Low dose naltrexone

Low dose naltrexone (LDN), where naltrexone is used in doses approximately one-tenth those used for drug/alcohol rehabilitation purposes, is being used as an "off-label" treatment for certain immunologically-related disorders. The use of LDN for such diseases as cancer was discovered and developed by Ian Zagon, PhD in animal and in vitro research, and LDN's broader clinical effects in humans were discovered by Bernard Bihari, MD.

The results of a successful open-label pilot study at Pennsylvania State University College of Medicine were reported to an international gastroenterology conference in Los Angeles in May 2006. The trial demonstrated the safety and efficacy of LDN in a group of patients with Crohn's disease, thought of as an autoimmune disorder by many Drs. Dr. Jill Smith, Professor of Gastroenterology at Pennsylvania State University's College of Medicine, found that two-thirds of the patients in her pilot study went into remission and fully 89% of the group responded to treatment to some degree. She concluded that "LDN therapy appears effective and safe in subjects with active Crohn’s disease." [*cite journal | author = Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS | title = Low-dose naltrexone therapy improves active Crohn's disease. | journal = Am J Gastroenterol | pages = 820–8 | volume = 102 | issue = 4 | month = Apr | year = 2007 | pmid = 17222320 | doi = 10.1111/j.1572-0241.2007.01045.x] Smith and her colleagues have since received a substantial NIH grant and are proceeding with a definitive Phase II placebo-controlled clinical trial.

In addition, there is some in vitro data that indirectly suggest the potential benefits of LDN therapy. Many anecdotal accounts and case reports have also been cited in favor of LDN therapy. Some of the many conditions for which LDN has been reported as beneficial include multiple sclerosis (in particular, the primary progressive variantcite journal |author=Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M, Cursi M, Franchi S, Martinelli V, Nemni R, Comi G, Martino G |title=A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. |journal=Multiple Sclerosis |volume=14 |issue=8 |pages=1076-83 |year=2008 |pmid=18728058 |doi=] ), Crohn's disease, HIV/AIDS, chronic fatigue syndrome, irritable bowel syndrome, psoriasis, fibromyalgia, ALS, autism in children, and cancer. Several clinical trials have been planned and a few are currently taking place.

Pharmacology

LDN has been theorized to work in multiple modalities. Without formal studies, there is no formal conclusion as of yet, but the generally accepted theory posited originally by Dr. Bihari is as follows:

Beta-endorphins are important regulators of the immune system. Naltrexone, which is a pure antagonist to narcotics, causes an artificial blockade of the endorphin/opioid receptors in the brain. However, unlike the normal (~50mg) dose of naltrexone used to treat drug addiction, which maintains this blockade continuously for 24 hours (preventing any derived pleasure from taking the forbidden drugs), low dose naltrexone (~3mg to 5mg) blocks the endorphin receptors for only a few hours. During that time, endorphins fail to attach to the receptors and the body apparently compensates by creating more. (Note that Dr. Bihari prescribes LDN to be taken at bedtime to take advantage of the body's pre-dawn boost in endorphin production.) Once the low dose naltrexone dose has been metabolized, the body is left with a "normal" amount of endorphins as compared to healthy controls, which consequently normalizes the immune function.

This theory of LDN's mechanism contradicts the widely-held belief that autoimmune diseases are caused by an overactive immune system. However, since 2005, at least 3 separate scientific reports have described an underlying immunodeficiency as being characteristic of four different autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, Crohn's disease and chronic fatigue syndrome. [*cite journal | author = Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P | title = Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients. | journal = Ann N Y Acad Sci | pages = 255–62 | volume = 1051 | month = Jun | year = 2005 | pmid = 16126966 | doi = 10.1196/annals.1361.066] [*cite journal | author = Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, Lees W, Novelli M, Bloom S, Segal AW | title = Defective acute inflammation in Crohn's disease: a clinical investigation. | journal = Lancet | volume = 367 | issue = 9511 | pages = 668–78 | year = 2006 | month = Feb | day = 25 | pmid = 16503465 | doi = 10.1016/S0140-6736(06)68265-2] [*cite journal | author = Vernon SD, Reeves WC | title = The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. | journal = Pharmacogenomics | volume = 7 | issue = 3 | pages = 345–54 | year = 2006 | month = Apr | pmid = 16610945 | doi = 10.2217/14622416.7.3.345] In addition, recent scientific research has demonstrated abnormally low beta-endorphins in all forms of multiple sclerosis. [*cite journal | author = Gironi M, Furlan R, Rovaris M, Comi G, Filippi M, Panerai AE, Sacerdote P | title = Beta endorphin concentrations in PBMC of patients with different clinical phenotypes of multiple sclerosis. | journal = J Neurol Neurosurg Psychiatry | volume = 74 | issue = 4 | pages = 495–7 | year = 2003 | pmid = 12640071 | doi = 10.1136/jnnp.74.4.495]

In April 2006 an LDN conference was held at the National Cancer Institute. Several lecturers were present discussing the use of LDN in Crohn's disease, multiple sclerosis, general autoimmune disease, and cancer. One participant, Burton M. Berkson MD PhD of Las Cruces, New Mexico discussed his successful experience treating metastatic pancreatic cancer and B cell lymphoma with LDN at bedtime.

Dr. Berkson described one patient who was diagnosed with "terminal" and metastatic pancreatic cancer at a well-respected oncology center. After treatment with a healthy life style program and LDN at bedtime he is alive, well, and back at work almost 5 years after diagnosis. Today, he is described as free of symptoms [6] .

Another patient with greatly enlarged lymph nodes in his neck, axillae, and groin and diagnosed with a B cell lymphoma was found to be free of signs and symptoms after 6 months of LDN therapy. [7] In his presentation, Dr. Berkson used before and after CT and Pet scans to show improvement, or reversal, of the disease process in four patients.

The most recent (now annual) LDN Conference was held on 20 October 2007 at Vanderbilt University, Nashville, Tennessee.

Controversy

LDN is a low-cost drug that is unlikely to enjoy ironclad patent protection. Many patients, who have benefitted substantially from the medication, suspect that clinical trials of LDN have been discouraged by the pharmaceutical companies, which prefer selling high-margin, patent-protected drugs. These claims are unsubstantiated at this time.Critics however point out that the drug companies, and doctors refuse to test LDN on multiple sclerosis patients, as LDN boosts the immune system, and since ms patients tend to have over-active immune systems, many do not feel that ldn is a safe drug for those with ms.Critics also point to the fact, that doctors who prescribe LDN to ms patients tend to do it via a telephone conversation, without even seeing the pateints, or their medical records, for which they recive a payment from the person that they prescribed to.Many who use LDN for multiple sclerosis can also suffer from side effects, including stiffness, and the long term effects of using the drug are still unknown.

External links

* [http://www.lowdosenaltrexone.org Low Dose Naltrexone] (LDN) Homepage
* [http://www.youtube.com/v/Kz52KK5IhOc&rel=0&color1=0xd6d6d6&color2=0xf0f0f0&border=0 "Wonder drug" LDN Could Help Treat Cancer, M.S.] WTEV‑TV (CBS 47) of Jacksonville, Florida, February 2008
*In multiple sclerosis: [http://www.ldners.org Research resources for those on LDN]
* [http://www.ldnresearchtrust.org LDN Research Trust Website] (multiple sclerosis)
* [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17222320 LDN Trial for Crohn's Disease ]
*http://ldnformultiplesclerosis.blogspot.com/
* [http://www.ahsta.com/ Alternative Health Solutions and LDN in Thyroid Autoimmunity]
* [http://www.casehealth.com.au/case/about.html Case Health - Health Success Stories website] LDN Health Success Stories
* [http://www.lymphomation.org/CAM-M-R.htm#LDN Lymphoma"tion.org" - Reasons for skepticism as a cancer treatment]
* [http://www.webspawner.com/users/introtoldn/index.html Article on personal experience with LDN as a treatment for MS by a caregiver.]
* [http://www.northernlightshealth.com Book on successful, personal experience with LDN as a means to control alcoholism.]
* [http://www.northernlightshealth.com Book about the use of LDN for disease prevention]
* [http://www.ldners.org Book: The Promise of Low Dose Naltrexone Therapy]
* [http://www.elaine-moore.com Elaine Moore Autoimmune Disease Education] Author: Promise of Low Dose Naltrexone Therapy

References

* [http://www.gazorpa.com/LDNFAQ.html Frequently-Asked Questions About Low Dose Naltrexone (LDN) as a Therapy for Multiple Sclerosis]

Further reading

* Berkson, BM, Rubin D, and Berkson AJ (2006) "Long term survival of a 46 year old man with pancreatic cancer and liver metastases and treated with intravenous alpha lipoic acid and low dose naltrexone." Integrative Cancer Therapies 5:1,83-89. PMID: 16484716

* Berkson, BM, Rubin D, and Berkson AJ (2007) "Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone."Integrative Cancer Therapies" Sep;6(3):293-6. PMID: 17761642
* [http://www.casehealth.com.au/case/about.html A free ebook entitled 'Those Who Suffer Much Know Much' features 29 health case studies attributing LDN with improved health - Multiple Sclerosis, Cancer, Hiv, Hep B, and Crohn's Disease - last updated July 2008, produced by the 'Case Health - Health Success Stories' website]