond positively subjectively and objectively to LDN. These findings sparked biotech company TNI, to purchase exclusive patent rights for LDN in 2013. They were able to purchase these rights through a FDA orphan drug status using it for Crohn’s in pediatric patients. If the results of these clinical trials are positive, we may see LDN FDA-approved for pediatric Crohn’s disease but likely with a massive price hike.

LDN has also been studied in other conditions like multiple sclerosis, neuropathic pain, HIV/AIDS, and cancer.

How LDN Works

LDN binds to toll-like receptor 4 (TLR-4), an important receptor found on microglial cells--specialized immune cells in the central nervous system. Toll-like receptors function to recognize patterns from foreign antigens or molecules produced by the body itself. Once these bind to a TLR, the receptor communicates the release of inflammatory byproducts from the cell. Some examples include cytokines like interleukin-1 (IL-1), tumor necrosis factor (TNF)-α, interferon-β, and nitric oxide.

The TLR of microglia is a vital constituent of our immune defenses when we encounter infection. The inflammatory and excitatory factors that are produced cause “sickness behaviors” like pain, fatigue, and general malaise. These effects lead us to stop and rest so that we can clear the infection. However, there is now evidence that a delicate balancing act can occur with microglia responding in kind or over-zealously. Over activation of microglia is associated with more severe symptoms including cognitive disruption, sleep disorders, mood disorders, and even degeneration of nerve tissue. Over activated microglia are associated with degenerative neurological disorders like Alzheimer’s and ALS.

LDN Should be the #1 Treatment for ME/CFS and Fibromyalgia

Brain imaging studies in ME/CFS and fibromyalgia have shown over activated microglia and generalized neuroinflammation. It is also suggested that these findings strongly correlate with disease severity. Read more about this in a previous post. Traditional anti-inflammatories are ineffective for these conditions because they do not act in the central nervous system. They cannot cross the blood-brain barrier. Medications that inhibit microglia directly, such as LDN, are a logical option.

LDN is believed to reduce neuroinflammation and associated symptoms by two mechanism. First, LDN enhances the release of the body’s natural opioids, endorphins. This effect alone could reduce pain and sickness behaviors but as one might expect is not an intervention geared at the main problem. Secondly, LDN acts by binding to TLR-4 to shut down the over activated microglia and reduce inflammatory cytokines—this an intervention targeted to the prime driver of symptoms. Studies have shown that LDN significantly reduces inflammatory cytokines like IL-6, TNF-α, transforming growth factor (TGF)-β, IL-17, IL-1, IL-2, and interferon-α. All of these inflammatory markers have been associated with ME/CFS or fibromyalgia.

Side Effects

It could be argued that LDN is the safest, best tolerated microglia inhibitor. It’s also the easiest to procure as you’ll see below. The most reported side effects in studies using LDN are vivid dreams and headache. These effects were minimized when the dose was reduced to 3 mg. Others report insomnia but these effects can be reduced by taking the drug earlier in the afternoon, not at bed time.

How To Get LDN

Not only is LDN very unlikely to cause side effects and toxicity. It is also exceptionally cheap. This is of course good for the consumer, but bad news for pharmaceutical companies and researchers who want to study it further. LDN is available in various preparations which also make it ideal for ME/CFS patients who are sensitive and require careful titration.

  • Capsule or tablet form 1.5 - 4.5 mg

  • Oral Liquid Formulation at 1 mg/1 mL

  • Sublingual drops

  • Topical LDN (I was unable to find evidence that this is effectively absorbed through the skin but it might be)

LDN is safe to take with other medications. There are no known drug interactions. If utilizing opioids, consult your doctor as dosages may need to be altered. Opioids and LDN can be used safely together when safely prescribed, and some literature suggests synergistic effects.

If your doctor is willing to prescribe, LDN is available at various compounding pharmacies: Check here.

If you live in the US, you can purchase LDN in capsule form without a prescription through Anti-Aging Systems. This is Dr. Craig’s preferred source. Be prudent before embarking on self-prescription. Talk with your doctor and take a look at the research for yourself.

For those in the UK and EU, you may get a prescription of LDN through Clinic 158, a telemedicine service. Here you can submit a medical record with evidence of diagnosis or have the clinic contact your GP to verify your condition. An online medication consultation will be established for £35, and the LDN prescription costs £20.

Dr. Craig’s Experience Using LDN

A recent trip to Zimbabwe included 2 layovers and 27 hours of sleepless flights. Upon landing I was understandably wrecked. All over pain, low-grade fever, general malaise, brain fog, can-barely-stand-fatigue. Naturally I rested but also took 4.5 mg of LDN that night. The next day I was up, pain and fatigue free, ready to explore. Without the LDN, the start of my trip would’ve needed at least 2 days to begin.

Last Fall I spent some time in Slovenia. I spent one day hiking around gorgeous Lake Bohinj, a mostly flat trail of 7.4 miles/12 km. Some fatigue set in late in the day afterward. A dose of 4.5 mg of LDN at night gave me the ability to ride back to Ljubljana the next day and climb the hill to Ljubljana Castle with a backpack full of Slovenian wines.

These are just two of many examples of how LDN has allowed me to physically do more than I could ever imagine. All the better, I don’t experience any side effects. While other interventions help improve my ME/CFS symptoms, LDN has been the only intervention that completely mitigates the post-exertional malaise.

Do you have experience using LDN? Comment below.


Younger J, Parkitny L, McLain D. (2014) The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 33(4):451-9.

Toljan K, Vrooman B (2018) Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 6(4). pii: E82.

Lehnardt S (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia. 58(3):253-63.

Parkitny L, Younger J (2017) Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines. 2017 Apr 18;5(2).

Cote B, Ross B, Fortner J, & Rao D  (2018) The Use and Utility of Low-dose Naltrexone Capsules for Patients with Fibromyalgia. Int J Pharm Compd. 22(3):252-256.

Dr. Craiginflammation, LDN