Researchers in the US and Italy are investigating whether the opioid receptor antagonist naltrexone, in a low dose, can relieve symptoms of multiple sclerosis.

By Ronald Hoffman, MD, and Skip Lenz, Pharm D, FASCP

Last month, Action looked at a new use of the drug naltrexone, which was invented to combat addictions to heroin and other opiods, that has the potential to treat a range of neurological and other conditions when taken at a low-dose. (That article, “Low-Dose Naltrexone (LDN) and MS,” is available here).

This month we will look at three studies around the world that are testing the ability of LDN to ameliorate symptoms of multiple sclerosis (MS).

Italian Study

A long-awaited pilot study of LDN therapy in MS has been implemented by the Milan neurological researcher, Dr. Maira Gironi. Dr. Gironi’s research team has long been a locus for significant research on endorphins in relation to illness, and this study will track accurate assessments of the patients’ beta-endorphin levels in response to their LDN treatment.

This will be a 6-month pilot, multicentric, open-label, therapeutic study of 40 patients with Primary Progressive MS between the age of 18 and 60. The subjects are over 3 and less than 6 on the expanded disability severity scale (EDSS). They are affected with spasticity, pain, and/or fatigue. Optimization of gabaergic or serotoninergic drugs before entering the study was requested. Any opioid-containing drug, immunosuppressive or immunomodulator medicines were not allowed. All 40 patients are being treated with LDN at a final dose of 5 mg after a 2-week titration of 2.5 mg.

Common involvement of the spinal cord mostly in the primary progressive form of MS explains a high prevalence of spasticity, pain, and fatigue accompanying the disease. People with PPMS are known to have low levels of beta- endorphins and a possible mild, diffuse infl ammatory reaction. Conventional anti-infl ammatory drugs seem to fail to cross the blood brain barrier (BBB) in people with PPMS.

The aim of the trial is to evaluate and document the safety and tolerability of LDN and its efficacy on the spasticity, pain, and fatigue experienced by the participants.

During the 32 weeks of the study, participants are undergoing periodic clinical and biomedical analyses to evaluate any adverse events. Moreover, neurological evaluations, using scales of spasticity, pain, and fatigue, are periodically performed. The measurement of peripheral blood mononuclear cells’ beta-endorphin levels both before and after treatment will confirm or deny the supposed increase of this opioid during LDN treatment. An LDN-driven increase in beta-endorphins might have an anti-inflammatory effect. This would suggest that LDN can cross the BBB.

The treatment phase of the study was scheduled to be completed this past autumn, then followed by analysis of the data.

Quality of Life

At the University of California at San Francisco Multiple Sclerosis Center, Dr. Bruce Cree and colleagues from the UCSF department of Neurology are running a randomized, double- masked, placebo-control, crossover clinical trial to evaluate the efficacy of LDN on the quality of life of patients with MS.

Naltrexone has been approved by the U.S. Food and Drug Administration (FDA) to treat alcohol and opioid addictions (using 50 mg dosages). Whether LDN has any benefit for people with MS is currently unknown.

LDN may assist with MS in one of two ways:

• By improving the immune system’s function through increasing the level of endorphins and enkephalins, chemicals which are produced by the nervous and immune systems.

• By reducing the activity of cells that damage the brain and spinal cord in MS. Participants will be randomly assigned to one of two groups. Both groups will receive LDN for eight weeks and a placebo for eight weeks, with one week between when both groups will take nothing. One of the groups will receive the LDN first, and the other group will receive it last. Neither the participant nor their doctor will know which group they are in until after the study is complete.

Patients will be asked to answer a questionnaire (called “MSQLI54”) at the baseline and at weeks 8 and 17.

This project began March 1, 2007. Data analysis is already underway. A substantial contribution toward the study was made by the LDN for MS Research Fund.

Symptom Severity

In May 2007, the MindBrain Consortium and the Department of Psychiatry of Summa Hospital System of Akron, Ohio, Kent State University, and the nearby Oak Clinic for the Treatment of MS, announced a new scientific study of the effects of treating MS with LDN. Psychologist/neuroscientist David Pincus and his colleagues are coordinating the study.

This is a 16-week, double-blind, randomized, placebo-controlled, crossover-design analysis of 36 patients with either progressive or relapsing-remitting MS. The study will examine symptom severity as well as any changes in quality of life, sleep patterns, and affective states.

The connection between the brain and MS as well as other “auto-immune” disorders may not be intuitively obvious, beyond the fact that opioid receptors were discovered all over the immune system in 1979 and have been thought to have a regulatory effect. Up until that time, opioids have only been associated with neural tissue such as in the brain, such as the beta endorphins which are part of the “runner’s high.”

While much remains to be understood about the function of the opioid receptors in the immune system, clinical anecdotal evidence tells us two things: LDN in low doses has the effect of increasing the naturally occurring beta endorphins in the brain by as much as 300%, and many people report remarkable improvement in their symptoms of MS. Also, we know that people on LDN report a sense of increased energy as well as increased dreaming and nighttime activity with LDN (about 30% of those in double-blind studies).

The MindBrain Consortium Kent- Summa-Oak Clinic study is interested in elucidating the effects of LDN on MS at multiple levels. This study is very much within the conceptual framework of the emerging field of psychoneuroimmunology.

Once these three trials have been completed and the results have been published, we will report the results to you in Action. In the meantime, if you are interested in finding out more about LDN, please visit www.ldninfo.org. This site provided most of the information being reported to you here.

Ronald Hoffman, MD, is founder and Medical Director of the Hoffman Center in New York City, author of numerous books and articles for the public and for health professionals, and host of the nationally syndicated radio program Health Talk. Skip Lenz, Pharm D, FASCP, is a pharmacist in Boca Raton, Florida.