Low Dose Naltrexone (LDN) Fibromyalgia and Chronic Fatigue Syndrome Resource Center


Low Dose Naltrexone (LDN) …

Low dose naltrexone is cheap, readily available and safe...but does it work in FM and ME/CFS?

Low dose naltrexone is cheap, readily available and safe…but does it work in FM and ME/CFS?

Low dose naltrexone (LDN) seems, at first glance, like a strange drug for people with chronic fatigue syndrome (ME/CFS) or fibromyalgia.  Usually used in high doses to combat alcoholism and narcotics withdrawal, Naltrexone blocks the opioid/endorphin receptors in the brain. LDN has the advantage of being cheap, easily produced in compounding pharmacies and safe.

But why would a drug that’s used to get people off of narcotics benefit people with fibromyalgia, ME/CFS and other disorders?

Feeling Good (Finally)

There are couple of reasons….For one LDN are a ‘feel-good’ drug and some studies suggest ‘feel-good’ agents such as endorphins are low in pain disorders like fibromygalgia and chronic fatigue syndrome (ME/CFS).  By blocking the receptors for endorphins, low doses of naltrexone appears to trick the brain into producing more of them. The 4-6 hours or so the drug remains in one’s system may be sufficient to boost endogenous opioid levels for 18-24 hours. Given that endorphins are known as ‘natural pain relievers’ more endorphins might be a very good thing for people with these disorders to have.

A recent case study involving suggested the endorphin scenario might be a viable one. A 37-year-old professor with sharp pains, burning sensations, dull pain, dry, painful eyes, sleep issue, difficulties with concentration and agitation received substantial relief from LDN but still had FM.

The Immune –  Autoimmune Connection

There’s another possibility as well. Endorphins enhance the responses of natural killer cells, a key immune factor in ME/CFS, and they reduce B-cell (antibody) activity. Rituximab is a B-cell inhibitor that several small studies suggest may work in chronic fatigue syndrome (ME/CFS), and ME/CFS has many characteristics that are associated with autoimmune disorders.  LDN’s effectiveness is currently being tested in several autoimmune diseases.

LDN  also may be able to regulate the activity of immune cells in the central nervous system called microglial cells.  When these cells get turned on they produce pro-inflammatory cytokines, reactive oxygen species (free radicals) and nitric oxide – all of which are under study in ME/CFS and/or FM.

Microglial cells, in fact, may be a key component of the ‘sickness response’ that produces the fatigue, fluey feelings, pain, etc. when we come down with an infection. Some researchers believe these cells may be chronically turned on in ME/CFS and fibromyalgia. LDN’s ability to block a key receptor (TLR 4) on microglial cells appears to inhibit them from becoming activated.

Easily compoundable at local pharmacies LDN will never get financial support from drug companies for drug trials but studies are slowly being done (see the Clinicaltrials.gov site.)


Many women chronic fatigue syndrome reportedly experience remissions during pregnancy when high levels of endogenous opioids are present. They then often experience relapses several months after pregnancy when the levels of those opioids fall. This pattern suggests that one or more of the opioid receptors that LDN effects could play a role in the progression of these disorders.

LDN Might Be Effective in Chronic Fatigue Syndrome and/or Fibromyalgia Because…

It may be able to reregulate immune functioning and increase neurotransmitters called endorphins that may be low in the disorder. LDN’s ability to modulate natural killer cell activity upwards and reduce B-cell activity could help to re-regulate the immune response in ME/CFS and/or FM. It’s ability to reduce microglial functioning could reduce the fatigue and pain and other symptoms.

Fibromyalgia LDN Studies 

Two small fibromyalgia studies from Stanford researchers suggest the drug can significantly help with the pain of FM. A 2009 single-blind crossover study found LDN significantly reduced pain, fatigue and stress levels.  Once patients were off the drug, their symptom levels quickly returned to normal.  Intriguingly, a measure of inflammation called erythrocyte sedimentation level (ESR) predicted 80% of the responses. The fact that higher ESR’s were associated with greater reductions in symptom severity suggests that inflammation may play a large role in some cases of FM.  Since ESR’s are not typically elevated in FM, ESR levels could be used to detect FM subsets that might do well on the drug.

A larger placebo-controlled, double-blinded, crossover study found significantly reduced pain, significantly improved mood,  and improved general satisfaction with life in subjects taking 4.5 mg/day of LDN. Fatigue and sleep, however, were not significantly affected.

Jarred Younger at the University of Alabama at Birmingham’s Neuroinflammation, Fatigue and Pain Lab has a variety of LDN studies planned. Their topics include

  • Determining proper dosage. A dose-ranging study will determine if lower or higher dosages work better for some people.
  • Determining if LDN helps in other conditions such as rheumatoid arthritis, osteoarthritis, CFS, and perhaps depression.
  • A chronic fatigue syndrome study
  • A large (200+ person) clinical trial of LDN and fibromyalgia

Read more: Low Dose Naltrexone, Inflammation, and Pain: A Different Approach to Fibromyalgia

Chronic Fatigue Syndrome/Fibromyalgia Doctors Report 

LDN is Dr. Nancy Klimas’ first-line treatment for the pain associated with fibromyalgia and chronic fatigue syndrome.  She has found the drug to be effective and safe. Dr. Ginerva finds the drug works in about 60% of her FM patients. (See link to blog below.)

Side Effects

Side effects are usually reported to be minimal but that belies testimonials from some patients who have had a great deal of difficulty with this drug. It’s clear that FM and ME/CFS patients should start low and go slow. Side effects can include priapism (prolonged erections), sleep dysfunction (at least in the beginning) and weight loss. In general side effects are described as ‘mild’ with few issues occurring even with much the higher naltrexone doses used in addiction and alcoholism.

Getting Low Dose Naltrexone

The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. (Younger et. al.)

  • Find doctors that prescribe LDN here and here.
  • Immune Therapeutics – the drug manufacturer licensed to market LDN drugs – partnered with KRS Biotechnologies in Jan. 2015 produce a standardized version of LDN for sale to the public and clinical trials. Costs for this high-quality source of LDN are $1 a tablet. Find more about this here.
  • Find pharmacies that compound LDN here and here.  LDN Science asserts many compounding pharmacies are not reliable. They provide a list of reliable pharmacies here.  They recommend that LDN not be used in its ‘slow-release’ form and that certain fillers not be used.

The LDN website states that LDN is sold by Mallinckrodt as Depade, and by Barr Laboratories as naltrexone, and that a one month supply ranges from $15 to $40.

Dr. Neil Beck reported “People vary so much in their condition, body mass, absorption, sensitivity to and excretion of Naltrexone that a Doctor can only generalize about dose sizes and then you have to find out for yourself depending on how you feel and perform, your blood tests and your physical examinations and scans. What’s best for other people may not be best for you.”

It is usually best to start with 1.5 mg and every week or two increase. (According to Dr. De Meirleir,  the doses in ME/CFS – a disease which features hypersensitivity to drugs – may be as low as 0.5 mg. and up to 5 mg. or more.) Go to 3 then 4.5 then 6 mg. Most people find 1.5 mg. isn’t enough and 6 mg. is too much and that from 3-4.5 mgs. is the best. He suggests that patients every few months decrease and increase their dose  to check that their requirements haven;t changed.

If you’re on narcotic pain drugs, do not take LDN until the drugs are out of your system. If you have Hashimoto’s disease, consult with your doctor and start off low.

How Long To Take LDN? 

Longer than you may think; Jarred Younger Ph.D. stated that it could take 8-10 weeks to determine if you will respond to the drug. Don’t stop taking it before then.

Health Rising Blogs


An impressive grassroots effort has sprung up on the web around LDN:



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