Talk:Low-dose naltrexone

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)

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 [1] — 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 [2], 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 [3] 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; [4], and this; [5], and this; [6]; 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. [7] 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. [8] 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. [9] 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)

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 [10] [11]

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 [12] [13]

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)

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)

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)