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LDN - how's it working for you?

I've been on LDN for...


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debored13

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So...I started taking LDN again. I've taken it in the past (2007) and worked my way up to 4.5mg rather quickly as I remember. I think I only stopped taking it due to finances.

I don't remember having that much trouble with this the first time. So this time, 10 years later, I started with 2.25mg for a few days then went to 4.5mg. 2.25 seemed okay, but when I went to 4.5, I had a headache immediately and was really uneasy, restless and felt generally ill. I figured out quickly that's what was new in my routine, so I stopped it.

With my good history with this medication, I confidently restarted again the other day with 1.5mg. But, I did that for a few days, and I feel like it's just making me feel generally ill. Heaviness in my stomach, insomnia, lessened appetite, I think more frequent urination and just general sickness and malaise.

My doctor originally restarted me on this to calm my immune system down. It was riled up from something else I took (it's activated, not suppressed according to blood tests) and I was feeling achy. He thought the LDN would help regulate my immune system and lower inflammation thus, lower these symptoms.

But now it seems LDN may be actually causing more malaise and sickness. Does LDN do this as described? Does anyone know?
Low Dose Naltrexone is still naltrexone. naltrexone is an opioid antagonist. like the opposite of an opioid, if that helps you understand. It probably simulates mild opioid withdrawal, since it's blocking your endorphins from binding to opioid receptors to some extent. emphasis on to some extent, since it's low dose naltrexone, what should happen is that your opioid receptors upregulate to compensate, thus causing you to be more sensitive to endorphins. This is all very approximate so I wouldn't find it odd to feel like shit for the first few days and then start feeling better, even hypomanic.
 

debored13

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Low Dose Naltrexone is still naltrexone. naltrexone is an opioid antagonist. like the opposite of an opioid, if that helps you understand. It probably simulates mild opioid withdrawal, since it's blocking your endorphins from binding to opioid receptors to some extent. emphasis on to some extent, since it's low dose naltrexone, what should happen is that your opioid receptors upregulate to compensate, thus causing you to be more sensitive to endorphins. This is all very approximate so I wouldn't find it odd to feel like shit for the first few days and then start feeling better, even hypomanic.
LDN probably also has effects on TLR4 receptors which are responsible for immune response and inflammatory cytokine release, so that's another thing I left out. sorry, very tired and brain foggy.
 

Thinktank

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Even a difference of 0.5 in dosage can make things better or worse.
We ran out of the 1mg pills so my gf has been on 1.5 for the past 2 nights and she had trouble sleeping, that's completely opposite to the effect 1mg has, which drastically improves her sleep!
 

2Cor.12:9

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Even a difference of 0.5 in dosage can make things better or worse.
We ran out of the 1mg pills so my gf has been on 1.5 for the past 2 nights and she had trouble sleeping, that's completely opposite to the effect 1mg has, which drastically improves her sleep!
That's been my experience too. I've been on LDN 2 years, got up to 4 mg and had to back down to 1 mg. I've been on 1 mg for a year and its perfect. Tried going off and within 2 weeks I could hardly move from pain and stiffness.
 

confetti11

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Thanks @debored13 @Thinktank @2Cor.12:9 for your input. I really appreciate it. From everyone's input, there seems to be a point where the body says "nope" and you have to work the dose up to move past that.

I guess I wouldn't have been surprised at all (because I can be extremely sensitive to things) if I hadn't taken this drug seemingly without incident before.

I think things may be dying down except....is there any reason why this stuff would stir up gastritis? I only took about 5 doses before I stopped the first time (2.25 and 4.5) and then a few days after I stopped...the burning and burping started and it's still going on about 2 weeks later. I hope this just clears up on its own. I'm not exactly sure what's causing it. I feel like a whack a mole of symptoms.
 

JES

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I think things may be dying down except....is there any reason why this stuff would stir up gastritis? I only took about 5 doses before I stopped the first time (2.25 and 4.5) and then a few days after I stopped...the burning and burping started and it's still going on about 2 weeks later. I hope this just clears up on its own. I'm not exactly sure what's causing it. I feel like a whack a mole of symptoms.
I did notice an increase in acid reflux symptoms, which I think is due to increased stomach acid from this drug. This acid reflux increase came even when I was careful and started with 1 mg. But thankfully, as I wrote, it went away after around 2 weeks, probably my body adjusted to the drug in that time. I would be more concerned about other symptoms than stomach symptoms, stomach symptoms are a common side effect of many medications. I get them myself almost on every second drug/herb I trial.
 

JeanneD

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It gave me (I think it was the LDN) more than just a flu-like feeling. It gave me a very dark emotional sensation along with the physical heaviness.
My daughter and I got this in the very beginning. Our doctor advised us to take the LDN at bedtime so we would be asleep during those symptoms. There's a biochemical reason why that happens and why it only lasts a few hours in many cases, but I've forgotten what it is in the ensuing years. Something about temporarily blocking certain receptors, perhaps?

[ETA: I see @debored13 explained it above "...it's blocking your endorphins from binding to opioid receptors to some extent. emphasis on to some extent..."]

Taking it at night worked like a charm. No more uncomfortable side effects.

We were also told that the dark emotional sensation is a sign (in most, not all, cases) that the dose is too large for the stage of adjustment. In other words, back down and increase much more slowly.

Anyway, I just kept taking it at night for years because why not? When the doc recently upped the dose, I needed to split it, so now I take the additional dose in the morning and have none of the uncomfortable side effects. Again, I'm increasing dose very slowly -- 0.1mg every day or two, starting at 0.1mg.
 
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JeanneD

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Even a difference of 0.5 in dosage can make things better or worse.
We ran out of the 1mg pills so my gf has been on 1.5 for the past 2 nights and she had trouble sleeping, that's completely opposite to the effect 1mg has, which drastically improves her sleep!
I could not tolerate that much of a dose change that suddenly! This med requires slow increases in most PWME. Some people can do great on 1.5mg and do poorly on 1.7 mg even after a long (non)adjustment period. Dosing seems very sensitive in some people.

Where are you getting 1mg pills? Where I am the minimum is 10mg and the LDN has to be compounded to get the lower doses.
 

confetti11

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@JeanneD that's interesting, thank you! I stopped it for now but will pick it up very small amounts at a time when I get a chance.

Do you guys this this drug could do weird things to your cycle? I'm supposed to be menopausal (somewhere in that process) and I feel like I almost had a mini period this month, with some premenstrual symptoms and everything. I haven't had that for a while.
 

JeanneD

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@JeanneD that's interesting, thank you! I stopped it for now but will pick it up very small amounts at a time when I get a chance.

Do you guys this this drug could do weird things to your cycle? I'm supposed to be menopausal (somewhere in that process) and I feel like I almost had a mini period this month, with some premenstrual symptoms and everything. I haven't had that for a while.
Also menopausal and had no menstrual symptoms. Neither did my daughter who is child-bearing age. Can you be more specific about the premenstrual symptoms? They might be related to ldn.

There are several reasons for post-menopausal spotting/bleeding unrelated to LDN. They are not particularly uncommon in the earlier stages like endometrial hyperplasia. It might bear checking into if it persists.
 

confetti11

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@JeanneD
Not overly worried about it at this point. I've had spotting all through this time because of HRT, but this time, it mimicked more like a period. No subtle way to put it...my boobs hurt.
 

JeanneD

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@JeanneD
Not overly worried about it at this point. I've had spotting all through this time because of HRT, but this time, it mimicked more like a period. No subtle way to put it...my boobs hurt.
Nope, nothing subtle about menstrual and premenstrual symptoms. :p Can't say either of us had that particular uncomfortable symptom. Sounds like a progesterone thing, but who knows?
 
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Hi all,

my wife is a CFS sufferer and we havent yet tried this option, she recently asked her GP ( we are UK based and it seems she cannot prescribe it and it goes to some special team...for which there's a waiting time of over a year. ) Can anyone UK based tell me a good source to buy LDN for her to try out?

Thank you
 

JES

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@shicky This website prescribes LDN based on online consultation with a doctor. The other option would be to order it without prescription from one of the well-established online pharmacies.
 

flitza

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I would love to hear about this from someone who has experienced something similar, or is good with pharmacology. Naltrexone is an interesting drug and it is the only thing that has helped me. Yet it has some intense side effects. If i could a) find the right dosing schedule or b) just stick to it as an occasional mood booster, I would be happy to use it.

I also think naltrexone at the right dose would be a great add to opioid or kratom use. Remember that I said at the right dose. At too high of a dose it would cause precipitated withdrawals when added to the mix. There is a difference, dose-wise, betweeen Ultra Low Dose Naltrexone and Low Dose Naltrexone. The latter (generally doses above 1mg, would almost certainly cause precipitated withdrawals if taken when a patient was already on opioids. However, if you wean totally off opioids/kratom first, and then add the Low Dose Naltrexone before the opioid, it does not cause precipitated withdrawals. However, if you can't wean off for some reason, Ultra Low Dose naltrexone is your best bet, as it can be taken in that dose range with no risk of precipitated withdrawals--in fact they are working on a pill (called oxytrex) that has ULDN alongside oxycodone.
I have started on LDN for a CFS diagnosis.

I figured Naltrexone has such few side effects even at higher doses, it would be unlikely if it had side effects at doses far lower. However, after a little reading up on the (admittedly scant) literature on LDN, and some odd effects, I'm a little less sure about its safety. I figured I'd ask here.

I have tried LDN and stopped a couple of times. Each time, I'd get initial benefit (mental energy mostly) with almost no side effects--no insomnia, anything, and then after a few days to a week it would gradually start to have more intolerable side effects. I initially felt overall more happiness/pleasure/mental energy and even sort of "high", but in a subtle way. Then each day after, these feelings would get more intense until it was distracting, not pleasurable or helpful anymore, and seemed even dangerous, as if the drug was building up in my system. I had insomnia, tension, and extreme mania (I have had no diagnoses that correspond with mania and have not experienced mania from, for example, stimulant medications).

I'm torn. On one hand, this is a really shitty disease and if it showed any benefit I want to see if it can be used, maybe at a smaller dose? On the other hand we don't even know if Low Dose Naltrexone is safe, and it seems quite possible that it has qualitatively different effects at a low dose. This paper https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/ notes those effects, and in way of context, discusses the fact that morphine, at doses 1/10 of analgesic doses, produces hyperalgesia. The main hypothesis in this paper is that naltrexone modulates microglia and has effects on TLR4, which explains its anti-inflammatory and immunomodulatory effects. However, they note that another possible explanation is that partial blockade of the mu-opioid receptor leads to compensatory upregulation, making people more sensitive to their endorphins. Dextro-naltrexone was proposed for more study because of not having any affinity for opioid receptors, yet having the same anti-inflammatory effects as naltrexone.

My guess is that I am experiencing the effects of upregulation of opioid receptors, with some downstream effects on dopamine, that could explain the mania and "high".

What is tougher for me to understand is why the effects seem cumulative and whether we could come up with a workable dosing schedule based on that. Could the cumulative effects simply be explained by a gradual upregulation of opioid receptors? Or would they be explained by the longer half-life (12-18 hours) of naltrexone's main metabolite? Or to the fact that smaller amounts can continue to be absorbed in the gut for up to days afterwards?

Sorry, this is a little rambling, but my main questions are: a) Why is this phenomenon happening? b) is there a physical danger? e.g. mania is obviously a scary effect, but is there an actual direct physiological danger to low dose naltrexone that's separate from normal doses of naltrexone, and c) Would it be possible/advisable to try a different dose or different dosing schedule for this patient?

If dextro-naltrexone was available, I would absolutely take that in a heartbeat. However, I don't think that will be available for a long time, unfortunatley.
Just a quick thought about the effects being cumulative as you suggested. I have heard that some people may have a slower clearing of their receptors and have found that skipping a day or two per week or taking on alternate days has helped...
 

debored13

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Just a quick thought about the effects being cumulative as you suggested. I have heard that some people may have a slower clearing of their receptors and have found that skipping a day or two per week or taking on alternate days has helped...
i may try that, thanks

the effects can be potent but unpredictable and have raised blood pressure temporarily, probably by raising ACTH... so while its occasionally a helpful get-out-of-bed tool, idk about regular use
 
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@shicky This website prescribes LDN based on online consultation with a doctor. The other option would be to order it without prescription from one of the well-established online pharmacies.
Can you give me an idea of these well established pharmacies as I cannot find it available? Is the online prescription route a much more expensive one?
 
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I spoke to a medical professional who has a dim view of LDN, due to it eventually leading to increased th17 cytokines, which is what happens when you suppress other arms of immunity when attempting to treat autoimmunity. I still am not clear on how LDN works, whether it suppresses, balances, increases immune function. I do not think it is as simple as the pro LDN sites present it as.
 
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Can you give me an idea of these well established pharmacies as I cannot find it available? Is the online prescription route a much more expensive one?
You can order the 50mg tablet from online pharmacies and dilute it yourself in water. It is much less expensive than compounding pharmacy. It is also available on a couple research chemical websites in liquid form ready for use.