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, reduce the severity of opioid withdrawal, or improve fibromyalgia symptoms, 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. The treatment has been widely promoted through websites run by organizations advocating its use.
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.
Scientific research 
A single-blind randomized, two-group clinical trial of Low Dose Naltrexone for HIV/AIDS was conducted in Mali from March 2008 to March 2010, published Journal of AIDS and HIV Research. The authors concluded that adding LDN to a three-antiretroviral regime used improved the recovery rate of CD4 count, suggesting "further exploration of LDN as part of an HIV+ treatment regime is warranted".
A single-cohort study of Low Dose Naltrexone in 55 HIV-positive asymptomatic untreated patients with CD4 counts between 350-600 was conducted in 2008-2009 showed that after 9 months CD4 percentages were maintained.
A pilot study to evaluate the safety and tolerability of low-dose Naltrexone therapy in children with moderate to severe Crohn's disease was conducted at the Penn State College of Medicine. The study enrolled 14 subjects in a placebo-controlled study for 8 weeks, followed by 8 weeks of open-label treatment. The study concluded, "Naltrexone therapy seems safe with limited toxicity when given to children with Crohn's disease and may reduce disease activity."
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. 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. 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. 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.
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. This preliminary research includes the finding of a reduction in fibromyalgia symptoms in a small pilot study.
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. There is some evidence that very low doses of opioid antagonists such as naltrexone reduce the severity of opioid withdrawal.
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. 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.
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. According to Steven Novella, a noted skeptic with the New England Skeptical Society and assistant 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."
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. These claims, however, are not yet supported by significant clinical research.
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- Novella, Steven. "Low Dose Naltrexone – Bogus or Cutting Edge Science?". Retrieved 5 July 2011.
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- Smith, Jill P.; D. Field, S. I. Bingaman, R. Evans, D. T. Mauger (December 13, 2012). "Safety and Tolerability of Low-dose Naltrexone Therapy in Children With Moderate to Severe Crohn's Disease: A Pilot Study". Journal of Clinical Gastroenterology. PMID 23188075. Retrieved 2 March 2013.
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