Talk:Naltrexone/Archive 1

Heading
In the "Pharmacology" section it is stated "Its mechanism of action in this indication is not fully understood, but as an opioid-receptor antagonist it's likely to be due[citation needed] to the modulation of the dopaminergic mesolimbic pathway which is hypothesised to be a major center of the reward associated with addiction (being one of the primary centers for risk-reward analysis in the brain, and a tertiary "pleasure center") that all major drugs of abuse are believed to activate." There is a citation needed and I'd like to provide it with additional details. This is the reference: "Neurochemical and functional correlates of naltrexone-induced opiate receptor up-regulation" http://www.ncbi.nlm.nih.gov/pubmed/2982011 Let me discuss reasoning for moment and then the proposed change: Mu agonism is known to lead to dopaminergic(reward) action. Anhedonia from mu opioid abuse is strongly correlated with downregulation of mu and dopamine receptors. Most addiction is strongly correlated with downregulation of dopamine in the NAcc and therefore less dopaminergic action and subsequently less reward. Antagonism is known to generally result in the up-regulation of the antagonised receptor. Up-regulation generally leads to increased activation via endogenous ligands Therefore it is likely that the positive effect of naltrexone is mediated through increased endogenous reward. And while alcoholism is not directly correlated with mu agonism, there is anecdotal evidence that alcohol is used to alleviate pain, physical and emotional (similarly experienced in the brain) so the additional endogenous pain relief may also be involved. I'm sure this could be added more concisely in the article and if someone else would like to do so when they add the reference I'd appreciate it. Nemesis75 (talk) 04:13, 5 March 2011 (UTC)

The statement, "However given that it is a long-acting antagonist, Naloxone would be a more ideal antidote in emergency situations," is incorrect (or atleast worded strangely). Naltrexone has a half life of 10 hours, while naloxone has a half-life of 1-2 hours. Both are effective at rapid opioid detox (onset 1-3 minutes), but "It is very important that the relatively short duration of action of naloxone be borne in mind, because a severely depressed patient may recover after a single dose of naloxone and appear normal, only to relapse into coma after 1-2 hours." from Basic and Clinical Pharmacology, 10th Ed., Katzung, pp 506-507. (1/2 life data and onset data also from this reference). 76.125.24.13 (talk) 00:18, 3 December 2008 (UTC)NAI

Naltrexone can also be admisistered as a low dose implant. These implants can remain effective for up to 12 months. They dissolve slowly and are usually put in under a local anaesthetic in the left iliac fossa. Although not licensed, they are available in the UK at specialist clinics, in the USA and in Australia. Jenny Sudell (Isle of Wight)

Jargon
I have a major complaint about this article: it's so full of scientific jargon that it's quite hard for the layman to read. I don't know anything about Naltrexone except that it's some kind of implant used to treat heroin addiction, and came here hoping to learn more, as most people do when they come to wikipedia. But I gave up after a couple of paragraphs because this is a page designed for people who already know what they're talking about, not for people like me who have degrees in literature and can't tell an "iliac fossa" from a hole in the ground. ;) Thing is, I think that this page draws more attention from people out of the know than people in the know.  I don't suppose one of you fine people might want to throw in a paragraph at the top or bottom that gives a simpler, jargon-free explanation of what Naltrexone is, and how it works?  Surely "iliac fossa" could, for one paragraph, be replaced by "plate of the hip bone," and "opioids" replaced by "opiates and similar drugs," or "drugs in the family of heroin, opium, and morphine"?  Stuff like that.  Just a thought. My rain face 01:08, 23 April 2006 (UTC)


 * I agree we could have some slightly more descriptive language. How about you chase the wikilinks and see whether you can add some useful descriptions (e.g. after "opioid antagonist" you can say "substance that blocks the action of opium-like drugs such as heroin"). JFW | T@lk  09:30, 23 April 2006 (UTC)

"Some of the conditions where LDN has been reported as beneficial include multiple sclerosis, Crohn's disease, HIV/AIDS, chronic fatigue syndrome, fibromyalgia, AD in children (Elchaar GM, et al. 2006) and cancer. " This reference is incomplete. What journal? --GangofOne 07:04, 2 August 2006 (UTC)
 * It is complete now. --WS 22:03, 2 August 2006 (UTC)

UPDATE: The 2010 edition of the free LDN resource book 'Those Who Suffer Much, Know Much' is now available online; 51 patient case histories, 19 health professional interviews and perspectives, related research and references in this comprehensive 2010 edition: ‘Those Who Suffer Much, Know Much’ 2010 edition http://www.ldnresearchtrustfiles.co.uk/docs/2010.pdf —Preceding unsigned comment added by 220.237.76.147 (talk) 20:53, 20 August 2010 (UTC)

Anyone care to hear from some one using it?
If anyone cares at this late date, I'd be happy to discuss FIRST HAND what it is like from THIS side of the perscription, and I can do it in terms anyone can understand...

Yes, i would. I'm looking into for treating my Churg-Strauss Syndrome. I just found out about it and am interested in getting info from you.Longinus876 (talk) 11:26, 13 April 2015 (UTC)

Other Uses???
My doctor has prescripted naltrexone to prevent self harm behaviors. I found a couple of journal articles related to this, but I didn't find any mention to this in the wikipedia article. Could more information on this be included?


 * My son's psychiatrist is talking about prescribing it, and there are at least a few articles that claim it's successful for some self-injurious behaviors, so I'm thinking it wouldn't hurt to at least have a small mention in here. Here's some article links:
 * http://www.springerlink.com/content/n825071469v30585/
 * http://www.soulselfhelp.on.ca/drm8.html
 * http://ajp.psychiatryonline.org/cgi/content/full/157/10/1574
 * http://www.mc.vanderbilt.edu/reporter/index.html?ID=461 —Preceding unsigned comment added by Nerdmaster (talk • contribs) 21:47, 17 March 2008 (UTC)

Rapid detoxification
The rapid detoxification subsection does not cite any sources and I believe many of the aspects are incorrect as they appear to be referring to ultrarapid detoxification. Additionally there appears to be references in this section to naltrexone maintenance therapy for opioid dependence which is a completely different treatment modality than detoxification as it is continued indefinitely whereas detoxification is a finite process. One could certainly undergo rapid detoxification using naltrexone and transition to maintenance naltrexone dosing to maintain opioid abstinence but this is utilizing two different treatment types. --Thiswouldbemark (talk) 20:20, 16 April 2008 (UTC)

I attempted to clarify this section and added a few references. Didymus (talk) 16:28, 4 January 2012 (UTC)

Inverse Agonist
Hey so I changed the description of its activity at the mu-receptors to being an inverse agonist rather than an antagonist, someone who knows how should clean up the references section because I and someone else apparently don't know how to add to the reflist —Preceding unsigned comment added by 24.12.64.109 (talk) 19:02, 17 April 2008 (UTC)

Low-Dose Naltrexone
I was doing a "drive-by" edit when I noticed that Crohn's is mentioned twice within the same section - once under the Low-Dose Naltrexone heading and one under its own heading. I don't know enough about Crohn's to decide whether it merits its own heading or not in this context...someone with a better understanding may want to re-work those two sections. --Rob (talk) 08:06, 11 January 2009 (UTC)

Why is putting in more than one reference about low-dose naltrexone excessive? Following this "logic", then one source on any subject would be enough... why read any other other authors? why reference anybody else who is using the same drug, for different purposes....? is it all excessive? since when is science advanced by only following one person's writings(s).... If the previous redactor would only realize that he has now cut the references on low-dose naltrexone to one site and ONE INDIVIDUAL, perhaps he might be a bit more open minded....  Naltrexone seems to help patients with multiple diseases... why not let those references be stated by those who post their own results...? Marcelo Hoffmann, writing from northern California, on July 2nd, 2005


 * Marcelo, you are linking subpages from one site that is dedicated to LDN. I think that is excessive. If your links had come from various sites that contrasted different approaches, their use would have been defendable.
 * It is a common mistake that by adding links you add information to Wikipedia. This is untrue. If you want to add information, just write more about LDN; in this case, you can use the links specifically as references to back up what you've written. JFW | T@lk  3 July 2005 09:34 (UTC)

Dear Jfdwolff. I did include what you loosely call "repeats" (two double references from the same site...), but could you just try checking the other sites that I previously referenced, and prove to me and others that they were from the same LDN source (individual/site ), as you claimed... particularly given that one is referenced to a U.K. site and one based in Boston, and completelely and provably separate from the LDN site in New York, N.Y.......: just try clicking on "Multiple Sclerosis Research Center" (UK; http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=777); and also on "Interview with LDN researcher Dr. Agrawal" (http://www.bostoncure.org:8080/article.pl?sid=05/01/27/1748256)  Are these repeats too.... ? Is writing/describing/referencing the same/related topic from a different site/author a repeat....???

I certainly do not claim such expertise to be able to choose the one and ONLY universal reference that you claim....  and in case you cared.... information about low-dose-naltrexone for multiple medical indications and from multiple original sources could be life-saving for those patients or interested parties who would read it for treatment possibilities for their disease....  but only, and just in case you cared....! Marcelo Hoffmann


 * Wikipedia needs original content, not links. Just stop it. JFW | T@lk  6 July 2005 20:46 (UTC)

What a dialogue....! instead of responding to my explicit logic and thinking, issue a perentory command to stop a reference-stating behavior that is at worst somewhat redundant, and at best contributory (at least for some people, some of the time...). But this time, claiming absolute knowledge of what is best, for him/others, and Wikipedia.....   I guess according to JFW, hyper-references should not be added to Wikipedia... after all, the statement "Wikipedia needs original content, not links..." is rather broad and would appear to leave no option(s)....   hardly worth bringing the topic of multiple references to the discussion section of naltrexone.... for this sort of "dialogue" (or lack thereof....) Marcelo Hoffmann July 6, 2005


 * No point in dialogue. You're wasting my time. JFW | T@lk  7 July 2005 06:42 (UTC)


 * If you want to know: is the only serious source I have found for LDN in a disorder not directly linked to opioid addiction. The author is, surprise surprise, the same Dr Agrawal. I think the subject should get the coverage it deserves as it stands at the moment: very little. It is a scientific hypothesis being tested, and not more notable that any other experimental treatment. One link is all that is necessary. JFW |  T@lk  7 July 2005 06:51 (UTC)


 * I've been on LDN for a while now. It'd be nice if this article linked properly. It works for me. Side effects include loss of appetite and sleep disturbances. For first hand information, I'd recommend the references section link to Dr. Gilhooly in Scotland, the original Bihari paper on LDN, Dr. Pat Crowley or Dr. Phil Boyle (fertility expert)(both base in Ireland) or Skips Pharmacy in the US. Penn state and Dr. Ian Zagon are also worth referencingShtanto (talk) 15:59, 22 February 2012 (UTC)
 * Please review our sourcing guideline for medical claims at WP:MEDRS. What "works for you" is not a reason to include in this article. Yobol (talk) 17:04, 22 February 2012 (UTC)

Alcohol Dependence
The second sentence states, "This is true even in those who continue drinking while taking naltrexone, but then it is less effective in helping people to stop completely.", however, the findings in the journal reference used are actually contrary to this statement. The findings were that naltrexone was MORE beneficial if prescribed to moderate or heavy drinkers vs. placebo compared to prescription to patients for which abstinence had already been achieved vs. placebo. In my opinion this statement should be removed. —Preceding JameOxford (talk) 21:46, 19 October 2015 (UTC)

"The first is to reduce craving while naltrexone is being taken. The second, referred to as the Sinclair Method, occurs when naltrexone is taken in conjunction with normal drinking, and this reduces craving over time. The first effect only persists while the naltrexone is being taken, but the second persists as long as the alcoholic does not drink without first taking naltrexone."

Am I alone in not being able to puzzle that out? I keep reading that as "naltrexone reduces craving" and "naltrexone reduces craving" - what am I missing? —Preceding unsigned comment added by 209.6.39.11 (talk) 05:27, 9 December 2009 (UTC)

If you drink while taking Naltrexone though you may get sick. I can't speak for anyone else, I can only speak for myself. —Preceding unsigned comment added by 67.241.11.185 (talk) 19:08, 10 March 2010 (UTC)

I can attest to that experience. Becoming sick is a side-effect however, and is not the method of efficacy. I only include this because many people assume it works like Disulfiram (Antabuse), which isn't the case. JameOxford (talk) 22:01, 3 October 2016 (UTC)

Naltrexone supresses Tetrahydropapaveroline-induced alcohol consumption-- reference.
This is thought to be a possible mechanism of action in alcoholism. Will be back to spiff. THP is a "natural opiate" that goes up with alcohol consumption.

Proc West Pharmacol Soc. 1988;31:277-9. The effect of tetrahydropapaveroline and naltrexone on voluntary ethanol ingestion in rats. Oster L, Martinez TT. —Preceding unsigned comment added by Nucleophilic (talk • contribs) 16:23, 13 October 2010 (UTC)

other brand names that naltrexone is found in
Could someone list the brand names of medications that naltrexone is found in? For instance Talwin is pentazocine+naltrexone, etc.  --159.178.230.51 (talk) 13:16, 14 January 2011 (UTC)

Criticisms
Surely one of the criticisms should be its cost. Vivatrol, according to a Nov 4, 2015 Marketplace.org show, is $1200 (in the USA) per dose. As a side note, I find it hard to beleive that the several (US) FDA reviews have all relied on a single (unethical) Russian study. (Unethical in the sense that ethics dictate the "best available therapy" be used as the control, any other study design couldn't be approved in the USA and many other countries.)216.96.77.183 (talk) 00:02, 5 November 2015 (UTC)

My edits at 17:50 and 18:01 today
Dear Jytdog:

I acknowledge that my edits at 17:50 and 18:01 today might have been annoying edits. (I never try on purpose to make annoying edits, but I've probably made quite a few annoying edits anyway.) But were they truly edit warring, and did they truly merit the uw-3rr final notice with an ominous-looking red Stop sign icon which you posted on my talk page?

cc: User:Doc James

TealHill (talk) 22:45, 26 September 2016 (UTC)
 * Typically stuff like this " It has no other mechanism of action. If the person reliably takes the medication an hour before every drinking episode, there may be for the person to take it on non-drinking days.)"
 * Goes on the talk page rather than in the article. Do we have references that state this? Best Doc James  (talk · contribs · email) 22:51, 26 September 2016 (UTC)


 * You have some issue with the content that your edits are not successfully addressing. Please use this page to articulate the issues so we can respond to them - they may be valid and addressable or may be invalid per the policies and guidelines of WP, but we do not know what the issues are. So please articulate them. Thanks again for coming to talk.  Jytdog (talk) 23:45, 26 September 2016 (UTC)


 * I thank you both for your replies; now I finally have a reasonable idea of why you didn't like my edits. Let me ask my questions below. Hopefully then I can better understand how naltrexone works, and we can better improve the article to make clear to readers how naltrexone should best be used. TealHill (talk) 18:20, 29 September 2016 (UTC)

Only then?
The article says: "The Sinclair method is a method of using opiate antagonist such as naltrexone to treat alcoholism by having the person take the medication about an hour before they drink alcohol, and only then". (Emphasis mine.) I'm no doctor, and I'm no expert, but "only then" seems to me like it might be too conservative. It may cost the patient some extra money, but in practice, I still think it could be a good safeguard during early sobriety for the patient to take naltrexone every morning, in case they forget to take it before their usual evening drinking session begins. No? Thanks in advance, TealHill (talk) 18:20, 29 September 2016 (UTC)
 * see above. Jytdog (talk) 18:29, 29 September 2016 (UTC)

Side effects
Dear all. The article says: "The Sinclair method is a method of using opiate antagonist such as naltrexone to treat alcoholism by having the person take the medication about an hour before they drink alcohol, and only then, in order to avoid side effects that arise from chronic use." (Emphasis mine.) User:Jytdog, you wrote the bit about side effects; thank you for writing that. You added in the edit summary: "[I]f you read the source you could have added this yourself". Dear all: Which source? Which side effects? (I did look at one of the two cited articles but had trouble understanding it. I don't even have a university degree, let alone a med-school diploma or PhD. I'm just an interested addict.) Thanks in advance, TealHill (talk) 18:20, 29 September 2016 (UTC)
 * I don't know how to explain this any more clearly.  Every drug has side  effects.  Aspirin, for example, hurts your stomach a little, every time you take it.  If you take a regular dose of aspirin every day for a year or two, you are going to end  up with serious stomach trouble.  So people take a regular dose of aspirin only when they have a headache or fever; not every day.  (people do take low-dose aspririn every day to manage the risk of a heart attack; that dose doesn't hurt your stomach).  So taking any drug just when you need it avoids the problem of side effects building up.
 * Naltrexone causes digestion problems and there is a risk it will hurt your liver. You reduce the chances of screwing up your liver, and reduce the chance of having diarrhea and cramping, if you take it only occassionally instead of all the time.  does that make sense? Jytdog (talk) 18:29, 29 September 2016 (UTC)
 * Ah. Now it makes complete sense; thank you very much for elaborating. TealHill (talk) 00:20, 30 September 2016 (UTC)
 * great. thanks for asking. Jytdog (talk) 00:24, 30 September 2016 (UTC)

Shader ref says N is an inverse agonist
The Shader ref - -- was used to support the content that naltrexone is a mu, kappa, and to a lesser extent, delta antagonist. i just read that paper. it is weird little thing, kind of a reflection, but it actually says that naltrexone is probably an inverse agonist at mu. the content said nothing like that. i added a ref that does support that content, a 2015 review.

because it is a weird little paper I am not sure we should source the inverse agonist thing from it, but just wanted to mention this. Jytdog (talk) 02:21, 14 November 2016 (UTC)

Vivitrol
Here's a major, relatively recent study of Vivitrol:

http://www.nejm.org/doi/full/10.1056/NEJMoa1505409 Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders Joshua D. Lee, et al. N Engl J Med 2016; 374:1232-1242 March 31, 2016 DOI: 10.1056/NEJMoa1505409

This was a randomized trial in which the Vivitrol group was compared to a group that got "usual treatment," which was "counseling," not methadone or buprenorphine.

Here's an earlier paper which describes the study in more detail, including the fact that users of methadone or buprenorphine were excluded from the study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380547/ Extended-Release Naltrexone To Prevent Relapse Among Opioid Dependent, Criminal Justice System Involved Adults: Rationale and Design of a Randomized Controlled Effectiveness Trial Contemp Clin Trials. Published online 2015 Jan 17. doi: 10.1016/j.cct.2015.01.005

--Nbauman (talk) 14:55, 1 April 2017 (UTC)
 * Okay. We should wait until the study is reviewed in a high quality review article IMO. Doc James  (talk · contribs · email) 16:11, 1 April 2017 (UTC)
 * You don't get much better than a RCT in the NEJM. We already have a section on Vivitrol based on on news stories, articles in the Lancet, and a 2009 article in Archives of General Psychiatry. Should we limit ourselves to review articles, the latest of which is from 2013? What should we do now? Delete all the non-review and non-WP:MEDRS citations? Should we leave them in, asking questions about Vivitrol, but ignoring the 2016 NEJM study that gives some of the answers? Or should we include the NEJM article because it gives the latest information that any reader would want to know about naltrexone depot (my preference)? --Nbauman (talk) 18:23, 1 April 2017 (UTC)
 * A recent primary source is still a recent primary source, and even the NEJM ends up retracting things or posting significant corrections. See here for some Jytdog (talk) 18:37, 1 April 2017 (UTC)
 * I know Retraction Watch. Review articles also have corrections (and changes). Are you going to delete everything in the entry that is not a review article? Are you going to delete everything after 2013?
 * I'd like to know what User:Doc James says. --Nbauman (talk) 18:53, 1 April 2017 (UTC)
 * Doc James gave the standard MEDRS answer, as did I.  You have been here long enough to understand MEDRS.  As discussed in the WP:MEDREV section of MEDRS, yes we can build content off recent primary sources sometimes.  You have not made the argument as to why we should here.  Jytdog (talk) 19:09, 1 April 2017 (UTC)

If you use a search for the generic name you will find lots of newer reviews. Doc James (talk · contribs · email) 20:35, 1 April 2017 (UTC)


 * I usually start with a search for review articles eg Most of those aren't extended release. The latest review article doesn't include the NEJM study. . I agree with WP:MEDRS that review articles are preferable. But WP:MEDRS also says, "If conclusions are worth mentioning (such as large RCTs with surprising results), they should be described appropriately as from a single study...." If there are no review articles that cover an important recent study (i.e., if the review article is not current), WP:MEDRS seems to say that we can include it. If there's a major NEJM article -- in this case, finally publishing the results of a large RCT -- why not include it? Are we supposed to keep it to ourselves and hide it from the reader? For examples of studies that we can't use, WP:MEDRS gives animal studies.
 * If we're only allowed to use review articles, does that mean that you would want us to delete all the citations to non-review articles from the article? Do you want us to delete the citations to news articles? --Nbauman (talk) 00:08, 2 April 2017 (UTC)

Antagonist vs. inverse agonist
This article states that naltrexone is an antagonist at the mu opioid receptor, but this is misleading. It is agreed that naltrexone is a partial inverse agonist (as any basic Google scholar search will confirm), which is an important distinction. — Preceding unsigned comment added by 24.213.246.226 (talk) 17:27, 27 April 2017 (UTC)

NPR article
We already note this a bit in the article, but NPR ran an article on Vivitrol. Could be a useful source for society and culture.

http://www.npr.org/sections/health-shots/2017/06/12/523774660/a-drugmaker-tries-to-cash-in-on-the-opioid-epidemic-one-state-law-at-a-time

Sizeofint (talk) 16:50, 13 June 2017 (UTC)

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First sentence
Needs to be written in reasonably easy to understand English. Terms such as "competitive antagonist of the opioid receptors" is not. Doc James (talk · contribs · email) 00:42, 7 November 2017 (UTC)

Sinclair Method
The Sinclair Method link just redirects you back to the section it's mention within (the part on alcoholism) — Preceding unsigned comment added by 2601:500:4100:2FC0:95CB:4821:521A:81DA (talk) 03:49, 30 October 2019 (UTC)

naltrexone
opioid addition? My doctor gave it to me for burning mouth syndrome 24.115.141.131 (talk) 21:47, 20 January 2022 (UTC)