Low Dose Naltrexone as a Treatment for Multiple Sclerosis

What's this "LDN" everyone is talking about?

Mixed race woman holding medication pills
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Low dose naltrexone (known to its friends as LDN) could be a huge, untapped solution for millions of people with multiple sclerosis (MS). However, some doctors are afraid that it could be, for lack of a better term, “snake oil.” The problem is that no one has really done a big, double-blinded, placebo-controlled phase III type study using LDN, so we continue to lack the kind of evidence that physicians need to prescribe it and drug companies need to make it (currently it is only available from a compounding pharmacy).

However, there is plenty of “buzz” around LDN in the MS community. With a fervor that I have not seen around any other drug (except maybe medical marijuana), lots of people with MS are saying, “Hey! This stuff works!”

Naltrexone is an opiate antagonist, and at the usual dosage of 50 to 100 mg is used to help people stop abusing alcohol or narcotics (opioid drugs). It works by decreasing the cravings for these substances, primarily by blocking the opiate receptors. LDN refers to the "off-label" use of naltrexone at a fraction of the usual dose.

What Do People Use It for?

If you look at the what the proponents of LDN for multiple sclerosis are saying, it:

But that’s not all. LDN has fans that claim it is a treatment for all sorts of things such as: AIDS, cancer, Parkinson’s disease, lupus, rheumatoid arthritis, and Crohn’s disease.

How Does It Work?

LDN is another one of those “no one really knows how it works” drugs for MS. One theory is that it increases the body’s sensitivity to its own endorphins, or even does something that helps the body make more endorphins (the feel-good hormones). There is some evidence that endorphins reduce inflammation as well as lessen negative sensations of pain, fatigue, and depression.

Another theory suggests that LDN somehow reduces the production of free radicals, almost acting like an antioxidant.

How Effective Is It?

The answer to this question depends on who you ask.

Let’s start with the scientific trials:

  • Animal studies have shown that in mice with EAE, LDN seemed to work. It lowered inflammation in the central nervous system and decreased disease severity and immune cell activation. Interestingly, in animal models, high doses of Naltrexone worsened the disease.
  • In an 8-week placebo crossover trial conducted at the University of California at San Francisco among 80 people with relapsing-remitting and progressive MS, it looks like LDN did not really help the physical functioning of participants but did produce statistically significant improvements in quality of life measures of mental health, pain and self-reported cognitive functioning. Interestingly, this trial was funded by patients who raised funds to sponsor it.
  • A 6-month phase II (safety) trial conducted among 40 people with primary-progressive MS in Italy had the following results:
    • Statistically improved spasticity: 47% improved; 42% remained stable; 11% worsened
    • No statistical change in fatigue: 33% improved; 26% remained stable; 41% worsened
    • Statistically worse pain: 28% improved; 15% remained stable; 56% worsened
    • No statistical change in depression: 56% improved; 11% remained stable; 33% worsened
    It is important to keep in mind that there was no placebo group to compare these results to, as this trial was done primarily to assess safety.

    Now, looking at what the proponents are saying about LDN on various Internet sites, it is easy to get caught up in the excitement as claims are made about 99% reporting no progression of disease, rapid resolution of symptoms when taken during an acute exacerbation, and all sorts of stories of reductions of every MS symptom out there. On one hand, it is easy for skeptics to say that this is simply anecdotal evidence and dismiss it out of hand. On the other hand, however, there are a lot of these stories and the two studies above have neither disproven or proven that LDN works. For that to happen, the studies would have to be bigger, longer, and double-blinded placebo-controlled (basically phase III) trials.

    Usual Dosage/How Taken

    For people with multiple sclerosis, the dosage of LDN ranges from 1.5 to 4.5 mg 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 9:00PM and 12:00AM, to work with the body’s natural peak release of endorphins which occurs sometime between 2:00 and 4:00AM. It can be taken with or without food.

    Side Effects

    At such a tiny dose (less than 10% of a typical dose of Naltrexone), LDN has very few side effects, with the most frequently-mentioned effect being lucid, or vivid, dreams at the start of treatment.

    In a couple of studies, the following slight abnormalities in bloodwork have been noted (although 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

    The most important thing to remember is that LDN should never be combined with any opiate-based drugs (narcotics). This includes drugs taken to control pain, like oxycodone (OxyContin) or hydrocodone (Vicodin). It also applies to seemingly-harmless drugs, like codeine-based cough syrup.  

    It's possible to end up in the hospital from inadvertently taking LDN with one of these drugs, and people can feel 100 times sicker than they could ever imagine, so be mindful of what you take in. 

    Avonex, Betaseron and Rebif: Based on pharmokinetics, scientists assume that LDN interacts with the interferon-based disease-modifying therapies, so patients on these drugs should not take LDN either. However, it is OK to be used in conjunction with Copaxone. 


    The bad news: Your insurance probably won’t cover it, as LDN for MS is still in the “experimental” category.

    The good news: It’s pretty cheap. A little over a dollar per dose at a compounding pharmacy.

    Additional Information/Points

    Sleep Interactions: LDN can interfere with sleep, primarily in the form of very lucid dreams. This happens mostly in the first week of taking it, although for some people this effect lingers. You can discuss the use of a sleeping aid, such as Ambien, with your doctor, especially when you first start using LDN. Some people take Benadryl for this reason. 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.

    See What the People Are Saying: Revolutionhealth.com is a favorite site for finding out what people are saying about a specific drug. Go to this link on Naltrexone, then make sure to use the scrollbar next to “Show reviews of Naltrexone for:” to find your type of MS.

    Remember that these results are undoubtedly influenced by “selection bias,” meaning people that experience extreme results (good or bad) are more likely to take the time to write in than those with neutral opinions, so be cautious. 

    Relapsing or Progressive: Keep in mind when you look at results (both scientific and anecdotal) of LDN treatment in people with MS that relapsing MS may be more “inflammatory” in nature, while progressive forms of MS may be more “degenerative.” Therefore, if it turns out that LDN works in MS because it reduces inflammation through some mechanism, it may be more effective (or work differently) in people with relapsing forms of MS. However, reports (again, both scientific and anecdotal) do support some action in people with progressive MS.


    Bowling, Allen C. Complementary and Alternative Medicine and Multiple Sclerosis. 2nd ed. Demos Publishing: New York. 2007.

    Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M, Cursi M, Franchi S, Martinelli V, Nemni R, Comi G, Martino G. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler. 2008 Sep;14(8):1076-83.

    National Multiple Sclerosis Society. http://www.nationalmssociety.org/news/news-detail/index.aspx?nid=148 Low Dose Naltrexone, Update. June 2, 2008. Accessed: April 2009.

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