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


LDN is one of the few things that I can say to people that the odds are pretty good that …(it) can reduce your pain.  Dr. Ginevra Liptan – Fibromyalgia specialist

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?

Could a low cost, easily available drug that most doctors don’t know about help with your pain or other symptoms? It just might.

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.

Blocking the receptors that activate the pain-killing opioid pathways or the good feeling producing endorphin pathways wouldn’t seem to be a good thing given that some studies suggest that the pain relievers produced by the body are low in chronic pain disorders like fibromygalgia and chronic fatigue syndrome (ME/CFS),

Are All the “Feel-Good” Pathways Blocked in Fibromyalgia and Chronic Fatigue Syndrome?

Feeling Good Again?

Low dose naltrexone (LDN), however, works differently than naltrexone. LDN  appears to prompt the opioid and endorphin systems to respond with a vigor – and produce more “feel-good” substances.

LDN”s blockage of the endorphin and opioid receptors in the brain appears to trick the brain in a kind of rebound effect, to produce more of them. The 4-6 hours or so the drug remains in one’s system is sufficient to boost the levels of endogenous opioids (those naturally found in the brain) for 18-24 hours. Given that endorphins are known as ‘natural pain relievers’ having more endorphins  floating around might be a very good thing for people with FM. ME/CFS and other pain disorders.

Inflammation Buster?

LDN also appears to 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 capable of tweaking the nerves that produce pain, fatigue and other symptoms.

Microglial cells appear to play a key role in produces the ‘sickness response’  responsible for the the fatigue, fluey feelings, pain, etc.  that we associate with colds , and which appears to be present in chronic fatigue syndrome (ME/CFS) and fibromyalgia.  Recent studies suggesting that neuroinflammation is present in both fibromyalgia and ME/CFS has put a new spotlight on these cells.

Fibromyalgia Neuroinflammation Finding Could Open New Treatment Options

LDN’s ability to block a key receptor (TLR 4) on microglial cells appears to inhibit them from becoming activated – and is another good reason to try it in two diseases, ME/CFS and FM, which appear to be associated with neuroinflammation.


Pregnancy, interestingly enough, might provide a clue as to why LDN is effective when it is. Some women with ME/CFS 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 naturally occurring opioids fall. This pattern suggests that one or more of the opioid receptors that LDN effects could play a role in this disease.

To sum up…

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

LDN’s ability to tamp down microglial functioning could reduce the levels of the pro-inflammatory cytokines responsible for producing pain, fatigue and other symptoms n ME/CFS and FM. it may also increase levels of the natural”feel-good” substances such as endogenous opioids and endorphins.

Fibromyalgia and ME/CFS Low Dose Naltrexone (LDN) Studies

LDN has not been well-studied in either disease but wo small fibromyalgia studies lead by Jarred Younger suggest LDN may be able to help some people with fibromyalgia.   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.  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 FM patients with more inflammation might benefit more from this drug.

A larger placebo-controlled, double-blinded, crossover study (dose 4.5 mg/day) produced similar results: reduced pain, improved mood, and general satisfaction with life. LDN was helpful in reducing about 30% of the pain in about 60% of the patients.

The first ME/CFS study – a retrospective study assessing the charts of 218 patients – found that about half the participants experienced some improvement in at least two more symptoms. A 2019 case report also fleshed out the experiences of three ME/CFS patients. An Australian laboratory study suggested that LDN may help with the natural killer cell problems found in ME/CFS.

Larger studies which assess the effects of different doses and different dose protocols and more fully fill out LDN’s effects are greatly needed.  Younger’s Neuroinflammation, Fatigue and Pain Lab at the University of Alabama at Birmingham has a variety of LDN studies planned. The NIH, however, recently rebuffed Younger’s efforts to fund an ME/CFS trial and a trial involving dextro-naltrexone (see below).

Chronic Fatigue Syndrome/Fibromyalgia Doctors Report

“I want to make a plug for Low Dose Naltrexone”  Dr. Nancy Klimas – Simmaron Roundtable Meeting on ME/CFS

  • 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 Liptan finds that LDN works in about 60% of her FM patients.
  • Dr Bela Chheda tries LDN in almost of all of her patients. Even when her patients do not respond she tends to keep them on for its beneficial immune effects.

Getting Low Dose Naltrexone

LDN, a compounded drug, is, fortunately, cheap and relatively easy to get. The biggest hurdle many patients may face is getting a prescription from a doctor unfamiliar with the drug.  Check out the “Starting the Conversation” chapter in The LDN Book for advice on how to enroll your doctor in writing a prescription for you.

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.
  • Find pharmacies that compound LDN here and here.  LDN Science asserts many compounding pharmacies are not reliable. They provide a list of 7 pharmacies they consider reliable here.  They recommend that LDN not be used in its ‘slow-release’ form and that calcium carbonate not be used. Avicel, lactose and sucrose fillers work fine.
  • Immune Therapeutics – the drug manufacturer licensed to market LDN drugs – partnered with KRS Biotechnologies in Jan. 2015 to produce a standardized version of LDN for sale to the public and clinical trials. Costs for this high-quality, but high cost source of LDN are $1 a tablet. Find more about this here.

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.


LDN Science reports that in Spring 2017 a month’s supply (30 capsules) was about 36 dollars plus a shipping fee.


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”.

Most people probably start with 1.5 mg/day and then increase over a couple of weeks or a month. Skip Lenz, a well-known compound pharmacist recommends starting at 1.5 mg/day for 30 days, then go 3.0 mgs for 30 days and then re-evaluate with your doctor to determine if you should move up to 4.5 mg/day

Dr. De Meirleir, an ME/CFS specialist,  reports that starting doses in ME/CFS can be as low as 0.5 mg/day and end up being 5 mg/day or more. In general he finds that 1.5 mg. isn’t enough and 6 mg/day is too much and that most people end up taking from 3-4.5 mg/day. He suggests that patients decrease and then increase their dose every few months to check that their requirements for the drug haven’t changed.

Some patients start off at even lower doses (.25 mg/day), and some respond positively to much higher doses of the drug. One formerly bedridden woman who received mild benefits from the drug at 3 mg/day fully recovered from ME/CFS while taking 12 mgs/day.

The Strangeness of Low Dose Naltrexone: Weird Dosing, Backward Protocols and Rejections – in ME/CFS and Fibromyalgia

Adjustment to the drug can take more time than expected as well. The woman who ended up taking 12mgs/day of the drug at first topped out at 3 mgs but months later was able to significantly increase her dosage without incident.

Stay Away from Internet Purchases

Skip Lenz, pharmacist, reported he assayed naltrexone from six different sites on the internet and not one passed the U.S. Pharmacopeia standards.

The Opioid Crunch

If you’re on narcotic pain drugs, do not take LDN until the drugs are out of your system. Many people with FM on opioid painkillers are, therefore, precluded from taking the drug.
Skip Lenz, a pharmacist, however, (who does not consider tramadol an opiate), stated that he has not found that doses in the range of 50 mg. taken 2-3 times a day, cause problems with LDN.

If surgery is coming up Lenz recommends being off LDN for seven days prior to your surgery. He recommends trying tramadol after the surgery.

How Long To Take LDN To Know If It’s Working

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

Possible Side Effects

Side effects are usually reported to be minimal but some patients can have a great deal of difficulty with this drug. By starting the dosage off low and going slow many patients can tolerate dosages that would otherwise be intolerable.

Side effects can include sleep dysfunction Iinsomnia, wild dreams) and more rarely things like priapism (prolonged erections) and weight loss. In general side effects are described as ‘mild’ with few issues occurring so long as the dose begins low and is slowly titrated upwards.

Skip Lenz, a pharmacist, reported in The LDN Book that survey of over 1000 people found that about 8% reported disturbed sleep, but except for one person the sleep issue disappeared within two weeks. All other side effects were found in less than 1% of the survey takers.

Dextro-Naltrexone – The Next Naltrexone?

Jarred Younger believes a better, a possibly much, much better naltrexone call dextro-naltrexone may be within reach. Dextro-naltrexone is a different form of naltrexone which may be more effective at reducing neuroinflammation and produces fewer side effects.

Jarred Younger III : Treatments – A Better LDN and the Hunt for Microglia Inhibitors

Health Rising LDN Blogs


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


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