Talk:Low-dose naltrexone/Archive 1

Archive 1

History of LDN

5.7.11 It appears someone is trying to re-write LDN's history to raise their own profile/s, so a new section for 'Further Reading' contains links to websites and publications that are relevant to the unique history of 'low dose naltrexone'. — Preceding unsigned comment added by 220.237.76.147 (talk) 19:54, 4 July 2011 (UTC)

Third opinion

With the exception of the ncbi.nlm.nih.gov link, none of the links that you added do not meet our reliable sources guidelines. The ncbi.nlm.nih.gov could be mentioned in the article, though a single study reporting effectiveness doesn't carry much weight. OhNoitsJamie ^Talk 22:06, 6 July 2011 (UTC)

Thank you for the comments. I should note that the content of the PubMed article you noted is already covered by several secondary sources in the article, so specific citation here or additional information would likely be WP:UNDUE here. Yobol (talk) 22:48, 6 July 2011 (UTC)

Entry has been restored. — Preceding unsigned comment added by 220.237.76.147 (talk) 05:52, 7 July 2011 (UTC)

So, you ask for a 3rd opinion, you get it, and then ignore it? That's not how Wikipedia works, 220. Yobol (talk) 14:39, 7 July 2011 (UTC)

Just FYI: I'm a Third Opinion Wikipedian and I stopped by here to see what had happened after the Third Opinion request had been removed. I see that Ohnoitsjamie has spotted the removal and weighed in with a 3O, but I also noticed the preceding remark about one editor ignoring the opinion. Let me clear up a potential misunderstanding. The instructions at the 3O page say:

This process is neither mandatory nor binding. Rather, it is a voluntary, nonbinding, informal mechanism through which two editors currently in dispute can request an opinion from an unbiased third party.

A 3O is just that, a nonbinding opinion issued by a neutral party with fresh eyes given with the hope of injecting some missed facts or new light into a generally-friendly dispute which has become stuck. It is in no sense a ruling, judgment, or tiebreaker (see history here) and neither party to the dispute is required to accept or follow it. (By the way, this is not intended to support, tear down, or second–guess Jamie's opinion. I've not looked at the links that Jamie has opined about and express no opinion about them or about his opinion. This is, instead, only to clarify the nature of a 3O opinion.) Regards, TransporterMan (TALK) 13:43, 8 July 2011 (UTC)

And let me clarify, I did not mean to imply that 3O was a binding process, but rather to express my frustration with this IP who is ignoring all input in favor of their own version of the article. Yobol (talk) 14:07, 8 July 2011 (UTC)

Very few references, despite there being many available

Unfortunately, I don't have the appropriate scientific background to meaningfully précis the many articles I've read into paragraphs fit for public reading. What I don't understand is that there appear to be a number of people, who do have such a background, who have added to the main article without finding the same sources. If anyone wishes to take this up, they could start by reading http://www.ebm.rsmjournals.com/content/236/9/1036.full (for a possible mechanism of action) and searching PubMed, where a search on low-dose naltrexone brought up 9 pages of results, including: http://www.ncbi.nlm.nih.gov/pubmed/20534644, http://www.ncbi.nlm.nih.gov/pubmed/19041189, http://www.ncbi.nlm.nih.gov/pubmed/21685240 and http://www.ncbi.nlm.nih.gov/pubmed/17222320. Glaciare (talk) 13:37, 18 September 2011 (UTC)

Our guideline for identifying sources for medical claims is clear that we use secondary sources, not primary ones like many of the ones you noted above. The one secondary source you provided is published in Medical Hypotheses, a journal with a poor reputation for publishing fringe ideas (and that until recently did not even practice peer review) and really has no place sourcing medical claims in a reputable encyclopedia. Yobol (talk) 13:45, 18 September 2011 (UTC)

Thanks for clarifying. I am confused as to why any of the four current citations are deemed acceptable, however; one is written by a self-proclaimed 'skeptic', one is inaccessible online, whilst the other two are merely reviews of some of the pilot studies, etc., which are classed as insufficient in themselves. They may be 'secondary sources', but why are they of any more quality/reliability than a journal with a poor reputation? If we apply the rules stringently, there could be no references at all, surely? Sorry to pick your brain, but I'm genuinely quite confused re. what is and isn't an acceptable reference - and keen to know what conclusions can reasonably drawn in this case... though 'more research needed' seems to be the main one. Glaciare (talk) 18:00, 18 September 2011 (UTC)

I can understand your confusion, as this particular article falls under two guidelines, WP:MEDRS, and WP:FRINGE (fringe for Wikipedia being any "ideas that depart significantly from the prevailing or mainstream view in its particular field" - in this case, low dose naltrexone has not been accepted as a treatment for any disease by the mainstream medical community). When dealing with WP:FRINGE medical topics, it is often necessary to use less than ideal sources for information, as there is not a lot of secondary source scholarship in the mainstream sources due it being fringe. In this case, the website meets this lower threshold; on the opposite end, extraordinary claims require extraordinary sources, so any discussion of how wonderful a miracle drug LDN is would require a high bar to meet, and Medical Hypotheses does not (I would not consider it a reliable source for much of any information, health related or not - it is that bad). The use of secondary sources is to determine how much due weight to give to any particular subject; that is why we avoid primary sources, because we use the secondary sources to determine how much weight in coverage to give. I hope this helps. Yobol (talk) 18:39, 18 September 2011 (UTC)

I think the article is biased to conflate "non-mainstream" with "pseudoscience" and "unproven claims" with "bogus claims." These latter are loaded terms being used without adequate justification. The mechanism behind LDN does "make sense," notwithstanding Mr. Novella's confusion on the matter; and if no acceptable sources have proved the health claims true then one must concede that no acceptable sources have proved them false. Rather, no acceptable studies have been performed and so there are no acceptable results one way or the other. Many proponents and users of LDN therefore think "bogus" and "pseudoscience" are inappropriate in an objective article on this topic. The origin of most miracle cures is that someone is trying to profit by their sale. Low-dose naltrexone does not fit this pattern. Indeed, many perceive that the debunkers are the ones with a financial stake in the matter. 69.209.34.24 (talk) 20:25, 19 March 2014 (UTC)

I agree with the last above statement. Every time I come to wiki, curious on new or up-in-coming, promising, not widely used medical advances or treatments, they tend to always be presented here with heavy bias or marginalized subtext in their overviews with the one surprising exception, the recent usage of some HIV medications for Ebola with promising results. There are no citations or in depth articles on wiki, just a few sentences regarding the dedicated wiki page for the specific drugs that were used in desperation during the recent Ebola outbreak.  — Preceding unsigned comment added by 38.88.222.106 (talk) 18:07, 16 January 2015 (UTC) 

Criticism

It is stated under Criticism: "Although many mechanisms of action have been proposed, none have been demonstrated in MS patients. No effects beyond the psychoactive have been demonstrated in any system." (emphasis mine)

This is in stark contrast to the study cited in the "Multiple sclerosis" chapter earlier where it is concluded: "A significant reduction of spasticity was measured at the end of the trial." This cleary is an effect beyond the psychoactive. Unfortunately, the article is locked, so no corrections can be made right now. —Preceding unsigned comment added by 84.114.147.43 (talk) 22:22, 19 February 2011 (UTC)

Deleted. —Preceding unsigned comment added by 84.114.147.43 (talk) 18:55, 24 February 2011 (UTC)

5.7.11 Please note that Maira Gironi's Multiple Sclerosis trial was misrepresented and has been corrected in line with trial results and Maira Gironi's own report on the trial. The validity of this claim is evidenced in the scientific references included in 'Those Whose Suffer Much, Know Much' 2010 edition, as well as Maira Gironi's own words in the interview in the same book. Removal of this valid correction on several occasions represents intent to falsify this record. The prior entry was not only misleading but also contained links that do not exist.

7.7.11 A scientific dissection of the pharmacology of naltrexone belongs under 'naltrexone', not 'low dose naltrexone'. — Preceding unsigned comment added by 220.237.76.147 (talk) 19:48, 6 July 2011 (UTC)

Endorphins and the immune system

Deleted following paragraph, because it is unsourced and probably unsourcable: "The evidence of an interaction of endorphins to the immune system is limited, and it is likely that endorphins are only a minor player in the immune system. The most cited literature is indeed not how endorphins modify the immune system, but rather the reverse. [...]"

Quite the opposite seems to hold true:

http://www.ncbi.nlm.nih.gov/pubmed/2981735

Enkephalins and endorphins as modifiers of the immune system: present and future.

"Furthermore, endorphins and enkephalins can influence several immune functions such as antibody synthesis, lymphocyte proliferation, and natural killer cytotoxicity."

http://www.ncbi.nlm.nih.gov/pubmed/2987737

Enkephalins and endorphins: activation molecules for the immune system and natural killer activity?

http://www.ncbi.nlm.nih.gov/pubmed/20141040

[Beta-endorphin as the endogenous regulator of immune processes].

http://www.ncbi.nlm.nih.gov/pubmed/14504158

Effects of endogenous and synthetic opioid peptides on neutrophil function in vitro. —Preceding unsigned comment added by 84.114.147.43 (talk) 19:04, 15 February 2011 (UTC)

Autoimmunity

The use of "autoimmunity" as a term in this article is loose. For it to be used correctly would require immune attack against self tissues. (unknown user, Oct 20, 2006)

All references to "autoimmune disease" in the article do refer to diseases in which the body's immune system attacks itself. However, whereas previously it was thought that the mechanism for autoimmune disease is a hyperactive immune system, it is now believed that immunodeficiency may be a contributing factor or even a primary cause in some, most, or all of these diseases. Andew2 07:18, 1 January 2007 (UTC)

The article author's statement that Crohn's is a "classic autoimmune" disorder was not stated with references and further is contradicted by several studies including the ones referenced on this author's own article. Autoimmune and under active immune system are not the same or similar even. Therefore the statements of this author's article are logically inconsistent, and factually incorrect on at lest one point. Several studies show that Crohn's disease can be treated with better success than the rates quoted in the author's article by using anti-mycobacterial treatments. [1] [2] [3] Therefore, the statement that Crohn's is autoimmune is not just an understatement but is totally inconsistent with logical conclusions from more effective treatments than those of the typical American pharmaceutical model. I.e. if the most effective treatments assume that Crohn's disease is causes by a bacteria and aided by a weak immune system, then Crohn's disease is not autoimmune and is probably bacterial in origin. Several studies over several years support the notion that Crohn's disease is bacterial in origin and aided by a weak immune system, therefore, Crohn's disease is not autoimmune and is probably bacterial in origin. The use of the term "autoimmunity" in reference to Crohn's disease must be deleted or changed soon. —Preceding unsigned comment added by 76.249.30.239 (talk) 20:07, 8 June 2008 (UTC)

I wish to change "The trial demonstrated the safety and efficacy of LDN in a group of patients with Crohn's disease, a classic autoimmune disorder. 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." to "The trial demonstrated the safety and efficacy of LDN in a group of patients with Crohn's disease, regarded by some Dr.s in many countries as an autoimmune disorder. 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." I would naturally provide sources to show that some Dr.s and researchers believe, regardless of the actual truth of the matter, that CD (Crohn's disease)is autoimmune. I then wold like to add a statement that this study and others call into question the unfounded assumption that CD is autoimmune. The links from my previous anonymous post just above should be helpful but I have more as well. I think I will edit this by Wed. unless I hear this is a bad idea. —Preceding unsigned comment added by Halej (talk • contribs) 03:12, 9 June 2008 (UTC) I am currently on LDN and have been for two years, I hav RRMS and really I would not be where I am today if it weren't for LDN. Before I started my treatment i could not even hold a pen or right after a really bad attack and now everything is fine and whats better is that it works just fine with m normal MS mediceince Copaxone. So long short of it LDN is a great drug that can help people and I have not noticed any advirse effects of it.

To advise people with MS, there should be a short section telling them that Copaxone is the only DMD that will work with LDN. All the other DMDs like Avonex, Rebif and Beta are interferons which damped the immune system while LDN is trying to bring it up (conflicting messages). LDN is also the only drug safe for pregnancy. The risk of teratogenicity with the other drugs is too high to risk testing, so although copaxone may be safe, it's too risky to prove that. LDN is known to be safe - I met a lady who had MS and 3 kids. Took it during all 3 pregnancies with beneficial effects. Look up Dr. Phil Boyle for more on this one. Shtanto (talk) 11:34, 22 July 2012 (UTC)

Use with ALS

The drug has been shown to reduce and stop the progression of the symptoms of the disease. This should D-E-F-I-N-I-T-E-L-Y be included in the article. I will add this after I find sources.Yamaka122 19:00, 23 June 2007 (UTC)

DATES need to be added to this section

The use of LDN for such diseases as cancer was discovered and developed by Ian Zagon, PhD in animal and in vitro research (WHEN?), and LDN's broader clinical effects in humans were discovered by Bernard Bihari, MD in the 1980s (DATE?). —Preceding unsigned comment added by 58.108.231.181 (talk) 07:06, 28 February 2008 (UTC)

Warnings about bogus science.

That proponents are being attacked or ignored by the establishment is a claim that should raise eyebrows and a big smile in any skeptik, so maybe someone should back it up with overtures to the establishment. That it's a solution for some of the most prolific and intractable problems in category:medicine should open somebody's wallet for research. I want to know which problem is most likely.

Aha. I see it in the category.
MS: An acronym for Multiple Sclerosis.
M$: An acronym for Monopolistic $cuzzball.
BrewJay (talk) 20:18, 27 May 2008 (UTC)

Conspiracy theorists should indeed raise eyebrows. Fortunately, the majority of people using LDN understand that the pharmaceutical industry cannot retrieve the new use patents from Dr Bihari and thus cannot profit. Worse, the use of LDN as a front line treatment will have a large impact on profits from other therapies. We know they invest a lot of money in assuring their revenue streams, so we can be sure that LDN suffers unjust dismissal as a by product of this work by the pharmaceutical industry. The main reason though for the apathy is that for autoimmune disease, the medical model is contradictory to the one currently in use. Bizarrely, this is not the case for cancer, where OGF is widely understood to control tumours, and OGF - met-5-enkephalin, is an endorphin which is boosted by LDN. To open a wallet requires profit. So the most likely wallet to open is one that will yield savings - ie government wallets, and this is close because of the sheer number of users of LDN - currently in the region of 100,000, and because of the hundreds of doctors who are now prescribing it. —Preceding unsigned comment added by Bwmbagus (talk • contribs) 15:05, 6 September 2009 (UTC)

God, this article is atrocious. I heartily agree with you. LDN might be a scam for some things but I don't think someone should go about brazenly attacking a different viewpoint, however misguided it may be. Especially on wikipedia, by making an article with a severe lack of citations and excess of ego. We are supposed to strive to be objective for god's sake. 99.12.87.231 (talk) 19:39, 1 July 2010 (UTC) —Preceding unsigned comment added by 99.12.87.231 (talk)

There's a conference on LDN coming up on the 17/9/2011 in Dublin. I plan to attend. I'm on LDN myself for MS, and it works for me. I noticed the article on MS doesn't link here; mentioned this in the MS talk page. I think a cross link is in order. LDN was originally licenced for doses of 50mg, so in doses of 4.5mg, I really doubt it's dangerous. Sure enough, big pharma won't make a dime off it because it's been out of patent for so long. For or against, I think the most important thing is awareness. That's the only way we'll get answers to our questions. — Preceding unsigned comment added by 46.7.165.130 (talk) 17:33, 8 September 2011 (UTC)

LDN has been out of patent for years. Industry won't spend a penny unless they can make money back on it. It will take some sizeable philanthropy to get the necessary research done. Charities like the MS society can't afford this sort of money. And even if it were done, skeptik would find something wrong with it. All we're likely to ever have to go on are patient testimonies and the people this drug has helped. There will always be some flaw with any research done. Sadly, that's not good enough for wikipedia. Thousands of people who know this drug has helped them are wrong because there hasn't been a proper trial done, due mainly to lack of funds.

For me, the drug helps every day. I tell everyone I know about it, where to get it, how it can be prescribed to them and how their pharmacy can get a supplier for them. The worst thing this drug can do is nothing at all, even after dosage adjustments. If you want 'do no harm' this is the stuff. Shtanto (talk) 11:40, 22 July 2012 (UTC)

Ulcerative Colitis

Why has the mention of it helping UC been removed? I first heard about it and it's use for UC here, on this page. As a result I've now been on it 10 months (on the NHS too) and in remission for the first time in 5 years! I would really like to see it's use for this condition back on the page as I want it to help others like it did me! —Preceding unsigned comment added by 78.156.70.229 (talk) 20:11, 25 March 2009 (UTC)

I think it may be because some editors only aknowledge treatment information that can reference clinical trials.

LDN is an Off-label_use of a known drug whose patent has expired (patent formally expired 1984 but DuPont was given an additional 7 years exclusivity). Therefore there is no economic motivation to fund such clinical trials. As noted in the Drug_development article the cost of drug testing and formal approval will be prohibitive unless the research can be recuperated by later sales. --Greylensman (talk) 19:48, 16 November 2010 (UTC)

What is BE concentration?

BE concentration is mentioned in the 2nd paragraph. Is that a reference to Base Excess, Beryllium, Branchial Efferent, or what? There is no definition nor embedded link. And the same goes for other abbreviations in the article. --74.124.187.76 (talk) 03:04, 1 July 2009 (UTC)

It is a reference to Beta Endorphins — Preceding unsigned comment added by 220.237.76.147 (talk) 08:54, 17 June 2011 (UTC)

This article excludes critical information about LDN

If anyone were to come to the LDN page for accurate comprehensive information about this drug they certainly would not find it. They would not learn of the thousands of people who are prescribed this offlabel use of Naltrexone. They would not learn what doctors are prescribing this drug for.

There needs to be a factual section on anecdotal experiences of people. Anecdotal experiences are different than claims. Thousands of people have had positive and negative experiences with LDN that would be of interest to a person looking to learn more about this drug. Because the drug is available by prescription only, every anecdotal experience comes from a person who has been prescribed this medication by a physician.

There are many pharmacists and physicians who would be happy to report on their experiences. This article is missing this information. That Wikipedia ignores so much information about this prescribed offlabel medication that is used internationally by thousands of people for a huge variety of illnesses is a testament to what seems to be Wikipedia's blatant attempt to present a particular point of view through exclusion.

What I have said is not in dispute. There *are* thousands of people taking this drug under the prescriptive care of their doctors. And those prescriptions include the diagnosis of UC, MS, HCV, HIV, Fibromyalgia, cancer, etc. This information is *not* in the article.

I added this information and it was removed for link spam (I included a link to reference my facts).

This was my first real contribution to Wikipedia, and due to this experience, will probably be my last.

Pmcg (talk) 00:49, 4 July 2010 (UTC)Browneyedman1228

It's important to remember that the threshold for inclusion in Wikipedia is verifiability, not truth. Publishing first-hand experiences or reports would be original research which is not appropriate for articles here. Wikipedia is not a publisher of original thought; please ensure that additions are sourced to reliable sources.

Your edit to the article (here) was simply an advert for discussion forums. Forums are not reliable sources - please consider locating alternate sources that meet Wikipedia's guideline on reliable sources. You may have the wrong idea of the purpose of Wikipedia; it is not a collections of external links, and should not be used to provide internet directories. Wikipedia has a guideline on additions of external links, as well as a guideline on external link spamming - please review those before attempting to re-add the content. --- Barek (talk • contribs) - 00:58, 4 July 2010 (UTC)

UPDATE: The 2010 edition of the free LDN resource book 'Those Who Suffer Much, Know Much' (Sapiencia parentibus in Latin) is now available onlineand int it you’ll find an explanatory article, 51 patient case histories, 19 health professional interviews and perspectives (pharmacists and physicians), related research and references in this comprehensive 2010 edition: ‘Those Who Suffer Much, Know Much’ 2010 edition www.ldnresearchtrustfiles.co.uk/docs/2010.pdf —Preceding unsigned comment added by 220.237.76.147 (talk) 20:45, 20 August 2010 (UTC)

Rewrite

I have re-written this page, to be more in line with WP:PSTS, using secondary sources only. I have also removed promotional EL that fail WP:ELNO. Yobol (talk) 23:01, 5 July 2011 (UTC)

Requested move

The following discussion is an archived discussion of a requested move. Please do not modify it. Subsequent comments should be made in a new section on the talk page. No further edits should be made to this section.

The result of the move request was: page moved. Yobol (talk) 04:00, 6 July 2011 (UTC)

---

Low-dose naltrexone → Low dose naltrexone – Secondary sources most commonly do not have the hyphen, so that should be the proper title, with the current article as redirect; see the secondary sources cited, they do not use hyphens. Yobol (talk) 03:34, 6 July 2011 (UTC)

The above discussion is preserved as an archive of a requested move. Please do not modify it. Subsequent comments should be made in a new section on this talk page. No further edits should be made to this section.

This entry is incorrrect and opinionated

The entry for Low Dose Naltrexone is not correctly written for this purpose. We need an entry which talks about the existing science and gives references to such. I will be organising a suitable write up of this subject and posting it here with the intention of replacing the drivel of Mr Novella. He is someone who campaigns against qwackery and I don't mind that, but he is the wrong person to write an informatve article about Low Dose Naltrexone. He thinks it is supposed to boost the immune system, but we know and can show in published work that it only boosts endorphins. When Naltrexone was being studied for use against opiate addiction, it was noticed that it accelerated tumours and T cell proliferation. This led on to work that shows that metenkephalin slows the proliferation of tumoursd and T cells and blocking the receptors is the cause of the observed acceleration by Naltrexone. Metenkephalin does the opposite of boosting the immune system. It acts on a receptor called the zeta receptor and inhibits cell proliferation. It is this effect that results in it's ability to control tumours and autoimmune problems. Cancers because metenkephalin or Opioid Growth Factor (OGF) puts the brakes on them growing and autoimmune conditions because OGF slows the rate of proliferation of T cells, which seems to allow our immune systems to return to homeostasis in chronic activation situations. Mr Novella is not aware of this published science, but we can write the replacement with the input from the scientists who are doing this work, giving references to their published papers. This is now under way so the corrected article will appear here soon. People look up LDN here because they want to know the reality, not be preached to by an evangelist! Finally, the references given are for pieces of journalism by the author and his supporters and not to peer reviewed papers. For a reference to be considered valid, it should reference a legitimate text. I would certainly appreciate it if you could see your way to removing all the opinion and the references from this entry, and when we provide you with the correct entry, to make sure it gets posted up instead. I represent and group of people concerned with presentinga correct scientific view of LDN and with seeing off the myths and disinformation surrounding it. We have no egenda for or against LDN, we just want people to have the facts so they can decide for themselves, which is what wikipedia is all about after all. This article is disinformation of the worst kind, from someone who claims to be fighting disinformation. We need something without an ideological agenda, which is something based on the real science. Bwmbagus (talk) 22:07, 16 October 2011 (UTC) — Preceding unsigned comment added by Bwmbagus (talk • contribs) 21:05, 16 October 2011 (UTC)

Any sources used for this article should be secondary, and not primary research, must discuss low dose naltrexone specifically, and must comply with our various guidelines and policies (notably WP:MEDRS and WP:FRINGE). The work of Dr. Novella applies here as he is an expert on fringe medical topics, under which LDN surely applies (see WP:PARITY). If you can find better or more sources, that would be great. Yobol (talk) 16:55, 17 October 2011 (UTC)

Fibromyalgia

I would not go so far as to say categorically that LDN was found to be of benefit; the review cites the only study which was a pilot study of 10 people. (Note that the article already mentions fibromyalgia as being one of the conditions which preliminary research has been done). Clearly it has not been found to be of clinical use yet. Yobol (talk) 00:55, 19 October 2011 (UTC)

...and I re-added the reference with a tweak at the end. It's in a review so it deserves some weight, but with a pilot study with an n of 10, we have to emphasize the preliminary nature of the research. Yobol (talk) 01:01, 19 October 2011 (UTC)

Yea, it does deserve a mention, I thought I worded it ok, mentioning that it was a small study. Also the lead is biased, needs mention of benefit of low dose opioid antagonists preventing and reversing of tolerance to opioids.Literaturegeek | T@1k? 01:14, 19 October 2011 (UTC)

Tweaked the lead per your suggestion, using the two reviews we have. Yobol (talk) 01:21, 19 October 2011 (UTC)

This medication works for Fibromyalgia, I am currently taking it, and have seen drastic changes in my symptoms. To report otherwise is to dismiss the effectiveness of this medication, and that is dangerous. There are people who are suffering with this disease. Please do not prolong the suffering by editing this article to be biased against LDN. Also, there is a blatant misstep in your article, it states that this medication is not licensed for use in the UK, according to my own physician, it is up to the physician to prescribe, and there are no rules for prescribing medication other than it being a medication that is already approved, and since this medication is already approved, although for other purposes, it does not require licensing. — Preceding unsigned comment added by 69.179.156.46 (talk) 01:47, 30 March 2012 (UTC)

Toll-like receptor 4

I didn't see a discussion of TLR-4 in the reference. Am I missing something? Yobol (talk) 01:37, 19 October 2011 (UTC)

Oh, I must have read it in a different reference, the toll-like receptor 4 is located on the microglia cells, it is just where it binds with high affinity on the microglia cell. I will delete it for now. We can always add it back at a later date.Literaturegeek | T@1k? 01:41, 19 October 2011 (UTC)

Article looking better

Article is nice and balanced now between what current science says versus unproven and sometimes dubious claims etc. :-) Time for me to sleep.Literaturegeek | T@1k? 01:44, 19 October 2011 (UTC)

Thanks for the good sources! Yobol (talk) 01:44, 19 October 2011 (UTC)

Penn State University Research Phase 1 and Phase 2 trials

I added a sentence pointing out the Penn State Phase 1 and Phase 2 trials for LDN for Crohn's.

Prior to this edit the published version of this article gave the impression there were no studies of LDN other than pilot studies which is just factually incorrect.

I am not sufficiently versed in Wikipedia to properly reference these trials but if someone with better wikipedia chops would care to it would be much appreciated.

The trial papers can be cited at these links -

Dig Dis Sci. 2011 Jul;56(7):2088-97. Epub 2011 Mar 8. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Source

Department of Medicine, The Pennsylvania State University, College of Medicine, GI Medicine H-045, 500 University Drive, Hershey, PA 17033, USA. jsmith2@psu.edu

http://www.ncbi.nlm.nih.gov/pubmed/21380937

Am J Gastroenterol. 2007 Apr;102(4):820-8. Epub 2007 Jan 11. Low-dose naltrexone therapy improves active Crohn's disease. Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Source

Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

http://www.ncbi.nlm.nih.gov/pubmed/17222320 — Preceding unsigned comment added by 157.203.42.50 (talk) 13:16, 22 October 2011 (UTC)

We need secondary sources, per WP:MEDRS to establish the weight of preliminary studies. The current language says that studies have "largely" been pilot studies (true) and also all been preliminary (also true). When a secondary source such as a literature review has mentioned the Penn State studies we can mention them here, until then we should leave them out for now. Yobol (talk) 14:39, 22 October 2011 (UTC)

So peer-reviewed scientific papers published in a journal do not count as valid sources? I'll cettainly lend little weight to anything in read in Wikipedia from now on then. Prior to today I've seen Wikipedia as a primary reference for the latest on a topic - it sounds like it is far from current and some years behind then. Very disappointing. — Preceding unsigned comment added by 157.203.43.103 (talk) 08:43, 23 October 2011 (UTC)

Please review our guidelines on identifying sources for medical claims. As an encyclopedia, Wikipedia is supposed to be behind the most cutting edge research. This is not a platform for the promotion of the latest flavor of the month in the research arena but to identify what has already been evaluated in seoncdary sources by others. Yobol (talk) 15:53, 23 October 2011 (UTC)

Errors in Page

Background

'LDN is not covered by insurance and therefore all expenses for its use should be expected to be paid for out of pocket.[6]'

Is this verifiably true for all US patients? Apart from anything else it is a US-centric statement that has no place in a global site like Wikipedia, for example many patients in the UK do not pay for LDN on the National Health Service and I am usure that the situation in Canada is like this, let alone the 100s of other countries where patients are being prescribed LDN. All that can factually be said is that 'Many (Or maybe most) US health insurers will not cover the cost of LDN' — Preceding unsigned comment added by 157.203.43.103 (talk) 08:55, 23 October 2011 (UTC)

We follow what reliable sources say. If you have sources that say otherwise, please present them/add them to the article yourself. Yobol (talk) 15:51, 23 October 2011 (UTC)

My dosage of LDN is covered by my insurance--Paula Randolph Vichy, Missouri, USA — Preceding unsigned comment added by 69.179.156.46 (talk) 01:50, 30 March 2012 (UTC)

Does your current source in [6] prove that 'LDN is not covered by insurance'? No it doesn't - so please remove or amend it. If you are insisting on these rules you need to abide by them too! At the very list you need to change this to refer to US insurance as your source does not refer to anything other than US insurance. When I find the time I will seek out a link to official UK NHS policy. I fail to see how I can provide a link that clarifies that not every US insurance company will not pay for LDN. — Preceding unsigned comment added by 157.203.42.50 (talk) 11:18, 24 October 2011 (UTC)

Yes, it actually does. "Finally, you should expect that you will have to pay for the LDN out-of-pocket because no insurance company or health care organization is currently covering LDN." Should you find other sources, feel free to add them. Yobol (talk) 11:47, 24 October 2011 (UTC)

Not it does not - please read. This US based site is talking about US health insurance - there are other countries in the world. Your reference states that 'LDN is not covered by US health insurance' not 'insurance' period. Are you seriously disputing this? — Preceding unsigned comment added by 157.203.42.50 (talk) 11:44, 24 October 2011 (UTC)

It may be covered outside of the US. Please provide reliable sources that it is, and we can add it to the article. The source does not make the distinction, and you have yet to provide any reliable sources that calls it into question beyond your own say-so (which does not belong in the article as it is original research). Yobol (talk) 11:47, 24 October 2011 (UTC)

OK, so I'm sitting in front of my computer in Malawi and I bring up this page, I read 'LDN is not covered by insurance'. Where? The sentence is not sufficiently qualified. If I click on the link I find the link is to 'US Department of Veteran Affairs' but I have to click the link before this is obvious. I fail to see why it is a problem to change 'LDN is not covered by insurance' to 'LDN is not covered by US health insurance'. The former is factually in error, though the link qualifies it correctly, the latter is factually correct regardless. If this article was subject to a sub-editor, which of the two sentences do you think they would want? This is not a dispute on a point of fact here, it's just my trying to put some writing in that is correct and easily understood on this page. Is it really such a problem to properly qualify one line of text? — Preceding unsigned comment added by 157.203.42.50 (talk) 12:07, 24 October 2011 (UTC)

My LDN comes paid for courtesy of the Irish HSE who gave me a medical card and cost it out of the Local Health Board budget. I call down to the chemist every month, pay them the 50p government levy and I'm all set. I can even ask for dosage adjustments if I need them. More of the Doctors here are aware of LDN than you might think, so I'm really very lucky. Shtanto (talk) 14:14, 3 June 2012 (UTC)

Pseudo Scientific Claims

"Steven Novella has noted that claims of treating a wide range of diseases with different etiologies should be a red flag to be skeptical about these claims which are likely to be "bogus treatment with claims that are literally too good to be true."[4]"

So, citing a peer reviewed scientific paper is out but citing the opinion of one man, an opinion that would rule steroids or biologics to be 'too good to be true' also, is valid? That doesn't add up to me. If we are dealing in facts and not opion so be it, but you can't have it both ways. — Preceding unsigned comment added by 157.203.43.103 (talk) 09:10, 23 October 2011 (UTC)

We have separated the true science from the WP:FRINGE pseudoscientific claims. Fringe claims, like the fact that it can treat HIV or cancer, which have no absolutely no scientific evidence backing it (as opposed to the preliminary research for fibromyalgia) - is covered by the guideline WP:PARITY, which will allow the use of Novella, who is an expert in the field of fringe pseudoscientific medical claims. Yobol (talk) 15:48, 23 October 2011 (UTC)

There is actually some evidence for effectiveness in certain cancers but (apart from case reports) only in a laboratory setting.[4], [5], [6] and [7] It is not fringe but rather very preliminary; it (use in cancer) has not been discussed in journal secondary sources and no controlled clinical trials have been conducted to my knowledge. Literaturegeek | T@1k? 21:26, 23 October 2011 (UTC)

Use in HIV seems dubious and couldn't find any evidence for a benefit other than a letter to the editor.[8] Literaturegeek | T@1k? 21:28, 23 October 2011 (UTC)

Use as a treatment of cancer certainly satisfies Wikipedia's definition of WP:FRINGE ("A fringe theory in a very broad sense to describe ideas that depart significantly from the prevailing or mainstream view in its particular field."); certainly use of LDN to treat cancer or HIV departs significantly from the mainstream medical view of LDN and cancer and HIV treatment, so WP:FRINGE applies here. Yobol (talk) 21:34, 23 October 2011 (UTC)

Actually yea, you are right, there is no evidence of it being effective (no clinical trials done) in 'treating' (people), but people are claiming it is, so yea it is fringe to make such claims. I take back what I said. Literaturegeek | T@1k? 23:31, 23 October 2011 (UTC)

I am a real patient with SPMS. The health systems are unable to help me, so I use my strong understanding of biochemistry to make calculated guesses. Yhis article should stick to real facts and lose the opinions of Novella. I dopn't care if he is an expert, he has failed in his expertise by writing a journalistic barrage against LDN by people like me who make educated guesses to try and stay alive. Get real please! — Preceding unsigned comment added by Bwmbagus (talk • contribs) 00:32, 24 October 2011 (UTC)

The key question has not been answered. If the key thrust of this page is to document known facts then the opionion of one individual is not valid and should be removed. — Preceding unsigned comment added by 157.203.42.50 (talk) 11:07, 24 October 2011 (UTC)

The purpose of this page is to identify and and give due WP:WEIGHT the various issues surrounding LDN, including the pseudoscientific claims. In the regards of these fringe claims, Novella is a reliable source. Yobol (talk) 11:36, 24 October 2011 (UTC)

If you are willing to express the arguments surrounding LDN, why are you unwilling to accept arguments based on the judgement of patients and supported by significant web sitres involved in the science. At present, the only opinion is one of cautious pessimism. Assuming we can provide good links to good sites, are you ready to accept the alternate viewpoints as expressed here for example http://www.ldnscience.org/ please comment on this as a source of citations Andrew Barnett (talk) 18:08, 25 October 2011 (UTC)

Yeah, if you're letting Novella in as con, you should let in testimonials and sites like http://www.ldnscience.org as pro. Fair's fair. This stuff works for me and many others. Shtanto (talk) 14:20, 3 June 2012 (UTC)

Why this entry is so offensive to intelligent LDN users

If it is wrong to make unproven claims about LDN, then it is also wrong to talk negatively for opinionated purposes. Low dose Naltrexone is a safe drug. You state that LDN is widely marketed through websites. Actually, it is not widely marketed at all. There are disreputable sites trying to sell LDN but the core of LDN users get their supply by prescription and from reputable sources. The paragraph stating it is widely marketed must be removed.

You keep talking about drug dependence use which is a high dose use so not relevant to an entry on Low Dose Naltrexone. Only the use of ultra low dose is relevant since this has preliminary evidence of being useful in preventing addiction for people like me, who also take opiates for pain control. LDN is covered by insurances and state health systems in most countries, and off label prescription is enough to enable people to get it these ways, so the line about it not being covered must be removed, it is actually a lie.

Talk about issues of justifying clinical use are not for comment by an unqualified individual like mr Novella. This is an issue of judgement for physicians so the statement about not justifying clinical use is pointless and should be removed.

LDN use is not advocated for anything. It would be better to say that “some claims are dramatic but we only have the science to evaluate this drug for ourselves and much of that is preliminary”

For MS, the proven therapies are unacceptable to most of us, only 12% of us in the UK use them, yet 7% of us in the UK use LDN! LDN is safe and seems to be effective though we cannot prove that in a statistically rigorous manner. This is why we use other things instead of ‘proven’ therapies. The proven therapy I took (Avonex)accelerated my MS by about 10 years in just 18 months and the next one (Mitoxantrone) I refused because it causes heart valve failure and other problems. So Mr Novella, get back in your box and stop trying to tell us sick people how to manage our health problems. We want doctors to advise us but they don’t have answers for us, but they can help sometimes.

You mention the ideas of LDN boosting the immune system. You do not mention the real theory of LDN use, which is that it only boosts endorphins by rebound effect. One of the boosted endorphins is met-enkephalin, which is also known as Opioid growth factor when it works with the zeta receptor. This OGF-OGFr action works to inhibit proliferation of tumour cells and T and B cells amongst others. Since this is an immune suppressive action, it is time to remove the part about how LDN use contradicts control of autoimmune conditions, because the control of T cell proliferation is actually what we want! Also, the ability of OGF to control tumour celss is proven in vitro so it is a useable bit of science for those who want to know.

The immune boosting myth seems to have evolved because Naltrexone antagonises the OGF receptor which results in accelerated proliferation of T cells! Naltrexone in high doses is thus not good for autoimmune conditions, so Low Dose use allows enough time between doses to metabolise the Naltrexone and then undo the increases of cells during the blockade and then to have a period of hours when the OGF does it’s work of modulating the immune system back to homeostasis. It does this by allowing apoptosis to reduce T cell populations. In chronic disease scenarios, T cells hang around and proliferate freely and OGF or OGFr levels are low.

So changes are needed regarding what claims you talk about. You should say that the immune boost is a myth and then comment on the immune modulation effect which is why we take LDN. Professor Zagon discovered this effect and not the internet myth ones.

In summary, this article does the negative face of what it is trying to avoid. It is full of opinion about how people should avoid LDN, and this is not the place for opinion like that. Please remove all this opinionated stuff. We don’t need advising by Novella, we want information about LDN and not what someone thinks about it in their agenda to rid the world of hippy medicine.

Nobody claims LDN can treat anything in the serious sphere of LDN research, we just wish to be able to talk about what we do know and there is not a lot to say. But LDN use is widespread so this entry is also offensive to many intelligent people who choose to use it based on what we can find out and we can only go away from this to warn the world about Novella and his evangelistic approach to disinformation. Let me explain that term, disinformation is when you state a truth and then attach it to implications of myth and lies – much like this wiki entry! So also known as propaganda. This entry is propaganda and therefore needs considerable revision by a neutral party who collates the real facts. Andrew Barnett (talk) 18:45, 25 October 2011 (UTC) — Preceding unsigned comment added by Bwmbagus (talk • contribs) 16:42, 24 October 2011 (UTC)

Medical claims generally need to be made using recent secondary sources, per WP:MEDRS such as reviews and meta-analysis's; reviews can be found by clicking on the review link after doing a search on pubmed or else academic books which can be found via searching google books or visiting your local library or both.--Literaturegeek | T@1k? 22:29, 24 October 2011 (UTC)

What Literaturegeek just said has been said to you many times, Bwmbagus. See WP:IDIDNTHEARTHAT. OhNoitsJamie ^Talk 22:36, 24 October 2011 (UTC)

(outdent) Maybe we could change the word 'marketed' to 'promoted'? Thoughts?--Literaturegeek | T@1k? 22:37, 24 October 2011 (UTC)

Maybe we should not say anything. LDN promotion or otherwise is not relevant. There are those who rave and promote but there are also most of us who try to know the truth and are trying to get the research done to answer the questions. There are around 100,000 people using LDN in the world now, so we do need the clinical research if only to silence Novella, I wouldn't say LDN works or doesn't, and I know it is a safe thing to take so what have I got to lose. Your article does miss that in spite of Naltrexone having been proven safe in trials at doses up to 300mg daily! But then the reference to that is a published large cinical trial so maybe it would be unnacceptable here. the real problem is that LDN use is widespread and the clinical research has fallen behind because there is too little profit margin in LDN. But you need to remove all talk about marketed or promoted, because this article just needs to talk about LDN itself and not get involved in advising people without allowing all viewpoints! Andrew Barnett (talk) 18:47, 25 October 2011 (UTC) — Preceding unsigned comment added by Bwmbagus (talk • contribs) 12:53, 25 October 2011 (UTC)

I know. I am a qualified researcher, I have a masters science degree and understand both the process and your shortcomings. I am objecting to the use of wikipedia for Novellas propaganda exercise, where he taints the bare facts with opinions about how we shoud avoid it for therapy. Either remove his propaganda - even if it has references - or allow the alternative propaganda. Currently this article is just offensive in it's agenda and needs revising to simply express the facts about LDN. Advising people to use LDN or to NOT use it is not acceptable, regardless of any refrenences. You should stick to the basics, that LDN is low dose naltrexone, that we know it's use causes a rebound boost of endorphins and that any therapy based on this is still experimental. We don't need advsiing about how to respond to those facts and shouldn't be 'advised' in wikipedia! Andrew Barnett (talk) 18:47, 25 October 2011 (UTC)— Preceding unsigned comment added by Bwmbagus (talk • contribs) 12:39, 25 October 2011 (UTC)

Do you have a peer reviewed journal reference for the rebound in endorphins (with once per day dosing)? Problem is that naltrexone produces a fairly long-acting active metabolite during metabolism, which while not as strong as the parent compound, would cushion any possible rebound effect, I would imagine. The active metabolite is why naltrexone can be administered once per day or in large doses once every 2 or 3 days for people dependent on heroin and other opioids. Another problem is that antagonists being antagonists do not produce a significant dependence generally as they neutrally modulate the receptor; their only pharmacological action is to block the actions of agonists or inverse agonists etc, therefore I would again suspect that a rebound effect would be minimal and probably non-existant within a 24 hour period due to this and also due to the active metabolite but I could be wrong.--Literaturegeek | T@1k? 13:56, 25 October 2011 (UTC)

The metabolisation issue is relevant, some people don't metabolise it quickly enough and need to take lower doses. Prof Zagon has found that once a week dosing is effective. I will return to you shortly with the refrence to a peer reviewed paper on the rebound effect. I know the rebound does occur but just need to look through the hundreds of papers to find the one you seek. The metabolites though are a source of problems but their impact is minimal too. I use 2mg every second day and get a good response from that. Some people also use higher doses to exploit levo-Naltrexones affinity for Toll Like Receptors. Research is in progres to see if this is also a useable process. Antagonists are not always inactive, they often illicit a different action on a receptor rather than just occupy the receptor.I will ask Prof Zagon, after all, he is also the person who did the research for Naltrexone in high doses for opiate addiction, and he discovered the rebound effect during this work. This is a list of his publlications http://fred.psu.edu/ds/retrieve/fred/investigator/isz1/completepub Andrew Barnett (talk) 18:47, 25 October 2011 (UTC) Bwmbagus (talk) 15:26, 25 October 2011 (UTC)

Thank you for your reply. Prof Zagon has found that once a week dosing is effective. Effective for what condition(s)? An antagonist is active in that they block the actions of endogenous agonists or inverse agonists. Did you find any references?--Literaturegeek | T@1k? 20:44, 26 October 2011 (UTC)

The once a week dosing study is in publication at this time so will be available soon. He has been doing work looking at different dosing patterns and is finding that less is more. Maybe interference from metabolites is more of a problem than thought. However, he has also told us that there are people who have problems with metenkephalin deficiency and these people cannot boost what doesn't work to start with. Some people lack receptors more and others are low on OGF but the rebound effect seems to be an established notion. I cannot find a study that deals with rebound per se, but I am going through studies I have got copies of to find where it is cited for you. Less frequent dosing though still seems to boost OGF and the zeta receptor too. There is debate with LDN users about how it seems to stop working after a while. It could be about the build up of metabolites or simply people taking too high a dose once metabolites have developed a residual presence. The metabolic half life of Naltrexone I believe is around 4 to 6 hours. Some people say a break helps sometimes too. I have reduced my dosing to every other day. This theorising is frustrating though, we need a clinical trial, but we thusands of patients are trying to get it done by someone but the world is not set up to listen to patients. In the age of the internet though, we become very well informed if we know how to. The time has come for patients to have a voice in the choice of research. Otherwise, LDN is not going to get looked at before we are all using it already - hard to do a trial then. This publication - http://www.ncbi.nlm.nih.gov/pubmed/21807817 - does explain the effect of LDN on OGF-OGFr axis and is very up to date.

Andrew Barnett (talk) 23:23, 26 October 2011 (UTC)

Thanks, the reference is to do with cancer and that research while interesting is still at the petri dish level of research; it is not relevant to my knowledge and not from that reference to MS or any other CNS disorder which is totally different in eitiology to cancer. I am not seeing any science even petri dish level science to back up claims of OGF in neurodegenerative disease (although if references exist saying otherwise with regard to opioid antagonists and OGF in CNS disorders I am happy to read them and eat humble pie). The fact that you are part of a group who campaign for LDN (based on what you say on your profile), it appears that your group do make claims which are pseudoscientific, or lack science such as claims regarding OGF being involved in relief of MS and other CNS disorders.

There however, is actually a very large body of research regarding the contributary and in some conditions possibly causative role of proinflammatory cytokines as well as free radicals to the aging process, contributing to alzeihmers disease, parkinson's disease, neuropsychiatric diseases (especially major depression). If and it is a big if, (large clinical trials needed to prove) there is a benefitial role for opioid antagonists in the treatment of autoimmune and/or neurodegenerative diseases/disorders it would be due to immuno-suppression of proinflammatory cytokines, via modulation of toll-like receptor 4 on the microglia cells and this is the proposed mechanism of action at least in fibromyalgia by researchers. By reducing inflammation in neurodegenerative disorders relief of symptoms is plausable. For what it is worth, I use low dose naltrexone and have done for past month with a significant benefitial effect (for a condition not listed on any LDN website) but I was prescribed it by my GP as I was able to argue from a scientific perspective, albeit a synthesis of scientific literature. :-P I doubt I would have been able to obtain it by arguing from a cell proliferation immune POV as I could not have backed that up with science to justify off-label prescribing. Anyway to wrap this up, without causing offense, what Steven Novella says about websites making a range of claims that are pseudoscientific in nature is true; had these websites started citing appropriately the well established role of proinflammatory cytokines in neuro-disorders with a good dashing of scepticism and calls for more research maybe the LDN community wouldn't be getting so heavily criticised by sceptics. Proinflammatory cytokines play a role in a wide range of disorders so Steven Novella's claim of lots of disorders possibly benefiting raising a red flag would hold less water had your community argued the science more sensibly. So in conclusion there is no point being angry with wikipedia, nor other wikipedia editors, but rather your own LDN activist community for approaching this topic with poor science and strong advocacy of poor science. If I am wrong in anything that I have said I apologise; you are welcome to continue this discussion on my talk page (as topic is starting to go off-topic) with references to change my mind. No one owns the truth, I am just an editor with an opinion and ultimately article content comes down to references, per WP:MEDRS.Literaturegeek | T@1k? 01:07, 27 October 2011 (UTC)

I too despair at the pseudoscience surrounding LDN. nAlso our group - LDNNow, does not make claims for LDN, we campaign for then research so that these questions get answered. Please have a good look at Dr Zagons work, many of your questions can be answered here - http://fred.psu.edu/ds/retrieve/fred/investigator/isz1/completepub . Prof Zagon is working hard on this but the truth is that the pseudos ience isn't helping, but now we know that OGF is immune suppresswive, it makes much more sense that it helps where steroids work. You say it quite well, Novella is just a do gooder though and we don't need his advice, he doesn't have to live with a disease that needs cytokines or LDN so he doesn't really understand our thought processes. I make my choices on viable biochemistry and look at the link and Dr Jarred Youngers work too for the anti pro inflammatory cytokines work too. LDN seeems to have stopped me getting new lesions now for 3 years so I am happy but dosing is a minefield. I wish we had more than basic science but we also know why we don't. Feel free to help us get clinical research commissioned though so this debate can be resolved properly. All said, I am still offended by your allowance for Mr Novella to express a propagandist message. Regardless of the situation with ill advised people making silly claims, I am suprised that Wikipedia allows itself to be used as a forum for advising people about the wisdom of a drug which is neither proven nor disproven. Novella is likely to have to eat his words as much as the LDN 'promoters', and because that is a truth, his writings are innapropriate. This entry needs to stick to stating that LDN has a lot of basic research but nothing conclusive yet. We don't need the advice to not use it in place of standard drugs or any other advice in wikipoedia, we can go to Novellas website if we want that. Either allow the supporters of LDN to express the alternative opinion or remove Novellas version. It would be enough to state that LDN is considered fringe by wikipedia, we don't need Novellas name involved and we don't need opinionated comment however qualified he is. This article is heavily biased in opinion and that is making it look a joke. People go to LDN websites for their guidance, and if wikipedia tries to stand out like this, people will simply disregard it and are doing so. Much of what is written is ok, but a lot needs removing too, because it does not focus on the facts about LDN, it tries to prejudice the readers thoughts and that undermines the purpose of wikipedia. More care in the construction of this article would be a good thing. Finally, you seem to be willing to dismiss me because we campaign for LDN research. We do not promote LDN! We came into this realising that there is a lot of pseudoscience about and set about trying to get the research done to end this. There are many believers, but we are not in that camp. Personally, I am gambling with my life on a safe drug that offers an interesting solution. It is clinically reasonable, if you read the references I have given you (and get the whole publications too) as you know being a user, but the wikipedia entry does not state that point does it! There is no clinical reason why people should not use LDN, either in place of or in conjunction with standard therapies for MS, cancer or any other problem that seems amenable. It is hard to ignore that cells that carry the zeta receptor, ie T and B cells and tumour cells, seem to respond to OGF by putting the brakes on proliferation. This is such a fundamental evolved process and you will find studies in Prof Zagons work that show this works in vivo and in vitro. As I say, patients demand the research now, and that needs to be enough to make the research happen. How about expressing that in wikipedia if you like opinions? So in summary, I want to see a more balanced entry, even if that means it gets chopped down to 2 lines. — Preceding unsigned comment added by Bwmbagus (talk • contribs) 18:40, 27 October 2011 (UTC)

In answer to the question of how do we know LDN does work to boost endorphins http://www.ldnscience.org/how-was-ldn-discovered and also if you put 'intermittent naltrexone zagon' into google scholar you will find all the refernces. Andrew Barnett (talk) 21:24, 27 October 2011 (UTC)

The onus to find specific appropriate references is on you, not others. lndscience.org, as an advocacy site, does not meet WP:Reliable sources. OhNoitsJamie ^Talk 21:28, 27 October 2011 (UTC)

Then the onus on novella is to avoid advocacy sites of his own, where he references his own comment about fringe medicine as a reference. Also, I wouldn't call LDNScience an advocacy site, you are truly bigoted about this issue if you think that. The purpose of LDNScience is to present the facts and not advocate anything thankyou very much! Wikipedia could learn a lot from that site on this issue. Let us examine some of the pertinent references in this entry. [4] is a journalistic article of the NOT advocate style. It is journalistic opinion on a site with an agenda. [5] does not refer to LDN at all. [6] if you read it supports LDN use far more than the use here would suggest and it is still journalism based. [8] is a better summary than the wiki entry. [7] is midirected because it responds to a fallacious mode of action for LDN even thoush that myth is widespread. [9] I cannot access.[1] [2] [3] seem ok but related to another interesting ue of LDN Andrew Barnett (talk) 23:33, 27 October 2011 (UTC)

(outdent) [4] Novella's credentials have already been established here. Nonetheless, if you find an article written by someone with similar credentials to Novella's who would provide a counterpoint, suggest that here. [5] The link was not "direct"; I've fixed that to link directly to the PDF containing that article, which is very much about LDN, and published by the National MS Society [6] I don't agree with that; read the concluding paragraph, in which is doesn't flat out discourage trying LDN, but it is nonetheless quite cautionary [7] your personal critique of what clearly qualifies as a reliable source doesn't hold much water here. OhNoitsJamie ^Talk 15:26, 28 October 2011 (UTC)

Thankyou for fixing the MS society of america entry. Interesting that this entry to wikipedia seems to be focussed on the US view of LDN. Also, MS societies around the world HAVE TO avoid anything fringe in medicine so their statement in the link is bound to be guarded as it is. My biggest issue though is that this entry about LDN should not get concerned with warning people about the use of LDN. Novella for example is not an expert on LDN and being known for his battle against bogus medicine, I imagine his mind is closed and wherever patients move against 'proven' therapies, he feels compelled to wade in and risk a face full of egg down the line. I just want this entry in wikipedia to talk about LDN only, andf not get involved in opinions for or against it. The evidence around LDN is preliminary in the most part and we only need here to talk about the small amount that is known about what LDN does, and this seems mostly limited to it's ability to cause a stimulation of endorphins including OGF, as long as a low enough dose is taken and the effect is not swamped by the metabolites. Can we also please just stick to stating that LDN is an experimental therapy which has attracted a lot of patient interest, which most patients find they need to fund themselves. I don't wish to include anecdotal claims of it's effectiveness and I don't want to see unproven claims of it being bogus science. This should be one of the smaller entries in wikipedia because there is not much to say about it in an encyclopedia. Currently, wikipedia is being hijacked here to expatiate agenda driven opinion and I don't see how Novellas speciality actually has anything to contribute to the entry for LDN in wikipedia. He does well enough running his own websites as much as promoters of LDN do running theirs. Also, what is your problem with the LDNScience website? This site is set up to deal with the mythmaking which surrounds LDN by publishing solid science and not making claims. It does not advocate LDN, but what it does do is give the information people need to make the best informed decision about their interest to use it. Novella will not influence one person with an autoimmune disease or cancer who chooses to look at LDN because they will look for whatever science there is, and treat Novella as a completely obvious point. We all know that LDN is unproven, but we want to know what is known about it so when we make our gamble with death, we do so with our eyes as open as possible. If you care about us sick people who look to LDN, help us get the trials done so we can end these silly arguments. If LDN is true in any degree, we all get sick in our lives and that makes it too important to be sidelined the way it is being, and all because it has no profit to offer the pharmaceutical industry. Please answer all the questions I pose here or we will be here a long time.Andrew Barnett (talk) 18:49, 31 October 2011 (UTC)

Recommendations for changes

"and LDN should be considered an "unproven treatment" and should not be used in replacement of more proven therapies, despite what some advocacy websites claim."

to be changed to

"and LDN should be considered an "unproven treatment" and use in replacement or in conjunction with more proven therapies is at the individuals own risk."

"very small pilot study"

to

"small pilot study"

the very is highly subjective

"In addition to the known scientific uses for low dose naltrexone, there have been a number of pseudoscientific claims (such as "boosting" the immune system) about its use in a wide range of diseases such as cancer, HIV, lupus amongst others on various websites. These claims are not only unsupported by clinical research, but are also contradictory. They claim LDN is able to treat diseases of immune dysfunction such as HIV in addition to autoimmune diseases where improving the immune system could make the autoimmune disease worse. Steven Novella has noted that claims of treating a wide range of diseases with different etiologies should be a red flag to be skeptical about these claims which are likely to be "bogus treatment with claims that are literally too good to be true."[4]

This section is entirely erroneous. LDN is not about boosting the immune ystem even though some people think it is. It would be better to say that the boosting the immune system idea is a myth of the internet and is in conflict with the science of LDN which supports an action which either suppresses or modulates the immune reponse. Also, since the action is on regulation of the immune system via controlling cell proliferation and inflammation, and has similarities to the action of hydrocortisone which does about 10% of this work, the wide range of conditions amenable to it is not suprising if it's mode of action is correct. Steroids, ibuprofem and many other drugs have wide ranging appplication too. All the diseases that have been treated with LDN obviously respond to one or other of the modes of action of LDN and we know of two at least, one is direct from Naltrexone and the other indirect from the effect of upregulating the OGF-OGFr axis.v So, yes, too good to be true is often the case, but not always so be wary of being quick to condemn.

"Basic science research has shown that opioid receptors may have other uses in the body than just for modulating pain, such as paradoxically increasing the production of the body's natural endorphins, and it is on this basis that supporters of the LDN have extrapolated the clinical claims as a treatment for a multitude of diseases.[4] Advocates have claimed that this increased endorphin production can reduce pain, spasticity, fatigue and other symptoms.[6] These claims, however, are not supported by significant clinical research"

to

"Basic science research has shown that opioid receptors may have other uses in the body than just for modulating pain, such as increasing the production of the body's natural endorphins and also regulating cell proliferation in certain cells such as T and B cells and tumour cells (refs available), and it is on these bases that supporters of LDN have chosen it as a treatment for selected diseases. Advocates have claimed that this increased endorphin production can help with pain, spasticity, fatigue, relapse rate and other symptoms. These claims, however, are not supported by clinical research which has not been done yet in spite of patient demand"

I have done some work here to de-politicise the comment. Some refs have been removed and should be replaced by refs which we can provide. Mostly I have adjustd the wording to eliminjate the opinionated waffle that colours thyis entry, so please see a way to accomodate this. I present this as an idea of what needs to be done here. — Preceding unsigned comment added by Bwmbagus (talk • contribs) 23:25, 27 October 2011 (UTC)

I have no objections to the removal of "very" and have done so. The Novella paragraph could certainly be refactored a bit, but it's not saying deviating significantly from what a lot of other sources are saying. If you found a clinician with similar credentials who countered that argument, feel free to suggest it or add it. I've also taken the liberty of following through on your suggestion regarding the "Basic science research..." paragraph. Others may disagree; I don't pretend to be an expert in this area. OhNoitsJamie ^Talk 15:30, 28 October 2011 (UTC)

Thankyou. One other point, the article claims that LDN is not available to patients on insurance in the USA. We are aware of patoens who do get it covered by insurance in the USA, the sritical factor is that a doctror prescribes it off label to the satisfaction of the insurance company. Thyerefore the state,ment it must be paid for off label is scare mongering and in fact, it is just difficult to get it on insurance or to get a doctor to prescribe it within a health system in any country. That said, people do get it within their various health systems because doctors are free to prescribe according to theirpowers in law to prescribe off label when they take responsibility. Many in the UK do this privately and ot on the NHS so many of us still must pay, but luckily LDN is very low cost and we can afford it. Not sure how to reflect this point in the article, any ideas?Andrew Barnett (talk) 19:47, 28 October 2011 (UTC)

Regardless of whether or not doctors circumvent insurance regulations, the fact is that it's still an off-label treatment at this time. Also, the article's current wording is "should be expected," which does leave some wiggle room. I don't think labeling something as "off label treatment" is tantamount to scaremongering. For years, propranolol as been used off-label for stage fright (well, not sure if it's still off-label or not). OhNoitsJamie ^Talk 20:14, 28 October 2011 (UTC)

The off label statement is correct and not scaremongering. What is scaremongering is the statement that people will be forced to pay out of pocket, with no mention of low cost and the fact that this statement is actually false. Many people actually can get it on their health insurance or on the NHS if it is prescribed off label. This is hard, just rttrying to make a point here gets diverted into misundersanding so easily. I also will have a full version of the last section and a set of references for you to verify very soon. Hwever, I am a very ill person with SPMS so don't expect speed from me. Andrew Barnett (talk) 18:20, 31 October 2011 (UTC) — Preceding unsigned comment added by Bwmbagus (talk • contribs) 16:10, 31 October 2011 (UTC)

As promised, a list of refreneces. Can someone please take a look at these and let me know which ones are considered acceptable for a discussion on proposed mechanism of ation. Then I can set about producng a version for you which is complete.

B lymphocyte proliferation is suppressed by the opioid growth factor-opioid growth factor receptor axis: Implication for the treatment of autoimmune diseases.

http://www.ncbi.nlm.nih.gov/pubmed/20598772

Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis.

http://www.ncbi.nlm.nih.gov/pubmed/19297547

http://ajpregu.physiology.org/content/296/6/R1716.full

Centrally-mediated opioid-induced immunosuppression. Elucidation of sympathetic nervous system involvement.

http://www.ncbi.nlm.nih.gov/pubmed/9666255

Combination chemotherapy with gemcitabine and biotherapy with opioid growth factor (OGF) enhances the growth inhibition of pancreatic adenocarcinoma.

http://www.ncbi.nlm.nih.gov/pubmed/15947928

Evidence that opioids may have toll like receptor 4 and MD-2 effects

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788078/

Low-dose naltrexone targets the opioid growth factor–opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model

http://www.ncbi.nlm.nih.gov/pubmed/21807817

http://ebm.rsmjournals.com/content/236/9/1036.full

IMMUNOLOGY OF MULTIPLE SCLEROSIS

http://www.ncbi.nlm.nih.gov/pubmed/15771584

http://www.direct-ms.org/pdf/ImmunologyMS/Martin%20Immuno%20MS%20Review.pdf

Low-dose naltrexone for disease prevention and quality of life

http://www.ncbi.nlm.nih.gov/pubmed/19041189

http://www.ldn4cancer.com/techpapers/ldn_for_disease_prevention_quality_of_life.pdf

Opioid growth factor suppresses expression of experimental autoimmune encephalomyelitis.

http://www.ncbi.nlm.nih.gov/pubmed/19931226

Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers.

http://www.ncbi.nlm.nih.gov/pubmed/19675283

T lymphocyte proliferation is suppressed by the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: implication for the treatment of autoimmune diseases.

http://www.ncbi.nlm.nih.gov/pubmed/20965606

Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study

http://www.ncbi.nlm.nih.gov/pubmed/19453963

http://www.rsds.org/pdfsall/Younger_LowDoseNaltrexone.pdf

I hope this leads us to a proper conclusionAndrew Barnett (talk) 18:22, 31 October 2011 (UTC)

We need to be using WP:MEDRS compliant sources, in this case review articles in the literature. The sources provided either are not reviews, or do not mention LDN directly, making mentioning them in this article as a proposed mechanism original research. I should note that Medical Hypotheses is a notoriously poor journal and would not be a reliable source for much of anything. Yobol (talk) 23:50, 1 November 2011 (UTC)

WP:MEDRS states "Wikipedia's articles, while not intended to provide medical advice, are nonetheless an important and widely used source of health information.[1] ". This is my criticism, the entry should not be offering medical advice, and statements advising people not to stray off the path and use LDN are innapropriate to wikipedia. You need to rewrite it to lose this aspect of advice to patients by your own credo! Interesting too that none of the references I have supplied are allowed when they are very informative too. Only one is related to medical hypotheses. The fact that many refer to OGF rather than LDN is relevant when others show that LDN use results in increased OGF which is the desired effect to get the benefit. As I say, the LDN entry should be quite minimal and refer to other entries for the interesting stuff, and needs to lose the medical advice re Novella's opinions. Tell him I'll even watch him wipe the egg off his face on youtube one day hehe Andrew Barnett (talk) 15:04, 6 November 2011 (UTC) — Preceding unsigned comment added by Bwmbagus (talk • contribs) 14:57, 6 November 2011 (UTC)

Do you think you can use this reference then?? http://en.wikipedia.org/wiki/OGFr83.104.48.89 (talk) 20:44, 21 November 2011 (UTC)83.104.48.89 (talk) 20:43, 21 November 2011 (UTC)

Here's a pseudoscientific argument which should be removed: "LDN supposedly treats many [seemingly] unrelated illnesses. As a noted skeptic, I often find quacks making similarly various claims which are certainly bogus. Therefore, we can assume that LDN is bogus too." The author is reasoning by analogy to reach a foregone conclusion, classifying LDN according to a subjective pattern of superficial observations rather than evaluating empirical and theoretical evidence. Aspirin, for example, is not bogus simply because it can treat headache, backache, toothache, fever, the common cold, heart attack, angina, stroke, hangover, arthritis, etc. Very many widely accepted drugs have long lists of FDA-approved and mainstream off-label indications that seem unrelated if one fails to consider the mechanism of action, but no effort is made to debunk mainstream medicine exactly because it's mainstream. This isn't quackbusting but question-begging. — Preceding unsigned comment added by 69.209.34.24 (talk) 18:57, 23 March 2014 (UTC)

Low-Dose Naltrexone (LDN): Tricking the Body to Heal Itself?

http://www.sciencedaily.com/releases/2011/09/110902133047.htm Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered the mechanism by which a low dose of the opioid antagonist naltrexone (LDN), an agent used clinically (off-label) to treat cancer and autoimmune diseases, exerts a profound inhibitory effect on cell proliferation.

What can be done to work this information in to this Wiki article?

Cbeymer (talk) 20:03, 30 March 2012 (UTC)

That information appears to be a reprint of a press release, and probably does not qualify as a reliable source for medical claims for use in this article. Yobol (talk) 23:41, 7 April 2012 (UTC)

How can this study be worked into this article?

www.academicjournals.org/jahr/PDF/Pdf2011/October/Traore%20et%20al%20(1).pdf

Impact of low dose naltrexone (LDN) on antiretroviral therapy (ART) treated HIV+ adults in Mali: A single blind randomized clinical trial

Abdel K. TRAORE, Oumar THIERO, Sounkalo DAO, Fadia F. C. KOUNDE, Ousmane FAYE, Mamadou CISSE, Jaquelyn B. McCANDLESS, Jack M. ZIMMERMAN, Karim COULIBALY, Ayouba DIARRA, Mamadou S. KEITA, Souleymane DIALLO, Ibrahima G. TRAORE and Ousmane KOITA

To implement an immuno-regulatory approach for reducing or preventing the onset of AIDS symptoms in HIV+ individuals we conducted a single blind nine-month randomized clinical trial to evaluate the impact of low-dose naltrexone (LDN) on asymptomatic HIV+ Mali adults undergoing antiretroviral (ART) treatment with CD4 counts below 350 cell/mm3. We measured differences between groups in CD4 count, CD4%, hemoglobin, viral load, interferon alpha, and standard chemistry panel five times during the clinical period. The random mixed model and restricted maximum likelihood method for estimating slopes for repeated measures on subjects were used to predict CD4 counts and CD4%.

The improvement in CD4 count in the treatment group (51 subjects) was significantly greater than the control group (49 subjects) at 6 months (p = 0.041) and marginally at 9 months (p = 0.067). Improvement in CD4% in the treatment group also was observed throughout the clinical period but these increases were not significant relative to the control group. Since, for this period of time, the combination of LDN + ART appears to be more effective in increasing CD4 count, and since LDN is inexpensive, easy to administer and without side effects, further exploration of LDN together with ARV treatment is recommended.

Cbeymer (talk) 19:59, 30 March 2012 (UTC)

In general, per WP:PSTS, WP:MEDRS, and WP:UNDUE, we wait for secondary sources to review a primary article (which the above appears to be) before we include it in the article. Yobol (talk) 23:41, 7 April 2012 (UTC)

16:30, 2 April 2012 (UTC)Biased, unscientific article on low-dose naltrexone

No scientific clinical trials have proven low-dose naltrexone to be ineffective for diseases other than alcohol and narcotic addiction. Consequently the empasis and overall tone of this article is biased, prejudicial and discriminatory, and needs to be amended to include the followoing information.

The late Dr. Bernard Bihari of New York City was the first to treat his patients with small doses of 4.5 milligrams per day of naltrexone (LDN). His results convinced him and many others that this medication was very effective in treating disorders of the autoimmune system. He prescribed it to patients with various cancers, multiple sclerosis, HIV/AIDS, multiple sclerosis, autoimmune disorders and various other diseases. His results have been summarized on the website http://lowdosenaltrexone.org/index.htm. Further elucidation of the benefits of LDN are contained in the book The Promise of Low Dose Naltrexone Therapy by Elaine A. Moore and Samantha Wilkinson, with a forward by Yash Pal Agrawal, M.D., Ph.D., published in 2009 by McFarland & Co., Inc., ISBN 978-0-7864-3715-3. Further information on LDN is contained in Honest Medicine: Effective Time-Tested, Inexpensive Treatments for Life-Threatening Diseases by Julia Schopick, ISBN 978-0-9829690-0-7. The reason that this drug has not found wider acceptance among the medical community is that the FDA has not approved it for uses other than that for which it was originally developed, i.e. alcohol and narcotic addiction, is simply that there have been no “Clinical Trials” run to determine its effectiveness in other applications. The problem here is that no pharmaceutical company is going to spend money on conducting such Clinical Trials on a drug whose patent has already expired.

Nabunturan (talk) 16:30, 2 April 2012 (UTC)

Please review our guideline on reliable sources for medical claims. Promotional websites and non-peer reviewed books generally do not qualify. Yobol (talk) 23:37, 7 April 2012 (UTC)

Dosages & Side effects

Clarks dosing guidelines for MS and LDN suggest patients should aim for weight in lbs * 0.03, so that'd be around 4.5mg for most people. I should say however that I've been on LDN myself now for about 6 months and dosage (in my case at least) is very sensitive to environmental factors like heat. If I go up even half a point of BMI I tend to have to go up a half mg. No mention of side effects here either. I've had sleep disturbances, vivid dreams and pruritus (itchyness, mild though, no big deal). I can vouch for LDN. Testimonials are easy to find. It is helping people and improving QOL scores all over the world.

Dr. Gilhooly (who I met at the 2011 LDN conference) suggests starting at 1.5mg and working up in half mg until you start feeling worse, then working back until you start feeling better. LDN is a very individual dependant therapy. All of us would need our own dose. I met a lady at my yoga class who found her ideal dose at 11mg.

The article is looking a lot better. I still think personal testimonials ought to be viewed as carrying more weight than they do. As it is. I get the feeling that wikipedia dismisses them too quickly. I know people using LDN. I use it myself. It works for them, and it works for me rather nicely. I feel very cynical about sceptics sometimes.

Also, be sure you go for the lactose free version fillers with LDN if you intend to take it yourself. Lactose free LDN is more effective. It doesn't chalk up on the way in. Shtanto (talk) 23:10, 10 July 2012 (UTC)

The talk page is for discussing improvements to the article, not for giving medical advice. We rely on our guideline for reliable sources for medical claims to guide which sources to use, and personal testimonials do not qualify. Please make specific suggestions sourced to specific sources that qualify, per our talk page guidelines. Yobol (talk) 23:20, 10 July 2012 (UTC)

Adding in new studies

Some editors have been adding small pilot studies with positive outcomes as if these ought to shift the general consensus towards efficacy. The policy WP:MEDRS is clear that the article should not become a shopping list of individual papers or editorial synthesis WP:NOR, and we should instead await a credible review article. Martinlc (talk) 23:14, 2 March 2013 (UTC)

TNI Biotech patent buyout

And so the saga continues. TNI biotech recently bought up the LDN patents. Maybe now we can look forward to some solid research. Worth a mention in the article I'd say. Shtanto (talk) 00:19, 3 March 2013 (UTC)

POV clean up; removing Bowling from HIV/cancer discussion

This article has some POV problems and I have attempted to maintain medical credibility by replacing ambiguous claims and weasel words with attribution as denoted by the sources.

I have also removed the sentence "The treatment has been widely promoted through websites run by organizations advocating its use," which cites Bowling on HIV/cancer; Bowling does not specifically state that spurious websites support HIV/cancer claims, and his article is primarily concerned with the potential treatment of MS. Please find another source for this. Memtgs (talk | contribs) @ 15:20, 13-06-2013 UTC 15:20, 13 June 2013 (UTC)

Reporting of single studies

Note that WP:MEDRS is clear that we should not be reporting individual studies as if their finding had clinical signifiacnce. Meta-analyses and clinical guidance notes from bodies such as NICE recommending adoption are required for inclusion. At present all the single-disease studies cited in the article do not meet the standard and should be removed.Martinlc (talk) 14:52, 4 October 2013 (UTC)

As proposed above I have removed the studies pending a statement of clinical significance.Martinlc (talk) 09:24, 12 October 2013 (UTC)

Re: Reporting of single studies

Diversitti (talk) 19:55, 12 October 2013 (UTC) Most of the primary references cited on this topic (until their removal on 12 October 2013) are recent, and so secondary review articles are not presently available. While I appreciate the clear preference toward secondary sources, when they exist, as expressed in WP:MEDRS, there is a section of that policy which allows them in certain circumstances:

"In other situations, such as randomized controlled trials, it may be helpful to temporarily cite the primary research report, until there has been time for review articles and other secondary sources to be written and published. When using a primary source, Wikipedia should not overstate the importance of the result or the conclusions. When in doubt, omit mention of the primary study (in accordance with recentism) because determining the weight to give to such a study requires reliable secondary sources (not press releases or newspaper articles based on them). If the conclusions of the research are worth mentioning, they should be described as being from a single study, for example:

"A 2009 U.S. study found the average age of formal autism spectrum diagnosis was 5.7 years." (citing PMID 19318992)"

I believe that the above section applies in this case, and also that the studies listed were framed in a manner that encouraged their proper weighting as individual studies. If there is disagreement on this point, then the framing might be improved in preference to removing the references in their entirety.Diversitti (talk) 22:52, 10 December 2013 (UTC)

Fair enough, but it is unhelpful to provided detailed summaries of each paper. As in the example cited, a simple statement of the conclusion is all that is needed, ie in this case "A small study in fibromyalgia applaications has has shown it to be safe and possibly effective". Also the statement should not go further than the source study report - that would ne Original research. Martinlc (talk) 08:52, 13 October 2013 (UTC)

Since you agree that the references are themselves useful and consistent with WP:MEDRS, and since you were the person who removed them, I hope that you will restore them yourself, and make any changes to their summaries that you think are required in order to make them more succinct. Wikipedia articles cannot exist without positive content, and a purely subtractive editing process would remove most of the value of this site in short order, as I think has occurred for this article through your removal of about 70 percent of its content in a single editing session. I don't live on this site and can't get involved in an endless struggle to maintain my own contributions, so my best option is to appeal to you to take a more positive approach to editing that retains as much useful content as possible. Diversitti (talk) 22:52, 10 December 2013 (UTC)

It was my intention to go back to the removed excessive detail and preapre a series of short summaries which referred to the studies without becoming overly long and complex, but I haven't had a chance. As you will be aware, this article has been something of a battleground, with both proponents of pseudoscientific miracle cures based on LDN operating in mysterious ways, and a desire of those who wish to expand the range of pharmaceutical uses of LDN. In my view a responsible encyclopedic article on LDN would provide 1 a short well-founded description of its established use, 2 mention of ongoing research without hinting that preliminary findings are of clinical significance.Martinlc (talk) 22:44, 11 December 2013 (UTC)

Re: Removal of entire Mechanism of Action section

The removal of the single studies from the article on 12 October 2013 was accompanied by the removal of the Mechanism of Action section, which may have been inadvertent. The Mechanism of Action section does not pertain to clinical efficacy.

Diversitti (talk) 19:55, 12 October 2013 (UTC)

The emachanism of action section covered naltrexone in general and belongs better in the main Naltrexone article. Martinlc (talk) 08:46, 13 October 2013 (UTC)

Actually, the mechanisms of action for low-dose naltrexone are quite different from those of naltrexone in standard (high dose) uses. The descriptions that you removed pertain almost entirely to effects that are specific to low-dose uses of the drug.

For example: "Naltrexone, in low doses, increases opioid activity through a "rebound" effect in which the body responds to the temporary daily blocking of opioid receptors from a small daily dose of naltrexone by increasing the number and sensitivity of opioid receptor sites, while at the same time increasing the amount of available opioids that bind to those receptors. After several hours, when the drug wears off, removing the blockade of receptors, these rebound effects persist for between 24 and 72 hours, typically leading to an increase in opioid activity of between 100 and 300 percent."

Note that regular (high) dose naltrexone suppresses opioid / endorphin activity continuously, while low-dose use creates a pulsed effect that allows the body to rebound with greatly *increased* endorphin activity. This kind of effect is known as hormesis, and so it definitely belongs in the low-dose naltrexone article and not in the general article on naltrexone, since higher-dose naltrexone's effect upon endorphin activity is distinctly different from, and opposite to, that of low-dose naltrexone.

The next paragraph removed was:

"Endogenous opioid (endorphin) activity is known to mediate some forms of analgesia. An increase in endogenous opioid activity through LDN use could thus result in an improved ability to manage pain."

Clearly, as explained above, since naltrexone only increases endorphin activity at low doses, this section also belongs in the low-dose naltrexone article.

The next two removed paragraphs deal with microglial calming effects. These effects on microglial calming have only been studied for low-dose applications of the drug. It is possible that high doses of the drug would also have such effects, but this has not been specifically studied, so we can only report this effect for low-dose applications.

The "Other proposed Mechanisms of Action" section that you also removed pertains specifically to up-regulation of endorphins, which, again, only occurs at low doses of naltrexone, not for higher doses of the drug.

The very first sentence under mechanisms of action does pertain to the general mechanism of action of naltrexone, but it is important to understanding the remaining parts of the two removed sections, all of which pertain to the specific effect of low doses.

I would add that if you actually believed at the time you removed these mechanisms of action (10/12/2013) that they belonged in the general article on naltrexone, then it would have made sense to have moved them to that article instead of simply removing them from the present one. I'm sorry to appear critical, but as you removed 70 percent of the total text of this article in a single editing session without any attempt to preserve what now appears to be mostly relevant and allowable content, to me that indicates a lack of care that in this case was harmful to the article.

If you agree based on the above that the two sections you removed actually pertain specifically to low doses of the drug, then would you please restore the removed sections to the article? It would be counterproductive for me to restore these myself if you still felt that they did not belong there.Diversitti (talk) 23:32, 10 December 2013 (UTC)

Non WP:MEDRS sources

I have removed the placement of a large number of non-WP:MEDRS compliant sourcing in this article. We should not be giving undue WP:WEIGHT to insignificant primary studies, but summarizing what high quality secondary sources that meet WP:MEDRS say. Wikipedia is not a repository for all the primary sources on a topic. If there are high quality sources to bring to up, do so, but addition of low quality sources degrade the article substantially. Yobol (talk) 04:11, 22 January 2014 (UTC)

Who watches the watchmen?

It seems the writer may be (say unconsciously) trying to raise his professional profile by reflexively rejecting a therapy he considers to be "fringe." MD's face a great deal of pressure from the professional establishment to steer patients away from "fringe" therapies. This article needs revision because low-dose naltrexone is on the extreme inner fringe and rooted firmly in mainstream science. This is made peculiarly evident in the entry by the curious juxtaposition of LDN's use for Crohn's disease, pat dismissal of the therapy's possible value for autoimmune disorders generally, and lucid mechanism of action. It's incorrect to call LDN "pseudoscientific" merely because the writer dismisses the science without citing sources. A true pseudoscience like astrology or humorism has no rational basis and is incompatible with scientific knowledge or method. Likewise, the standard for calling something "bogus" should be verified falsity, not unverified truth. No sources are cited demonstrating that LDN is bogus. The true pseudoscience in this article is practiced by the author. Paraphrasing, "LDN supposedly treats many [seemingly] unrelated illnesses. As a noted skeptic, I often find quacks making similarly various claims which are certainly bogus. Therefore, we can assume that LDN is bogus too." The author is reasoning by analogy, classifying LDN according to a subjective pattern of superficial observations rather than evaluating empirical and theoretical evidence. Aspirin, for example, is not bogus simply because it can treat headache, backache, toothache, fever, the common cold, heart attack, angina, stroke, hangover, arthritis, etc. Interferon treats multiple sclerosis, HIV/AIDS, a long list of cancers, hepatitis B & C, and warts. However, the author presumably does not contend that interferon is pseudoscientific or bogus. Very many widely accepted drugs have multiple indications that seem unrelated if one fails to consider etiology and mechanism of action, but the author likely makes no effort to debunk mainstream medicine exactly because it's mainstream. This isn't quackbusting but question-begging. — Preceding unsigned comment added by 69.209.34.24 (talk) 21:46, 25 March 2014 (UTC)

Caduceus ouroboros reductio

This article seems to implicitly assume that mainstream medicine is "science-based medicine" and alternative medicine is pseudoscience, two manifestly false equivalencies. The most indoctrinated practitioner needn't think mainstream medicine precisely coextensive with its putative scientific basis. Astonishingly, the writer of this entry must do. He derogates LDN therapy for no coherent reason except that it lies slightly outside the perimeter.

I previously debunked the canard that LDN must be bogus because it's claimed to treat many illnesses. Many mainstream drugs like aspirin have multiple diverse indications; many bogus treatments like Arnica Montana 30X HPUS have few specific indications.

How else do we know LDN therapy is bogus? Mainstream treatments undergo pre-marketing clinical trials costing tens of millions of dollars whereas alternative treatments have less systematic clinical data to support them. So LDN therapy is an alternative treatment because the studies are small. What else besides LDN lacks FDA approval due to insufficiently substantiated claims of efficacy? Homeopathy. Crystal healing. Quackery. So logically, if LDN has the same weight of evidence as quackery, it's pseudoscientific and therefore bogus.

By similar logic, if a woman "weighs the same as a duck, she's made of wood and therefore a witch" (Monty Python and the Holy Grail, 1975). It is a disservice to readers that this entry continues to be maintained in such self-referential, unencyclopedic form, even by courtesy of a "noted (by whom?) skeptic"[citation needed]. — Preceding unsigned comment added by 68.255.45.213 (talk) 04:07, 24 April 2014 (UTC)

Revision of article explanation

What an article! It goes back and forth between preliminary or pseudoscientific claims and Novella's dispute in nearly every paragraph. We really need a source to supplement Novella ASAP.

Some changes I have made:

• Revised opening to clean-up language and better match sources.
• Changed some section titles to better describe their contents
• Adding Nation MS Society as source, which reviews pilot studies of LDN in human and animal models of MS
• Removed phrse "based on anecdotal evidence" from MS discussion; it does not appear in the source, which describes research which does not certainly fit the definition of anecdotal evidence.
• Revised the following passage, which stuck me as quite snarky:
  • "Claims made by some personal testimonials suggesting LDN to be a "cure" or a "wonder drug" are not borne out by research, and as such, LDN should be considered an "unproven treatment" not to be used in place of more proven therapies, despite what some advocacy websites claim."
• Revised MS section to better match sources and reduce POV
• Corrected three instances of link rot using archive.org; really, we need to keep these in check -- at least half of the sources were either deadlinks or paywalled.
  • The UK MS study only shows the summary, the document was not archived. I cannot find it.
• I have added a link to http://lowdosenaltrexone.org/. This will probably be a contentious decision, but the site appears to be the primary source for misinformation and unsupported claims. The article repeatedly mentions websites that promote dubscious claims, and at least once should be specified. Both Novella and Bourdette mention it, and I have put it in the context of supporting pseudoscientific claims to be in (perhaps zealous) compliance with WP:ELPOV.
• The article cites an article in favor of LDN by Gluck, the editor of lowdosenaltrexone.org, as an example of making pseudoscientific claims. Gluck obviously does not claim his assertions are pseudoscience. Novell calls out his website as dubious, but does not mention Gluck personally. In any case, Gluck's article is either being reinterpreted or synthesized, and this is against policy. If the point is to dismiss the sort of claims Gluck makes, Novell has that territory well-covered. I have removed the Gluck citation because I don't know what else to do with it, except promote LDN as a clinically valid treatment for cancer, which would be contentious and inappropriate to say the least.
• Removed "Steven Novella also writes that claims of treating a wide range of diseases with different etiologies should be a red flag to be skeptical about these claims, which are likely to be 'bogus treatment with claims that are literally too good to be true.'"
  • While Novella's statement may be accurate, the word "bogus" and phrase "literally too good to be true" express a definitely opinionated point of view. Although he is a highly-regarded expert on the subject, his source is still self-published and does not provide formal citations nor is peer-reviewed; his website is not a medical journal. Thus, we should be careful as to what parts of his post we choose to include, regardless of his credentials. Novella's more neutral discussion on the topic is already included in the article, and conveys a similar message.
• Removed "scare quotes" in several places, as I don't see their purpose.
• Replaced instances of "LDN" with "low-dose naltrexone," I'm not sure what the official style policy of this is.
• Added dosing information for naltrexone, and LDN. Can't find dosing information for ultra LDN, I presume it's in the article "Antagonist treatment of opioid withdrawal translational low dose approach" but I can't get through the paywall.
• General clean-up, added wls, etc.

Looking forward to help and comments from you all!

Memtgs (talk | contribs) @ 20:09, 12-05-2014 UTC 20:09, 12 May 2014 (UTC)

I have restored the "bogus" phrase as relevant and on-point to his discussion of LDN. There is no prohibition on including an "opinionated point of view" in Wikipedia, especially when it is properly attributed. As I have noted elsewhere, Novella is a widely respected source on fringe medicine and is therefore a reliable source for this quotation. Yobol (talk) 15:30, 15 May 2014 (UTC)

Debunktion junction, donate button

The “contradictory” nature of claims mentioned in the controversial section rests upon a simplistic idea of immunity as a kind of light bulb in a circuit with one dimmer control, intensity hi-lo being the only parameter which can be exogenously modulated. Perhaps acknowledging the oversimplification, the author proceeds to offer a subtle retraction by saying that LDN could worsen autoimmune disorders instead of stating that it actually does. The could-be possibility of the promised contradiction is trivial and irrelevant speculation. In fact, there is no contradiction unless one accepts the above, erroneous model.

Stimulating the immune system will generally exacerbate autoimmunity: that much is well understood and widely accepted. However, endorphins are considered to play a modulatory and not a strictly stimulatory role in the immune response. http://www.ncbi.nlm.nih.gov/pubmed/11727759 The biological complexity inherent to this system results in many apparent but resolvable paradoxes like the one discovered by the author. For example,

Interferon “boosts” the immune system; interferon treats autoimmune and inflammatory diseases. http://www.webmd.com/multiple-sclerosis/interferon-beta-for-multiple-sclerosis HIV/AIDS weakens the immune system; HIV/AIDS associated with autoimmune disorders. http://www.ncbi.nlm.nih.gov/pubmed/12848988 "Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo)." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118208/ "There is increasing evidence that immune stimulation prevents autoimmune diseases." http://www.ncbi.nlm.nih.gov/pubmed/10648113

The author cites no independent sources in this connection. He merely links to his own website, where donations are prominently solicited. This should be a huge red flag to the greenest of skeptics. — Preceding unsigned comment added by 68.255.46.113 (talk) 02:42, 15 May 2014 (UTC)

While Novella's explanation might be "simplistic", he is also correct. Autoimmune diseases are generally treated with medications that disable part of the immune system (corticosteroids, biologics, etc.) While there are bound to be exceptions to any rule, that doesn't make the rule dubious, if those exceptions are rare, which they are in this case. If you have specific information about LDN being able to treat both immunosuppressive and autoimmune disorders, be my guest and present them. If you are basing your "dubious" tag only on what you as an editor feel, unfortunately, we don't place much weight on that. Yobol (talk) 15:26, 15 May 2014 (UTC)

Further revisions re. attribution and specificity

I have made the following changes:

• Restored [lowdosenaltrexone.org] external link to be in the article text. I understand that external links typically get their own section, but this website is specifically mentioned Bourdett and criticised by Novella. Ambiguously referring to "advocate websites" is unnecessary when an example can be specified.
• Restored the "dubious" tag to Novella's autoimmune comment. As 68.255.46.113 mentions above, Novella does not cite any source for his comment and is indeed self-publishing. Although he is a highly regarded neurologist, I do not feel this particular publication format necessarily constitutes a reliable medical source. I will leave the passage in the article, however, as it is useful commentary and if we can find another source for it, certainly belongs here. Novella's full comment on contradictory autoimmunity claims, which is not fully explained nor a pivotal passage in his article, is as follows:

"Further, there is an inherent contradiction in simultaneously treating diseases that are auto-immune (the immune system attacking the host), and immunodeficiency diseases (like AIDS) and claiming to treat cancer by “boosting” immune activity. Increasing immune activity actually worsens auto-immune diseases, and suppressing the immune system would worsen AIDS. This is a difficult contradiction to resolve."

• Restored "can reduce pain and benefit mental health in multiple sclerosis patients" specification in UK MS study discussion. These are the effects of the treatment as specified in the source, why should they be reduced to the less-informative "improve symptoms"?
• Comments such as "There is not enough evidence to prove [LDN] is effective in treating [disease]" are voiced in the passive tense and severely lack specificity in attribution to their sources, giving the article a biased slant. I have begun to add attribution tags where relevant.

We're making lots of progress cleaning the article up, good work :D

Memtgs (talk | contribs) @ 04:57, 15-05-2014 UTC 04:57, 15 May 2014 (UTC)

• Per WP:ELPOINTS, "External links should not normally be used in the body of an article.[1] Instead, include appropriate external links in an "External links" section at the end of the article, and in the appropriate location within an infobox, if applicable."
• I will address this above. Whether or I or an IP finds it convincing is immaterial. We give it weight because he is a reliable source of matters of pseudoscience/fringe medicine.
• Discussion of specific symptoms is premature when we don't even know whether or not it works
• No in-text attribution is necessary when there is no disagreement among reliable sources about a statement (see WP:ASSERT). In this case, Bourdette, the UK NHS and the MS Society sources all agree that there is not enough evidence to say LDN works for MS. Yobol (talk) 15:17, 15 May 2014 (UTC)

“[C]laims… unsupported by clinical research”

Strictly speaking, this phrase means that no clinical research exists to support the claims. Less strictly but still reasonably, it could mean that conflicting research on balance doesn’t support the claims. Each of these two possible interpretations is objectively false: some clinical research exists with mostly positive results. The strength and validity of the research is open to question, but its existence is not.

Contriving ways to disregard unwanted data is a characteristically unscientific mode. It’s explained how some clinical studies fall below Wikipedia standards and therefore don’t bear mentioning. Criteria can justify non-inclusion. They cannot justify positive denial of existence. If two studies are required, for example, then the first one separately cannot have zero evidentiary value, let alone no independent existence. Put another way, the writer cannot affirmatively deny the existence of something while the editor affirmatively bans the very, supposedly nonexistent thing belying the denial. Moreover, it’s unseemly to disallow published research on technical grounds while citing a blog entry apparently written by oneself.

The ironically-entitled “Pseudoscientific claims” section never specifies its referent “claims.” Must these claims not be repeated lest they gain credibility? Is it hoped the uncritical reader will accept nonliteral claims as “literally too good to be true”? The critical reader will instead find this too clichéd to be true. It evokes clueless cranks touting a panacea. In fact, reputable professionals consider LDN a legitimate therapy but never claim it to be curative of anything. True literalness—concrete specificity—would serve to disabuse the reader of the section’s imputations.

Nietzschean fighters of quacks might take care lest they become quacks themselves. Examples of this include climate change deniers and debunkers of Darwinian evolution. Using fallacious logic and faulty semantics, these anti-quack quacks practice a type of “skepticism” that seeks merely to justify predetermined conclusions. Obscurantism cannot defeat pseudoscience. Obscurantism is pseudoscience. Sunlight is literally the best disinfectant, clinically proven to kill 99.97% of bogus claims.

The "pseudoscientific claims" listed are ostensibly scientific. Those regarding HIV/AIDS in particular have numerous reputable primary sources. Even claims based entirely upon speculations, anecdotes, and case reports are not inherently pseudoscientific. The term "pseudoscience" applies only when the claimants themselves intentionally or unintentionally manipulate, exagerrate, misinterpret, misrepresent, or imagine science. "Pseudo-" means false, not unproven or unconvincing. Derogating apparent science as "pseudoscientific" requires evidence, but the entry supplies only vague hand-waving.

"Too good to be true" is just an expression. It is a figure of speech, not a logical argument. It could describe penicillin, MRI scans, Apollo moonshots, smartphones, Boston creme pie, teenage crushes, etc. Things which are idiomatically "too good to be true" may still be true--even if the word "literally" has been prepended to the expression. The "literally" adds no probative value. How, why, and on what evidence does LDN treat each condition for which its claimed use is pseudoscientific? This is what would need to be debunked.

Multiplicity and differing etiologies are termed a "red flag." This would be very reasonable--except that "red flag" is mistaken to have almost the exact opposite of its usual sense. A red flag is a warning used to call further attention to something, not to obviate that which is already resolved or accomplished. Cornwallis did not use a red flag of surrender; Marines did not raise a red flag atop Mt. Suribachi. Flagging should elicit closer scrutiny, not dismissal out of hand. The sense of "red flag" in the entry seems conflated with "red light," "red herring," and "red-handed," the intention being to make a simple observation sound momentous, definitive, even culpatory. That is, "red flag" is misused as a buzzword.

"Pseudoscientific" is a similar usage. Weak evidence and/or weak efficacy are not inherently pseudoscientific, nor is inferiority to approved standards of care. Obsolete SOCs aren't considered pseudoscientific. In the case of HIV/AIDS, for example, LDN is not claimed by reputable proponents to be a very good treatment by modern standards. It is clearly inferior to current antiretroviral therapies. Nevertheless, available evidence on balance shows that LDN most likely does slow CD4+ cell count decline in HIV infection, as claimed. Although this effect may have limited value today for most patients who can access ARVs, there is no apparent reason to label this specific CD4+ claim "pseudoscientific." The same can be said about the other claims: if LDN is a jack of many trades, it is master of none (and therefore not too good to be true). There are 3 possibilities: 1) the list maker knows something we don't know about the claims which he should share, 2) the very unspecific list refers to entirely different and spurious strawman claims which he should specify, and/or 3) "pseudoscientific" is just a polysyllabic buzzword meaning "subjectively fishy-sounding."

Having a clinical neurologist edit an off-label immunomodulatory drug he has never prescribed is a bit like having a master plumber edit "Coriolis effect." Kooks claim the Sun's movement across the sky from east to west causes eddies, vortices, whirlpools, hurricanes, cyclones, Jupiter's Great Red Spot, a long list of disparate and grandiose phenomena. According to noted skeptic Mario the plumber, these claims are not just unsupported by drainpipe-based evidence but actually contradictory. If the Coriolis effect spins hurricanes counter-clockwise, it ought to stop cyclones rotating clockwise. This logic doesn't stop quacks like Frank the physicist from trying to butt in and peddle their unsafe pseudoplumbing. (Frank, of course, says Mario peddles pseudophysics.) Luckily, "for any entry concerning water in relation to pipes, a licensed member of the plumbing profession shall approve all revisions." Plumbers' real-world, hands-on experience makes them pre-eminent authorities on Newtonian fluid mechanics. Plumbers and not physicists are the ones who have to deal with the flooded bathrooms of impressionable laymen convinced they can flush Kleenex down their toilets. — Preceding unsigned comment added by 98.226.64.65 (talk) 00:12, 15 July 2014 (UTC)

Per this consideration, I have replaced the header "Pseudoscientific Claims" with "Off-label use". I moved the "psuedoscientific" labeling to make it more obviously associated with Novella's statements. Memtgs (talk | contribs) @ 20:58, 1-08-2014 UTC 20:58, 1 August 2014 (UTC)

That particular section is not a discussion of off-label use, but of pseudoscientific claims about its use (which are not justified by any scientific evidence). The previous title is clearer and more informative of the section content. Yobol (talk) 21:33, 1 August 2014 (UTC)

It's something of a red flag that both links that seem intended to show opposing mechanisms currently point to the same page (Autoimmune disease): "He further argues that the claim that low-dose naltrexone as an effective treatment for both immune dysfunction and autoimmune diseases is contradictory". It's understandable though, since boosting some parts of immune system might increase the autoimmune symptoms. Both of those topics could be covered in one article about a complex system that has opposing actions like inflammation and anti-inflammatory functions that are triggered by countless sources. But that's also why it could be possible that those seemingly contradictory claims have some chance of being reasonable. The immune system is too complex to accurately describe with a simple evaluation of two generalizations. Throw in concepts like cell differentiation, expression regulation, and allosteric modulation and it becomes feasible that seemingly opposing outcomes can occur, especially in different areas of the immune system.

I wouldn't put much stock in LDN proponents' unverified claims, nor would I put much stock in over-simplified rationales based on those claims. There's not enough data in this section to generate something of value from it. It would be more appropriate to list the specific claims and ask the reasonable questions about contradictions (and let the reader draw conclusions) rather than blandly characterize the claims and then produce conclusions based on those characterizations. Sc0llier (talk) 19:54, 1 October 2015 (UTC)

Article in journal Clinical Rheumatology

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

Clin Rheumatol. 2014; 33(4): 451–459. Published online Feb 15, 2014. doi: 10.1007/s10067-014-2517-2 PMC 3962576

This 2014 review acknowledges "opioid rebound" as a possible mechanism but posits that LDN's "clinically beneficial effects" arise from some undetermined anti-inflammatory activity or activities at any of "multiple and varied sites." The authors state that "there is a consistent theme of LDN efficacy in controlling diseases with inflammatory components" and that "[t]his area of research is being vigorously pursued by multiple laboratories."

Ongoing scientific research of a drug with multifarious pharmacological activities in multifarious inflammatory pathways belies the relevance of Dr. Steven Novella's opinion that unspecified uses of LDN are "pseudoscientific." Therefore, this opinion should be deleted.

Novella is speaking specifically about the claims it can treat both an immunodeficiency and an autoimmune process at the same time, not whether it has any immunological effect. I should note that the source cited says all work on LDN is preliminary and no conclusion can be made about any clinical effect, but it should probably be incorporated into the possible mechanism of action section. Yobol (talk) 17:56, 18 November 2014 (UTC)

Lack of clinical studies & claims of pseudoscience for HIV/AIDS application

There are in fact several clinical studies on this topic

Low Dose Naltrexone in the Treatment of Acquired Immune Deficiency Syndrome (1988)

Single cohort study of the effect of low dose naltrexone on the evolution of immunological, virological and clinical state of HIV+ adults in Mali (2011)

Impact of low dose naltrexone (LDN) on antiretroviral therapy (ART) treated HIV+ adults in Mali: A single blind randomized clinical trial (2011)

Skeptical neurologists may deem these unconvincing, but the terms "lack" and "pseudoscientific" are objectively unwarranted. — Preceding unsigned comment added by Senn590 (talk • contribs) 10:15, 7 July 2015 (UTC)

Lack of clinical studies for HIV/AIDS application; warning about misinformation on the web

There are several clinical studies on HIV/AIDS:

Low Dose Naltrexone in the Treatment of Acquired Immune Deficiency Syndrome (1988)

Single cohort study of the effect of low dose naltrexone on the evolution of immunological, virological and clinical state of HIV+ adults in Mali (2011)

Impact of low dose naltrexone (LDN) on antiretroviral therapy (ART) treated HIV+ adults in Mali: A single blind randomized clinical trial (2011)

www.academicjournals.org/journal/JAHR/edition/October,_2011

Skeptics may deem these studies unconvincing, but "lack" is inaccurate as it implies total nonexistence.

An encyclopedia entry should not be used to complain about false information on the subject which the writer has noticed on uncited external websites. Misinformation exists on the Internet about virtually all drugs; therefore, the fact of its existence does not need to be recapitulated for any particular one. The way to countervail false information elsewhere is simply to provide correct information in the entry. Senn590 (talk) 11:16, 7 July 2015 (UTC)

LDN gene expression and dose intermittency (June 2016)

International Journal of Oncology: 'Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy'; Authors - Wai M. Liu Katherine A. Scott Jayne L. Dennis Elwira Kaminska Alan J. Levett Angus G. Dalgleish - Published online Tuesday, June 7, 2016: https://www.spandidos-publications.com/10.3892/ijo.2016.3567 — Preceding unsigned comment added by 110.23.167.134 (talk) 00:37, 11 June 2016 (UTC)

This is a WP:PRIMARY source reporting in vitro results. Per WP:MEDRS we don't use these kinds of sources for content about health. Jytdog (talk) 04:33, 11 June 2016 (UTC)

At least the following statements from the above <link redacted> journal article are review statements and strongly deserve appropriate inclusion in this Wikipedia article.

• Subsequent studies have also hinted at the importance of treatment schedule in determining efficacy, with intermittent administration of lower concentrations of naltrexone achieving the greatest antitumour response (28).
• we have recently shown with other drugs that exhibit this protracted cell cycle blockade character that cell death can be enhanced by introducing a drug-free phase in the treatment schedule (16,19).

--Hyperforin (talk) 05:08, 16 June 2016 (UTC)

I removed that link as it violates WP:ELNEVER. Never do that again. If you are talking about PMID 27279602 that is a primary source. There is a world of garbage out there about LDN and there is no way content about health is coming into this article other than based on a high quality review article. Jytdog (talk) 08:39, 16 June 2016 (UTC)

Missing the point: endorphines and the immune system

It is important to distinguish the cause and the effect. Some researchers have extremely low opinion on using low dose naltrexone and some users have extremely high opinion, why the discrepancy? It seems that recent research (see pubmed central) uncovers a connection between endorphines and the immune system, that some very low levels of endorphines is necessary for the immune cells to act properly, thus in persons with unusually low availability of endorphines, the immune system may act incorrectly. It seems that a portion of moderate cases of autoimmune problems could be improved with LDN (such as irritable bowel syndrome), but severe cases (Crohn's mentioned in the main aricle) would not be the case.

While naltrexone molecule alone can have some effect, the main effect is supposed to be secondary and tertiary (via rising enkephalin levels, improving mood and mental functions, tertiary via corrected immune functions with interaction of endorphins). So, unless the primary->secondary->tertiary pathway has a reason to work, we can't expect any reasonable effects of naltrexone taking place. If the problem isn't caused by chronically low endorphin levels, how is naltrexone supposed to help it? But if it is, of course you would see "inexplicable" improvements.

So, the whole article could be concentrated more into how endorphines and immune system interact. Autoimmune conditions are rarely caused by a single factor, but if a single factor is prevalent, and you change it, patient outcomes are going to be evident, but if the contributing factor you are changing has been a minor part of the condition, the improvement may not be observable or relevant.

Many apologies for not posting references, I read those articles last week, not going to fish out from the history. Hope this helps. — Preceding unsigned comment added by 90.64.8.255 (talk) 08:42, 25 October 2016 (UTC)

References

I'd also like to suggest the following change to the reference list - different order, plus 4 new references.

1. Younger, J; Parkitny, L; McLain, D (April 2014). "The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.".

2. Segal, D; Macdonald, JK; Chande, N (Feb 21, 2014). "Low dose naltrexone for induction of remission in Crohn's disease.".

3. Ngian GS, Guymer EK, Littlejohn GO (February 2011). "The use of opioids in fibromyalgia.". (PDF).

NEW --- 4. Frech T., Novak K., Revelo M. P., Murtaugh M., Markewitz B., Hatton N., Scholand M.B., Frech E., Markewitz D., Sawitzke A.D., (2011). “Low-Dose Naltrexone for Pruritus in Systemic Sclerosis”. International Journal of Rheumatology Volume 2011, Article ID 804296, 5 pages, 14 July 2011 [9] [10]

NEW --- 5. Cree, Bruce. A. C. MD PhD MCR, Kornyeyeva E. MD, Goodin, D.S. MD (19 February 2010). “Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis.”. Ann Neurol. 2010 Aug;68(2):145-50. doi: 10.1002/ana.22006. http://onlinelibrary.wiley.com/doi/10.1002/ana.22006/abstract https://www.ncbi.nlm.nih.gov/pubmed/20695007

6. Bowling, Allen C. (2009). "Low-dose naltrexone (LDN) The "411" on LDN". National Multiple Sclerosis Society.

NEW --- 7. Younger, Jarred, PhD, Mackey, Sean, MD, PhD. (2009). “Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.”. Pain Medicine (May 2009). DOI: http://dx.doi.org/10.1111/j.1526-4637.2009.00613.x 663-672 First published online: 1 May 2009 http://painmedicine.oxfordjournals.org/content/10/4/663

8. Webster LR (August 2007). "Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation".

9. Mannelli P, Gottheil E, Van Bockstaele EJ (2006). "Antagonist treatment of opioid withdrawal translational low dose approach".

10. Shader RI (August 2003). "Antagonists, Inverse Agonists, and Protagonists."Journal of Clinical Psychopharmacology".

11. Smith, Katie (6 November 2015). "What is the evidence for low dose naltrexone for treatment of multiple sclerosis?".

12. "Low-Dose Naltrexone". National MS Society. Retrieved 12 May 2014.

13. Bourdette, Dennis (December 2009). "Spotlight on low dose naltrexone (LDN)". US Department of Veteran Affairs.

14. Novella, Steven (5 May 2010). "Low Dose Naltrexone – Bogus or Cutting Edge Science?".

15. "Ultra-low-dose opioid antagonists enhance opioid analgesia while reducing tolerance, dependence and addictive properties.".

NEW --- 16. FURTHER RESEARCH: https://www.ncbi.nlm.nih.gov/pubmed/?term=%22low-dose+naltrexone%22%5BALL+FIELDS%5D+NOT+(dependence%5BTitle%5D)+NOT+(dependent%5BTitle%5D)+NOT+(oxycodone%5BTitle%5D)+NOT+(withdrawal%5BTitle%5D)+NOT+(cocaine%5BTitle%5D)+NOT+(morphine%5BTitle%5D)+NOT+(itch-related%5BTitle%5D)+NOT+(drinking%5BTitle%5D)+NOT+(alcohol%5BTitle%5D)+NOT+(cigarette%5BTitle%5D)+NOT+(smoker%5BTitle%5D)+NOT+(smoking%5BTitle%5D)+NOT+(smokers%5BTitle%5D)+NOT+(nicotine%5BTitle%5D)+NOT+(detoxification%5BTitle%5D)+NOT+(gambling%5BTitle%5D)+NOT+(self-biting%5BTitle%5D)

110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 03:54, 14 November 2016 (UTC)

the references are numbered by Wikipedia's software in the order they are used. Jytdog (talk) 06:28, 14 November 2016 (UTC)

Okay, I understand. Can references be included in the list if they haven't been referenced within the body of the entry? And if so, can the new references I listed above be included please? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 23:21, 14 November 2016 (UTC)

No. if they are useful they can be listed as further reading. what entries above are new? Jytdog (talk) 00:13, 15 November 2016 (UTC)

These are new:

Frech T., Novak K., Revelo M. P., Murtaugh M., Markewitz B., Hatton N., Scholand M.B., Frech E., Markewitz D., Sawitzke A.D., (2011). “Low-Dose Naltrexone for Pruritus in Systemic Sclerosis”. International Journal of Rheumatology Volume 2011, Article ID 804296, 5 pages, 14 July 2011 [11] [12]

Cree, Bruce. A. C. MD PhD MCR, Kornyeyeva E. MD, Goodin, D.S. MD (19 February 2010). “Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis.”. Ann Neurol. 2010 Aug;68(2):145-50. doi: 10.1002/ana.22006. http://onlinelibrary.wiley.com/doi/10.1002/ana.22006/abstract https://www.ncbi.nlm.nih.gov/pubmed/20695007

Younger, Jarred, PhD, Mackey, Sean, MD, PhD. (2009). “Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.”. Pain Medicine (May 2009). DOI: http://dx.doi.org/10.1111/j.1526-4637.2009.00613.x 663-672 First published online: 1 May 2009 http://painmedicine.oxfordjournals.org/content/10/4/663

FURTHER RESEARCH: https://www.ncbi.nlm.nih.gov/pubmed/?term=%22low-dose+naltrexone%22%5BALL+FIELDS%5D+NOT+(dependence%5BTitle%5D)+NOT+(dependent%5BTitle%5D)+NOT+(oxycodone%5BTitle%5D)+NOT+(withdrawal%5BTitle%5D)+NOT+(cocaine%5BTitle%5D)+NOT+(morphine%5BTitle%5D)+NOT+(itch-related%5BTitle%5D)+NOT+(drinking%5BTitle%5D)+NOT+(alcohol%5BTitle%5D)+NOT+(cigarette%5BTitle%5D)+NOT+(smoker%5BTitle%5D)+NOT+(smoking%5BTitle%5D)+NOT+(smokers%5BTitle%5D)+NOT+(nicotine%5BTitle%5D)+NOT+(detoxification%5BTitle%5D)+NOT+(gambling%5BTitle%5D)+NOT+(self-biting%5BTitle%5D)

110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 05:40, 15 November 2016 (UTC)

unreadable mess. ignoring this. search results have no value. Jytdog (talk) 06:19, 15 November 2016 (UTC)

I don't understand your response: Within the full list I first posted above - numbers 4, 5 and 7 were clearly noted as being 'NEW'. Yet, you still asked me to post them all again, although they were clearly noted and legible, not a 'mess'. I complied with your request. Are you saying none out of the 3 new references I listed meet the criteria for inclusion? Are you saying you're not willing to list any of the new references within the reference list? Are you also saying you won't include the search string listed at No. 16? If any of the 4 are not eligible for inclusion in the reference list, why can't they be placed under 'Further Reading'? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 18:47, 16 November 2016 (UTC)

So it is three articles - Frech, and Cree, and Younger, is that correct? Jytdog (talk) 21:18, 16 November 2016 (UTC)

*Frech, T; et al. (2011). "Low-dose naltrexone for pruritus in systemic sclerosis". International journal of rheumatology. 2011: 804296. PMC 3171757. PMID 21918649. {{cite journal}}: Explicit use of et al. in: |last2= (help)

*Cree, BA; Kornyeyeva, E; Goodin, DS (August 2010). "Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis". Annals of neurology. 68 (2): 145–50. PMID 20695007.

*Younger, J; Mackey, S (2009). "Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study". Pain medicine (Malden, Mass.). 10 (4): 663–72. PMC 2891387. PMID 19453963.

if so these are all primary sources and we generally don't list a bunch of primary sources under Further Reading. Jytdog (talk) 21:23, 16 November 2016 (UTC)

Though this is a primary source, it is included at reference (8) in secondary source (1), that is already listed: Cree BA, Kornyeyeva E, Goodin DS (2010). "Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis.". Ann Neurol 68(2):145–150 doi: 10.1002/ana.22006. https://www.ncbi.nlm.nih.gov/pubmed/20695007 http://onlinelibrary.wiley.com/doi/10.1002/ana.22006/abstract 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 08:06, 17 November 2016 (UTC)

And this is included at reference (15) in secondary source (1) already listed: Younger, Jarred, PhD, Mackey, Sean, MD, PhD. (2009). “Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.”. Pain Medicine (May 2009). DOI: http://dx.doi.org/10.1111/j.1526-4637.2009.00613.x 663-672 First published online: 1 May 2009 http://painmedicine.oxfordjournals.org/content/10/4/663

110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 08:06, 17 November 2016 (UTC)

there is no end to the primary sources that could be listed. WP is not a bibliography. Jytdog (talk) 10:55, 17 November 2016 (UTC)

Why can't this entry have a 'Further Reading' section? Why can't they be listed there? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 22:06, 17 November 2016 (UTC)

because there is no end to primary sources. There are 102 references in Pubmed to "low dose naltrexone". The question to you is "why these three?" and the only you will be able to provide will be some kind of WP:OR. Jytdog (talk) 23:12, 17 November 2016 (UTC)

Earlier, you wrote; 'if they are useful they can be listed as further reading'. These are on topic, relevant, and useful primary sources, and two of them are listed within the reference list of the secondary source at (1). Yet now you say they can't be listed as further reading? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 06:16, 18 November 2016 (UTC)

You ignored what i wrote. Jytdog (talk) 06:58, 18 November 2016 (UTC)

I didn't ignore your last comment, Jytdog. Your comment referred to the large number of (potentially no end to) primary sources - and that had no relevance to my suggestion of 3 sources that were on topic, relevant, and useful - to be added to a 'Further Reading' section - and where two of those sources are listed within the reference list of the secondary source at (1). Why won't you allow this topic to have a 'Further Reading' section containing primary sources, 2 of which are listed in the secondary source? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 07:33, 18 November 2016 (UTC)

You have provided no rationale as to why those three and not three of the other ~100 primary sources we could list. All 100 are relevant as they are about LDN; many of them are also cited in articles that we already cite. Jytdog (talk) 08:46, 18 November 2016 (UTC)

The search string I provided brings up a refined list of around 60 (58 of which are highly relevant to this article). It's not feasible to include 58 individually, which is why I included the refined search string as a single item. If you create a 'Further Reading' section and include the refined search string, that would be all that is needed under 'Further Reading'. Following repeated rejection, I focussed on these 3 for Further Reading, but the refined search string would suffice. My question remains unanswered. Why won't you allow this topic to have a 'Further Reading' section containing primary sources that includes either the refined search string, or a small list of individual primary sources as previously proposed? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 19:09, 18 November 2016 (UTC)

(Arbitrary outdent)

There is no advantage to the reader to have an extensive uncurated list of Further Reading they could compile themselves through searching. Further reading should be a list of material providing additional information about topics covered in briefer form in the article text. Content which is too weakly sourced under MED:RS to be included in the article doesn't belong in Further Reading either.Martinlc (talk) 19:28, 18 November 2016 (UTC)

Primary source

User:110.23.167.134 about this diff and this diff, the ref you are adding, (ref - not in pubmed) is a "primary" source, as defined in WP:MEDRS. We use secondary sources - literature reviews or statements by major medical/scientific bodies. Also I am not sure about the quality of this journal - they don't say on their About site where they are indexed but this article is not in pubmed. Jytdog (talk) 00:18, 26 October 2016 (UTC) (add missing words via redaction Jytdog (talk) 14:56, 27 October 2016 (UTC))

Sorry, I couldn't find anything in the 'talk' area earlier regarding any discussion, and I apologise if my addition was clumsy. However; I have now found my way to this page, and I urge you to reconsider the removal and reinstate. The source; Sage Publishing; is well-known and trusted, being founded in 1965. The article is backed by researchers at Pennsylvania State University, one of whom has been publishing his research on low dose of naltrexone (Dr Ian Zagon) since the 1980s. Not it's not in Pub Med (yet), but all sources are verifiably solid sources. Please read, then reinstate (wherever within the article you believe is appropriate): 'Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis' 29 Sept 2016: Michael D Ludwig, Anthony P Turel*, Ian S Zagon, Patricia J McLaughlin [13] — Preceding unsigned comment added by 110.23.167.134 (talk) 07:29, 27 October 2016 (UTC)

Congratulations on finding the Talk page! (I mean that). Talking is crucial. So too is following Wikipedia's policies and guidelines. This place is not a wild west - there is a kind of "rule of law" here. So - within that foundation, the things you are saying about the source are irrelevant. Please read my note above and the link there to the definitions section of MEDRS. The key issue is that this is what we call a "primary source". Once you have, if you have any questions please write back. Thanks. Jytdog (talk) 07:33, 27 October 2016 (UTC)

Okay, thank you. I have now perused the pages you referred me to. As a result, I now request a response to the following 2 questions:

(1) I understand all citations must be primary sources listed in Pub Med, or secondary or tertiary to be included here, yet 'Low Dose Naltrexone – Bogus or Cutting Edge Science?', a May 2010 article (6 years old) written by Steven Novella is listed. The Science Based Medicine website is an independent site which is supported by corporate and other donations (potential for conflicts of interest). Articles are not peer-reviewed, and Steven Novella's article does not include supporting citations (primary, secondary, or tertiary).

QUESTION 1: As Steven Novella's article doesn't appear to qualify as a primary, secondary, or tertiary source, can you please advise on what basis this article remains worthy of citation?

(2) I understand all citations are supposed to be kept up-to-date with the most recent research. This article from The National MS Society magazine 'Momentum' of 2009 (7 years old) is still listed, when a PubMed (primary source) search for 'naltrexone AND low dose' reveals recent research listed in this primary source (examples a, b, c, and d are included below) aren't included in the LDN entry?

QUESTION 2: Why does an old tertiary citation remain listed while these recent primary citations are excluded?

(a) A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway. Patient and prescriber characteristics, and dispense patterns. A drug utilization cohort study. (https://www.ncbi.nlm.nih.gov/pubmed/27670755). THIS CONTAINS STATISTICAL EVIDENCE OF CONTINUED USE OF LDN (continued efficacy).

(b) Functional modulation on macrophage by low dose naltrexone (LDN). (https://www.ncbi.nlm.nih.gov/pubmed/27561742) THIS CONCLUDES: Therefore it is concluded that LDN could promote function of macrophage and this work has provided concrete data of impact on immune system by LDN.

(c) Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. (https://www.ncbi.nlm.nih.gov/pubmed/27736689) THIS CONCLUDES: LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.

(d) Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. (https://www.ncbi.nlm.nih.gov/pubmed/27279602) THIS CONCLUDES: Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule.

(e) Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats. (https://www.ncbi.nlm.nih.gov/pubmed/27392602) THIS CONCLUDES: Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. — Preceding unsigned comment added by 110.23.167.134 (talk) 21:44, 27 October 2016 (UTC)

110.23.167.134, it is within your privilege to remove health promoting or demoting claims that are not supported by a secondary source, i.e. a review or meta-analysis article in a peer-reviewed journal. Feel free to go ahead and carefully remove the relevant statements that are not adequately sourced, but with an explanatory edit summary. The only time when I use a primary source is to report critical safety data for which no secondary source is available, although this can be subject to deletion especially if it's controversial. --Hyperforin (talk) 23:30, 27 October 2016 (UTC)

With respect to the Novella article, please see WP:PARITY. Jytdog (talk) 00:33, 28 October 2016 (UTC)

Thank you both for your responses, however; I'm reluctant to just proceed with editing now as someone may ascribe it as an 'edit war'.

If possible, I'd prefer to know what I have approval to do in advance.

(1) Can I remove the Novella article, and if so, what is the appropriate edit notation?

(2) Can I add this: 'Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis' 29 Sept 2016: Michael D Ludwig, Anthony P Turel*, Ian S Zagon, Patricia J McLaughlin [14], and if so, what is the appropriate edit notation?

(3) Can I add any of the new research links listed at a,b,c,d,e above, and if so, what is the appropriate edit notation?

(4) Can I then edit text where it is relevant to those links, and if so, what is the appropriate edit notation? — Preceding unsigned comment added by 110.23.167.134 (talk) 05:04, 28 October 2016 (UTC)

If writing about LDN, I would consider using one or more of these secondary sources, with a small preference for recency. If your favorite primary source is not one of them, just wait a few months to a few years while it gets included in a review. Note also that one of the search results is about multiple sclerosis. This doesn't mean that some other editors won't still object to the use of one or more of these secondary sources, but it's a start.
About Novella, it might be more palatable to downweight and possibly drop his statements once the article is significantly strengthened by secondary sources. This is because WP:PARITY only applies to fringe theories, and demonstrating in the article that LDN is non-fringe would mean that WP:PARITY no longer applies.
With regard to an "edit notation", all I can suggest is an example of an article that I worked on this year using secondary sources. --Hyperforin (talk) 07:12, 28 October 2016 (UTC)

Thank you so very much for posting this secondary sources. It's sincerely appreciated because from that I was able to formulate this search [15] which dramatically increased the list relevancy to this topic. That was really helpful. I don't have time to progress all this further at present, but do hope this new search string with high relevancy search results is acceptable to use here. More later.

It helps if editors sign their contributions.Martinlc (talk) 10:43, 28 October 2016 (UTC)

By sign, does that mean you want me to add my name somewhere, and if so, where? I hope I don't need to make an account or something because I'm not a regular contributor or editor to anything.

Hello again :-) I will soon upload edited versions of Mechanism of Action and Research to bring them up-to-date - something long overdue. The edit is supported by extensive research - yet I have been mindful of retaining the right degree of balance. It is my understanding from discussions that I have followed/met guidelines and that this edit won't be reversed without further discussion and agreement. — Preceding unsigned comment added by 110.23.167.134 (talk) 21:23, 11 November 2016 (UTC)

• • My edit was finalised, then removed minutes later by someone, without any justification noted under 'talk' here. Can the person who removed my update please explain why they removed it? Thank you.**

• • Jytdog pointed me to this 'talk' section to discuss the intended updates/changes. I followed Jytdog's instruction (after I eventually found it) and the discussion/outcome appears above. Jytdog, however; chose not to continue to participate in the above ensuing discussion instigated by Jytdog. Instead, Jytdog used a different location (https://en.wikipedia.org/wiki/User_talk:110.23.167.134#Edit_war_warring_again) today, to again accuse me of an 'edit war' with an accompanying threat to 'block me'. — Preceding unsigned comment added by 110.23.167.134 (talk) 01:06, 12 November 2016 (UTC)

yes you need to discuss your edit here. as i mentioned in my editnotes, the edits (first this and then this) removed sourced content and replaced it with unsourced content and content that was really WP:SYN. That is not OK. Content needs to be directly supported by a source and that source needs to comply with WP:MEDRS. I suggest you propose the next version here instead of making it directly in the article. Jytdog (talk) 01:12, 12 November 2016 (UTC)

Jytdog, thank you for responding. I hope you agree that research such as this; [16], and this; [17], and this; [18]; PLUS the 60 or so research articles included in the NIH search string I included in the research update - has a higher degree of relevance and a higher combined weighting - than an opinion piece written 5 years ago by Steven Novella that, whilst it may have some value in presenting an alternate view, isn't supported by research? — Preceding unsigned comment added by 110.23.167.134 (talk • contribs) 01:46, 12 November 2016 (UTC)

the links you provided are to primary sources, some of which are very old. You are not engaging with WP:MEDRS, and you need to. Jytdog (talk) 03:00, 12 November 2016 (UTC)

As previously mentioned, there are some 60 related research papers in the search string/link I included which you deleted - all good non-conflict-of-interest research (the type we should all support) - all highly relevant to this topic - all insightful - all contributing to advancing knowledge and progress in relation to this topic - AND YET - that collective bundle of 60 is to be rejected outright based on a rigid application/adherence to what is a generic definition of primary, secondary, or tertiary. I'm sure the original intent of those guidelines was not to extinguish or quash all new knowledge, advances and insights - as is occuring here - at great detrimental expense to this particular topic. When the weight of research builds and tips the scales - as it has clearly done in this case - the definitions should be flexible enough to acknowledge, and accommodate that significant progress. The collective data certainly holds far greater weight than your protected source content [5] and others. — Preceding unsigned comment added by 110.23.167.134 (talk • contribs) 05:42, 12 November 2016(UTC)

i fixed your indenting again, and signed for you again. this is the last time i will do it; i will ignore future comments you make that you don't indent and sign. These two things are the foundations of talk page discussions. Jytdog (talk) 06:20, 12 November 2016 (UTC)

again, please propose specific content, supported by specific sources that comply with WP:MEDRS. If you make general comments in the future, without proposing or discussing specific content and specific sources, the comment will be removed. This is not a page for general discussion of the topic. It is for making specific improvements to the article. Jytdog (talk) 06:22, 12 November 2016 (UTC)

I don't understand what you mean by fixing my indenting and 'signing for me' again. I thought the indenting was your choice of format, and that signing was occurring automatically when my IP address was logged, but then again, I also thought wiki had fairer processes to what I've experienced to-date. I did propose specific content and sources for discussion that would improve the article - and which I believe should comply with WP:MEDRS - and I also explained my reasoning, i.e.; why I believe they should collectively comply. In the interests of moving forward, I have indented this response as you instructed, using the same ident style - and I will copy and paste the string you entered at the end of my comment to 'sign'. 110.23.167.134 (talk • contribs). 110.23.167.134 (talk) 07:10, 12 November 2016 (UTC)

If you look at the history of this page, you will see regular edit notes from me saying "indent and sign unsigned". In addition, I left an explanation on your talk page. Jytdog (talk) 11:59, 12 November 2016 (UTC)

Jytdog, that issue has now been corrected. Being new to all this, I'm still learning. We're supposed to be jointly interested in improving and updating this entry, not fixated on whether I've mastered all the wiki ropes of indenting and signing and dating. It is entirely understandable, and forgivable for a novice to miss those things. Our collective time is better spent clarifying/correcting, improving and updating this entry - so very long overdue. This statement, in particular, requires urgent clarification/rectification to minimize associated risk; ' ... Thus, regular doses of low-dose naltrexone can be used to increase a patient's endorphin and enkephalin levels. ... '. I edited/corrected it - then you deleted my edit without discussion - so the onus is now with you to correct it as soon as possible. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 22:01, 12 November 2016 (UTC)

glad you have figured out how to use a talk page. If you would like to see a change to this article, please propose the change here, along with the MEDRS-compliant source(s) it is based on. Thanks. Jytdog (talk) 23:17, 12 November 2016 (UTC)

Let's begin with the MEDRS-compliant source that supports this statement; ' ... Thus, regular doses of low-dose naltrexone can be used to increase a patient's endorphin and enkephalin levels. ... '. What MEDRS-compliant source was this statement based on? Thanks. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 23:54, 12 November 2016 (UTC)

As a courtesy, just letting you know that I'm out of time for now, and won't have some time to respond until at least tomorrow, when I hope we can discuss the MEDRS-compliant source that supports this statement; ' ... Thus, regular doses of low-dose naltrexone can be used to increase a patient's endorphin and enkephalin levels. ... '. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 00:24, 13 November 2016 (UTC)

addressed here. Jytdog (talk) 00:37, 13 November 2016 (UTC)

First things first - thank you very much Jytdog for that edit :-) . I'm hoping we can go further to clarify this sentence; ' ... As of 2015, the theory behind low-dose naltrexone's mechanism of action is that by inhibiting opioid receptors, it causes the body to increase production of endorphins and upregulates the immune system ... '. Standard doses used during drug dependency treatment consistently inhibit opioid receptors, and as a consequence, also inhibit production of endorphins/immune system. LDN's mechanism of action is different - it limits the duration of inhibition each day, i.e.; limits the opioid receptor blockade (typically to around 4 hours, and typically while asleep), and it is this much shorter duration of inhibition once a day that is key to increasing production of endorphins and upregulating the immune system. May I suggest this; (1) ' ... As of 2015, the theory behind low-dose naltrexone's mechanism of action is that by inhibiting opioid receptors for a much shorter period of time (around 4 hours at night), the body compensates for lack of production of endorphins and enkephalins by escalating production, which upregulates the immune system. ... '. And to further clarify, may I also suggest following (1) with this; (2) ' ... After the low dose of naltrexone has been eliminated by the body, escalated levels of endogenous opioids are thought to persist for most of the following day. A single low-dose of naltrexone taken at bedtime is said to increase a patient's endorphin and enkephalin levels through exploiting the body's circadian cell cycle rhythms [citations needed]; though alternate views are held on the import of time of administration in respect of enkephalin [citation needed]. ... '. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 22:15, 13 November 2016 (UTC)

Content needs to be based on MEDRS sources. Do not propose content with a "citation needed" tag. Jytdog (talk) 23:22, 13 November 2016 (UTC)

Okay, fair enough, point accepted. Herewith proposed content that both clarifies and is also grounded in the same, previously accepted MEDRS sources: ---- FIRST PARAGRAPH --- ' ... Naltrexone and its active metabolite 6-β-naltrexol are competitive antagonists at μ- and κ-opioid receptors, and to a lesser extent at δ-opioid receptors.[4] Clinical doses of naltrexone (50–150 mg) cause the blockade of opioid receptors, which is the basis behind its action in the management of opioid dependence—it reversibly blocks or attenuates the effects of opioids. ... ' --- SECOND PARAGRAPH --- ' ... LDN refers to daily dosages of naltrexone that are approximately 1/10th of the typical opioid addiction treatment dosage. [19] As of 2015, the theory behind low-dose naltrexone's mechanism of action is that by inhibiting opioid receptors, it causes the body to increase production of endorphins and upregulates the immune system. [20] These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. [21] It also appears to antagonize Toll-like receptor 4 that are found on macrophages, including microglia, and its apparent anti-inflammatory effects might be due to that. ... ' 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 23:52, 13 November 2016 (UTC)

Thank you for the edit. With reference to this sentence; ' ... Low-dose naltrexone refers to doses at about 1/10th the size of the dose used normally. ... '; the terms 'doses' (infers multiple daily doses) - and 'used normally' (infers 'normal' as being 150 mg used in treating drug dependency) - both need further clarification. May I suggest; ' ... Low-dose naltrexone refers to a single nightly dose up to 1/10th the size of a standard naltrexone 50 mg dose. ... ' 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 23:15, 14 November 2016 (UTC)

we don't discuss details of dosing per WP:MEDMOS - it was useful to define what was meant by "low-dose" since that is the distinguishing thing, but that is as far as we go. Jytdog (talk) 00:17, 15 November 2016 (UTC)

Okay. Can you think of alternate way of expressing this, please? Low-dose naltrexone refers to a single daily low dose at about 1/10th the size of a standard tablet. This is important - because 1/10th of 'normal' could be misinterpreted as 1/10 of anywhere up to 150 mg (normal for drug dependency), and the word 'doses' could also be misinterpreted as multiple daily doses (which could actually increase risk). 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 05:33, 15 November 2016 (UTC)

no. Jytdog (talk) 06:18, 15 November 2016 (UTC)

Research and trials to-date have used no more than a single daily low dose. I understand your concern regarding dose size, but it is possible to clarify without providing dose size: Can we replace this; ' ... Low-dose naltrexone refers to doses at about 1/10th the size of the dose used normally ... ' -- with this -- ' ... Low-dose naltrexone refers to a single dose that is a small fraction of a standard naltrexone dose. ... '? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 18:26, 16 November 2016 (UTC)

what is the source for that. Jytdog (talk) 21:17, 16 November 2016 (UTC)

In your current reference list number (1) you'll find the following clearly stated: ' ... In both trials, LDN was administered at 4.5 mg daily, once at night before bedtime. ... The typical dosage of LDN in published research is 4.5 mg. The medication is commonly given approximately an hour before bedtime, though some individuals reporting insomnia as a side effect are moved to a morning dosing. ... Other dosing schedules, such as twice a day, have not been explored in clinical studies. ... highlighted by animal research that suggests, for example, that while LDN may suppress tumors when used in the typical fashion, it may actually enhance tumor growth when administered more frequently [48]. ... '.

In respect of the above (1), can we now replace this; ' ... Low-dose naltrexone refers to doses at about 1/10th the size of the dose used normally ... ' -- with this -- ' ... Low-dose naltrexone typically refers to a single nightly low dose that is a small fraction of a standard naltrexone dose. ... '(1)? 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 08:09, 17 November 2016 (UTC)

"small fraction" could be 1/10th or 1/100th or 1/1000th. and for the last time no on "single nightly" - we do not go into dosing details per WP:MEDMOS which applies the policy WP:NOTHOWTO. done here it seems. Jytdog (talk) 10:58, 17 November 2016 (UTC)

You may be done. I'm not. Please pass this on to a different editor: The suggested sentence does not provide dosing details in 'small fraction' of 'standard dose' (so it is well within guidelines). And, the suggested sentence better clarifies that LDN is not taken in multiple 'doses' daily (as the current sentence suggests), but is taken as a single nightly dose. This is very important to clarify because; 'low doses of naltrexone may actually enhance tumor growth when administered more frequently than once a day(1). I have justified this change. Please replace the current sentence with this suggested sentence, which does not provide dosing in any detail that anyone could use, and so is within guidelines: ' ... Low-dose naltrexone typically refers to a single nightly low dose that is a small fraction of a standard naltrexone dose. ... '. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 22:03, 17 November 2016 (UTC)

Your suggestion violates the policy WP:NOTHOWTO and the guideline WP:MEDMOS, both of which are the product of community WP:CONSENSUS. What you want (of even if was unschooled enough in policies to agree with you) would eventually be removed by someone else; local consensus or desires cannot overcome community consensus. Go get consensus to change them - the policy first, then the guideline, and then you will have something to talk about. Until then this discussion is done. You will get the same answer from everybody. Jytdog (talk) 23:14, 17 November 2016 (UTC)

Sorry Jytdog but I still can't find anything in my suggested replacement (clarifying) sentence that breaches/violates policy, guideline or consensus. Dose size has not been stated in the sentence - 'small fraction' is sufficiently vague that it does not provide any info on dose that could be linked to/associated with the words 'single nightly', or extrapolated into a dosing schedule. It's too vague and can't be done, so the words don't even resemble a dose guide or instruction, which means the sentence remains within guidelines. If you perceive otherwise, please refer me to something specific within the policy, guideline or consensus, with respect to this suggested replacement sentence: ' ... Low-dose naltrexone typically refers to a single nightly low dose that is a small fraction of a standard naltrexone dose. ... '. Please copy and paste the specific words of the policy, guideline or consensus that you believe confirm violation. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 07:14, 18 November 2016 (UTC)

My final comment in relation to this has been put under the more relevant header; 'Mechanism of Action'. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 01:35, 21 November 2016 (UTC)

Mechanism of Action

I clearly explained why, and still maintain that this sentence; ' ... Low-dose naltrexone refers to doses at about 1/10th the size of the dose used normally.[1] ... ' is potentially unsafe. It has the potential to contribute to making what is presently an unfounded 'criticism'/warning on the same page; ' ... that improving the immune system could make the autoimmune disease worse ... '; a reality. I suggested a replacement sentence that's been repeatedly rejected. I requested detailed justification for the rejection. There's been no response. I've done all I can to explain why clarification is needed, why it's necessary to minimize risk, why the suggested replacement sentence should be perceived as being within guidelines - but this door remains firmly closed. I have grave and genuine concerns about this entry, but others hold it's lock and key, and there's clearly nothing more I can do. 110.23.167.134 (talk • contribs) 110.23.167.134 (talk) 01:35, 21 November 2016 (UTC)

Summary of Current Evidence Section

I think we need a summary of the evidence from meta analysis and reviews of LDN for different indications. Understandably this is an evolving field with some diseases having more available but I think a short summary would be helpful for an outside reader.Chickpecking (talk) 23:26, 7 December 2017 (UTC)

Yes this would be a good addition. When a credible meta analysis appears it should be added. Martinlc (talk) 23:31, 8 December 2017 (UTC)

Thus far there seem to be two systemic reviews. My summary of the conclusions are below. Both spoke of the need for more data. There are other reviews that are literature reviews which could be helpful in describing mechanisms of action etc.

A 2014 Cochrane review concluded there is insufficient evidence to support the use or safety of low dose naltrexone in active Crohn's disease due to the extremely limited data though the data suggested benefit and lack of harm.

A 2015 review from the Norwegian Institute of Public Health noted that there was currently insufficient evidence to determine whether low-dose naltrexone is effective and safe in treating Crohn's disease, multiple sclerosis, fibromyalgia, cancer, HIV, addiction problems and various chronic pain disorders and opioid dependence.Chickpecking (talk) 04:25, 9 December 2017 (UTC)

Since there is no evidence that it is effective there is no need to speculate about mechanism of action.Martinlc (talk) 15:31, 9 December 2017 (UTC)

These are current meta analysis. There is evidence from trials regarding LDN and I think expert opinion in a review would be pertinent and carry due weight.Chickpecking (talk) 20:23, 9 December 2017 (UTC)

References

Why focusing on LDN's efficacy at causing remission of AI diseases?

The majority of LDN users use it for reduction of chronic pain and brain fog symptoms that are a result of other conditions. As such, shouldn't the evidence for or against its efficacy focus on the reduction of these symptoms? Hamytime (talk) 01:07, 15 March 2018 (UTC)

No mention of Dr. Bihari?

I think there should be some mention of low dose naltrexone and the work Dr. Bihari did on it. Without him we wouldn't have nearly as much information as we do. Also we should add in something about Mary Boyle Bradley. It's a remarkable story, and one that should at least be linked in the article

Shtanto (talk) 15:07, 5 March 2017 (UTC)

Since his main work on LDN was not accepted by a medical journal for publication it's unlikely to meet the required level of notability. Martinlc (talk) 14:41, 6 March 2017 (UTC)

But Steven Novella's "work" on LDN meets the required level of notability? And as designated editor/gatekeeper for this entry he links to his own site which solicits donations.... Bihari, B. Low-dose naltrexone for normalizing immune system function. Altern. Ther. Health Med. 2013, 19, 56–65. — Preceding unsigned comment added by Senn590 (talk • contribs) 22:06, 23 March 2019 (UTC)