Low Dose Naltrexone

Have any of you heard or tried LDN? I've been doing a little research on it and have a friend who takes it for Hashimoto's and another autoimmune disease I cannot recall, and it has changed her life. I also joined a Facebook group called "Sjogrens, Lupus, RA, Scleroderma & Low Dose Naltrexone (LDN)" which has oodles of information in their files section as well as personal experiences.

It's my understanding that B lymphocytes are what's attacking the moisture glands and that LDN can reduce/regulate that action. I have yet to see a Rheumy, but I imagine he won't be too keen on prescribing it and will want to do something more traditional. But I am very worried about the side effects of the traditional meds and while the side effects of LDN either seem to be insomnia or sleepiness, those issues can easily be adjusted by taking it during the day or night.

Anyway, I just wanted to know if anyone has heard of LDN for autoimmune disorders and/or had experience taking it and what were your experiences.


Olive LaRue

Your understanding of B-cell ymphocytes attacking the moisture glands and causing SS is incorrect. In any event, non-selectively interrupting the immune response, if in fact LDN did so. would have no effect on disease beyond severely immunosuppressing individuals.

LDN has had some effect in pain control by mitigating the hyperalgesia effects of nerve type pain because of its anti-opioid effects. It hasn't generally been accepted for use in those diseases except as a last ditch effort because of the unpredictable side effects. It may provide some pain management when the bodies pain management system is damaged. It is also known to screw it up. After all its design is to block the bodies opiate receptors those things that make us feel good - sex, exercise, excitement, etc.

There may be folks with more experience at the FMS or CMT sites. Its not something you would find used with SS all that much

Olive, I didn’t know much about low-dose naltrexone, so I looked it up. The wikipedia article isn’t a bad source for understanding this medication. I can see why tj was advising caution, as the article states that there have been many pseudoscientific claims about low-dose naltrexone without proper evidence from clinical trials. Testimonials can be very misleading, particularly if the folks who are testifying have conditions that are different from yours. I think your rheumatologist will be your best guide here. Do you have an appointment soon, I hope?

I understand the caution, as I understand the caution with the other more traditional medications that are prescribed for Sjogren's. It's just so overwhelming reading the side effects and hearing about what other people have experienced (damage to eyesight, hair loss, liver damage, etc.), that I'm somewhat desperate looking for things that may be helpful but have less side effects. Also, I'm unsure if any of them are contraindicated with my CMT type 2, so that's something I'll be discussing with my neurologist (who happens to prescribe LDN for his CMT1A patients). My Neurologist is the Director of the CPMC Forbes Norris MDA/ALS Research and Treatment Center in SF.

I will be seeing my Rheumatologist on January 6th so I'll be able to get more answers - and probably more testing will be done. I'm hoping he does know of the research with LDN and is open to treating with it, either as a stand alone or in combination with something. I was thinking of posing it as a short term experiment (since my symptoms aren't that bad...I mean, I'M THE ONE who requested the testing based on my swollen lymph nodes and lacrimal glands, which have been monitored by my ENT and Ophthalmologist). Of course those worry me and I don't want them to grow to gargantuan size as I've seen online, but I'm not sure how the medications work exactly. I know he'll be able to explain the mechanism of how they help with Sjogren's, but there is always those darn side effects. Not sure if this is necessarily true, but I've heard that they tend to be tougher on smaller people, which I am.

It's difficult as I was just coming to an acceptance of my CMT - obviously knowing that I'd have more obstacles along the way with that disease and have to deal with them as they come - but suddenly getting hit with this is just....well, I'm shell shocked and completely frightened to be honest. Being 33 and hit with two major diseases in the span of 8 months is a bit much, also realizing that with the additional tests the Rheumy will do may bring up something else. It's all a lot to handle.

It certainly is a lot to handle, Olive, and 33 is very young, as you say. It sounds like you have a great team working on your behalf, which is a huge plus. I hope there is no "something else" and that the side effects go easier on you than you may expect. You are not alone, and we are here to help you through this unpheaval. CMT and Sjogren's may be a unique combination, so your path may be a bit different from some others on the group, but we are here to support you.

Naltrexone has been FDA approved for Type 1 CMT for some time now. It is somewhat effective with Myelin sheath problems. Consequently it has been used with MS, Chrons, and FMS, all of which have myelin involvement. Trials are less than encouraging. In fact with Type 1 , the approval is as an Orphan Drug. Type 2 CMT as you know has no myelin involvement. These things tend to develop a life of their own once they hit the internet.

Okay, I'm confused because EVERYTHING I've read indicates a b cell dysfunction or proliferation in SJS. Maybe "attacking" wasn't the right term to use, but they definitely play a role.

tj1 said:

Your understanding of B-cell ymphocytes attacking the moisture glands and causing SS is incorrect. In any event, non-selectively interrupting the immune response, if in fact LDN did so. would have no effect on disease beyond severely immunosuppressing individuals.

LDN has had some effect in pain control by mitigating the hyperalgesia effects of nerve type pain because of its anti-opioid effects. It hasn't generally been accepted for use in those diseases except as a last ditch effort because of the unpredictable side effects. It may provide some pain management when the bodies pain management system is damaged. It is also known to screw it up. After all its design is to block the bodies opiate receptors those things that make us feel good - sex, exercise, excitement, etc.

There may be folks with more experience at the FMS or CMT sites. Its not something you would find used with SS all that much

Every immune response without exception involves B cells. There may be A cells, their may be T cells, but there is always B cells.

One of the most effective B cell inhibitors out there is called lelunomide (Aravara) Works great (when it works) It used often with auto immune. Use it with Type 2 CMT, you will likley die. B Cells are just a fancy name for white blood cells. If all we had to do was inhibit the formation, we could cure any disease. They form to fight disease. There is an entire industry making a killing (literally and figuratively) medicalizing basic physiology, but with quasi-scientific explanations are offering cures and treatments for everything from cancer to autoimmune disease.

B Cell proliferation is a way of saying inflammation. Inflammation certainly is a problem for many with SS, but its a result of the disease, not a cause.

Totally agree with Tj1

It's more likely "natural T killer cells that do the most damage, but the moderation of the immune system by cytokines and other "chemical messengers" and B cells is complex and a series of finely tuned interactions both positive and negative - that way the strength and length of response can (in "normal" people) be very fine tuned with only limited overshoots but in Sjogrens this fine tuning is not fully functioning.

The evidence for any compounds currently available to change this "tuning" is not there for me - although some chinese herbs have very limited test data in this field and not enough to say yes this is an effective option. The trials have been very small and suffer from flaws in their set up. I am not against "alternative therapies" at all but one needs to be careflu about who you believe as there are so many vested "commercial" interests.

You do realize that there are many vested commercial interests in drug companies as well, right? I like to look at the big picture...what works for some may not work for another, even within Western medicine. I also have to be careful because of my CMT type 2 and some of the Sjogren's medication may not be viable for me. I not only have to be careful with medications that are potential neurotoxins (which are added to the cmtausa.org site yearly), but I have be careful with medications that cause muscle weakness. I have found relief with alternative treatment like acupuncture, Chinese medicine, and my naturopath.

And thankfully my Sjogren's is very mild so according to my ENT - which I'm aware isn't my Rheumy but he is friends with him - he believes my treatment will be conservative at this point. I'm going to try alternative treatments right now since I clearly don't need any of the heavy duty medications. I don't even need eye drops for eff's sake!

Thanks for all of your input! I have tons of questions for my doc, so I expect to be getting more detailed and accurate explanations about this disease from my Rheumy.

Thanks again!

Olive - or course I realise that there are vested interests everywhere and I trust no one unless I can check the data for myself and that includes "big pharma" - I used to work for a VERY large international chemical company in R&D so am well aware of the commercial pressures that permeate the whole of human activities.

I totally agree that we are all different genetically and environmentally and Sjogrens is a very variable disease, so few of us have exactly the same symptoms. This makes diagnosis and treatment more complex than may be the case in other diseases.

You say your eyes hardly trouble you yet for me and many others the dryness to eyes nose and mouth is very severe and the most "disabling" aspect of the disease so be thankful for your mildness. This is often quoted as being a difference between so called primary and secondary SS symptomatically.

I do not write off Chinese herbal medicine or accupuncture - a dear friend of mine is both and MD and a "doctor" qualified in Vietnam under Chinese medicine and acupuncture and she uses all methods but carefully and in light of her patients symptoms and diagnosis.

So if acupuncture works for you great but it many not for others.

I tried it many years ago under this lady for back pain (unrelated to SS) and it did nothing for me - as you say we are different.

I claim no expertise in CM as I haven't studied or researched it - hence my being on the Sjogrens forum. I am well aware that all medicines have side effects and again in some the side effects may be more severe than others.

I hope your rheumatologist can answer some of your questions.

Part of the mildness of my symptoms may be due to age. I am 33 and it seems that most people get diagnosed after 40. And believe me...I am thankful. However, I do experience swollen salivary glands which aren't pleasant and that's what brought me to the SS diagnosis. Because of my research and requesting these specific labs I was diagnosed earlier than I would have been otherwise. Thank goodness for my neuroticism!

Doctors are fallible and don't often connect the dots. I have some of the best doctors in my city and it took me to get the diagnosis. One of my goals is to get them all on the same page, but who knows if that will happen. I may just have to be one of those annoying patients. ;-)

P.S. Right now my left parotid is slightly swollen. If any of you have experienced this, what did you do to help relieve it? My ENT said to do some massage and use warm and cold compresses. Unfortunately my submandibular's are chronically swollen but not noticeable to others...just me. Miss Neuroticism.

I have studied up on it and have begged my MD to try it, but she flat-out refuses. From what I have read, the low dose does not really have a narcotic effect.

I have gotten the most info from Julia Shopick, www.honestmedicine.com

She gives webinars on this subject and interviews experts on LDN: David Borenstein, MD and Skip Lenz, RPh compounder.

Olive, I get the same swelling. I've found that cold works better for me than warm (for whatever reason) and the massages help relieve some too. That is in addition to taking Advil. Its annoying but thankfully it doesn't usually go past that though it can last several days before chilling out. My doc basically says to pay attention to yourself as we know ourselves best and to call or come in if it seems like something more.

And just to add quick…you said something in one of your earlier posts about being one of those annoying patients…its not uncommon to have to advocate for yourself. It gets easier once you have a good trustworthy team around you so I hope that is soon the case for you.

Guys I know we are all desperate for effective treatment/cures for SS and LDN appears to offer some hope but going to heavily commercial sites such as this one is not the way to go IMHO.

It certainly won't help you convince more "traditional" medics support you.

There are other sources of information out there pub med and NIH have some studies on LDN not many as funding is an issue.

In the UK there is a charity called LDN research trust who are raising money and setting up trials and lobbying the UK governemnt for trials and support.

This seems to me to be a more reliable way to go and also help persuade medics to look at it as a possible therapy.

My research suggests there is little evidence as yet to support LDN for SS some evidence that it may help fibro crohns and IBS but the mechanisms are not agreed and studies are small.

I am VERY wary of sites that sell books and products on the back of our fears and hopes and hope fellow members will look with open eyes too.

The use of LDN is LOADED with side effects HUGE side effects, MASSIVE side effects, DANGEROUS side effects. These bunko artists pushing it as one of the five secret cures etc etc should be locked up IMO. We may well find a use for the stuff beyond its intended purpose. Even for that purpose it is/was rarely used except in extreme cases of the worst kind of opiate addiction where other attempts at rehab and detox have failed.

This medication is designed to alter the chemical response in the body so they do not respond to the Opioid receptors which are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. These despite the name "opioid" are naturally produced in the body to control pain, give energy, allow pleasure (orgasm) etc.

When pain exceeds the ability of these receptors to handle, we sometimes help the body out by stimulating the body to produce more. This is done with "pain meds" Of course sometimes they produce pleasure which is why there is addiction. These opioid receptors do not handle certain types of pain particularly nerve pain. In the past few years there have been medications developed to help that pain. More progress is needed of course.

Enter LDN and entire new industry (profit motivated) to dispense it (real docs won't for the most part unless every option is exhausted.) They make self proclaimed experts via the Internet along with tons of "testimonials" which creates great SEO (search engine optimization) and suddenly its a buzz. Books are sold speakers are hired alternative practitioners are making tons of cash (insurance won't generally cover it) Nobody mentions (or knows) the outcomes or effects of the medication although the narcotics groups do (and they hate it)

There are a few conditions where early studies seem to indicate it may help NONE of those conditions are close to SS and if in fact the work the way they think it does, is likely to make SS worse by suppressing the ducted gland system.

Could you post a link to the side effects? I've found side effects for Naltrexone and they don't really seem HUGE or DANGEROUS. And Naltrexone is obviously the full force version, not low dose.


Obviously LDN is still being studied, but they do mention that it's low cost and that side effects are mild. And not to get completely off subject but I read a study that that Plaquenil was no more effective than a placebo. Of course the study was only for 24 weeks, but I find it interesting. According to my rheumatologist they don't know how or why it works in some SS patients, but it's only a very small subset of SS patients and it only helps with joint pain and fatigue, not the dry eye or mouth part. I've also seen it described as being able to slow the progression of the disease...but my rheumy didn't allude to that in any way. He said it was possible that it may help with some of my symptoms. But nothing about slowing the progression or protecting from organ involvement.


The study the medscape article refers to was done in France (not that thats bad) It studied ONLY the effects on SICCA. One needs to understand the European view of SS and the North American view of SS is two entirely different diseases.There are part of Europe where they still refer to it as SICCA disease. They don't recognize it for what it is/can be. There is some of that attitude in the US as it frequently is just SICCA and is treated primarily as by Ophthalmologists and Oral medicine specialists and pretty effectively if you see the right ones (there aren't a lot of oral medicine specialists) However the Rheumatologists treat it much differently with additional evidence of disease. They recognize it as a fairly severe Autoimmune disease. The closer you get to the West coast the more aggressively it is treated. (along with most other Autoimmune diseases) Most of the West coat and Northwest trained Physicians will hit it with every tool in the box. Often they start with the old stand-by of MTX as Plaquenil is not aggressive enough for some of the joint conditions they see and that is their primary concern

Although the leading research on LDN in the country has been done by UCSF, they have backed off its use except for MS. There has been about a 10% SE rate with LDN similar to that of full dose. So at this point they are not separating the two. Considering the side effects of mental fog, fatigue, dry mouth etc. its not been tested for SS. so the use with MS, FMS that has some success rate of about 30% (compared with the pretty normal rate of 20% placebo) is not overwhelming

I'm pretty neutral on its use when used where it has been researched and prescribed by a patients long tern team, I am NOT neutral on the LDN industry springing up around it. Whats happening now is LDN isn't indicated for any but a few conditions and then as a last resort (The studies that have found it helpful generally report a 30% success rate as opposed to 22% for placebo)Because of all the "press" folks are going away from their standard treatments to alternative docs and pill mills to get it.

All of this based on phony books. It may be a fine therapy when we know more about it. Its not a treatment without risk, a deep secret kept by conspiracy, nor a miracle

In terms of side effects, keep in mind that even at low doses you can not take most any pain medications including some NSAIDS, limited steroids, and no muscle relaxants or the risks of seizure and very serious events is high. We also have no clue because this is effecting certain glandular action what the long term effects are including and especially the adrenals (think prednisone)

Olive, its important to note that it is well known that it takes Plaquenil as long as 6 months to build up in the system. I've always questioned why they even published a study that only ran for 24 weeks knowing that. I am one of the lucky ones that has seen a vast improvement in fatigue and joint pain. If you haven't suffered from the fatigue its hard to describe how debilitating it is (or was). As far as the joint pain, it doesn't knock it out totally but it makes the flair ups last for a much shorter duration and they occur less frequently. It is true that it started as a malaria medication when they realized that those with RA, etc were doing better. My doc said the same thing that they don't know why it works but it does and the side effects are not only rare, they are easy to monitor for..... I'd say be careful reading some of these studies as they don't always give complete pictures.

I felt my best while on LDN. The side effect profile at this low dose is very low. The only side effect I had, despite my penchant for bad stuff happening with meds, was that it worked like an anti-depressant. I was so happy all the time, it was silly. It worked that way for another person I know too. I did spend the first month or two having vivid dreams, but that passed quickly. Frankly, it was nice to dream again.

I don’t think it typically works that well for Sjogrens, however, it did seem helpful enough for me that it was worth it. I have several autoimmune diseases. It’s so cheap too! I only stopped because my pain became so severe I had to start long acting pain meds. You can’t take opioids while taking LDN, and it was an excruciating choice to make. For many people, LDN is very helpful for their pain. I didn’t get lucky enough to have that side effect though.