Low Dose Naltrexone (LDN) For Multiple Sclerosis (MS)

Overview:

Low dose Naltrexone is a significantly reduced dose of a medication called Naltrexone.  Naltrexone itself has been used for years to break alcohol and narcotic addictions however in 1985 a physician in New York City in the United States discovered than much smaller dosing of naltrexone had an effect on the body’s immune system.

Dr. Bernard Bihari found that a low dose taken at bedtime of approximately 3mg enhanced patients response to the HIV virus.  In the mid 1990’s he also found in patients in his practice with cancer such as lymphoma and pancreatic cancer saw benefits and in some cases a dramatic benefit.  He also noted that people who had autoimmune diseases often showed vast improvements when taking low dose naltrexone (LDN).

Low dose naltrexone is an “off label” use of naltrexone.  Normal naltrexone usage to break addictions is 50mg – 100mg.  Usage of low dose naltrexone ranges in the area of 3mg – 4.5mg dosing and is prescribed in an oral pill form and is quite inexpensive.

Since LDN’s initial explorations it has been prescribed for varieties of cancers showing reduction in tumor cells, ALS, Multiple Sclerosis, Parkinson’s, Alzheimer’s and over 50 other disorders.

Low Dose Naltrexone and Multiple Sclerosis:

As with many medications especially related to autoimmune diseases it is not exactly known how LDN works within the complexity of the immune systems related to multiple sclerosis.  Yet, many many people who have engaged using LDN have witnessed significant reduction in symptoms whilst others seem to have little benefit or moderate benefits.

Among MS patients LDN has been reported to reduce fatigue, depression, spasticity, urinary incontinence, improve cognition and even heat intolerance in some people.

A friend of MS Unites locally who had a PML incident on Tysabri some 2 years ago recently was prescribed LDN.  Before she began taking LDN she had serious cognition and mobility problems as well as depression and a sheer lacking to do much of anything.  We have now heard from her twice in the past two months.  Her mobility has increased significantly, her depression is nearly gone and for the first time in 2 years she is baking cakes and her cognition has improved significantly.

Many people with MS have found taking LDN to be highly beneficial to their quality of life and many have noticed minimal if any changes.

How does LDN work?

Naltrexone, when given to mice and people at high doses, raises endorphin levels in the body’s effort to overcome the naltrexone blockade. This drug became the focus of Dr. Bihari’s research group. When the group discovered that endorphins are almost all produced in the middle of the night, between 2 AM and 4 AM, the studies focused on small doses (1.5-4.5 mg at bedtime) with the hope that a brief period of endorphin blockade before 2 AM might induce an increase in the body’s endorphin production. In fact, the drug did so in this dosage range. It had no effect below 1.5 mg and too much endorphin blockade at doses over 5 mg.

Studies:

There have been limited clinical studies of LDN and its usage for multiple sclerosis patients.

A pilot clinical trial involving 60 people with all types of MS testing low-dose Naltrexone suggested that it may improve several measures of mental health quality of life and pain, and that further testing in larger numbers of individuals may be warranted.

• The study, by Bruce Cree, MD, Douglas Goodin, MD, and colleagues (MS Center, University of California at San Francisco), was published in the Annals of Neurology (Volume 68, Issue 2, pages 145–150, August 2010).
• Some participants were using standard disease-modifying therapies during the trial and some were not. All participants received both the LDN for eight weeks and inactive dummy pills (placebo) for eight weeks in a study design known as “crossover,” with one week free of treatment in between. Some received the LDN during the first eight-week period and some during the second eight-week period.
• Participants were given a Web-based battery of quality of life tests called the MS Quality of Life Inventory (MSQLI) before the first treatment period and after each study period. The MSQLI asks the individual to report on mental and physical aspects of their condition including mental health, pain, perceived cognitive deficits, fatigue, and visual, bladder and bowel symptoms and sexual satisfaction.
• The investigators found that LDN significantly improved quality of life (specifically, mental health, pain and self-reported cognitive function), but no impact was observed on aspects of physical quality of life (such as fatigue, bowel and bladder control, sexual satisfaction, and visual function). Vivid dreaming was reported during the first week of treatment by some patients, but no other adverse effects were reported. The investigators emphasized that the results did not support the use of LDN instead of proven MS treatments.
• The investigators suggest that LDN may provide symptomatic relief for MS. Based on some published laboratory studies, the investigators cite the possibility that LDN increases levels of endorphins in the brain, which are the body’s natural pain relievers. Unfortunately, as noted by the investigators, due to dropouts and incomplete data, they had complete data on only 60 of the 80 original participants, which weakened the statistical power of the trial results. They suggested that their findings require confirmation in a larger, multi-center clinical trial.

Results of a small trial of LDN were presented by Dr. Gianvito Martino (San Raffaele Hospital, Milan, Italy) at the 2008 Academy of Neurology meeting. The team administered 5 mg of LDN to 40 people with primary-progressive MS for six months, evaluating its safety and effects on spasticity, pain and fatigue. Five patients dropped out. Significant improvements were shown in fatigue and depression. Transient increases in liver enzymes, urinary tract infections, mild agitation and sleep disturbance were the most common adverse events.

A 17-week randomized, controlled study of low-dose naltrexone in 96 people with MS, published in 2010, found no statistically significant differences between the naltrexone-treated and placebo-treated groups on any of the following quality of life variables: pain, energy, emotional well-being, social cognitive and sexual functions, role limitations, health distress and overall quality of life. The authors concluded that although naltrexone appears to be a safe treatment option, a controlled trial of longer duration would be needed to demonstrate its effectiveness in improving quality of life for people with MS.

LDN has also been investigated to a limited degree in animal models of MS. The National MS Society funded a pilot study by Ian Zagon, PhD (College of Medicine at Pennsylvania State University) looking at the effects of both low- and high-dose Naltrexone in mice and impacts on the MS-like disease, EAE. Based on earlier findings that opioids (which occur naturally on cells in the nervous system) may regulate immunity, wound healing and cell renewal, Dr. Zagon and colleagues were looking to see if mice treated with Naltrexone demonstrate any changes in their MS-like symptoms or underlying disease activity. His team found that low-dose naltrexone, but not high-dose naltrexone, was somewhat protective against the development of EAE. (Exp Biol Med (Maywood). 2009 Nov; 234(11):1383-92.)

Dosing Information:

For people with multiple sclerosis, the dosage of LDN ranges from 1.5 to 4.5 ml per day. It is recommended that people with any form of spasticity take no more than 3 mg per day, as the LDN can contribute to muscle stiffness (although, paradoxically, it is also reported by some to help with MS-related spasticity symptoms).

LDN is taken at night, between 9:00 pm and 12:00 midnight, to work with the body’s natural peak release of endorphins, which occurs sometime between 2:00 and 4:00 am. It can be taken with or without food.

The usual adult dosage is 4.5mg taken once daily at night. Because of the rhythms of the body’s production of master hormones, LDN is best taken between 9pm and 3am. Most patients take it at bedtime.

Notable exceptions:

• People who have multiple sclerosis that has led to muscle spasms are advised to use only 3mg daily and to maintain that dosage.
• For intial dosage of LDN in those patients who have Hashimoto’s thyroiditis with hypothyroidism and who are taking thyroid hormone replacement medication.

Rarely, the naltrexone may need to be purchased as a solution — in distilled water — with 1mg per ml dispensed with a 5ml medicine dropper. If LDN is used in a liquid form, it is important to keep it refrigerated.

The therapeutic dosage range for LDN is from 1.5mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with its effectiveness.

Side Effects:

LDN has very few side effects, with the most frequently-mentioned effect being lucid, or vivid, dreams at the start of treatment.  Problems sleeping can often be mitigated through common sleep mediation medications.

In a few studies, slight abnormalities in bloodwork have been noted though none were severe enough to discontinue treatment:

• liver function
• blood counts
• elevated serum cholesterol

A couple of studies have also observed irritability in participants as a side effect.

Potential Interactions and Warnings:

LDN should never be combined with any opiate-based drugs (narcotics). Including drugs taken to control pain, like oxycodone (OxyContin) or hydrocodone (Vicodin). It also applies to seemingly-harmless drugs, like codeine-based cough syrup. It is very important to make sure to never take LDN with any forms of these medications as you can get EXTREMELY ill.  It is also wise to make sure that this facet is well known by your caregiver(s) and noted in your medical profile.  The last thing you want to happen is be in say a hospital environment and be given substances that will adversely react with LDN.

Some sleep based medications such as Benadryl people often use.

Again, it is extremely important that you do not use ANY narcotics-based drugs while on LDN, including those which may have been used in the past to help you sleep.

Make absolutely certain that no medications you take will interact with LDN.

1. Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one’s system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely.
2. Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range (1.5mg for an adult). Be aware that LDN may lead to a prompt decrease in the autoimmune disorder, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.
3. Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.
4. People who have received organ transplants and who therefore are taking immunosuppressive medication on a permanent basis are cautioned against the use of LDN because it may act to counter the effect of those medications.

Make sure and consult your neurologist as well before seeking to use LDN as the medication.  Avonex, Betaseron and Rebif, for example it is assumed that LDN will interact with the interferon-based disease-modifying therapies, so patients on these drugs should NOT take LDN. However patients taking Copaxone have not reported significant problems.

With infusions or oral pill disease modifying therapies again it is important to discuss usage of LDN with your neurologist.

More Information:

IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form.

Videos:

Note: Below is a playlist of hundreds of interviews with people using LDN.

You can access the playlist from the icon in the upper left corner of the videos.

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