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Relevance:5 Technical Level:5

Page Synopsis: If you subscribe to the CDR theory of CFS then administration of LDN is the logical next step


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Low Dose Naltrexone helps fibromyalga, anecdotal reports it helps with CFS


From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment'


A low-dose naltrexone regimen (3 to 4.5 mg daily, taken before bed can have positive effects for various autoimmune and neurodegenerative diseases. Dr Chia finds LDN helps only a small percentage of ME/CFS patients, but for those it helps, it does so very significantly.1 LDN seems to help most fibromyalgia patients.1 LDN is cheap, costing $6 per month.


LDN has several metabolic effects: it blocks the mu\-, delta\- and kappa-opioid receptors briefly  which is thought to up-regulate endorphins, it increases levels of met-enkephalin and its receptor, blocks TLR-4 on microglia, and LDN is believed to increase natural killer cell function  NK function is often low in ME/CFS patients. Note: it is possible that vitamin D3 may be essential for LDN to work properly, so it may be good idea to take vitamin D3 5,000 to 10,000 IU with LDN — see here

More info on LDN: LDN for ME/CFS, LDN Overview, Low dose naltrexone - MEpedia


Maija Haavisto author of “Reviving the Broken Marionette: Treatments for CFS/ME and Fibromyalgia” on Treating Chronic Fatigue Syndrome


"I’ve been using LDN for over seven years now. It was almost like a miracle, stopping my rapid disease progression, pretty much completely eliminating PEM  ! and increasing my ability to walk from some 50 meters to 5 km or more. I wasn’t cured but I’d sometimes work 15-hour days writing my medical books. I’ve also benefited significantly from nootropics. After starting nimodipine and piracetam I’ve written six novels, four non-fiction books, three plays and a screenplay."

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.


Is Fibromyalgia a Low Endorphin Disease?


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.


Check out a fascinating video from the Stanford University Medical Center on Fibromyalgia which includes LDN

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.

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

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

  • Does Low Dose Naltrexone Improve Natural Killer Cell Functioning in ME/CFS?
  • The Strangeness of Low Dose Naltrexone: Weird Dosing, Backward Protocols and Rejections – in ME/CFS and Fibromyalgia
  • A Better Naltrexone? Jarred Younger to Study Potentially Much More Effective Dextro-Naltrexone
  • Dr. Liptan on Low Dose Naltrexone’s Effectiveness in Fibromyalgia and the “Opiate LDN Quagmire”
  • An Immune Disease? LDN Trial Suggests Fibromyalgia Has Inflammatory Side
  • Low Dose Naltrexone Drug Combination Proposed for Chronic Fatigue Syndrome  ME/CFS
  • Finally Found – A Natural Killer Cell Enhancer for ME/CFS?
  • Pharmaceutical Grade” Low Dose Naltrexone Now Available for ME/CFS and Fibromyalgia Patients
  • Low’ Dose Naltrexone, Inflammation and Pain: A Different Approach to Fibromyalgia
  • Successful Low Dose Naltrexone Fibromyalgia Trial Points to Safe, Low Cost Therapy; Implications for Chronic Fatigue Syndrome
  • Low Dose Naltrexone Becoming ‘Standard Treatment’ for Chronic Fatigue Syndrome and Fibromyalgia Resources


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

  • Got Endorphins? LDN  Low Dose Naltrexone is a very active LDN Facebook  site.
  • LDN Research Trust – lots of information plus videos, doctors’ lists,  forums, LDN radio, conferences and more.
  • LDN Science – a science based website with information on  plus patient stories, doctors lists, one preferred pharmacy, interviews with experts, etc.
  • LDN World Database –  features, yes, a great deal of data on LDN
  • The LDN Book – The LDN Book: How a Little-Known Generic Drug ― Low Dose Naltrexone ― Could Revolutionize Treatment for Autoimmune Diseases, Cancer, Autism, Depression, and More – From the LDN Research Trust.
  • Maija Haavisto’s LDN webpage is loaded with information and resources
  • Documentary video on LDN
  • The Promise of Low Dose Naltrexone – medical reference book on LDN


Low Dose Naltrexone Website

Naltrexone is a microglial inhibitor among its other modes of action. There is constant disagreement whether large or small LDN doses are more effective and some have suggested only using the enantiomer D-naltrexone  which is a microglial inhibitor with no opioid blocking effects or using a heterochiral mixture  more D-naltrexone than L-naltrexone. Then people could take large amounts of the microglial inhibiting isomer and smaller amounts  or none of the opioid blocker. But this is something the pharmaceutical industry must do, you can’t have your pharmacy compound it.


Most drugs and supplements that inhibit microglial activation also have other potentially useful modes of action


A new form of LDN without side effects, Jarred Younger is exploring a potentially more effective and side-effect free version of LDN called dextro-naltrexone


This is one of the most important pages, do not skim. It is potentially a 'cure' (in as much as it has put many patients into remission, though not entirely a cure as patients must continue intermittent dosaging). The accompanying protocols are intricate and complex



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