

www.lowdosenaltrexone.org www.ldninfo.org LDN and Multiple Sclerosis (MS) In Brief Special Notices Recent Developments Noteworthy Cases Background

LDN & Autoimmune Disease LDN Homepage

In Brief 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. Special Notices People who have multiple sclerosis that has led to muscle spasms are advised to begin LDN treatment with just 3mg daily and to maintain that dosage.

are advised to begin LDN treatment with just 3mg daily and to maintain that dosage. Patients who are exposed to undue fatigue, heat, or a febrile illness may demonstrate a recurrence of prior symptoms, stemming from an area of old neurologic involvement. These areas tend to have increased irritability of nervous tissue surrounding old healed MS scars ("plaques"). Such an episode may be very transient and may not represent a true relapse. Recent Developments As 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

Subject: Naltrexone

Date: October 23, 2003



As I have said before, if I had MS, the only drug that I would absolutely be taking is LDN..... In 4 years of dispensing LDN, with over 10,000 patient months, I have heard of only three cases of exacerbation... this is truly a no-brainer. I would find someone to prescribe it no matter the cost or effort.



Skip Lenz, Pharm. D.

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: One is reduction in spasticity when this is present, sometimes allowing easier ambulation when spasticity in the legs has been a prominent element of a patient's difficulty in walking or standing. This is unlikely to represent a direct effect of LDN on the disease process, but rather reduction in the irritability in nervous tissue surrounding plaques. Endorphins have been shown to reduce irritability of nervous tissue, e.g., by reducing seizures in patients with epilepsy.

The other area of symptomatic improvement in some patients is a reduction in MS-related fatigue. This is, also, not likely due to a direct effect on the MS disease process, but rather an indirect one caused by restoration of normal endorphin levels improving energy. 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. Noteworthy Cases 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: A 31-year-old patient has a history of relapsing-remitting MS, and recently had developed not only slurred speech and trouble finding the right word (dysphasia) but also had noted weakness in one hand and one leg. She started LDN and reported that within one week her problems with speech had substantially cleared,and there was a marked improvement in her gait and in the use of her hand. The patient who is 44 years old has chronic progressive MS (as do the other two women to be discussed below). She had reached the point some time ago where she needed to use a walker in the home in order to get around. On the third night after starting LDN, she got up and went to the bathroom without using the walker — for the first time in two years. She reports having experienced a prompt 20%-30% improvement in her balance, apparently due to decreased spasticity. The third patient, a woman in her early 50's, reported prompt improvement in walking within four days after starting LDN, apparently due to decreased spasticity. The fourth case came to Dr. Bihari's attention in late April 2000 when a woman telephoned his office to leave a message of thanks for him. She has the diagnosis of MS and for the past ten years has had variable visual impairment in one eye, to the extent that she has had to wear eyeglasses to mask that eye. She said her neurologist had begun to prescribe LDN three months earlier. Within two days after starting LDN she regained unimpaired binocular vision. She said that she had recently forgotten to take her LDN at bedtime for two nights in a row, and the eye problem returned — only to subside within a day or two after restarting the medication. Background 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. 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