treatment for so many diseases...
What is Naltrexone?
Naltrexone belongs to a group of drugs known as ‘opioid receptor antagonists’. The primary use for such drugs has been in the management of opioid and alcohol dependence using 50mg doses.
However, in recent years interest has been sparked in the possibility of using Naltrexone at much lower doses (typically between 3-5mg per day) for the treatment of a number of chronic diseases including:
The results of Low Dose Naltrexone (LDN) therapy for sufferers of such diseases have been remarkable with patients reporting benefits such as improved quality of life and even remission (see below for more details relating to some specific conditions).
One of the leading advocates of LDN has been Bernard Bihari MD, who discovered LDN’s broad clinical effects in humans. His work has been supported by a number of other research teams who, through their clinical trials, continue to demonstrate that LDN holds real promise for the treatment of a whole range of diseases.
Whilst the diseases that appear to respond well to LDN therapy seem at first glance to be extremely diverse, they are all linked together by the fact that they are all immunologically related disorders, that is to say the immune system plays a central role in all of them. Even people with fibromyalgia and chronic fatigue syndrome have experienced marked improvements from using LDN which would suggest that these conditions too have an autoimmune component.
However, it is the fact that LDN therapy appears to significantly benefit people suffering from such autoimmune based diseases that has lead to controversy. It has turned on its head the long accepted view that autoimmune diseases stem from overactive immune systems. LDN therapy contradicts this view because it is based on the theory that autoimmune diseases develop as a result of immunodeficiency rather than immune system over activity. More specifically, LDN therapy works on the theory that low blood levels of endorphins contribute to the disease-associated immune deficiencies (see below for the theory of how LDN works).
The history of Naltrexone
Naltrexone is certainly not a new drug. It has been around for over thirty years. It was originally approved back in 1984 as a drug to help addicts come off heroin and opioids. In this context, Naltrexone works by blocking the receptors in the brain that trigger the affects of these narcotics. It is used in the same way to fight alcohol addiction.
In 1985-86 Bernard Bihari conducted a groundbreaking clinical trial into the use of LDN therapy as a treatment for those suffering from HIV/AIDS which, at the time, was untreatable. He discovered that LDN could be effective in protecting the battered immune systems of his patients. Since then Dr Bihari has gone on to spearhead research into the use of LDN therapy for a number of other conditions.
His discovery opened the door for research into this remarkable treatment. Recent years have seen significant steps forward in the development of LDN therapies - which typically use one tenth of the dose used for combating addiction. In April 2006 an LDN conference was held at the National Cancer Institute in the United States. LDN conferences are now held annually in the States, with the first European conference being held at The Western Infirmary in Glasgow in April 2009, which shows the significance of this treatment regime.
How does LDN therapy work?
As yet, there has been no formal conclusion as to exactly how LDN therapy works. However, the generally accepted theory is the one originally put forward by Dr. Bihari namely:
But not only does LDN increase the body's production of metenkephalin and beta- endorphins, blood tests have indicated that it can also double or even triple the activity of natural killer cells (NK cells). NK cells form a distinct group of lymphocytes (lymphocytes are white blood cells that play an important and integral role in the body’s immune system). They constitute between 5 to 16% of the total lymphocyte population. Their specific function is to kill infected and cancerous cells.
The underlying theory behind the mechanism of LDN therapy is, therefore, that autoimmune diseases and diseases where the immune system plays a key role, must result, in part at the very least, from immunodeficiency and not overactive immune systems. Gradually this rather radical view is becoming more and more accepted. For example, in the 13th November 2003 edition of the New England Journal of Medicine it was noted that “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."
Recent studies have shown that abnormally low levels of beta-endorphins have been found in all forms of multiple sclerosis and since 2005 at least 3 separate scientific reports have described an underlying immunodeficiency as being a characteristic of four different autoimmune diseases - Crohn’s disease, rheumatoid arthritis, chronic fatigue syndrome and multiple sclerosis.
Medical conditions responding to LDN therapy
LDN is currently under experimental use for many conditions with very encouraging preliminary results. Below we look in more detail at some of the conditions that may respond to LDN therapy.
In a recent study carried out at Stanford University, (April 2009)1, researchers concluded that LDN may make a good treatment for fibromyalgia. Fibromyalgia is a painful rheumatic condition, which, according to the American College of Rheumatology, affects somewhere between 3 and 6 million people in the USA alone. This makes it the most common arthritis related illness after osteoarthritis. It occurs mainly in women of childbearing age, but children, the elderly, and men can also be affected.
The researchers tested LDN as a fibromyalgia treatment in 10 women who had each been suffering from fibromyalgia for an average of 10 years. Most of the women (6 out of 10) responded to the LDN treatment. The women initially took a placebo pill once a day for two weeks. They were not aware that the medication they had been given was only a placebo. They reported a 2.3% drop in the severity of their symptoms. The women were then switched to the LDN pills. Again they took the medication once a day but this time they took the pills daily for eight weeks. The women reported a 30% drop in the severity of their symptoms. While they were taking LDN, the women also showed a greater tolerance for pain and for hot temperatures.
Given the promise shown by LDN therapy, the researchers have already commenced a larger trial.
Myalgic Encephalomyelitis (ME), otherwise known as Chronic Fatigue Syndrome (CFS), a severe flu-like illness, usually precipitated by a virus (commonly glandular fever). Symptoms include headaches, memory and concentration problems, sore throat, muscle and joint pain, irritable bowel syndrome, disturbed sleep, exhaustion after minor effort, food allergies/ sensitivities and sensitivity to bright light and noise. Anecdotal evidence clearly points to the benefits of LDN for ME/CFS sufferers, with patients reporting for example that taking LDN has halted the progression of their disease.
LDN treatment appears to work in those cancers that have opioid receptors. As discussed above, LDN therapy causes a rise in endorphin levels (both metenkephalin and beta-endorphin). The endorphins attach to the cancers’ opiate receptors, shrinking the tumours and inhibiting their growth. If metenkephalin and/or beta-endorphins are attached to cancer cells while they are dividing, programmed cell death (apoptosis) appears to be stimulated. This causes some of the cancer cells to be killed. Added to this is the fact that LDN therapy appears to double or even triple the activity of NK cells (see “How does LDN therapy work?” above) and acts to increase other healthy immune defences against cancer.
By mid-2004 Dr Bihari had treated over 300 patients with various cancers. All of these patients had failed to respond to standard treatments. After 4-6 months of LDN therapy some 50% of cancer sufferers had begun to demonstrate a halt in their cancer growth and, over a third had shown significant tumour shrinkage. Other proponents of LDN therapy have reported similar findings. For example at the 2006 LDN conference held at the National Cancer Institute in United States, a Dr Berkson detailed his successful experience treating metastatic pancreatic cancer and B cell lymphoma with LDN at bedtime. After following a healthy lifestyle program and receiving daily LDN therapy, the patient was alive and well, symptom free and back at work.
Given all of this, it is easy to see why researchers are excited about the possibilities that LDN therapy may hold for the treatment of certain types of cancer.
Crohn’s disease is an incurable, inflammatory bowel disease. Although classed as a bowel disease, it can affect any part of the gastrointestinal tract from the mouth to the anus. It causes a wide variety of symptoms including abdominal pain, diarrhoea, vomiting and weight loss. Known to be an autoimmune disease, it’s caused by the body’s immune system attacking the gastrointestinal tract which leads to inflammation. Although Crohn’s disease can develop at any age, it tends to present initially in the teens and twenties, with another peak incidence in the fifties to seventies. Both men and women are equally affected. There does appear to be a genetic link and smokers are 3 times more likely to develop the disease.
With no cure, treatment is targeted at controlling symptoms, maintaining remission and preventing relapse. In a recent clinical trial conducted by Pennsylvania State University2, LDN again showed promise in helping Crohn’s disease sufferers. The researchers established that LDN could help significantly in putting patients into remission. Seventeen patients were enrolled into the cohort and received LDN every evening for a 12 week period. 89% of patients exhibited a response to the therapy and 67% achieved a remission. Patients recorded improvements in their quality of life.
The researchers concluded that “LDN therapy appears effective and safe in subjects with active Crohn's disease. Further studies are needed to explore the use of this compound”.
In light of their results, the research team were awarded a significant grant which is enabling them to continue their work in this area.
Multiple sclerosis (MS) is an autoimmune condition that affects the central nervous system and leads to demyelination. Demyelination is the process whereby the protective sheath (myelin) around the nerve fibres in the brain and spinal cord become damaged, causing random patches called plaques or lesions. These affect the ability of nerve cells in the brain and spinal cord to communicate with each other.
Almost any neurological symptom can occur with MS and no two people experience the disease in the same way. It is an unpredictable disease which makes prognosis difficult.
Between attacks a person may be symptom free but often permanent neurological damage occurs. As yet, MS is incurable.
MS treatments attempt to return function after an attack, prevent new attacks, and prevent disability but medications are often poorly tolerated and can have adverse effects.
Dr Bihari has worked closely with some 400 MS sufferers - indeed they form the largest group of patients that he has treated with LDN therapy. His results have been impressive. By maintaining regular nightly LDN therapy, less than 1% of the MS sufferers he has treated have experienced fresh MS attacks.
Not surprisingly, research into LDN and MS is on-going because results such as these cannot be ignored particularly when dealing with such a debilitating disease. However, treating MS patients with LDN therapy is not without its harsh critics. This again is based on the prevailing theory that MS patients have overactive immune systems which means that LDN must not be a safe drug for them because it serves to boost the immune system.
One of the most recent studies was implemented at the University of California, San Francisco in early 2007, funded in part by the MS Research Fund. Eighty MS patients were enrolled into the double-blind study cohort. Each subject received either LDN or a placebo for 8 weeks, followed by one week without either, and then a further 8 weeks on the alternate capsule. The lead researcher, Bruce Cree MD, presented the study’s conclusions at the World Congress on Treatment and Research in Multiple Sclerosis, held in September 2008 in Montreal, Canada. The study conclusions were that:
Even as far back as the mid-1980’s LDN has consistently shown itself to have positive beneficial effects for those suffering from HIV/AIDS. Some patients use LDN alone but others have combined LDN therapy with other standard AIDS treatments. When combined with HAART (Highly Active Anti-Retroviral Treatment – a drug therapy that is composed of multiple anti-HIV drugs and is prescribed to many HIV-positive people, even before they develop symptoms of AIDS), LDN has shown itself to be an absolute preventive regime for abnormal body fat changes (lipodystrophy), as well helping to reduce viral breakthroughs and restoring CD4 cell levels. CD4 cells (or T-cells) form part of the immune system.
Unfortunately, HIV attacks CD4 cells and uses them to make more copies of HIV. Inevitably, this means that HIV weakens the immune system, making it unable to protect the body from illness and infection.
By September 2003, Dr. Bihari had been treating 350 AIDS patients LDN in combination with standard AIDS therapies. More than 85% of these patients showed no detectable levels of the HIV virus nor did they experience any significant side effects.
As mentioned above, the trick to LDN therapy is to keep the daily dose of Naltrexone low (about one tenth of that used to treat addiction).
A regular dose of one 4.5mg capsule should be taken each night at bedtime; i.e., between 9pm and 3am. By taking the medication at bedtime advantage can be taken of the body's pre-dawn (2am-4am) boost in endorphin production.
Naltrexone side effects
LDN appears to be extremely well tolerated with virtually no side effects whatsoever. In the Younger and Mackey study1 any side effects were noted to be mild and brief. Two women reported having more vivid dreams during the study, and one woman reported transient nausea and insomnia during the first few nights of taking the pills.
In the Smith study2, the most common side effect was sleep disturbance, occurring in seven out of seventeen patients.
The only drug interaction with LDN appears to be with narcotics (such as morphine, Demerol and Percocet), which it briefly blocks.
Naltrexone cannot be shipped to the UK or EU.
Naltrexone should not be used by pregnant or lactating women.
Naltrexone should be kept in cool dark conditions, out of the reach of children and should be consumed before end of expiry date.
This product and its statements have not been evaluated by the FDA. This product is not intended to treat, cure or prevent any disease.
1. Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study. Younger J, Mackey S. Pain Med. 2009 Apr 22 (Epub ahead of print)
2. Low-Dose Naltrexone Therapy Improves Active Crohn's Disease. Smith J, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon I (2007). American Journal of Gastroenterology 102 (4): 820–8
Naltrexone- a unique immune regulator showing promise in all manner of autoimmune diseases including HIV
Over recent years there has been a growing recognition that autoimmune diseases result from immunodeficiency, specifically a disturbance of the ability of the immune system to distinguish its "self" from "non-self".
The experiences of individuals with autoimmune diseases who have begun a regime of low dose treatment with naltrexone have been remarkable. Patients with diagnoses as diverse HIV, lupus, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, ALS (Amyotrophic Lateral Sclerosis) and Crohn's disease have all benefited.
In addition, people with fibromyalgia and chronic fatigue syndrome have had marked improvement using low dose naltrexone, suggesting that these conditions also have an autoimmune issue as well.
Naltrexone was originally approved in 1984 to help addicts come off opioids and heroin by blocking the receptors in the brain that trigger the affects of these narcotics. To this end naltrexone is usually available in dosages of 50mg tablets to assist persons wishing to “kick their habits.”
However more recently it has become apparent that a low dose of naltrexone (3mg to 5mg) has a significant effect in normalizing the immune system. For example, the November 13, 2003 issue of the New England Journal of Medicine stated: "Opioid-Induced Immune Modulation: the 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."
With this in mind naltrexone has been used by a number of leading physicians to assist their patients with numerous disorders that are essentially of an autoimmune nature.
354 patients with cancer have been treated by leading naltrexone supporter- Dr. Bernard Bihari. Over a 6-monht period 86 have shown objective signs of significant tumor shrinkage and 75% have shown tumor reduction. Of the total, 125 patients have stabilized and are moving toward remission.
Research by others on various human tumors, has found opioid receptors in many types of cancer, including: brain tumors, breast cancers, endometrial cancer, head and neck squamous cell carcinoma, myeloid leukemia, lung cancer and neuroblastoma.
In May 2006, clinical trial researchers at Pennsylvania State University College of Medicine reported: "LDN therapy offers an alternative, safe, effective, and economic means of treating subjects with active Crohn's disease."
It has been noted that patients with autoimmune disease such as ALS (Lou Gehrig's Disease), Alzheimer's Disease, Autism Spectrum Disorders, Chronic Fatigue Syndrome, Emphysema, Endometriosis, Fibromyalgia, HIV/AIDS, Irritable Bowel Syndrome, Multiple Sclerosis, Parkinson's Disease, Primary Lateral Sclerosis, Rheumatoid Arthritis and Systemic Lupus that none have failed to respond to low doses of naltrexone and that all have experienced a halt in the progression of their disorders. In some patients there is a marked remission in the signs and symptoms. The greatest numbers of patients (some 400) treated by Dr. Birhari are those suffering from multiple sclerosis, yet to date less than 1% of these patients has ever experienced a fresh attack of MS whilst they have maintained their regular low dose naltrexone nightly therapy.
As of September 2003, Dr. Bihari has been treating 350 AIDS patients using low dose naltrexone in conjunction with standard AIDS therapies. In this time more than 85% of these patients have shown no detectable levels of the HIV virus along with no significant side effects.
The regular dose of naltrexone is between 2.5mg and 5mg, taken each night at bedtime; i.e., between 9pm and 3am.