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Low dose Naltrexone use in autoimmune diseases and cancer

What is low dose Naltrexone (LDN)?


Naltrexone was approved as a drug by FDA in 1983 for substance abuse. The recommended dose for opioid addiction is 50-300 mg. Low dose Naltrexone refers to very small doses of LDN (1-4.5 mg) that are used off-label for chronic conditions particularly autoimmune diseases, cancer and Fibromyalgia.


How does LDN work?


Autoimmune Disease


LDN has been found to have a very unique mechanism of action. It’s effectiveness in inflammatory diseases such autoimmune diseases has been attributed to its impact on the nervous system. The microglial cells in the brain and spinal cord are immune cells that can be activated by different stimuli. Once activated these cells release inflammatory factors that lead to symptoms such as chronic pain, fatigue, mood changes, cognitive dysfunction etc. LDN opposes the inflammatory actions of these cells and protects other cells of the brain and spinal cord from becoming inflamed.


In addition, it has also been found to have an anti-inflammatory impact on the immune cells (macrophages) outside the nervous system.


Another mechanism of action proposed for the impact of LDN is ‘rebound opioid effect’. According to this hypothesis, LDN produces a small and transient block on the opioid receptors which leads to up-regulation of the body’s endocannabanoid system. This causes the body to release endorphins that lead to an analgesic effect, enhanced mood, memory and sense of well being.




There is research that shows that LDN can inhibit the growth of cancer cells by 3 possible mechanisms


The first mechanism is production of metenkephalins from the pituitary and adrenal glands. These lead to activation of the delta opioid receptor which acts an anti-growth factor for the cancer cells.


The second mechanism is direct activation of opioid receptors on cancer cells which is lethal for the cells in even small quantities.


The third is activation of immune cells called Natural Killer cells that help get rid of cancer cells.


What conditions can LDN be used for?


LDN is not approved by FDA as a therapeutic modality for autoimmune disease. It is used by functional and integrative practitioners on the basis of data obtained from research as well as the work of Dr. Bernard Bihari. Studies have shown that it plays a critical role in multiple chronic diseases.


  1. Fibromyalgia: Reduction in pain as well as sedimentation rate [marker of inflammation]

  2. Crohn’s Disease-LDN showed a decrease in self reported pain, objective markers of inflammation and disease severity scores (on endoscopic evaluation) in Crohn’s Dz.


  3. Multiple Sclerosis-LDN showed significant improvement in quality of mental health.


  4. HIV/ AIDS-Improves CD4 count


  5. Cancer including pancreatic, lung, colon, ovarian, esophageal, parotid, and unknown primary etc.


Dr. Bihari did pioneer work in providing insight into the role of LDN for chronic diseases such as cancer and autoimmune diseases. He showed that LDN can be effective in


  6.   Lupus and Rheumatoid Arthritis


  7.   Autoimmune thyroid disease ( Hashimoto’s disease)


  8.   Sarcoidosis


  9.   Parkinson's disease and Alzheimer's disease


  10. IBS ( Irritable bowel Syndrome)


When should LDN be initiated?


Autoimmune Disease


In my experience, LDN is best utilized after priming the patient, meaning that the basic root causes that lead to autoimmunity need to be identified and addressed prior to the addition of LDN. Sometimes addressing the root causes is adequate to improve the symptoms significantly and then addition of LDN helps breaking the vicious cycle of inflammation.




LDN is used in cancer as part of the protocol with Intravenous nutrients. Dr. Burton Berkson, a well known integrative Functional Physician has published cancer cases where he has used LDN along with intravenous alpha lipoic acid in patients with advanced cancer diagnosis.


What are the side effects of LDN?


LDN has not been shown in research studies to have any serious side effects nor interactions with other medications except opioid pain medications.


One reported side effect is vivid dreams and headaches.


No withdrawal effect of LDN has been observed.


There is no potential for abuse with LDN.







  • Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology. 2014;33(4):451-459. doi:10.1007/s10067-014-2517-2.

  • Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009;10(4):663–672.


  • 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):820–828.


  • Smith JP, Field D, Bingaman SI, Evans R, Mauger DT. Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn’s disease: a pilot study. J Clin Gastroenterol. 2013;47(4):339–345.


  • Ann Neurol. 2010 Aug;68(2):145-50. doi: 10.1002/ana.22006.
    Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis.
    Cree BA1, Kornyeyeva E, Goodin DS.


  • Journal of AIDS and HIV Research Vol. 3(10), pp. 180-188, October 2011
    Single cohort study of the effect of low dose naltrexone on the evolution of immunological, virological and clinical state of HIV+ adults in Mali.


  • J Immunol. 1983 Apr; 130(4): 1658-62. Enhancement of natural cytotoxicity by beta-endorphin. Mathews PM, et al.


  • Brain Behav Immun.1992. Enhancement of human natural killer cell activity by opioid. Peptides: similar response to methionine-enkephalin and beta-endorphin. Puente J et al.


  • J Immunol. 1986. Beta-endorphin augments the cytolytic activity and interferon production of natural killer cells. Mangler RN, et al.


  • Anti cancer Res. 2014. Metabolic treatment of cancer: intermediate results of a prospective case series. Schwartz L, et al.


  • Integr Cancer Ther. 2009. Revisiting the ALA/N (alpha-lipoic acid/low dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases. Bergson BM, et al.


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