LDN : Emerging Treatment Shows Promise
Low-dose naltrexone (LDN) holds promise for treating chronic pain associated with a wide range of conditions, including fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In fact, pending further study, LDN might offer a low-cost, nonaddictive opioid alternative for patients with chronic pain, according to Jarred W. Younger, PhD, director of the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama, Birmingham.
Opioids work fast, but they may cause pain sensitivity when used long-term, so I think they should be used for only short periods of time. LDN lowers pain sensitivity over time, so may be a better choice for chronic pain,” Younger told Medscape Medical News.
Naltrexone
Naltrexone is an opiate antagonist currently available in a daily 50-mg tablet dose for the treatment of alcohol and opioid dependence. But in addition to opioid receptor antagonism, the drug also appears to exert anti-inflammatory effects via a separate mechanism targeting microglial cells.
Paradoxically, the dosage found to reduce pain is roughly one tenth the substance abuse treatment dose, around 4.5 mg per day. The low-dose version is not approved by the US Food and Drug Administration and must be specially compounded.
The Immune – Autoimmune Connection
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 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 FM. LDN’s ability to block a key receptor (TLR 4) on microglial cells appears to inhibit them from becoming activated.
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LDN Might Be Effective in Chronic Fatigue Syndrome and/or Fibromyalgia
LDN 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. Its ability to reduce microglial functioning could reduce the fatigue, pain and other symptoms.
How Does LDN Work?
Researchers don’t yet understand the drug’s exact mechanism of action. Some researchers theorize that LDN blocks certain receptors in the nervous system that cause symptoms of fibromyalgia and chronic fatigue syndrome. Some evidence suggests that LDN works as an anti-inflammatory in the central and peripheral nervous systems, possibly by limiting the activity of specialized cells called microglia. Research also suggests that LDN may help normalize the immune system, which may be why it appears to help people with autoimmunity and other immune-system illnesses.
Fibromyalgia LDN Studies
Two small Stanford fibromyalgia studies suggested low dose naltrexone can significantly help 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 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 could play a large role for some with FM.
A larger placebo-controlled, double-blinded, crossover study had (dose 4.5 mg/day) similar results: reduced pain, improved mood, and general satisfaction with life. Fatigue and sleep, however, were not significantly affected. Jarred Younger has leaded the way in demonstrating LDN’s effectiveness in FM. His lab at the University of Alabama at Birmingham (the Neuroinflammation, Fatigue and Pain Lab) has a variety of LDN studies planned:
- >>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
LDN calms the microglial cells
Younger believes the symptoms of ME/CFS and fibromyalgia may be caused by brain inflammation. The brain contains microglial cells, which are constantly scanning and looking for problems within the central nervous system. When they discover a problem, these cells release chemicals, which cause fatigue, pain, cognitive disturbances and other symptoms commonly associated with ME/CFS and fibromyalgia.
In a healthy person, these chemicals are supposed to slow down the body, so the immune system can focus on healing. But in ME/CFS and fibromyalgia, some researchers think this normal bodily response gets activated and won’t shut off. LDN may work in fibromyalgia (and also possibly in ME/CFS) patients because it calms the microglial cells and reduces brain inflammation. “Naltrexone, in very general terms, crosses the blood/brain barrier, and it suppresses that inflammation,” Younger explained.
LDN for Fibromyalgia
A series of Stanford University studies has shown positive results as much as a 30 percent decline in symptoms compared to placebo. Researchers say results are best in people with higher sedimentation rates, which indicates an inflammatory response in the body.
(A high sed rate could indicate an overlapping condition as it’s not typically elevated in fibromyalgia.) Results also indicate that the drug is well tolerated. However, these studies have all been small and more work needs to be done before we know how safe and effective LDN is for this condition. LDN is not FDA approved for fibromyalgia but is sometimes prescribed off-label.
Dosage
“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 mgs and then increase over a couple of weeks or a month. (According to Dr. De Meirleir, an ME/CFS specialist, starting doses in ME/CFS can be as low as 0.5 mg. and end up being 5 mg. or more.) In general he finds that 1.5 mg. isn’t enough and 6 mg. is too much and that most people end up taking from 3-4.5 mgs. a 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.
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
Side effects were reported as rare, mild, and transient in Stanford studies. To safe take LDN, people with liver and kidney diseases need specific tests and diagnosis; so that they may be avoid the adverse effects of the medication. This drug may be harmful to an unborn baby, so it’s not safe to take it in pregnancy. We don’t know exactly that whether it can pass through the breast milk, or it’s safe for lactating mother.
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Note: If you’re interested in trying LDN, talk to your doctor about the possible pros and cons. While some doctors do prescribe LDN for people with these illnesses and many others, it’s still considered an emerging treatment, so your doctor may be unwilling to consider it.
References:
- 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.
- Featured Image via Counting My Spoon
