LDN and Multiple Sclerosis (MS)
Over the past few years, growing experience with the clinical use of LDN demonstrates its consistency in preventing further attacks in people with MS. In addition, a majority of such patients note reductions in spasticity and fatigue.
Recent DevelopmentsAs of May 2004:
In preparing a proposed clinical trial protocol for the use of LDN in the treatment of multiple sclerosis, Dr. Bihari assembled the latest data from his clinical practice. As of May 2004, Bihari has almost 400 patients with MS in his care. Of that group he knows of only two patients who showed signs or symptoms of new disease activity over the years while taking LDN treatment. One was a 41-year-old woman who, after 18 months on LDN, had an episode of optic neuritis which cleared in 4 weeks. The other was a patient who, after 8 months on LDN, had an episode of numbness in the left leg that had not been experienced previously and which cleared after 3 weeks.
As of October 2003:
The following excerpted posting, written by the chief pharmacist of Skip's Pharmacy of Boca Raton, Florida, appeared on a different website:
From: Dr. Skip
As of March 2002:
Clinically the results are strongly suggestive of efficacy. Ninety-eight to 99% of people treated with LDN experience no more disease progression, whether the disease category is relapsing-remitting or chronic progressive. Dr. Bihari has more than 70 people with MS in his practice and all are stable over an average of three years. The original patient on LDN for MS, now on it for 17 years, has not had an attack or disease progression for 12 years since the one missed month that led to an attack.
In addition, 2,000 or more people with MS have been prescribed LDN by their family MDs or their neurologists based on what they have read on the LDN website or heard about in internet chat rooms focused on MS. Many such patients with MS, not under Dr. Bihari's care, use the e-mail link on the LDN website to ask questions. Many prescribing physicians do not generally know about LDN.
Only once has a patient reported disease progression while on LDN. In this case, it showed itself five days after he had started the drug. The onset of the episode had apparently preceded the start of LDN.
In addition to the apparent ability of LDN to stop disease progression, approximately two-thirds of MS patients starting LDN have some symptomatic improvement generally apparent within the first few days. There are two types of such improvement:
Patients who are in the midst of an acute exacerbation when they start LDN have generally shown rapid resolution of the attack. In two patients, chronic visual impairment due to old episodes of optic neuritis has shown fluctuating improvement.
It should be emphasized that in spite of the plentitude of clinical experience described above, in the absence of a formal clinical trial of LDN in MS, these results cannot be considered scientific, but rather anecdotal. A clinical trial, preferably by a pharmaceutical company with some experience with MS, is clearly needed to determine whether these results can be replicated. If they can be, they are likely to lead to widespread use of this extremely non-toxic drug in the treatment of MS.
In May 2000, Bernard Bihari, MD reported four occurrences of surprisingly rapid clinical improvement in people with multiple sclerosis, presumably related to LDN use. Three were female patients for whom Dr. Bihari had prescribed nightly LDN.
As of March 2002, all four have sustained the improvement originally seen. Since those four cases were first reported, there have been several dozen more patients who have had similar relief of spasticity allowing better ambulation and relief of MS-related fatigue.
The occurrences Dr. Bihari originally reported in May 2000 were as follows:
Naltrexone was licensed in 1984 by the FDA in a 50 mg dose as a treatment for heroin addiction. It is a pure opiate antagonist (blocking agent) and its purpose was to block the opioid receptors that heroin acts on in the brain. When it was licensed, Dr. Bihari, then involved in running programs for treating addiction, tried it in more than 50 heroin addicts who had stopped heroin use. None of the patients would stay on the drug because of side effects experienced at 50 mg such as insomnia, depression, irritability and loss of feelings of pleasure, all due to the effect of the drug at this dose in blocking endorphins. These are the hormones in the body that heroin resembles. Physicians treating heroin addicts therefore, for the most part, stopped prescribing naltrexone. In 1985, a large number of heroin addicts began to get sick with AIDS-studies showed that 50% of heroin addicts were HIV Positive.
Dr. Bihari and his colleagues decided to shift their research focus to AIDS, in particular focusing on ways of strengthening the immune system. Since endorphins are the hormones centrally involved in supporting and regulating the immune system, levels of endorphins were measured in the blood of AIDS patients. They were found to average only 25% of normal.
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. A placebo-controlled trial in AIDS patients showed a markedly better outcome in patients on the drug as compared with those on placebo.
During the trial, a close friend of Dr. Bihari's daughter had three acute episodes of multiple sclerosis over a nine-month period with complete spontaneous recovery from each. Because of his knowledge of MS as a neurologist and of recent evidence of an autoimmune component in the disease, Dr. Bihari started his daughter's friend on naltrexone at 3 mg every night at bedtime. She took it for five years with no further attacks. At that point, when a particular month's supply ran out, she stopped it because of some denial that she had MS. Three and a half weeks later, she developed an episode of weakness, numbness, stiffness and spasms in her left arm and resumed LDN, which she has stayed on since. This episode cleared and over the 12 years since, she has had no further disease activity.
The apparent mechanism of action of LDN in this disease parallels that in AIDS and other immune-related diseases. A small dose of the drug taken nightly at bedtime triples the endorphin levels in the body all of the next day restoring levels to normal. Since endorphin levels are low in people with MS, immune function is poorly orchestrated with significant impairment of the normal immune supervisory function of CD4 cells. In the absence of normal orchestration of immune function, some of the immune system cells "forget" their genetically determined ability to distinguish between the body's 100,000 unique chemical structures (called "self") and the chemical structures of bacteria, fungi, parasites and cancer cells (called "non-self"). With this loss of immunologic memory, some cells begin to attack some of the body's unique chemical structures. In the case of people with MS, the tissue attacked by immune cells (particularly macrophages) is primarily the myelin that insulates nerve fibers. These attacks result in scars in the brain and spinal cord called plaques. LDN in such patients works by restoring endorphin levels to normal, thereby allowing the immune system to resume its normal supervision and orchestration.