Low-Dose Naltrexone for Fibromyalgia

Low-Dose Naltrexone for Fibromyalgia

By: Dr Alex Robber

LDN : Emerging Treatment Shows Promise

Low-dose naltrexone (LDN) is promising to treat a wide range of conditions associated with chronic pain, including fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS). According to Jarred W. Younger, PhD, director of the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama, Birmingham, LDN may in fact offer a low-cost, nonaddictive opioid alternative for patients with chronic pain pending further study.

Opioids work quickly, but when used long-term, they can cause pain sensitivity, so I think they should only be used for short periods. With time, LDN decreases pain intensity so chronic pain might be a safer option, “Younger told Medscape Medical News.


Naltrexone is an opiate blocker commercially available for the treatment of alcohol and opioid dependency in a 50 mg tablet dosage per day. But besides the antagonism of opioid receptors, the drug also tends to exert anti-inflammatory effects through a separate mechanism targeting microglial cells.

Paradoxically, the dosage used to relieve pain is about one-tenth the dosage of medication for the drug abuse, about 4.5 mg daily. The low-dose form is not licensed by the US Food and Drug Administration and has to be prepared in a specific way.

The Immune – Autoimmune Connection

LDN also tends to be able to control immune cell function in the central nervous system known as microglial cells. We generate pro-inflammatory cytokines, reactive oxygen species (free radicals) and nitric oxide when these cells are turned on–both of which are being examined in ME / CFS and/or FM.

In addition, microglial cells can be a key component of the’ sickness response’ that triggers tiredness, fluey feelings, pain, etc. when we come down with an infection. Some researchers believe that ME / CFS and FM can chronically turn these cells on. LDN’s ability to block the activation of a central receptor (TLR 4) on microglial cells tends to inhibit them.

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

READ ALSO:  Milk problem for those suffering from fibromyalgia

LDN may be able to reregulate the functioning of the immune system and increase neurotransmitters called endorphins which may be weak in the condition. The ability of LDN to modulate upward natural killer cell activity and decrease B-cell activity may help to re-regulate immune response in ME / CFS and/or FM. Its ability to minimize the functioning of microglia can minimize fatigue, pain and other symptoms.

How Does LDN Work?

Researchers also do not understand the exact mechanism of action for the drug. Some researchers theorize that LDN blocks those nervous system receptors that cause fibromyalgia symptoms and chronic fatigue syndrome. Some evidence indicates that LDN functions in the central and peripheral nervous systems as an anti-inflammatory, likely by reducing the function of specialized cells, called microglia. Research also indicates that LDN may help normalize the immune system, which may be why people with autoimmunity and other diseases of the immune system tend to be improved by it.

Fibromyalgia LDN Studies

Two small studies of Stanford fibromyalgia suggested low dose naltrexone can significantly help with fibromyalgia/ A single-blind crossover study in 2009 found LDN significantly reduced levels of pain, fatigue and stress. Once patients were off the drug, their levels of symptoms soon returned to normal. Intriguingly, 80 per cent of the responses were predicted by an inflammation indicator called erythrocyte sedimentation level (ESR). The fact that higher ESR’s have been associated with higher symptom severity reductions suggests inflammation could play a major role with FM for some.

A larger, double-blinded, placebo-controlled crossover study had similar results (dose 4.5 mg / day): reduced pain, improved mood and general life satisfaction. However, fatigue and sleep were not impacted significantly. In demonstrating the efficacy of LDN in FM, Jarred Younger has led the way. His laboratory at Birmingham University of Alabama (neuroinflammation, exhaustion and pain study) has planned a number of LDN studies:

  • Determining appropriate dosage. An analysis of dose levels will decide if lower or higher dosages function better for certain individuals.
  • Determining whether LDN helps in other conditions such as rheumatoid arthritis, osteoarthritis, CFS and possibly depression.
  • Study of chronic fatigue syndrome.
  • A broad (200 + person) LDN and fibromyalgia clinical trial.
READ ALSO:  Issues of growth hormones having with Fibro?

LDN calms the microglial cells

Younger believes that ME / CFS symptoms and that fibromyalgia may be caused by inflammation of the brain. The brain contains microglial cells, which inside the central nervous system are constantly scanning and seeking problems. When they discover a problem, these cells release chemicals that are usually associated with ME / CFS and fibromyalgia causing weakness, discomfort, cognitive problems and other symptoms.

These chemicals are meant to slow the body in a healthy person, so the immune system can concentrate on cure. But some researchers in ME / CFS and fibromyalgia think this natural body response gets triggered and won’t be shut down. LDN can function in patients with fibromyalgia (and possibly in ME / CFS), as it calms the microglial cells and decreases inflammation of the brain. “Naltrexone crosses the blood / brain barrier in very general terms, and it suppresses the inflammation,” Younger explained.

LDN for Fibromyalgia

A series of studies by Stanford University showed promising outcomes as much as a 30 percent reduction in symptoms compared to placebo. Researchers suggest the best findings are in people with higher sedimentation levels, suggesting an inflammatory response within the body.

(A high sedation rate could indicate overlap as it is not typically high in fibromyalgia.) Results also indicate that the drug is well tolerated. These studies, however, have all been limited and more research is needed until we know how safe and efficient LDN is for this disorder. LDN for fibromyalgia is not approved by the FDA but is sometimes prescribed off-label.


“People differ so much in their weight, body mass, absorption, reaction to and excretion of Naltrexone that a doctor can only generalize on dose sizes and then you need to find out for yourself how you feel and do the blood tests and physical exams and scans.

READ ALSO:  Polyphenol-rich diets Improve the quality of life of people with fibromyalgia

This might not be right for you what is right for other people. Most people probably start with 1.5 mgs and then rise for a few weeks or a month. (According to the ME / CFS specialist, Dr. De Meirleir, starting doses in ME / CFS can be as low as 0.5 mg and end up 5 mg or more.) In general, he finds that 1.5 mg. That’s not enough, and 6 mg. It’s too much and most people get 3-4.5 mgs. One day. He recommends patients go down and then increase their dose every couple of months to test that their medication requirements have not changed.

Side effects:

While naltrexone appears to be well-tolerated possible side effects include:

  • dizziness and syncope
  • headache
  • insomnia
  • anxiety and nervousness
  • sleepiness and fatigue
  • nausea, vomiting, diarrhea, abdominal pain, cramping, decreased appetite
  • injection site pain and swelling
  • joint pain
  • excessive muscle contraction
  • upper respiratory tract infection
  • sore throat

In Stanford studies, side-effects were reported as uncommon, mild, and temporary. To take LDN safely, people with liver and kidney disease require specific monitoring and treatment, so that the adverse effects of the drug can be prevented. This drug can be harmful to an unborn baby so taking it during pregnancy is not safe. We don’t know exactly whether it can move through the breast milk, or whether it’s healthy for the mother to lactate.

Note: If you are interested in trying LDN, explore the potential pros and cons with your doctor. While some doctors prescribe LDN for patients with these and many others, it is still considered a new procedure, so your doctor may not be willing to take it into consideration.


  • Ablin JN, Buskila D. Expert opinion on emerging drugs. 2010 Sep;15(3):521-33. Emerging therapies for fibromyalgia: an update.
  • Plesner KB, Vaegter HB, Handberg G. Ugeskrift for laeger. 2015 Oct 9;177(43):V03150248. Low dose naltrexone for treatment of pain. [Abstract referenced. Article in Danish.]
  • Younger J, Mackey S. Pain medicine. 2009 May-Jun;10(4):663-72. “Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study.”
  • Younger J, et al. Arthritis and rheumatism. 2013 Feb;65(2):529-38. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.
  • Younger J, Parkitny L, McLain D. Clinical rheumatology. 2014 Apr;33(4):451-9. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.

Leave a Reply