LDN & Multiple Sclerosis – FAQ

		Frequently-Asked Questions About Low Dose Naltrexone (LDN) as a Therapy for Multiple Sclerosis What is Low Dose Naltrexone? Naltrexone is short for Naltrexone Hydrochloride (C20H23NO4-HCl), an opiate antagonist. Naltrexone was approved by the FDA (at a 50mg dosage) in 1984 for opiate addiction, and again in 1995 for alcohol abuse.   At a much lower dose (1.75-4.5mg), it has been gaining popularity as a treatment for symptoms of auto-immune disorders such as Multiple Sclerosis.  Low Dose Naltrexone is administered orally, usually in capsule form. What MS symptoms does LDN help? Primarily neuromuscular spasm, fatigue, and urinary problems, although patients have also reported improvements of other symptoms.  In addition, patients who start LDN while in the middle of an acute relapse often show rapid resolution of the attack. Does LDN halt progression of MS? Evidence suggests that LDN can significantly reduce the chances of either a relapse or progression for many MS patients. How does LDN work? It is believed that LDN briefly obstructs the effects of brain endorphins (the brain’s natural painkillers).   Sensing an endorphin deficit, the pituitary signals for increased production of endorphins, which re-balances the immune system, thus reducing the activity of the MS.  The effect lasts around 18 hours. But how can this work?  Isn’t MS is caused by an overactive immune system? Although there is a long-held theory that MS might be caused by an overactive immune system, this theory has never been proven.   Recent clinical studies indicate that this theory might not be true at all.  The October 2004 issue of The Archives of Neurology reports a clinical study which found that intravenous immunoglobulin therapy applied after the first signs of MS significantly reduced the probability of developing clinically definite multiple sclerosis.  Patients receiving this immune-system boosting therapy also suffered fewer brain lesions.  [Intravenous Immunoglobulin Treatment Following the First Demyelinating Event Suggestive of Multiple Sclerosis; a Randomized Double Blind, Placebo-Controlled Trial; Arch. Neurol. Oct. 2004; 61:1515-1520.] How fast does LDN work? Although some patients have no symptom changes, around two-thirds of MS patients report some symptom improvement within the first few days.  Other patients report improvement over the course of several weeks or even months. What dosage and frequency are usually prescribed? The usual adult dosage of LDN for the treatment of MS is 1.75-4.5mg taken orally once daily at bedtime. Because of the natural rhythms of the body’s hormone production, LDN is best taken between 9pm and 2am.  It is generally recommended that the patient begin on 3.0mg per day, and adjust the dosage if necessary.   Prescribing 1.5mg capsules allows easy adjustment of dosage.  (For example, the patient can take either 2 capsules for 3mg, or 3 capsules for a 4.5mg dose.) How is LDN prepared? LDN is usually prepared by a compounding pharmacist, who makes capsules by either grinding up 50mg Naltrexone tablets, or using Naltrexone powder purchased from a primary manufacturer.  (The most popular Naltrexone tablet is the 50mg “ReVia” Naltrexone tablet, usually prescribed for treatment of drug and alcohol addictions.) LDN may also be prepared in a solution of distilled water, with 1mg per ml dispensed with a 5ml medicine dropper.  If LDN is used in a liquid form, it is recommended that it be refrigerated. Are there any side effects? All sources indicate that LDN has virtually no side effects.  Some patients report vivid dreams, and occasionally, during the first week of use, patients may complain of difficulty sleeping.  (Reports indicate that sleep disturbance is rare, occurring in less than 2% of users.)  If this persists after the first week, dosage can be reduced from 4.5mg to 3mg. Full-dose Naltrexone (50mg 3x day) carries a cautionary warning for patients with liver disease. (This warning was placed because adverse liver effects were noted in early experiments involving 300mg daily, given for alcohol abuse.) The 50mg dose does not apparently produce impairment of liver function nor, of course, does the much smaller 3mg – 4.5mg dose. LDN is virtually non-toxic, simple to administer, and, compared with other MS drug therapy, very inexpensive – usually costing less than $40 per month. What about cautionary warnings? Because LDN blocks opioid receptors throughout the body for three or four hours, people using narcotic medication such as Ultram, morphine, Percocet, Tramadol, Duragesic patch or codeine should not take LDN until such medicine is completely out of the system. Steroids would counteract the effects of LDN, and so should not be combined.  LDN should probably not be taken during pregnancy. LDN should not be used by people already receiving interferon (Beta Seron, Avonex, or Rebif). Because LDN stimulates the immune system and interferon suppresses it, the two therapies are incompatible.   The combination of these therapies does not cause any adverse reactions, but it is believed that they cancel out each other’s effectiveness. What does it feel like to be on LDN? At both high and low dosages, patients taking Naltrexone usually say they are largely unaware of being on medication.  Naltrexone usually has no psychological effects and patients (at both high and low dosages) don’t feel either “high” or “down” while they are on naltrexone.  It is not addicting. Why isn’t LDN routinely prescribed for MS? Many physicians simply have not yet learned about the positive effects of LDN on MS symptoms. Because Naltrexone is a generic medication, there are no commercial marketing campaigns to increase awareness of LDN in the medical community.   Other doctors may be hesitant to prescribe LDN because it hasn’t yet been approved as an MS treatment by the FDA. Why hasn’t LDN been approved by the FDA for MS? Naltrexone (in the higher 50mg dosage) was approved by the FDA in 1984 for opiate abuse therapy, and again in 1995 for alcohol addiction.   Its safety and efficacy have been proven in clinical trials.   In the much lower dosage of 3 or 4.5mg, Naltrexone has not yet been submitted for FDA approval.  Federal regulations prevent the FDA from approving LDN as an MS therapy until it undergoes specific clinical trials for MS. Why hasn’t LDN gone through a clinical trial as an MS therapy? Clinical trials are usually initiated and funded by pharmaceutical companies, and these companies are not interested in promoting or marketing LDN. Why aren’t pharmaceutical companies interested in exploring the possibility of  LDN as an MS therapy? Naltrexone was developed so long ago, it is now a generic drug, manufactured by many different companies.   Since no single company owns exclusive manufacturing rights, Naltrexone can be manufactured and sold very inexpensively by any pharmaceutical company. This means that LDN can’t make anyone any money.  Pharmaceutical companies are not eager to fund clinical trials for a drug that will make them no profit.  Also, if LDN were FDA-approved and became a preferred treatment for MS, the pharmaceutical companies who make the expensive ABCR drugs could lose millions of dollars. Are there any plans for a clinical trial for LDN as an MS therapy? In May 2007, the MindBrain Consortium, the Department of Psychiatry of Summa Hospital System of Akron, Ohio, and the Oak Clinic for the treatment of Multiple Sclerosis, announced a study of the effects of treating MS with LDN. In March 2007, the University of California, San Francisco Medical Center, implemented a double-blind, randomized, placebo-controlled, crossover-design study of the effects of LDN on 80 MS patents. In December 2006, a study of LDN in MS was begun in Milan by neurological researcher, Dr. Maira Gironi. In August 2004, the LDN Research Trust (www.ldnresearchtrust.org) was created in England. Organized by a group of patients who have been helped by LDN, the Trust’s mission is to raise funds for the initiation of clinical trials for LDN.  In conjunction with the Trust, Dr Alasdair Coles, a neurologist and MS specialist from Cambridge University, and Dr Robert Lawrence of Wales, himself an MS patient, are currently working on a proposal for a clinical trial of LDN for the treatment of MS. Since LDN has also shown promise as a therapy for other autoimmune disorders, there has research activity in that area.  In September 2007, the Institutional Review Board in Bamako, Mali, approved plans for a clinical trial of LDN in HIV-infected citizens of Mali.  In July 2007, Stanford Systems Neuroscience and Pain Lab began organizing a study of LDN for the treatment of fibromyalgia. Has LDN as an MS therapy been reported in any of the major medical journals? Most medical journals are not interested in reviewing a drug therapy that has not yet had a clinical trial.  However, the peer-reviewed medical journal Medical Hypothesis recently published an article about the LDN’s success as an MS therapy.   (For full text, see: ldners. org/Articles/LDN_Medical_Hypotheses.pdf ) Can a doctor legally prescribe LDN? Yes.  While it is illegal for a pharmaceutical company to market or promote a drug for a use other than that approved by the FDA, it is NOT illegal for a physician to prescribe an FDA-approved drug for a non-FDA-approved use.  This is called an “off-label” prescription, and physicians do it all the time.  (Neurontin, for example, was approved by the FDA in 1993 for the treatment of epilepsy; yet it is routinely prescribed off-label for the treatment of MS.)   All physicians understand that the responsible off-label use of an FDA-approved medication such as Naltrexone is perfectly ethical and legal. Who first thought of using Low Dose Naltrexone for MS? Initial research on LDN was conducted by Ian S. Zagon, Ph.D., Professor of Neural and Behavioral Sciences at Pennsylvania State University.  The use of LDN for MS is credited to Dr. Bernard Bihari, a practicing neurologist in New York.   Dr. Bihari, who received his MD from Harvard and is board-certified in psychiatry and neurology, began prescribing LDN for his MS patients in 1985.  (To read a transcript of a 1993 radio interview with Dr. Bihari, click on  “Interview with Dr. Bihari” located on the menu at left.) Does anyone profit from the promotion and sale of LDN? No.  Some people are initially suspicious of LDN, thinking that it might be an internet “snake-oil” scheme, but no one markets or sells LDN for profit.   Naltrexone is an inexpensive, generic medication, manufactured by a number of large pharmaceutical corporations.   Low-Dose Naltrexone is compounded at individual compounding pharmacies, and is not marketed by anyone. How many MS patients are taking LDN for Multiple Sclerosis? No one is sure of the exact number, but it is known that thousands of MS patients worldwide are now using LDN, and the number is increasing.   Without the financial support of the pharmaceutical industry, the growing reputation of LDN has been driven solely by positive reports from MS patients. Are MS patients getting positive results from LDN? A review of the anecdotal evidence shows that most MS patients taking LDN have experienced considerable improvement, often within days or weeks of beginning the treatment. The first annual LDN Conference was held on June 11, 2005, at the New York Academy of Sciences, New York City.   It was attended by more than 80 members of the medical community – doctors, patients and researchers from all over the world. The Second Annual LDN Conference was held on Friday, April 7, 2006 in the Lister Hill Center Auditorium of the National Library of Medicine (NLM) in Bethesda, Maryland. The Third Annual LDN Conference will be held October 20, 2007 at Vanderbilt University in Nashville. For more information about the conference, visit:  http://www.lowdosenaltrexone.org/events.htm. =============================================================================== Site last updated 10/15/07 =============================================================================== Pharmaceutical Information about Low Dose Naltrexone The protocol is 1.5 to 4.5mg at bedtime.  It must not be a timed-release preparation and should be given at bedtime.  Up until recently, Dr. Bihari had routinely used 3 mg, reducing it down to as low as 1.5 mg in the rare patient who experienced a mild sleep disturbance.  (Many patients report improved sleeping.)  However, recently, he has noted that some patients who did not respond to 3 mg did respond to 4.5mg and has begun to use this dose more frequently.  No more than 4.5mg must be used.  Occasionally, lower doses are necessary. The usual, commercial oral preparation of naltrexone is 50 mg; so, the 1.5 to 4.5 mg dose must be made up by a compounding pharmacy.  A month’s supply should run about $30.  Although there are no known significant side effects to the treatment, in about 1 out of 50 patients, the patient will experience a sleep disturbance.  In this case, Dr. Bihari recommends that the pharmacy make up a 100-ml. solution containing naltrexone in distilled water at a concentration of 1 mg/ml.  The patient is told to take 1 to 1 ½ ml. at bedtime—possibly working up to 2 ml. or 2 mg. — Michael B. Schachter, M.D., CNS, F.A.C.A. December 6, 2001 ——————————————————————————————————————————– For further information about LDN, visit this site: http://lowdosenaltrexone.org ====================================================== Pharmacies Recommended for Compounding LDN – Irmat Pharmacy, New York, NY  (212) 685-0500 Gideon’s Drugs, New York, NY  (212) 575-6868 The Compounder Pharmacy, Aurora, IL  (800) 679-4667 The Medicine Shoppe, Canandaigua, NY  (800) 396-9970 Skip’s Pharmacy, Boca Raton, FL  (800) 553-7429 Smith’s Pharmacy, Toronto, Canada  (800) 361-6624 Several of these pharmacies do a significant mail-order LDN business.  However, most Compounding Pharmacies now have experience with LDN, because LDN is becoming an increasingly effective part of the treatment of AIDS, cancer and various other immune disorders. http://www.gazorpa.com/LDNFAQ.html