We see a lot of autoimmune conditions in our clinic. We also see a fair amount of other conditions that are the result of impaired immune dysfunction. Many of these issues can be very frustrating to treat. However, there is a therapy that holds great promise for a number of problems. This therapy is known as Low-Dose Naltrexone (LDN).
What is Naltrexone?
Naltrexone is a medication that was approved by the FDA in 1984. Its primary purpose is to block the opiate receptor and prevents medications such as morphine and heroine from being able to bind to those sites. The typical doses for opiate blockage is 50-150mg. Blocking these receptors also prevents some of the hormones made in your body from working. Hormones such as endorphins and enkephalins. Over the last 2 decades, these hormones have been shown to have an effect on the immune system regulation. [1, 4-6]
Why Use Low-Dose Naltrexone (LDN)?
It appears that a brief blockage of these opiate receptors between 2:00-4:00 am causes an up-regulation of vital components of the immune system by increasing these endorphins and enkephalins. Most of these chemicals are generally produced in this time window. Blocking these receptors briefly causes an increase in the endorphin and enkephalin production in the body which is the body’s way of trying to overcome the blocked receptors. Dr Bihari noted that taking this low-dose naltrexone (LDN) at bedtime led to a doubling to tripling of low levels of beta-endorphins. It is believed that this increase in endorphins and enkephalins work on cancer cell opioid receptors and may induce cell death (apoptosis). The endorphins and enkephalins also appear to increase Natural Killer (NK) cells and other healthy immune system functions against cancer. The idea is that since these endorphins and enkephalins play a role in immune function, increasing their levels helps to regulate the immune system which ultimately improves many immune conditions. Low-dose naltrexone (LDN) is important because higher doses will block the receptors for a longer period of time and decrease the beneficial effect. The LDN also needs to be immediate acting meaning that it can’t be in a sustained release formula or you will lose much of the effectiveness.
What conditions can be benefited with Low-Dose Naltrexone (LDN)?
LDN therapy has been used for a number of immune related medical issues. Some physicians have noted success in a variety of diseases:
- colon & rectal
- lung (non-small cell)
- lymphocytic leukemia
- lymphoma (Hodgkin’s & non-Hodgkin’s)
- malignant melanoma
- multiple myeloma
- renal cell carcinoma
- throat cancer
- Neurodegenerative issues
- ALS (Lou Gehrig’s)
- Alzheimer’s Disease
- Autism spectrum disorders
- Hereditary spastic paraparesis
- Multiple Sclerosis
- Parkinson’s Disease
- Primary Lateral Sclerosis
- Progressive Supranuclear Palsey
- Transverse Myelitis
- Ankylosing Spondylitis
- Behcet’s Syndrome
- Celiac Disease
- Chronic Fatigue Syndrome
- Hashimoto’s Thyroiditis
- Irritable Bowel Syndrome (IBS)
- Myesthenia Gravis
- Nephrotic Syndrome
- Primary Biliary Cirrhosis
- Rheumatoid Arthritis
- Sjogren’s Syndrome
- Stiff Person’s Syndrome
- Systemic Lupus Erythematosis (SLE)
- Ulcerative Colitis
- Wegener’s Granulomatosis
- Other Diseases
- Common Colds
How do I take Low-Dose Naltrexone (LDN)?
As previously stated, the majority of the benefit comes from blocking the receptors between 2-4am. Therefore, it is recommended that you take your LDN at night before bed. We generally start the LDN therapy between 1.5-4.5 mg per day. If you have Multiple Sclerosis (MS) which has led to spasticity of your muscles then it is recommended that you stay on a 3mg dose. For patient’s with Hashimoto’s thyroiditis we start at a lower dose (1.5mg per day) because the LDN may cause a decrease in the autoimmune disorder allowing the thyroid to work more efficiently. This could cause an elevation in thyroid hormones which may require an abrupt decrease in thyroid medications in order to avoid hyperthyroidism.
Don’t some people say LDN doesn’t work?
There is a lot of information about the use of low-dose naltrexone (LDN). However, there is not a wealth of randomized, placebo controlled, double-blinded studies (RCTs) which are generally the gold-standard for scientific evidence. The first dictom of medicine is Primum non nocere – First do no harm. Physicians have a responsibility to their patients. Basically, doctors work by 2 rules:
- Don’t do anything that could harm your patient
- Do everything you can, except things under rule #1, to help your patient
Medicine is both art and science. However, we have lost our art and tend to religiously stick to the science part. This becomes a problem when we neglect potentially helpful therapies but don’t use them because there isn’t enough evidence. Not using good interventions simply because of a lack of data is throwing the baby out with the bathwater! The best example I’ve seen of the ridiculousness of this approach was published in the British Medical Journal where the authors searched for randomized controlled trials proving the effectiveness of the use of parachutes to prevent death. The authors concluded “As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomized controlled trials. Advocates of evidence based medicine have criticized the adoption of interventions evaluated by using only observational data.” Just because there is a lack of evidence supporting the use of a medication, intervention, supplement, or procedure does not mean it doesn’t work! LDN is very safe and is an FDA approved medication being used at a fraction of the dose originally approved. Additionally, there are a number of studies which show significant promise for the use of LDN is many of the conditions listed above.
- Donahue RN, et al. Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model. Exp Biol Med 2011 Sept;236(9):1036-50.
- Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res 1996;21:1375-1386
- Risdahl JM, Khanna KV, Peterson PK, Molitor TW. Opiates and infection. J Neuroimmunol 1998;83:4-18
- Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol 1994;4:69-82
- Morch H, Pedersen PK. Beta-endorphin and the immune system: Possible role in autoimmune diseases. Autoimmunity 1995;21(5):161-71
- Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn’s disease. Am J Gastroenterol. 2007;102(4):820.
- Bihari B, Drury FM, Ragone VP, et al. Low Dose Naltrexone in the Treatment of Acquired Immune Deficiency Syndrome. Oral Presentation at the IV International AIDS Conference, Stockholm, Jun 1988.
- Smith GCS, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomized controlled trials. BMJ 2003;327(7429):1459-1461.
- Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blinded, placebo controlled, counterbalanced crossover trial assessing daily pain levels. Arthritis Rheum 2013 Feb;65(2):529-38.