March 25, 2015
One of the most widely disputed treatments for multiple sclerosis is low dose naltrexone (LDN). While a plethora of patient testimonies and anecdotal evidence suggest immense benefits of LDN for multiple sclerosis, many clinicians are wary due to the lack of FDA approval outside of treating heroin and alcohol addiction.
Starting with the basic biology of LDN, the opiod antagonist drug is suggested to protect oligodendrocytes from cell death by reducing inflammation in the brain as a result of inducible nitric oxide synthase (iNOS) inhibition. In other words, less oligodendrocyte apoptosis means a greater potential for myelination, the key activity that could restore myelin damaged in multiple sclerosis. An alternative explanation for LDN activity is that low doses (less than 5 mg/day) of naltrexone cause the drug to act as an opiate agonist to regulate neurotransmitter activity between neurons.
Regardless of the mode of action, “Low Dose Naltrexone Therapy in Multiple Sclerosis,” published in the journal Medical Hypotheses, reports that over 70,000 LDN capsules are dispensed from a single pharmacy in only 8 months. Such a high demand for LDN resulted in the first trial for LDN initiated in December 2006 (completed in August 2007 and published in September 2008).
Led by researchers in Milan, Italy, the trial was a six-month, multi-center pilot Phase 2 trial that treated 40 patients with primary progressive multiple sclerosis (PPMS), a more severe form of the disease. “A significant reduction of spasticity was measured at the end of the trial,” wrote Dr. Gironi, lead author of the study “A Pilot Trial of Low-Dose Naltrexone in Primary Progressive Multiple Sclerosis,” published in the journal Multiple Sclerosis. Dr. Gironi further described, “Our data clearly indicate that LDN is safe and well tolerated in patients with PPMS.”
In this study, patients were dosed with 2 mg oral LDN at bedtime for four weeks. Patients were monitored by their clinicians via phone call, and the dose was increased to 4 mg if warranted. In-person follow-up visits allowed clinicians to track the progress of patients. Only one patient experienced a progression of neurological disability, and adverse events did not interfere with daily living for the patients who remained in the study.
Around the same time as the study in Milan, psychologist David Pincus announced a study to treat patients with either PPMS or relapsing-remitting multiple sclerosis. This trial was a 16-week trial with 36 patients. Unfortunately, at the close of the study, Dr. Pincus acknowledged problematic outcomes in the study. “We did not exclude patients on existing immunosuppressants,” stated Dr. Pincus. “The existing immunosuppressants may have inhibited the LDN effects in this population.” There was no apparent difference between placebo-treated and LDN-treated patients in terms of symptoms or energy levels.
The first placebo-controlled trial for LDN in multiple sclerosis was conducted by the University of California, San Francisco in early 2007 with neurological researcher Bruce Cree, MD as the lead. “A Randomized Placebo-Controlled, Crossover-Design Study of the Effects of Low Dose Naltrexone” was a Phase 3 study that dosed 80 patients with either 4.5 mg of naltrexone or placebo for eight weeks before treatment was crossed-over.
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