Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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Microglial Inhibition by LDN.

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Ema, Nov 20, 2014.

  1. Ema

    Ema Senior Member

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    I understand that there are two pathways that LDN can work by - either by blocking the opioid receptor or through the TLR4 pathway.

    As far as dosing LDN, I've also read that dosing once a day is best for increasing the endorphin levels through the rebound effect but that dosing twice a day (or more) may be more helpful for reducing the overall inflammation through the TLR4 pathway. It seems like this might be the more useful method in ME/CFS if indeed LDN works by inhibiting the microglia more than through the endorphin boost.

    I wonder if there is anyone out there that has experimented with dosing LDN twice a day versus the more commonly suggested once a day plan?

    Thanks!

    Ema

     
  2. melamine

    melamine Senior Member

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    @Ema - I recently tried LDN at 1.5mg and by day 2-3 was feeling worse enough to stop, but unsure whether it was that. I resumed a few days later, trying a lower dose for several days or more but increased nervous system symptoms and fatigue again led me to stop. Whatever caused it, I still have not "recovered" to my former status since more than a week. Although I had increased fatigue for a week or so before beginning the LDN trial, it seems the most likely source of exacerbation and I have pretty much decided to try to sell my remaining meds. It is compounding pharmacy Rx and I have nearly 6 months supply when dosed per usual recommendation.

    btw - someone posted a link on pr recently to an "Autoimmune Summit" hosted by Amy Myers, MD, in which she was asked if she ever prescribes it and she said she has or does at times, but said not everyone responds. She didn't sound all that enthusiastic about it. I'm curious myself about how many people have had bad experiences with it and what kind of trial they did before concluding that.
     
  3. Ema

    Ema Senior Member

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    I started out at 1.5 mg as well and had a massive candida flare. I didn't even know I had a yeast problem until then though it is not surprising given Lyme antibiotic treatment. So I took a week off to start Diflucan and Nystatin and then restarted the LDN.

    It also has been causing me some symptoms and I've gone back and forth on whether or not to ride it out because they are all commonly mentioned when people talk about starting LDN. I've mostly had some increased pain and spasm in my bad shoulder and headaches. I've also had to increase my daily cortisol dose.

    The worst has been increased anxiety though. I just feel edgy all the time. Ugh!

    I was taking it in the morning because while it makes me sleepy at first, I tend to wake up 3-4 hours later as it wears off. Now I'm taking 3 mg at night and that seems to be fine. Knock wood.

    But I can't decide if it would be better or not to take a split dose. I guess all I can do is try!

    I'm pretty much committed to giving it 6 months. That seems to be when people start raving about it. Wish me luck!
     
    Last edited: Nov 20, 2014
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  4. Sushi

    Sushi Moderation Resource Albuquerque

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    I am one who has taken it successfully for years, though it took over 4 months to get up to dose with bumps in the road each time I increased.

    I have always taken it at night out of concern about how I'd feel during the period that the opiod receptors were blocked.

    Still, reading about microglial inhibiting properties, maybe I'll experiment with splitting my dose.

    Sushi
     
  5. Ema

    Ema Senior Member

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    How much are you taking now @Sushi?

    I plan to stay at 3 mg for a while. Hopefully things will level out again. It's a change anyway. Hopefully a positive one someday!
     
  6. andre79

    andre79 Senior Member

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    @melamine i have read a lot about LDN lately. Maybe your issue is that you started with a rather high dose? In the case i decide to try i would start with 0,25 mgs and slowly increase it.

    About the candida, it would make sense to supplement with a strong probiotic during the ldn treatment? I really don't want a candida flare and i have that tendency.

    @Ema i have not idea about splitting the dose, but reading the ldn forums it seems to be a trial and error matter. Some people feel better taking it in the morning, others in the night and some twice a day. So i guess you will have to figure out which one is good for you, trying the different protocols.
     
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  7. melamine

    melamine Senior Member

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    @ Ema - I think your anxiety symptoms are probably something I also experienced - muscles tense but vibrating, like neuromuscular anxiety on its way to paralyzing fear, feeling like microspasms in windpipe, pressure around heart and lungs. I guess if I were feeling better by now instead of same/worse, I would be feeling more optimistic that I can handle it and that it would do any good.

    @ Sushi - do you recall what were your worst symptoms in early days of use? Did you ever have to stop and start?
     
  8. Ema

    Ema Senior Member

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    I'm taking VSL #3 along with the Diflucan and the Nystatin. I think a probiotic is definitely a good idea.
     
  9. Sushi

    Sushi Moderation Resource Albuquerque

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    I am taking 3 mg now. I took 4.5 mg for a year or more then it started to make me groggy in the a.m. I now adjust my dose according to its effect on my wake/sleep cycle.

    Sushi
     
  10. andre79

    andre79 Senior Member

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    What was your start up dose @Sushi ?
     
  11. melamine

    melamine Senior Member

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    @ andre79 - Thanks, andre. Probably the lowest dose I tried was .5 - .75.
     
  12. natasa778

    natasa778 Senior Member

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    I found it extremely dose sensitive, had to stick to between 2.5 and 3.5. Anything over or UNDER was bad, but staying within that frame was very good.

    Not saying it would work for everyone, but I've heard it from few others too that bad effects go after dose is increased, after that 'sweet spot' is found... But as Sushi said it may need readjusting again after a while
     
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  13. Sushi

    Sushi Moderation Resource Albuquerque

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    I started at 1.5 mg but that seems to be too high for many. Each time I increased the dose I waited until about a week after any new symptoms settled down, before raising it again.

    Sushi
     
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  14. NK17

    NK17 Senior Member

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    I've been taking 3mg once every other day for several months, in the early afternoon.

    I might start to take it every day, instead of on a sort of as needed basis. It does help with pain, not sure if it's helping my immune system, my NK cells function is at the bottom of the barrel.

    When I first started taking LDN at night, a few years ago, it gave me sleep disruption problems, that is why when I restarted it at 3mg I took it in the daytime.

    I'm planning to continue taking it.
     
    Last edited: Nov 20, 2014
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  15. Ninan

    Ninan Senior Member

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    I started taking 4,5 mg three years ago and had immediate effect: More energy, a bit of insomnia. Sadly the effect wore off completely after a few weeks. I've continued taking it for RLS. (It takes away my RLS symptoms after only 15-30 minutes so I've thought that must be another mechanism.) But since reading that some people take lower doses I'm considering trying a lower dose. Any input on this? Is it possible that a lower dose might work when 4,5 mg doesn't? Or is the only reason to try lower doses that you don't tolerate the higher dose?
     
  16. melamine

    melamine Senior Member

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    Ninan - I had a bad response at any dose, having started at the prescribed 1.5 and experimenting with much lower doses after that. You appear to be a very good responder and highly tolerant of a dose that is for many people, only tolerable after weeks or months of titrating up. Maybe you would want to consider working up to a higher dose in that case, since 4.5 is only an average max. and dosing is highly individual. Some experts believe that a pulsed dosing schedule will reap more sustained benefits from immunomodulatory therapies, including LDN, once an effective dose is found.
     
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  17. bertiedog

    bertiedog Senior Member

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    I have been taking LDN for over 5 months now with some good benefits but I still cannot take more than 1.2 mg. I have been very sensitive to it right from the start and the effects come on very quickly. I can get extremely light headed with it and then it will affect my vision. These effects I found to be very unpleasant and would cause bad anxiety which I don't usually suffer from so it is obviously affecting my CNS.

    However after a couple of weeks and gradually building up to 1 mg the side effects stopped. The benefits seem to be much better mood, less pain, less migraines though still a tendency to get bad ones and greater energy. My immune system is also improved but this is also probably due to 3 months + of some of the Cowden herbs plus Andrographis and Japanese Knotweed. Also my excema is improved.

    I did stop it for 3 weeks at the end of September but definitely lost ground so I did an Excel spreadsheet to check out how I had been before LDN and after and it was very obvious that I benefitted from it so restarted and again suffered side effects for about a week.

    I have wondered whether the side effect is anything to do with the fillers or if its the medication itself. I get mine in a liquid form from Gibsons pharmacy in Glasgow.

    Pam
     
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  18. melamine

    melamine Senior Member

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    @bertiedog - In my case there may be an exceptional reason: after many years of illness I have developed a complicating condition called IgM MGUS - monoclonal gammopathy of undetermined significance - except in my case there appears to be significance: although a number of people with labs suggesting this may be symptom-free at first ("undetermined significance"), I have a progressing neuropathy that could very well be related to it, as no other cause has been found. Researching this past week, I discovered that neuropathies associated with the IgM form - of a cluster of related conditions - is the least treatable and in particular, is considered to be unresponsive to standard immunomodulatory therapies. For this additional reason I have stopped even a very low dose of naltrexone for now until I can gather more information.
     
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  19. Indigophoton

    Indigophoton Senior Member

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    Timely post for me: I have just started LDN (day 9 today) and, contrary to my expectations, have so far found that, on days where I notice effects, I feel better while the opiod receptors are blocked than when they are released. The difference is enough that I had actually wondered whether taking it more often would be a good thing.

    I started at 1mg, and wimped out of possible (extra) insomnia strategically scheduled it for the morning. I thought I would feel really rough for a few hours with the reduced opiod action, so I was very surprised to find that within about 15 minutes after taking the first dose I suddenly felt a lot better - a sudden, distinct, and very welcome uplift from feeling terrible from a very rough night to feeling rather good. A feeling of cognitive brightening too. I was so surprised that I spent a while trying to figure out what could be causing it, because I thought it couldn't be the LDN acting that fast.

    After about 1hr 45 mins I felt enough physical energy that I actually needed to sit up in bed. This I can rarely do, and usually only for a few minutes before all my energy drains away and I have to lie down again. This time, however, I was still merrily sitting (well, OK, slumped, as no muscle strength) 45 minutes later, and no PEM!

    Day 2, no cognitive brightening but after 40 mins a noticeable physical shift away from rough to quite pleasant, and my very stiff and painful neck and shoulder muscles loosened and melted (this also happened on day 1); the stiffness has not returned since day 2.

    Day 3, no noticeable effects, other than a mysterious absence of the usual kind of PEM, and same until day 8 when I upped the dose to 2mg: again the feelgood effects almost immediately.

    Day 9, today, didn't really notice anything.

    Overall so far my PEM threshold seems to have shifted, body feels more comfortable (despite still sleeping very badly, which pre-dates the LDN by several months), my stuck glands (swollen, painful) have gone down, and when I have overdone it the result has been exhaustion and feeling bad but without any immune aspect - no fever, fluey symptoms etc.

    That said, it's all relative: I am still rather less functional than a zombie (they're very mobile, after all ;)), but it seems a promising beginning.

    I can't say for sure whether I have any extra energy because I am still sleeping very poorly, which is very debilitating, and maybe muddying things a bit. I am still quickly exhausted, but it feels different: less sick, more very unfit, in a way.

    I've been a bit mystified as to why the feeling better started so soon after taking the drug; it can't be an opiod-related result. One could suspect placebo, but as I expected to feel bad whilst the opiod receptors were blocked, that doesn't seem to fit very well. I have also wondered whether it is microglially related.

    I wonder whether @Jonathan Edwards could comment on whether blocking microglial action could have such a rapid effect, and whether it could reduce immune type symtoms in general?
     
    Last edited: Nov 30, 2014
  20. Ninan

    Ninan Senior Member

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    My RLS relief comes within 30 minutes and the energy effect I had in the beginning came within 20 hours. It's definitely not placebo.
     

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