ThisIsMS.com Responds to NMSS Article on Low Dose Naltrexone
Cites errors and misrepresentations; Study referenced by NMSS to purportedly show dangers of LDN actually indicates LDN has therapeutic value

May 17th, 2004, 5:30am EST

On May 11, 2004, the United States National Multiple Sclerosis Society (NMSS) published an article entitled “Low Dose Naltrexone Update.” This article discourages the use of Low Dose Naltrexone (LDN) as a possible therapy for MS, discrediting the idea in numerous ways. After thoroughly investigating the article, ThisIsMS.com has uncovered a number of chilling facts that expose the NMSS article as a fraudulent piece that distorts facts, and as exposed below, even resorts to blatant misrepresentations of the truth in an inexplicable attempt to discredit and inspire fear in what is, at the very least, an extremely promising potential treatment for Multiple Sclerosis worthy of clinical trials.

Paramount amongst the attacks in the referenced article was a citation of research purportedly studying the use of Low Dose Naltrexone in Experimental Allergic Encephalomyelitis (EAE). Quoting from the NMSS article: 
       

“In fact, the one study of low dose naltrexone in experimental allergic encephalomyelitis (EAE)-the animal model of MS-demonstrated a disease worsening (Panerai et al. 1994. J Neuroimmunol 51(2):169-176).”

ThisIsMS.com has investigated this citation and uncovered some very disturbing revelations. The result of this investigation has shown that not only is the NMSS assertion patently false, it is purposefully misleading and misrepresents facts in a clear effort to discredit low dose naltrexone as a possible MS therapy. The study cited, as it turns out, was not of LDN at all, but in fact high dose naltrexone (HDN), which has a very different effect on the body than the lower dose form currently taken by hundreds of MS patients.  

A conversation with one of the lead researchers of the cited article revealed that the amounts of drug used in this study were 5 milligrams per kilogram of body weight, administered not once but twice per day! Compare this to the recommended LDN intake of 4.5 mg’s total per day (keeping in mind that the average adult human weight is well over 50 kilograms) and the realization that this study has absolutely nothing to do with LDN, and instead pertains to the administration of HDN, is sudden, obvious, and given the agenda of the NMSS article and the expertise of the author—absolutely disturbing.

With the clear differentiation now established between the high doses of Naltrexon used in the study, and the low doses used by MS patients, reading the conclusion of the study proves incredibly fascinating.

”The administration of the opiate receptor antagonist naltrexone worsens the development of [EAE], suggesting that the increase of the opioid beta-endorphin might represent a mechanism to downregulate the immune response.”

The first part of the sentence speaks to the administration of the high dose naltrexone. Naltrexone, given in its full dose, blocks the brain’s opioid receptors in a near-total fashion 24 hours a day. It is in this fashion that the drug earned approval for use as a therapy for opium addiction (as it prevents opium from being received in the brain, and thus prevents the associated “high”). In other words, the study is saying that the near-total and constant block of opioid receptors worsened EAE.

Now, this action of HDN is what the NMSS article states Low Dose Naltrexone does—“…the one study of low dose naltrexone in [EAE]…demonstrates disease worsening.“

But much to the NMSS’ chagrin, in reality LDN does not at all behave the same way as HDN! Being a tiny part of the intended Naltrexone dose, LDN blocks the opioid receptors just for a short period of time—not the whole day as HDN does. During that time, the body, tricked into believing it is not producing enough beta-endorphins (which also attach to the opioid receptors) responds by increasing beta-endorphin production. In a few short hours, the LDN is metabolized and the opioid receptors are free to function normally for the rest of the day with an increase of endorphins as compared to not having taken the LDN (please reference I. Zagon’s prolific research to understand the clinical proof for these claims).

With that in mind, the last part of the study’s conclusion proves what turns out to be an incredible point, and reveals the true nature of the NMSS article for what it is—a blatant lie.  Looking at it again:

“…suggesting that the increase of the opioid beta-endorphin might represent a mechanism to downregulate the immune response.”

In simple terms, blocking the opioid receptors (and thus the reception of beta-endorphins), all the time by using HDN increased disease progression. The implication is that beta-endorphins might have a beneficial effect, because without them the disease gets worse. LDN boosts the production of beta-endorphins, and this fact, according to the very same study the NMSS would have one believe demonstrates that LDN may be harmful for MS, “might represent a mechanism to downregulate the immune response”!

Yes, you are reading correctly: According to this article LDN should actually be beneficial for MS! How’s that for irony?

This is just the most blatant example of the errors in this article. Others include:

• [NMSS Article says]:
  “Naltrexone is an opioid antagonist that has been approved by the U.S. Food and Drug Administration (FDA) since the early 1990s for the treatment of addictions to opioids and alcohol”
  
  [This is MS responds]:
  While Naltrexone (full 50mg dose) was indeed approved for the treatment of alcoholism in 1995 (http://www.niaaa.nih.gov/press/1995/naltre.htm), it was approved for the treatment of opium addiction much earlier, in 1984 (http://www.naltrexzone.com/FDAmeet.htm). Neither of these dates are “early 1990s.” The fact that a drug has been around for an extra decade is an important difference and though this is a minor error, an article that purports to be a serious evaluation of a possible therapy should ensure its facts are straight.
  
  
• [NMSS]:
  “At significantly lower doses, [Naltrexone] has been marketed on the Internet as a treatment for a variety of diseases including various types of cancers, HIV/AIDS, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), emphysema, as well as MS and other autoimmune diseases.”
  
  [TIMS]:
  Actually, treatment with low dose naltrexone was not promulgated over the internet as this sentence implies, but by Dr. Bernard Bihari, MD, in 1985. Dr. Bihari, who has an active clinical practice in New York City, discovered the effects of a very low dose of Naltrexone (approximately 3mg once a day, while the FDA-approved dosage for heroin addiction was 50mg’s) on the body's immune system and realized the therapeutic potential on a wide variety of illnesses. Dr. Bihari’s CV is available here.
  
  In short, real doctors prescribe and perform research on LDN. The attempt to associate it with an internet marketing scam is a rather weak ploy. A great deal of LDN information is indeed shared by LDN users, but that does not make it any less effective of a therapy as something with a high-budget advertising campaign.
  
  
• [NMSS]:
  ”There are, however, no published reports of placebo-controlled clinical trials demonstrating the safety and efficacy of naltrexone in any of these diseases [listed in above bullet point]. The marketing efforts rely entirely on anecdotal reports.”
  
  
• [TIMS]:
  This is misleading and false. A quick search on PubMed reveals the following study (among others):
  
  Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system (Lissoni P et. al., Neuroendocrinol Lett. 2002 Aug;23(4):341-4).
  
  To add insult to injury, this study concludes:
  
  
  ”…it is probable that a cancer neuroimmunotherapy with IL-2 plus both MLT and NTX [Low Dose Naltrexone] to activate TH1 and suppress TH2 cells respectively, may deserve more promising results in the treatment of human neoplasms according to the psychoneuroimnunological knowledge.”
  
  
  Not to mention the clinical trial underway investigating the use of LDN as a therapy for Crohn’s disease (http://www.thisisms.com/article1.html), an auto-immune illness affecting the gastro-intestinal tract…
  
  There are others, and the major point is that the “marketing efforts” of LDN absolutely do not “rely entirely on anecdotal reports.”
  
  
• [NMSS]:
  ” Naltrexone is said to work in MS and other diseases by adjusting the level of endorphins in the body to enhance immune function. Enhancement of the immune system, however, is not recommended for anyone with MS.”
  
  [TIMS]:
  According to Webster’s dictionary, ”enhance” means “to improve.” Enhancing what they are calling a broken immune system is not recommended?  No further comment is necessary on this downright shocking statement.
  
  

• [NMSS]:
  ”The goal of currently approved treatments is to inhibit the overactive immune response rather than boost it.”
  
  [TIMS]:
  While this is a true statement, has the NMSS lost sight of the fact that the CRABs, which for the most part aim to squash the immune system, show a meager ~30% efficacy rate, and oftentimes struggle with statistical significance? This is, of course, independent of their oftentimes brutal side effect profiles. Is it beyond the realm of possibility that the currently approved treatments are incorrect? This would have been a perfect time for them to explore that possibility and suggest a trial for LDN to see if the direction of treatment should be changed, but there is nothing but ominous silence and further slander…
  

As a whole this is a sloppy, ill-informed and manipulative article. It first claims to “know it all” about LDN and why it would be bad for an MS patient, then “plays dumb” when it comes to misrepresenting a study that on basic analysis actually supports the use of LDN instead of indicating against it. We are quite honestly shocked to see this article attributed to Dr. Bowling, who has previously done such good for the MS community, particularly with respect to research on complimentary alternative medicine.  

The NMSS is a savvy organization that is well aware that publishing this information would create fear and uncertainty in the public, both amongst patients and especially doctors who are too busy to investigate the article’s claims for themselves and would instead take them at face value. While it may have been their genuine aim to protect the public from what is admittedly an experimental treatment, it was an irresponsible, reckless, and insulting move to publish an article with such inconsistencies and questionable motives. A retraction and/or correction should be published immediately. Furthermore, given this article’s clear agenda, the NMSS owes an explanation to its constituency on why it has no serious interest in funding a study on an affordable, easy-to-use drug that hundreds of MS’ers already swear by.  

The goal of ThisIsMS is ultimately to no longer exist—when MS inevitably becomes a routinely treatable disease, there will be no need for our site. We embrace that fate, because it means millions of people across the world will no longer suffer. With that in mind, when we spot situations where it seems there is heavy and suspicious resistance to the exploration of extremely promising alternative therapies, we will act to defend our community. We are a tiny site, but we can do a great deal of good because the truth is omnipotent. 

Remember, LDN is an experimental treatment and may or may not be efficacious for MS-- always consult your doctor before undertaking any therapy, particularly one that is not FDA-sanctioned. However the motivation for this article is to prevent outright lies from a very respectable organization from discouraging the use, interest, and ultimately necessary clinical trials to answer the LDN question for us once and for all.

Please feel free to republish this article, as long as you include a link back to ThisIsMS.com and do not alter the text. All inquiries may be addressed to talk@thisisms.com

Good luck to all,

-ThisIsMS.com