User:Memtgs/Low-dose naltrexone

Low-dose naltrexone (LDN) describes the off-label use of the medication naltrexone at low doses (usually 4.5 mg) 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.

Some proponents of low-dose naltrexone have made unproven or pseudoscientific claims about its efficacy in treating a wide range of diseases, including cancer and HIV. Low-dose naltrexone organizations have promoted its use on their webpages. Neurologist and skeptic Steven Novella has criticized these claims, pointing out a lack of clinical trials supporting them.

Approved uses of naltrexone
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.

The U.S. Food and Drug Administration have approved the use of naltrexone for chronic treatment of opioid dependence and for drug detoxification. Recommended dosing for orally-administered naltrexone for this purpose range 50mg to 150mg; for comparison, low-dose naltrexone is usually prescribed at 4.5mg.

Research and off-label use
Organizations promoting low-dose naltrexone have advocated it as a treatment for a variety of medical conditions. However, currently no peer-reviewed studies that would justify clinical use of low-dose naltrexone have been published. Research on the use of low-dose naltrexone in treating Crohn's disease, fibromyalgia and autism is preliminary and should not be used to justify clinical treatment. One small pilot study found a reduction in fibromyalgia symptoms in patients treated with low-dose naltrexone.

The benefits in multiple sclerosis patients have not been evaluated in large controlled studies. Personal testimonials describing low-dose naltrexone as a cure for multiple sclerosis are not supported by clinical evidence. Medical practitioners have advised against using it in place proven therapies, that the safety of low-dose naltrexone treatment for multiple sclerosis is unknown, and that patients who chose to undergo the treatment should be fully informed of the limited research backing its use. The UK National Health Service found that there is insufficient evidence to support LDN's effectiveness in the treatment of multiple sclerosis, and such use in the UK would be unlicensed.

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, websites run by low-dose naltrexone advocates such as lowdosenaltrexone.org make unproven and pseudoscientific claims of its efficacy in treating various conditions, including: various types of cancer, Alzheimer's disease, HIV/AIDS, rheumatoid arthritis, and others. Skeptic Steven Novella of the Yale University School of Medicine disputed these claims as unsupported by rigorous clinical research. Novella further argues that the claim that low-dose naltrexone as an effective treatment for both immune dysfunction and autoimmune diseases is contradictory, and that improving the immune system could make the autoimmune disease worse.

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 are not as of yet supported by significant clinical research.