Low Dose Naltrexone

[Foreigner]

I've already UTFSE and have had limited info about my question -- plus the threads were old.

I'm considering asking my doctor for an RX for low dose naltrexone, probably in the 2-4mg range. My intention is to see if it would help my auto-immune condition. People with autoimmune have a dysfunctional ratio of the different kinds of T lymphocytes, and the endorphin up-regulation may help stabilize the immune system along with the inflammatory response.

What I'm researching intensely is the dosage ratio. Most people report success in the 1-4mg range. A lot of people start at 1mg and then upgrade to a max of 4mg. Apparently beyond 4mg it doesn't work the same. The immuno-modulatory effect is at 4mg and below. Some people talk about ultra low dose regimens, like below 0.5mg, but this seems a bit preposterous to me. Any thoughts on dosage?

Could I please get some correction on this from anyone with expertise? ---> My understanding is that the low dose antagonizes opiate receptors, in turn causing them to upregulate / increase growth. (I am thinking this could be similar to how low dose ketamine acts on pre-frontal synapses.) The body responds by increasing endorphin release, which has an immuno-modulatory effect. There is a correlation (causation not yet understood though) between people with low endorphin output and dysregulated immune systems. Am I correct in my understanding?

My other question is... if you're doing LDN and suddenly stop, are one's opiate receptors going to suddenly get flooded by endorphins, causing down-regulation again? What I'm wondering is, IF the drug works for my intended purposes, would I have to be on it forever?

Low doses are cheap and non-toxic so it's worth a try. I am just having a hard time finding definitive research. Big Pharma doesn't care about it anymore because it's off-patent, so most of the reporting is anecdotal from individuals who post their stories online. Some stories are miraculous, frankly.

Any experience or theoretical insight would be GREATLY appreciated as I am about to become my own guinea pig. Wanting to gather as much info as possible before the attempt, and I may post an experience report later.

Thanks!!

 

[Cotcha Yankinov]

Hi there

Naltrexone is theorized to work for chronic pain (with a pain amplification component) by binding to and blocking Toll-Like receptors located on microglia - these microglia normally facilitate the pain sensitized state by influencing neurotransmission of the peripheral nerves/spinal cord. Whereas opioids are well known to worsen pain sensitization syndromes like complex regional pain syndrome because opioid agonists bind to and activate microglia. Chronic administration of opioids is actually one way to induce sensitization in animals. The doses used for chronic pain are in the 1mg-4.5mg range. The idea with keeping it below 4.5mg is that there isn't significant antagonism of the opioid receptors at that level, which would worsen pain in those with complex regional pain syndrome etc.

The questions in my mind are
1. Do microglia appreciably contribute to your autoimmune disease
2. If no, are toll like receptors expressed on other immune cells?

Toll Like receptors are upregulated on "activated" microglia and I think that is also part of the reason for LDN's efficacy.

But the MAO for enhancing opioid analgesia is very different, Doses in the .125-.25mg range are used - this has more to do with the opioid receptors themselves (preventing a weird coupling phenomenon) but when it comes to the immune effects and effects on pain, those still occur with dextro-naltrexone, which has negligible affinity for the opioid receptors. Ultimately I think its safe to say that the effects of naltrexone are not due to enhancing endogenous endorphins etc

In regards to rebound after being on naltrexone, naltrexone is probably an inverse agonist meaning that it kinda causes the receptor to disappear, rather than something like a silent antagonist that sits on the receptor and just blocks things from binding, while more and more receptors pop up.

 

[Foreigner]

Thanks for your detailed reply!

In regards to rebound after being on naltrexone, naltrexone is probably an inverse agonist meaning that it kinda causes the receptor to disappear, rather than something like a silent antagonist that sits on the receptor and just blocks things from binding, while more and more receptors pop up.

So that would mean it is still technically harmful, no?

 

[Cotcha Yankinov]

I wouldn't expect too much rebound, I personally didn't get much rebound after being on a couple mg for a couple weeks.

I think side effects like insomnia, restlessness and headaches aren't uncommon towards 4mg though - so there is definitely an advantage to using below 2mg.

 

[Foreigner]

The most reasonable protocol I read is to start at 0.5-1mg and increase to 4mg over the course of 4-8 weeks. The range suggests starting low and then custom tailoring towards one's own physiology. Most of the people I've read about who start right at 4mg get the side effects. So I think I might ask my doctor for 1mg pills, which I can break in half to do 0.5mg or increase to 2mg as desired.

The insomnia thing concerns me. My sleep is already kind of wonky, and I have a lot going on in my life that requires me to be well rested. Some people have written that their first 2 weeks - 1 month of use was chaotic with side effects but after that the benefits became very noticeable; whereas some people said they felt benefit right away. Some said it did nothing, and the minority of the three groups said it caused bad side effects. So it's worth trying.

I seem to be in that sweet zone where I am not in the acute phase of condition and I am about 80% better, but not in remission. Naltrexone may push me over the edge into remission, at least that's my hope. Although there have been many let downs over the past few years in terms of promising treatments, this one has the most potential of anything I've read. So we'll see.

Any last words of advice? TIA

 

[Foreigner]

I just wanted to add that one of my concerns is that this may behave as an immunosuppressant. If it does act on toll-like receptors and microglia, then it would affect the body's ability to recognize invaders in some way. However, this could be a good thing because in auto-immune conditions there is some kind of dysfunction of native cell recognition vs. pathothenic invasion. I'm just trying to weigh the factors. I wonder what happens to people with sub-acute infections who do LDN?

 

[asecin]

extremely hard and expensive drug to get. as most, im curious of its anti-addiction potential but good luck with the current lineup of incompetent doctors i deal with regularly

 

[Cotcha Yankinov]

I'm not aware of any significant immunosuppressant properties of naltrexone, but you think this would be noted in the higher dosages used for abstinence (50mg+). It might be negligible when it comes to fighting off infection. I think naltrexone is mostly useful for subduing activated microglia, which may only play a big role in fighting off CNS infection, T cells etc may be relatively unaffected by naltrexone. I'm not very well read on what immune cells express toll like receptors, and as far as I've seen naltrexone only has efficacy in treating disease involving microglia like chronic pain.

In other words, naltrexone may not do an incredible amount for your condition but it has the potential of stressing you out which could in turn worsen your condition (the diarrhea could be bad for IBS), so I would proceed with caution and avoid doses like 4.5mg which is typically used for chronic pain. Ultimately it comes down to whether or not toll like receptors are relevant to your condition, even if indirectly.

 

[Foreigner]

That's the odd thing though... a lot of people with inflammatory bowel (that's IBD, not IBS) report that naltrexone has put them in remission. Some say it did nothing. A small minority said it aggravated them.

What that probably points to is that the disease name may have different etiologies and naltrexone is treating one branch.

They have pretty much exhausted all options for treating my condition, short of surgically removing my bowels, which is something I won't do. So if things flare up again I could die.

My plan is to try no more than 2mg at the outset, assuming my MD will even go for it.

 

[Cotcha Yankinov]

Hmmm... Well glia are known to influence neurotransmission and neurotransmission is known to influence glia, there is certainly a bridge between the immune system cells and neurotransmission, so you might have a scenario that goes something like naltrexone modulates microglia -> microglia modulate the enteric nervous system, then the neuronal activity of the enteric nervous system could affect the immune cells more directly responsible for UC etc..

But the current "prednisone -> humira -> colon removal" regiment is a bit depressing, you would think that we'd have more to throw at something like ulcerative colitis in this day and age.

 

[Foreigner]

Your theory about the mechanism makes sense. IBD is very sensitive to stress and emotions. One of my holding patterns for emotional challenges is in my gut. It gets tensed and stressed out there. There's already research showing that increased stress modifies gut flora. So maybe if naltrexone can moderate that pathway, it would at least downgrade the condition.

The colon removal / ostomy thing is such a sham. They were making headway with IBD in the late 70's when they were researching the similarities between Jone's Disease in cattle and Crohn's in humans. They were developing testing methods for certain kinds of pathogens that likely had root affects on the condition. But then in the 80's all the funding shifted to steroid research. The pharmaceutical industry is corrupt as shit. They have put all of their eggs in the basket of suppressing the inflammatory response, rather than immuno-modulation or pathogen research.

IMO the root reason for this obtuseness is that if they came out and said that there is a pathogenic origin to IBD, then that would implicate our food systems. The IBD rate in North America has gone up by over 300% since the year 2000. It's not just people's crappy genetics. Something is up with the food.

 

[Sturnam]

The most reasonable protocol I read is to start at 0.5-1mg and increase to 4mg over the course of 4-8 weeks. The range suggests starting low and then custom tailoring towards one's own physiology. Most of the people I've read about who start right at 4mg get the side effects. So I think I might ask my doctor for 1mg pills, which I can break in half to do 0.5mg or increase to 2mg as desired.

LDN therapy will have to be done via a compounding pharmacy; tablets aren't mass produced at doses less than 50mg. Which means you will either get individual capsules (not amenable to breaking) or a liquid solution. Liquid solution will provide more accurate dosing with better increments, but it can go 'off' more quickly. Either way it might incur a fair bit of cost.

An alternative is to source out some 50mg pills and make your own solutions with it. You can use the dilution method (50mg pill in 50mL; then 1mg/mL) for dosing and freeze any excess solution which will help it last longer. Thaw as needed.

IMO the root reason for this obtuseness is that if they came out and said that there is a pathogenic origin to IBD, then that would implicate our food systems. The IBD rate in North America has gone up by over 300% since the year 2000. It's not just people's crappy genetics. Something is up with the food.

It's probably something to do with food, although that doesn't necessarily mean it's a pathogen. Maybe it's a lack of beneficial microbes. Or something unique related to our geographical location. Do you think that it's pathogenic bacteria? Viruses?

 

[Foreigner]

It's probably something to do with food, although that doesn't necessarily mean it's a pathogen. Maybe it's a lack of beneficial microbes. Or something unique related to our geographical location. Do you think that it's pathogenic bacteria? Viruses?

People like me are canaries in the mine. Our GIs were weak from a young age for various reasons, so the toxic foods set us off first. Wheat is #1 because they drench it in glyphosate before harvest, a chemical which is known to erode the GIs of animals. Soy is another. The GMO foods are all suspect, not because of their genetics but because they are resilient to ten times more pesticide than regular plants, which people end up eating. Most of the food people are eating now is nutrient depleted. Industry thinks that spraying food with nitrogen, potassium and phosphorus is all that's needed because it grows healthy looking plants, but the soil is completely depleted of other nutrients and beneficial bacteria. People eat empty food which weakens their bodies, and then it makes them more susceptible to leaky gut and pathogenic invasions.

I also think the factory meat industries are involved somehow in introducing chronic pathogens into people's diets. Bacteria and protozoa are problems, but they tend to cause more acute problems. I'd be much more suspicious of mycobacteria, especially in dairy, and of viruses. The level of food borne contamination in the U.S. has skyrocketed in recent years. All the antibiotic use has created super bugs, and the regulatory agencies are more hands off now so factories are not as stringently inspected. You have vegetables often being processed in the same mega factories as meat. How else do people die of e. coli poisoning from eating spinach?

Monsanto co-owns many pharmaceutical companies now. So they create the problem and then create the "treatments", which are drugs that just suppress the immune system. Obama passed the Monsanto Protection Act which prevents anyone from suing them. The level of greed in corporate society is ridiculous, it has infected everything.

 

[DixiChik]

Foreigner...I, like you, am facing the grim reality of losing my colon (if not my life). My GI issues are complex too, but detailed in my posts dating back to join date at BL in 2015.

I, like you, REFUSE to surrender my colon even though I am much older than you (55).

I am subscribing to your thread, as I desperately need answers too.

Meanwhile...Your last paragraph especially rings my bell, as I feel that I am "living" (am I?) proof.

(((HUGS)))

 

[serotonin2A]

People like me are canaries in the mine. Our GIs were weak from a young age for various reasons, so the toxic foods set us off first. Wheat is #1 because they drench it in glyphosate before harvest, a chemical which is known to erode the GIs of animals. Soy is another. The GMO foods are all suspect, not because of their genetics but because they are resilient to ten times more pesticide than regular plants, which people end up eating. Most of the food people are eating now is nutrient depleted. Industry thinks that spraying food with nitrogen, potassium and phosphorus is all that's needed because it grows healthy looking plants, but the soil is completely depleted of other nutrients and beneficial bacteria. People eat empty food which weakens their bodies, and then it makes them more susceptible to leaky gut and pathogenic invasions.

I also think the factory meat industries are involved somehow in introducing chronic pathogens into people's diets. Bacteria and protozoa are problems, but they tend to cause more acute problems. I'd be much more suspicious of mycobacteria, especially in dairy, and of viruses. The level of food borne contamination in the U.S. has skyrocketed in recent years. All the antibiotic use has created super bugs, and the regulatory agencies are more hands off now so factories are not as stringently inspected. You have vegetables often being processed in the same mega factories as meat. How else do people die of e. coli poisoning from eating spinach?

Monsanto co-owns many pharmaceutical companies now. So they create the problem and then create the "treatments", which are drugs that just suppress the immune system. Obama passed the Monsanto Protection Act which prevents anyone from suing them. The level of greed in corporate society is ridiculous, it has infected everything.

Can you go into more detail about how you define "empty food", or how food that is not measurably nutritionally deficient can be defined as nutritionally deficient? I've certainly heard these kind of claims before, but they never make much sense to me. It has always been my impression that deep down they are based on an emotional discomfort with modern farming and agricultural methods, rather than any type of objective assessment.

It is also my general impression that people in Europe/N. America tend to be overnourished, as evidenced by the current obesity epidemic. People have a lot of health problems due to over-consumption of processed food and poor diet, but actual nutrient deficiencies seem to be very uncommon.

 

[Foreigner]

Can you go into more detail about how you define "empty food", or how food that is not measurably nutritionally deficient can be defined as nutritionally deficient? I've certainly heard these kind of claims before, but they never make much sense to me. It has always been my impression that deep down they are based on an emotional discomfort with modern farming and agricultural methods, rather than any type of objective assessment.

It would be hard to summarize my years of experience. I've worked in biodynamic farming and done a huge amount of research as part of my own health condition. When you eat fruits and vegetables, you are basically eating a converted form of the earth. Try to think of it that way. So all the beneficial microbes in the soil, interwoven ecology, and nutrition ends up in food. Most land is left fallow for at least a full season following a crop. On non-conventional farms they rotate the crop fields to different locations yearly. The field that is left fallow is tilled and enriched throughout the season in prep for next year. One farm I worked on had enough acreage that they left sections fallow for 3-4 years.

Industry farming doesn't do that. They basically strip mine the soil until there is nothing left, and the soil desertifies. They compensate with huge amounts of petrol-derived fertilizers that in of themselves sterilize the soil due to their concentrations. There is very little probiotic content in the food because it has been chemically sterilized. A chicken's egg is a great example... chickens raised free range without antibiotics can lay eggs that stay good in the open air for a week or more. The probiotic content on their shell prevents spoilage. Not so with conventional eggs. The same is true of raw milk. It contains all the enzymes necessary for digestion, plus probiotic content to furnish the bowels with healthy flora. But after a single TB outbreak decades ago, they decided all milk must be pasteurized, which kills everything that protects the milk from being invaded by harmful micro-organisms. A dominant theory in the IBD community is that paratuberculosis (a different strain) actually thrives in modern dairy for this reason, and may be a leading cause of IBD. There is a Crohn's researcher in Ireland working on a testing method and vaccine for this microbe right now, with clinical trials set to begin this year. No current testing method is available. PTB can only be killed with a harsh triple antibiotic regimen for minimum 90 days, and even then it might not work. Industry cattle get their equivalent of IBD in the form of Jone's disease, and it's always in cattle who have received chronic antibiotic treatment. Their own gut flora are sterilized and they become susceptible to infection, the same thing that happens to humans when they eat meat that was treated with anti-biotics.

Even so-called "organic" food on the market is conventional-organic. They are mass producing food and not using traditional methods which preserves its integrity.

I could go on and on...

It is also my general impression that people in Europe/N. America tend to be overnourished, as evidenced by the current obesity epidemic. People have a lot of health problems due to over-consumption of processed food and poor diet, but actual nutrient deficiencies seem to be very uncommon.

That's not exactly accurate. As a society's standard of living increases they tend to eat more nutrient-deficient luxury foods. High calorie, not much nutrition. So that is part of it. The other part is that processed food contains a lot of additives that behave like synthetic estrogens. If you look at the obesity in the U.S. and compare it to the "fat" of other countries, the U.S. "fat" is very watery, includes all parts of the body and not just the trunk. Extracellular fluid is greatly increased in the presence of these pseudo-estrogens. People are eating more and more calorie rich food in order to scavenge missing nutrients, nutrients that are either missing from the food completely (due to being in the junk food category) or because the food itself is depleted. The medical industry's solution now is to provide gastric bypass surgery, so that people eat less and lose weight, even though they are still de facto starving. People don't eat non-stop unless they are deficient in some way, or the food additives have made them addicted.

Recent research shows that multivitamins are poorly absorbed. The standard stuff most people buy has a 10-20% absorption rate. It's a bit concerning because part of what the biomedical industry has done is try to tell people they can make up for their lost nutrition with supplementation, but it turns out that may not be true at all. We may only be able to get an efficient amount of what we need from whole food, and if the food systems are deficient then we have a population that is basically starving even though they have access to enormous calorie intake.

 

[Nagelfar]

Foreigner...I, like you, am facing the grim reality of losing my colon (if not my life). My GI issues are complex too

(please read the tagged "post-script"/'afterword' of this post as to (I earnestly hope) allay the possibility of offense to this serious issue from one to whom you were not even directing your business)

If the colon comes off just use the semi-colon; most'll never notice the omission of the punctuation.

*Afterword*
P.S. However I must commiserate my own very tenuous path, very possibly fraught with unrealized peril at a future as a "bowel cripple" (as one LPN dubbed it colloquially)- I have been taking loperamide at or above 200mg (100 tablets) daily for over two and a half years; I have discovered those in real time who claim family members (her mother, this specific case) have been taking nearly as much for 12 (twelve!) years. I wish you the best in dodging this pitfall, our mindset begins our lack of respect to our bodies and I wish we all find the peace we need to heed the calling resulting in the best to our health always.

 

[DixiChik]

Huh?

I had IBS with horrid diarrhea for almost a decade, after gastric bypass surgery. Lomotil kept me from soiling myself on the daily. In 1993 I finally got a true diagnosis, but only during liver failure. I had stage 4 endometriosis. The disease choked my bowels and bladder. My IBS with D became "with C".

Nagelfar...I don't understand your post, using my quote. For now, it remains my decision whether or not to undergo surgery, which may or MAY NOT correct my issue.

I have no desire whatsoever to derail Foreigner's thread. I wish you the best, whatever your situation. Meanwhile, I'm lost in the translation.

 

[Foreigner]

Just wanted to post a follow up.

My doctor was sympathetic and prescribed 1.5mg naltrexone compounded capsules. I'm doing 1.5mg for 4 weeks then upgrading to 3mg after that. I realize these doses could be sub-optimal given what all the anecdotal reports say, but my body never fits the standard model when it comes to drugs so I'm starting small.

I slept like shit on my first night, which was last night. I also had diarrhea at dawn, but it might have been from something I ate.

I took it at 11:30pm and fell asleep, woke up at 12:45am. It actually reminded me ever so slightly of a ketamine blockade and I was surprised at the minor mind altering effect. It also concerns me because I don't want this to affect me cognitively. I am now reading that naltrexone can behave like a novel anti-depressant... this explains the change I am experiencing.

It is said that the LDN protocol has most of the side effects in the first 1-2 weeks. So I'm going to give it that amount of time to sort out. If I start feeling that mind-numbing quality that anti-depressants induce, I'm aborting the protocol. I know it's not a traditional anti-depressant but my life right now is stone cold sober and I don't want my cognitive perceptions fucked with one iota.

 

[Mysterie]

yeh foreigner it took me about 3-5 days at 0.5mg foreigner, at least i think thats what i started on i forget but i had a thread here about it. after then the insomnia goes away and whatever side effects there are, they were too subtle for me to feel.

once you increase the dosage by say 0.5mg the insomnia comes back for about 3 days, most people seem to say you get full positive benefits once your at 4mg.

i thought it was a worthwhile experience, from what i read people will take it for 3-4 weeks, then break for a month and do that again?

i hope it works out for you, i know that feeling of hoping for redemption in the pill, the excitement wore away for me as it usually does with trying novel drugs. my purpose was depression though and its promising the anecdotal evidence for anti-inflammatory properties.