Low-dose naltrexone

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Low-dose naltrexone (LDN) describes the "off-label" use of the medication naltrexone at low doses and for other diseases such as multiple sclerosis. Naltrexone is typically prescribed for opioid dependence or alcohol dependence, as it is a strong opioid antagonist. Preliminary research suggests low-dose naltrexone may be useful in preventing opioid tolerance and dependence when combined with an opioid,[1] reduce the severity of opioid withdrawal,[2] or improve fibromyalgia symptoms,[3][4] though more research needs to be done before it can be recommended for clinical use.

There have also been pseudoscientific claims about its efficacy in treating a wide range of diseases such as cancer and HIV, which are not supported by clinical trials.[5] The treatment has been widely promoted through websites run by organizations advocating its use.[6]

Background

Naltrexone is an opioid receptor antagonist, meaning it binds to opioid receptors in cells. These receptors bind endogenous pain relieving compounds such as endorphins as well as opioids such as morphine. Naltrexone also works to bind against the effects of heroin, which is synthesized from morphine, and is useful to alleviate opioid dependence. Government regulatory agencies such as the U.S. Food and Drug Administration have approved the use of naltrexone for chronic treatment of opioid dependence and for drug detoxification.[7]

Scientific research

There are no studies that have been published that justify clinical use. Pilot studies have suggested future directions in research.[5]

LDN use has been advocated for the treatment of multiple sclerosis, based on anecdotal evidence. The benefits in those with multiple sclerosis have not been evaluated in large studies. A pilot study performed at the University of San Francisco reported a significant increase in "mental health quality of life indices," though the authors noted that the dropout rate in the study reduced its statistical power.[7][8] Claims made by some personal testimonials suggesting LDN to be a "cure" or a "wonder drug" are not borne out by research, and as such, LDN should be considered an "unproven treatment" not to be used in place of more proven therapies, despite what some advocacy websites claim.[7] The National Multiple Sclerosis Society notes that more rigorous studies are needed before it can be confirmed that LDN has a positive effect on multiple sclerosis symptoms or is even safe for use.[6] The UK National Health Service has also found that there is not enough evidence to support LDN's effectiveness in the treatment of multiple sclerosis, and such use in the UK would be unlicensed.[9]

There has also been research on the use of LDN in treating Crohn's disease, fibromyalgia and autism, but this research is in the most preliminary of stages and does not currently justify clinical use.[5] This preliminary research includes the finding of a reduction in fibromyalgia symptoms in a small pilot study.[3] A somewhat larger study conducted in 2013 noted a reduction in fibromyalgia pain levels [4]

Ultra-low-dose naltrexone can reverse or prevent the development of tolerance to opioids, and its use is being investigated in the combination drug Oxytrex, which combines oxycodone with ultra-low-dose naltrexone.[1] There is some evidence that very low doses of opioid antagonists such as naltrexone reduce the severity of opioid withdrawal.[2]

Known mechanism of action

The mechanism of low-dose naltrexone in reversing or preventing the development of tolerance of opioids involves its high-affinity binding to filamin A.[10] The interaction of naltrexone with microglia cells within the central nervous system is believed to be how the drug exerts its beneficial effects in individuals who suffer from fibromyalgia; this interaction on microglial cells results in a reduction of proinflammatory cytokines as well as neurotoxic superoxides.[3]

Pseudoscientific claims

In addition to the known scientific uses for low dose naltrexone, there are a number of pseudoscientific claims on various websites (such as "boosting" the immune system) about its use in a wide range of diseases such as cancer, HIV and lupus, amongst others.[11] According to Steven Novella, a noted skeptic with the New England Skeptical Society and professor from Yale University School of Medicine, these claims are not only unsupported by clinical research, but are also contradictory. They claim LDN is able to treat diseases of immune dysfunction (such as HIV) in addition to autoimmune diseases, where improving the immune system could make the autoimmune disease worse. Steven Novella also writes that claims of treating a wide range of diseases with different etiologies should be a red flag to be skeptical about these claims, which are likely to be "bogus treatment with claims that are literally too good to be true."[5]

Proposed mechanism of action

Opioid receptors may have other uses in the body than just for modulating pain, and it is on these bases that supporters of LDN have chosen it as a treatment for selected diseases. Advocates have claimed that increased endorphin production can help with pain, spasticity, fatigue, relapse rate and other symptoms.[7] These claims, however, are not as of yet supported by significant clinical research.[5]

References

  1. ↑ 1.0 1.1 Webster LR (August 2007). "Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation". Expert Opin Investig Drugs 16 (8): 1277–83. doi:10.1517/13543784.16.8.1277. PMID 17685875. 
  2. ↑ 2.0 2.1 Mannelli P, Gottheil E, Van Bockstaele EJ (2006). "Antagonist treatment of opioid withdrawal translational low dose approach". J Addict Dis 25 (2): 1–8. doi:10.1300/J069v25n02_01. PMID 16785213. 
  3. ↑ 3.0 3.1 3.2 Ngian GS, Guymer EK, Littlejohn GO (February 2011). "The use of opioids in fibromyalgia" (PDF). Int J Rheum Dis 14 (1): 6–11. doi:10.1111/j.1756-185X.2010.01567.x. PMID 21303476. 
  4. ↑ 4.0 4.1 Younger J, Noor N, McCue R, Mackey S (2013). "Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.". Arthritis Rheum 65 (2): 529–538. PMID 23359310. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Novella, Steven. "Low Dose Naltrexone – Bogus or Cutting Edge Science?". Retrieved 5 July 2011. 
  6. ↑ 6.0 6.1 Bowling, Allen C. "Low-dose naltrexone (LDN) The "411" on LDN". National Multiple Sclerosis Society. Retrieved 6 July 2011. 
  7. ↑ 7.0 7.1 7.2 7.3 Bourdette, Dennis. "Spotlight on low dose naltrexone (LDN)". US Department of Veteran Affairs. Retrieved 5 July 2011. 
  8. ↑ Giesser, Barbara S. (2010). Prrimer on Multiple Sclerosis. New York: Oxford University Press US. p. 377. ISBN 978-0-19-536928-1. 
  9. ↑ Smith, Katie. "What is the evidence for low dose naltrexone for treatment of multiple sclerosis?". National electronic Library for Medicines, National Health Service. Retrieved 24 October 2011. 
  10. ↑ Burns LH, Wang HY (November 2010). "PTI-609: a novel analgesic that binds filamin A to control opioid signaling". Recent Pat CNS Drug Discov 5 (3): 210–20. PMID 20726836. 
  11. ↑ Gluck, David. "NCI Needs to Get Over Its Alternative Treatment Bias". Retrieved 30 March 2012. 

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