Low Dose Naltrexone (LDN) …
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 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 is 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 in producing more of them. 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 improved of FM suggested suggested the endorphin scenario is a viable one. In this case 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.
Interestingly, endorphins are produced by the HPA axis which appears to be impaired in both FM and ME/CFS.
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, of course, is a B-cell inhibitor that appears to have great promise for chronic fatigue syndrome and ME/CFS has many characteristics associated with autoimmune disorders. LDN’s effectiveness is currently being tested in several autoimmune diseases.
LDN also appears to affect the functioning of the regulatory immune cells in the central nervous system called microglial cells. When these cells become infected or damaged they produce pro-inflammatory cytokines, reactive oxygen species (free radicals) and nitric oxide – all of which are under study in ME/CFS.
Microglial cells, in fact, may be a key component of the ‘sickness response’ that produces fatigue, fluey feelings, pain, etc. when we come down with an infection and some researchers believe they could be chronically turned on in ME/CFS and fibromyalgia. LDN’s abiity 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 being done. (The FM trials, below, were sponsored by the American Fibromyalgia Association.) In 2013 23 LDN trials (underway or completed) on disorders ranging from fibromyalgia to alcoholism abuse to multiple sclerois to narcotics withdrawal were listed at the Clinicaltrials.gov site .
Interestingly, many women with multiple sclerosis or chronic fatigue syndrome experience remissions during pregnancy when high levels of endogenous opioids are present and often experience relapses several months after pregnancy, when the levels of those opioids fall.) This suggests that one or more of the opioid receptors that LDN affects could play a role in the progression of these disorders.
LDN Might Be Effective in Chronic Fatigue Syndrome/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 also help to re-regulate the immune response in ME/CFS. It’s ability to reduce microglial functioning could reduce the fatigue and pain and other symptoms associated with the ‘sickness response’.
- Check out a fascinating video on Fibromyalgia that includes LDN from the Stanford University Medical Center.
Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Studies
Two small fibromyalgia studies from Stanford researchers suggest the drug can significantly help with pain. 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, erythrocye sedimentation levels (ESR) predicted 80% of the responses with higher ESR’s associated with greater reductions in symptom severity. Since ESR is not typically elevated in fibromyalgia, ESR levels could be used to detect FM subsets that might do well on LDN.
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 mgs/day of LDN. Fatigue and sleep, however were not significantly effected.
Jarred Younger at Stanford has a variety of LDN studies planned. Their topics include
- Determine if inflammatory markers in the blood decrease when someone improves with LDN
- Determining the proper dosage? This 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.
- They hope to do a large (200+ person) clinical trial of LDN and fibromyalgia
Chronic Fatigue Syndrome (ME/CFS) Doctors Report
LDN is Dr. Klimas’ first-line treatment for the pain associated with fibromyalgia and chronic fatigue syndrome. She has found the drug to be effective and safe.
are usually reportedly minimal but 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. Some people with ME/CFS and/or need to ramp their dosage up very slowly.
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.
- 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.
According to Dr. De Meirleir the doses in ME/CFS may be as low as 0.5 mgs and up to 5 mgs or more. The 4-6 hours or so the drug remains in your system is sufficient to boost endogenous opioid levels for 18-24 hours.
Dr. Neil Beck reported “I have been treating people with Naltrexone for 18 years, first with High Dose 10 to 80mg for heroin blocking and Alcoholism, then with Micro Dose 3/4mg for heroin withdrawals and LDN 1.5 to 6mg for the usual disorders and addictions.
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. Go to 3 then 4.5 then 6mg. Most people find 1.5 isn’t enough and 6 is too much and 3 or 4.5 is the best. Finding what is not enough and what is too much helps pinpoint the right dose. Every few months decrease and increase again to check that your requirement hasn’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.”
Health Rising Blogs
- 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
Low dose naltrexone’s easy availability will probably ensure that it’s never the subject of huge studies or marketing campaigns by drug companies. but a impressive grassroots effort has sprung on the web that seeks to promote it and which explains how it works, how it should be taken, etc.
- Got Endorphins? LDN (Low Dose Naltrexone) is a very active LDN Facebook site.
- LDN Research Trust – lot of information plus videos, doctor’s lists, conferences and more.
- LDN Science – Science based website featuring LDN
- LDN World Database – features, yes, a great deal of data on LDN
- 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