| Patient Information Sheet: The Treatment of Multiple Sclerosis with Low-dose Naltrexone. These notes are important. It is essential that you read and thoroughly understand them before starting the Low-dose naltrexone (LDN) treatment. LDN is a treatment method that has been in use in the USA since 1985 but is relatively new in the United Kingdom. Despite its claimed successful use in America, until fully proved here, it must be considered as experimental and that no beneficial response can be guaranteed. In addition, despite the fact that the drug is at a very low dose, the absence of significant introductory or prolonged side-effects cannot be excluded. The treatment can only be provided if these conditions are accepted. Naltrexone is a drug, referred to as an opiate antagonist. Its normal use is to treat opiate drug addicts addicted to such as heroin or morphine. Doses used for this purpose is usually 150 mg or more each day. This method was devised, and has since been developed, by Dr Bernard Bihari, a practicing neuro-physician in New York, USA. Dr Bihari is qualified in Internal Medicine, Psychiatry and Neurology. His address is 29w 15th Street, New York, New York; telephone number (212) 929 4196; fax: (212) 229-9371. The website (www.lowdosenaltrexone.org), describing his method, is presented by Dr David Gluck. The method was first put to use, in the treatment of MS, in 1985. It has since been reported that those receiving this drug in the treatment of MS, initially at a dose of just 3 mg per day, have experienced a range of improvements, including such as: reduced spasm and fatigue, improved bladder control, improved heat tolerance, with improvements in mobility, sleep, pain, tremor and other symptoms. The two main symptoms that appear to improve most significantly are muscle spasm and fatigue. The usual maximum recommended dose is 4.5 mg per day, taken between 9 pm at night and 3 am in the morning. The introductory dose however, remains at just 3 mg for the first month of treatment. After this period, in the absence of any introductory side-effects, and for greater therapeutic response, the dose may be increased to 4.5 mg/ day if desired. Exceptionally, an even higher dose of 6 mg is also available for those needing a dose of this magnitude. For those unable to tolerate even the 3 mg dose, an ultra-low, 2 mg, or even 1 mg, dose is also available. This is intended to introduce the therapy more slowly, allowing more time for the necessary endorphin response to develop. How Naltrexone Works: The benefits of this drug are apparently due to the temporary inhibition of brain endorphins (a natural pain-killer, produced in the brain). This results in a reactive increase in the production of endorphins, which would expectedly result in a reduction in painful symptoms and an increase in the sense of wellbeing. In addition, increased levels of endorphins would also be expected to stimulate the immune system, promoting an overall increase in the numbers of T lymphocytes. This effect has been observed in Dr Bihari’s research. This increase in T-cell numbers apparently restores a more normal balance of the T-cells such that the effects of the disease process are significantly reduced. Thus, it has been observed that, in those suffering the relapsing-remitting form of MS, the number of relapses is reduced, and the rate of progression of the disease is diminished. In fact, Dr Bihari’s research suggests that no-one receiving this treatment as a regular therapy, has experienced a relapse while actually on the treatment. Occasionally however, there may be a short-term increase in symptoms during, for example, periods of infection or stress, arising from previously active lesions already present in the brain or spinal cord. In chronic, progressive MS (either primary or secondary) there appears to be a similar reduction in the progression of disease symptoms. Despite these promising findings it must be emphasised that a positive beneficial response to this treatment cannot be assured or guaranteed. Side-Effects: When starting this therapy in the treatment of MS, the possibility of adverse side-effects due to the drug, cannot be entirely excluded. The likelihood of damaging side-effects is believed to be minimal however, as the drug is used at such a low dose. Reversible liver damage has been found to occur only in those receiving doses greater than 300 mg per day. Due to the possible toxic effects of this drug upon the liver and kidneys it is required that anyone suffering previous liver or kidney problems should report this condition before starting therapy. This risk is believed to be minimal, however, as the dose of the drug is extremely low. Even after many years of continuing use, no toxic effects have been found in those already using LDN. Introductory Side-effects: There may be some initial transient, though temporary, increase in MS symptoms during the adaptive period when the LDN is first introduced. This usually lasts no more than one week but if symptoms are severe, or more prolonged, then the initial dose of 3 mg may be reduced to a lower dose until the anticipated improvements begin to develop. Introductory symptoms, on starting this treatment, may include such as disturbed sleep, occasionally with vivid, bizarre and disturbing dreams, tiredness, fatigue, muscle spasm and pain. Symptoms related to increased endorphins: These may include such as nausea or constipation. These symptoms diminish gradually as the body adjusts to the increased endorphin level. Symptoms related to previous use of opiate analgesics: On starting LDN the recent use of opiate analgesics will result in an opiate withdrawal syndrome, with increased pain, muscle spasm, and possibly vomiting and diarrhea. These symptoms may be prevented by stopping all opiate analgesics at least two weeks before starting the LDN. Symptoms related to the use of Lactose filler: If lactose filler is used in the capsules some individuals may be sensitive to this sugar and, usually after a few weeks of treatment, will develop diffuse but persistent muscle or joint pain. This may be avoided by using an alternative filler, such as calcium carbonate or Avicel. The latest supplies of naltrexone capsules use Avicel (methyl cellulose) filler. Despite dispersal testing showing that calcium carbonate capsules will dissolve as quickly as Avicel there has been much discussion on the internet suggesting that calcium carbonate filler may be subject to compaction problems, which can potentially reduce the dispersal and absorption rate. It has therefore been decided that, to avoid any doubts regarding this question, Avicel would be the preferred choice. The early introductory, but temporary, increase in symptoms may also perhaps be explained when we consider the manner in which this drug is expected to work. Contrary to the common belief that MS is due to over-activity of the immune system, MS actually occurs due to a reduction in immune system activity. Specifically, it is the reduction in number of the suppressor T-cells within the immune system that permits the damaging CD4, helper T-cells to do their harm. Thus, during an acute relapse, the overall number of T-cells is reduced, the normal balance of helper T-cells and suppressor T-cells is disrupted and the CD-4, helper, T-cells tend to predominate. This is the situation most pronounced during an acute relapse but a similar situation occurs, perhaps to a lesser extent, in chronic progressive MS. Under the influence of LDN it has been demonstrated that the numbers of T-cells may increase by more than 300%. Thus, when the number of T-cells is initially increased, the overall predominance of CD4, helper T-cells, at this time, will expectedly increase the intensity of the MS, therefore temporarily increasing some symptoms. As the number of T-cells continues to increase, the normal balance of suppressor to helper T-cells is restored, the activity and intensity of the disease process is reduced, and symptoms once again diminish and improve. Suggested Method of Therapy: Take the 3 mg starting dose, one each day, for the first month. If there are no significant introductory side-effects at this dose, immediately start the 4.5 mg dose for a further month. If there is any prolonged increase in adverse symptoms, such as stiffness (tonic muscle spasm), pain, or tiredness, at any dose, this might suggest that this dose is too high. In this circumstance, simply reduce the dose to the previous beneficial dose level or, if in doubt, call for further advice. It should then be found that these adverse symptoms will once more diminish and the improvements become more apparent. Continuing symptoms after reducing the dose suggests some other exacerbating factor, such as physical (eg, infection, excessive heat), or emotional stress (eg, grief, anxiety etc). If you are unable to tolerate the usual 3 mg starting dose, it may be necessary to use the ultra-low, 2, or even 1 mg, dose until your body becomes adjusted to the method. In anticipation of a possible addictive dependency on this drug, where a progressively higher dose may be required to maintain the same effect, it has previously been suggested that a method of intermittent therapy be used, taking a break every week or ten days. In practice, because the drug remains in the body for just three to four hours, experience has clearly demonstrated that this does not occur. In fact, it has been found that prolonged use of LDN tends to increase the response to the drug, thus necessitating a progressive reduction in dose in order to maintain the same effect. Current advice therefore is that, although an occasional break of just one or two days will not significantly affect the positive response to the treatment, it is now no longer considered necessary to take such regular breaks. Contraindications and Special Precautions: Because LDN stimulates the immune system and many of the drugs routinely used by the NHS in the treatment of MS further suppress the immune system, LDN cannot be used in company with steroids, beta interferon, methotrexate, azathioprine or mitozantrone or any other immune suppressant drug. If there is any doubt, please submit a full list of the drugs you are presently taking so that their compatibility may be assessed. In addition, because LDN will also block the analgesic effects of any opiate drugs (includes codeine, dihydrocodeine, tramadol, morphine, pethidine or diamorphine) presently being taken, the use of LDN will initially greatly increase the level of pain experienced. It is therefore advisable that any opiate-like drugs be discontinued at least two weeks before this treatment is initiated. When using the treatment please report any adverse side-effects immediately so that the treatment process may be re-assessed and, if necessary, modified. Dr M R Lawrence. Dietary Research Ltd: February 2006. © Multiple Sclerosis Resource Centre |
