Low Dose Naltrexone: Hope for PPMS

Primary progressive multiple sclerosis (PPMS) is a particularly nasty form of MS affecting about 10-15% of MS patients. Those with PPMS never experience more than minor remissions from their illness with progressive disability from the start. It is generally considered untreatable by current MS drugs. Some doctors even believe PPMS should be considered a separate entity from other forms of MS.

The new study was an Italian open-label trial on 40 patients to evaluate safety and tolerability of LDN in PPMS. It was published in the medical journal Multiple Sclerosis. Open-label means that everyone was receiving the medication; it was not compared with placebo.

LDN

Naltrexone is an opioid antagonist used in the treatment of addiction. In large doses it blocks the effects of endorphins. In very small doses, however, it actually stimulates the production of endorphins, which are not only natural painkillers but important immunomodulators as well. Beta-endorphin levels have been shown to be low in MS and other autoimmune diseases.

What is interesting about LDN is that it is not considered immunosuppressive like most drugs used in the treatment of autoimmunity. Thus it is not expected increase the risk of infections and cancer, as immunosuppressants do.

LDN showed excellent efficacy in a Crohn's disease study published in 2007. It is currently in clinical trials for fibromyalgia, autism, HIV/AIDS and several cancers.

Study Results

LDN markedly reduced spasticity, while pain, fatigue and depression did not improve (or improvement didn't reach statistical significance). The study did not evaluate urinary frequency, a common symptom of MS and often reportedly helped by LDN. It should be noted that LDN is not intended for symptom improvement, but to slow down illness progression, though some patients do experience symptom relief.

During the six-month study neurological disability progressed only in one patient, which is quite a low number considering it was done on people with progressive multiple sclerosis. The study, however, was a preliminary one to assess safety and tolerability, not efficacy.

LDN was also shown to increase blood levels of beta-endorphin. Interestingly the highest levels were measured one month after cessation of the drug. Some of the symptoms were also at their lowest at this point. This raises the question whether LDN should be taken intermittently in PPMS for the best effects, but this is merely speculation.

Adverse Effects

The study abstract lists two "major adverse effects", but this is quite misleading, as they were advanced lung cancer in a 40-cigarette-a-day smoker and kidney failure caused by a urinary tract infection (UTIs are very common in MS due to impaired bladder control). The study authors are obliged to list any such occurrences, even if any connection with the drug is highly unlikely.

Most of the reported adverse effects were mild and could have been caused by MS. Irritability occurred in a few cases. Two patients had elevated liver enzymes and one had elevated bilirubin - but he was also taking methotrexate, though, which should not be taken with LDN anyway. Cholesterol levels increased in six patients.

The study concluded that LDN was safe and well-tolerated. The side effects were negligable compared to current MS drugs. More studies are needed to demonstrate the efficacy of LDN in the treatment of MS, but tens of thousands of patients have already drawn on their conclusions and swear by it.

References

Vukusic S, Confavreux C. Primary and secondary progressive multiple sclerosis. J Neurol Sci. 2003 Feb 15;206(2):153-5.

Smith JP, Stock H, Bingaman S, et al. Low-dose naltrexone therapy improves active Crohn's disease. Am J Gastroenterol. 2007 Apr;102(4):820-8.

Gironi M, Martinelli-Boneschi F, Sacerdote P, et al. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Mult Scler. 2008 Sep;14(8):1076-83.

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