Naltrexone, Low Dose
Low-dose naltrexone (abbreviated LDN) holds great promise for the millions of people worldwide with autoimmune diseases or central nervous system disorders or who face a deadly cancer. It is the first low-cost, easy to administer, and side-effect-free therapy for HIV/AIDS. Naltrexone was approved by the FDA in 1984 in a 50 mg. dose for the purpose of helping heroin and opium addicts. It acts by blocking the by blocking opioid receptors, and thus the effect of such drugs. Naltrexone also blocks the reception of the naturally produced opioids (yes, your body makes opioids!) in the brain and adrenal glands: beta-endorphin and metenkephalin. Many body tissues have receptors for these endorphins and enkephalins, including virtually every cell of the immune system.
In 1985 Bernard Bihari, M.D., a New York City physician, discovered the effects of a much smaller dose of naltrexone (approximately 3 mg. daily) on the body’s immune system. He found that this low dose, taken at bedtime, enhanced a patient’s response to infection by HIV. Subsequently, the optimal adult dosage of LDN has been found to be 4.5mg. In the mid-1990’s, Dr. Bihari found that patients with cancer such as lymphoma or pancreatic cancer also benefitted from LDN, in some cases dramatically. Also, people with autoimmune diseases (such as lupus) often showed prompt control of disease activity while taking LDN.
Mecahinism of Action
LDN boosts the immune system by its action on the naturally produced endorphins (internal opioids). As stated in the November 13, 2003 issue of the New England Journal of Medicine “Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected. Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system.”
By taking a bedtime dose of LDN the brief blockade of opioid receptors between 2 a.m. and 4 a.m. produces a prolonged up-regulation of the immune system causing an increase in endorphin and enkephalin production. Study subjects who have taken LDN in this fashion are found to have much higher levels of beta-endorphins circulating in their blood in the following days. Animal research by I. Zagon, PhD, and his colleagues has shown a marked increase in metenkephalin levels as well.
Bihari says that his patients with HIV/AIDS who regularly took LDN EVEN before the availability of HAART (Highly Active Antiretroviral Treatment) were generally spared deterioration of their important helper T cells. In human cancer research by Zagon inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone has been demonstrated. It appears increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors’ opioid receptors — and, perhaps, induce cancer cell death (apoptosis). It is also believed they act to increase natural killer cells and other healthy immune defenses against cancer. In diseases partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body’s normal production of endorphins is the major therapeutic action of LDN. By blocking the opioid receptors, there is a rebound overproduction of these enorphins.
Diseases Which Are Treated with LDN
Bernard Bihari, MD, as well as other physicians and researchers, have described beneficial effects of LDN on a variety of diseases.
bladder, breast, carcinoid, colon and rectal, glioblastoma, liver, non-small cell lung, chronic lymphocytic leukemia, lymphoma (Hodgkin’s and non-Hodgkin’s), malignant melanoma, multiple myeloma, neuroblastoma, ovarian, pancreas, prostate, renal cell, throat, uterine
As 2004, Dr. Bihari reported having treated over 300 patients who had a cancer that had failed to respond to standard treatments. Of that group, some 50%, after four to six months treatment with LDN, began to demonstrate a halt in cancer growth and, of those, over one-third have shown objective signs of tumor shrinkage.
amyotrophic lateral sclerosis (ALS, Lou Gehrig’s), Alzheimer’s, autism, Behcet’s disease, celiac disease, chronic fatigue syndrome, CREST, Crohn’s disease, emphysema, COPD, endometriosis, fibromyalgia, pemphigoid, irritable bowel syndrome, multiple sclerosis, psoriasis, rheumatoid arthritis, sarcoidosis, scleroderma, systemic lupus erythematosis, transverse myelitis, ulcerative colitis, Wegener’s granulomatosis
Within the group of patients with autoimmune diseases, none have failed to respond to LDN and all have experienced a halt in progression of their illness. In many there is a marked remission in signs and symptoms of the disease. Among some 400 MS patients in Dr. Bihari’s practice. Less than 1% of these patients has ever experienced a fresh attack of MS while they maintained their regular LDN nightly therapy.
As of September 2003, Dr. Bihari had treated 350 AIDS patients using LDN in conjunction with accepted AIDS therapies. In the previous seven years over 85% of these patients showed no detectable levels of the HIV virus, a much higher success rate than most current AIDS treatments, and with no significant side effects. Many HIV/AIDS patients have been living symptom-free for years taking only LDN with no other medications.
Central Nervous System Disorders
Anecdotal reports continue to be received concerning beneficial effects of LDN on the course of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease), and primary lateral sclerosis (PLS). Dr. Jaquelyn McCandless has found a very positive effect of LDN, in appropriately reduced dosage and applied as a transdermal cream, in children with autism.
Some pharmacies have been supplying a slow-release form of naltrexone. Pharmacies should be instructed NOT to provide LDN in an “SR” or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt “spike” in the blood stream, its therapeutic effects may be inhibited. The use of calcium carbonate as a filler will interfere with absorption of the LDN capsule. Therefore, it is suggested that calcium carbonate filler not be employed in compounding LDN capsules. Either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers cana be used. The usual adult dosage is 4.5mg taken once daily at night. Because of the rhythms of the body’s production of master hormones, LDN is best taken between 9 PM and 3 AM. Most patients take it at bedtime. People who have multiple sclerosis that has led to muscle spasms are advised to use only 3 mg. daily and to maintain that dosage. The therapeutic dosage range for LDN is from 1.75mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with its effectiveness.
Occasionally, during the first week’s use of LDN, patients may complain of some difficulty sleeping. This rarely persists after the first week. Should it do so, dosage can be reduced from 4.5mg to 3mg nightly. Otherwise, LDN has virtually no side effects.
Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one’s system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely. LDN should probably not be taken during pregnancy until research into that question is completed. Full-dose naltrexone (50 mg.) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300 mg. daily. The 50 mg. dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3 mg. and 4.5 mg. doses. People who have received organ transplants and who therefore are taking immuno-suppressive medication on a permanent basis are cautioned against the use of LDN because it may act to counter the effect of those medications.
The job of the FDA is to evaluate the safety of drugs and if found safe to certify them as safe. After that doctors are free to use a certified drug for the approved indication, or for an “off-label use.” Physicians understand that appropriate off-label use of an already FDA-approved medication such as naltrexone is perfectly ethical and legal. Because naltrexone itself has already passed animal toxicity studies, one could expect that once testing is able to begin, LDN could complete its clinical trials in humans and receive FDA approval for one or more uses within two to four years.
Consult Your Doctor
This website is not intended as a substitute for professional medical help or advice. A physician should always be consulted for any medical condition.
Bernard Bihari, MD, is the discoverer of the major clinical effects of low dose naltrexone. A private practitioner in Manhattan, he retired in March, 2007. Dr. Bihari is a Board-certified specialist in Psychiatry and Neurology.
Integrative Cancer Therapies 5(1); 2006 PP. 83-89