Low Dose Naltrexone (LDN) Support
People's personal Experience on LDN
Discussion started by jamison 12 years ago
I'm just about to start LDN and thought it would be a good idea to create a discussion so those currently on treatment can share their experiences with others. I am convinced that immune disturbance and allergy is a major player in my CFS and became interested in LDN when I learned it could help modulate and rebalance the immune system as well as make one feel much better by raising endorphin levels. I'm just about to take my first dose of 3 mgs and plan to post about my progress here. So here goes....
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Redozipous
I stopped LDN a couple of days ago, and now I've got this creepy tingle across my body. Been here two days now. I guess it'll subside soon.
Been on LDN for about 1/2 year, at a dose I guess is more than many take.
Thinking about beginning on LDN again some time in the future.
Been on LDN for about 1/2 year, at a dose I guess is more than many take.
Thinking about beginning on LDN again some time in the future.
12 years ago
Maff
I agree with Redo. I am sure the vast majority of those of us using LDN for CFS would only see an improvement in symptoms and our functional capacity as a success. Of course a disease like MS is different entirely as it is denegerative so stabilization would undoubtedly be a great result.
Redo - Control genes can apparently be defined "as genes that are ubiquitously expressed at stable levels in different biological contexts, have been used to standardize quantitative expression studies for more than 25 yr." So they serve as a "normal" reference in quantitative testing as far as I can tell. The role they would play in immunological testing and their importance for tests such as those performed by Red Labs - I just don't know.
The results provided by Red Labs ARE relative since they are presented as ratios between Th1 and Th2 cytokines. What I am interested in is that my results showed Th1 dominance for one ration and Th2 for the other - so they are inconsistent with dominance of either type of response across the board. But hey, things are never simple with CFS!
Since I have been hijacking this LDN thread I have created a new group - Immunological Issues in Environmental Illnesses - where I have posted my results. Would be great if you would join and post images of your results there too. Look forward to seeing them.
Redo - Control genes can apparently be defined "as genes that are ubiquitously expressed at stable levels in different biological contexts, have been used to standardize quantitative expression studies for more than 25 yr." So they serve as a "normal" reference in quantitative testing as far as I can tell. The role they would play in immunological testing and their importance for tests such as those performed by Red Labs - I just don't know.
The results provided by Red Labs ARE relative since they are presented as ratios between Th1 and Th2 cytokines. What I am interested in is that my results showed Th1 dominance for one ration and Th2 for the other - so they are inconsistent with dominance of either type of response across the board. But hey, things are never simple with CFS!
Since I have been hijacking this LDN thread I have created a new group - Immunological Issues in Environmental Illnesses - where I have posted my results. Would be great if you would join and post images of your results there too. Look forward to seeing them.
12 years ago
Redozipous
@Viewpoint. Thanks. I am doing it for CFS. I have not got worse without it (I have had long periods without), but I get your point. E.g. MS sufferers are often happy that it doesn't progress. "and you certainly don't want to reach a point where LDN is building up in your system thereby finding it no longer working" I appreciate that info. I think I'll give it a rest for a long while, and rather come back it later. What I was expecting (or hoping for) was some sort of symptom improvement.
@Maff. "If anyone can shed any light on them please let me know!". I've done the same tests at the same lab, and luckily my doctor is a scientist specializing in this field. The short story was that the tests didn't use a so called "control gene" (don't know what it is), and that their reference material was too small, so he didn't put any weight on the results I got.
I took the same test at VIPdx (before they outsourced it to UNEVX clin. labs.) and the interleukin values where much different at that lab . If you'd want I could upload my results from both labs.
About which interleukins fall into the category T helper cell 1 and T helper call 2, you can check page 19 of this document: www.wpinstitute.org/news/docs/… can't verify that it's right though. But what I do can concur to is what ABarnett is saying about their interaction, and how relative numbers are important.
@Maff. "If anyone can shed any light on them please let me know!". I've done the same tests at the same lab, and luckily my doctor is a scientist specializing in this field. The short story was that the tests didn't use a so called "control gene" (don't know what it is), and that their reference material was too small, so he didn't put any weight on the results I got.
I took the same test at VIPdx (before they outsourced it to UNEVX clin. labs.) and the interleukin values where much different at that lab . If you'd want I could upload my results from both labs.
About which interleukins fall into the category T helper cell 1 and T helper call 2, you can check page 19 of this document: www.wpinstitute.org/news/docs/… can't verify that it's right though. But what I do can concur to is what ABarnett is saying about their interaction, and how relative numbers are important.
12 years ago
ABarnett
Maff
No Idea, the cytokine system is complex, theres around 50 or so of them all interacting
No Idea, the cytokine system is complex, theres around 50 or so of them all interacting
12 years ago
Maff
Thanks ABarnett. The question then is why if my IL-1 is high relevant to IL-2...why isn't my IFNg? Surely IFNg should be stimulated by the IL-1 and Th1 cascade? Anyway, I am hijacking the LDN group here so will create another group for such musings!
12 years ago
Viewpoint
Redo - what are you taking LDN for and can I ask what benefits are you expecting? If there's no progression in your disease when taking LDN, that is excellent news and one which many would describe as a 'result'.
With LDN and the new research coming out from Dr Zagon (I believe he has 15 papers coming out this year), it is proving that 'less is more' and you certainly don't want to reach a point where LDN is building up in your system thereby finding it no longer working. I'd definitely take heed of advice to lower the dose and see if it makes any difference but again, I do wonder what it is you're expecting? Many thanks!
With LDN and the new research coming out from Dr Zagon (I believe he has 15 papers coming out this year), it is proving that 'less is more' and you certainly don't want to reach a point where LDN is building up in your system thereby finding it no longer working. I'd definitely take heed of advice to lower the dose and see if it makes any difference but again, I do wonder what it is you're expecting? Many thanks!
12 years ago
ABarnett
Th1 tends to IL1 led while Th2 is IL2 led. The other cytokines tend to follow these two mostly
12 years ago
Maff
Redo - I've not experimented with LDN myself yet but from the research I've done I'd fully agree with ABarnett (who knows a lot more about the pharmacodynamics!) that 5mg seems a bit on the high side and perhaps a lower dose may be more effective.
Jamison - Just a bit of personal experience with the Th2-dominance theory of CFS. I was on board with this until I had various cytokines measured by Red Labs in Belgium. They used the IL-2/IL-4 and IFNg/IL-4 ratios to determine Th1/Th2 balance. In my case IL-2/IL-4 was 40% above reference range while paradoxically IFNg/IL-4 was borderline low. Clearly then my immunological dysfunction does not fit neatly into either Th1 or Th2 dominance, it seems to be generally all over the place. I have not seen a doctor expert enough in immunology to offer an explanation for these results. If anyone can shed any light on them please let me know! Might be worth having cytokine profiling done by Red Labs if you've got any money left Jamison.
Jamison - Just a bit of personal experience with the Th2-dominance theory of CFS. I was on board with this until I had various cytokines measured by Red Labs in Belgium. They used the IL-2/IL-4 and IFNg/IL-4 ratios to determine Th1/Th2 balance. In my case IL-2/IL-4 was 40% above reference range while paradoxically IFNg/IL-4 was borderline low. Clearly then my immunological dysfunction does not fit neatly into either Th1 or Th2 dominance, it seems to be generally all over the place. I have not seen a doctor expert enough in immunology to offer an explanation for these results. If anyone can shed any light on them please let me know! Might be worth having cytokine profiling done by Red Labs if you've got any money left Jamison.
12 years ago
ABarnett
To be honest, that doesn't tell me which is which very well, it is the suggestion that dextro doesn't block endogenous opioids that confuses me here. Best stick with the idea that the dextro is for endorphin boosting and levo may act on TLR's, hmmm, since we don't get the two forms seperately yet, I don't think we need to worry about it yet though.
12 years ago
ABarnett
regarding which one works on endorphins, Dr Younger told me that. He also said there are people trying to seperate the two forms, so good news there.
"That compound is called dextro-naltrexone. It has the microglia action, but not the neuron action – so we can increase the dose and not worry about blocking endogenous opioids (like beta-endorphins). Levo-naltrexone (also not available for human use) would probably not work very well, because it is active at neurons but not microglia."
There is much to learn as you say.
"That compound is called dextro-naltrexone. It has the microglia action, but not the neuron action – so we can increase the dose and not worry about blocking endogenous opioids (like beta-endorphins). Levo-naltrexone (also not available for human use) would probably not work very well, because it is active at neurons but not microglia."
There is much to learn as you say.
12 years ago
ABarnett
jamison.
The TLR4 effect does seem to work briefly, I feel the same, but it doesn't last long. I find galprofen works just as well.
Dr (professor actually) Zagon was the researcher who discovered the LDN effect in the late 1970's and it was he who told Dr Bihari about it. He has also done most of the research on LDN and OGF (metenkephalin). Dr Gilhooly is a physician who is experimenting with the TLR4 effect based on work by Dr Jarred Younger. Dr Younger has told us that the higher doses need more research before they can be confirmed and that it is not wise to sacrifice the OGF boost for the sake of TLR effect if it is effecive at all. The TLR effect is not necesarily that strong with Naltrexone.
However, Dr Younger says that it is ok fo a physician to follow his nose as Dr Gilhooly is doing, but we hear of many people who do not do well on twice a day dosing, and more is not necessarily better with LDN.
Dr Zagon has papers that show that taking LDN once every 2 or 3 or even 7 days is just as effective as daily, but too much is not good because Naltrexone actualy stimulates T cell proliferation because it blocks the OGF receptors which allow OGF to inhibit cell proliferation - again he has published papers on this.
My approach to LDN has always been based on my taking my own gamble based on my enhanced capability to research and understand the biochemistry of cytokines, immunology and so on, because I am a physicist who finds it not too difficult, chemistry is complex but if you persevere you can learn enough to make the best guess possible for yourself andf I started researching biochem for my brother who had aids in the 1980's.
Unfortunately, the dynamics of chronic diseases are not easy to follow, read Plotnikoff et al book, cytokines, stress and immunity, but it is dense.
Th1 responses are relevant to responses in the serum. Th2 responses work with humoral responses in places like the lungs, gut wall and outside the serum. It needs a different type of response because the normal cell response in serum can't reach it. Hence, asthma, chrons etc are Th2.
I hope this helps.
The TLR4 effect does seem to work briefly, I feel the same, but it doesn't last long. I find galprofen works just as well.
Dr (professor actually) Zagon was the researcher who discovered the LDN effect in the late 1970's and it was he who told Dr Bihari about it. He has also done most of the research on LDN and OGF (metenkephalin). Dr Gilhooly is a physician who is experimenting with the TLR4 effect based on work by Dr Jarred Younger. Dr Younger has told us that the higher doses need more research before they can be confirmed and that it is not wise to sacrifice the OGF boost for the sake of TLR effect if it is effecive at all. The TLR effect is not necesarily that strong with Naltrexone.
However, Dr Younger says that it is ok fo a physician to follow his nose as Dr Gilhooly is doing, but we hear of many people who do not do well on twice a day dosing, and more is not necessarily better with LDN.
Dr Zagon has papers that show that taking LDN once every 2 or 3 or even 7 days is just as effective as daily, but too much is not good because Naltrexone actualy stimulates T cell proliferation because it blocks the OGF receptors which allow OGF to inhibit cell proliferation - again he has published papers on this.
My approach to LDN has always been based on my taking my own gamble based on my enhanced capability to research and understand the biochemistry of cytokines, immunology and so on, because I am a physicist who finds it not too difficult, chemistry is complex but if you persevere you can learn enough to make the best guess possible for yourself andf I started researching biochem for my brother who had aids in the 1980's.
Unfortunately, the dynamics of chronic diseases are not easy to follow, read Plotnikoff et al book, cytokines, stress and immunity, but it is dense.
Th1 responses are relevant to responses in the serum. Th2 responses work with humoral responses in places like the lungs, gut wall and outside the serum. It needs a different type of response because the normal cell response in serum can't reach it. Hence, asthma, chrons etc are Th2.
I hope this helps.
12 years ago
ABarnett
Redo, Dr Zagon recommends the lowest dose that works. You may be taking too much, try dropping it to 2mg.
12 years ago
Redozipous
Just thought I should shoot in my experiences with LDN. I am very glad for anyone getting better, but I haven't been so lucky.
I've used LDN for the past 1/2 year, at a dose of 5 mg at 22.00 each evening. I am still using it. I have used it some years ago also, for a prolonged period of time. If it have given me any benefits, they are subtle. Because I can't tell.
I've used LDN for the past 1/2 year, at a dose of 5 mg at 22.00 each evening. I am still using it. I have used it some years ago also, for a prolonged period of time. If it have given me any benefits, they are subtle. Because I can't tell.
12 years ago
jamison
Thanks ABarnett and Viewpoint for your replies. God it is quite complicated stuff this LDN isn't it!? I have undergone experimental regimens before at great detriment to my health and well being so I take what you say very seriously. I do have a couple of questions though:
Whenever I take LDN I notice its effects very quickly (usually within 5-10 minutes). Surely this is too quick for the endorphine rebound effect to have happened? My understanding was that LDN acts as an antagonist but that it takes 2-4 hours before more endorphines are produced? This makes me think that the TLR4 or some other mechanism not yet researched may be playing a significant role in the drug's action...
ABarnett I'm not trying to nitpick here but Tom Gilhouly seems to think it is the levo rather than the dextro side of the drug that acts on the TLR's. In the article that Viewpoint has just posted Tom Gilhouly writes: "The more interesting part regards the left handed molecule, which acts on the Toll-like 4 receptors on the surface of immune cells and acts as an immune modulator...The left handed (levo) naltrexone binds to these receptors and reduces the inflammatory chemicals that are pouring out of these cells". Is this disparity between what is the levo and dextro side of the drug significant? i.e. Is there some disagreement as to what consists of the levo/dextro side of the drug?
You both say the science backs the opiate hypothesis; that it is the significant increase in endorphines that accounts for the improvement in peoples symptoms. However, is not the research performend and published by Dr Rachel Allen and Dr Younger just as valid? I get the impression that the research carried out by Ian Zagon is considered more weighty by you both. Why is this?
Finally ABarnett you say that split dosing, if useful at all, will likely be of greater benefit to those with a Th2 rather than Th1 illness. I'm not quite sure what you mean by this. I think a central mechanism in the pathogenesis of ME/CFS is that the Th2 arm of the immune system is elevated whilst the Th1 arm is suppressed. Would this be considered a Th1 or Th2 illness?
Sorry for all the questions but I'd really appreciate both your thoughts...
Best wishes,
Whenever I take LDN I notice its effects very quickly (usually within 5-10 minutes). Surely this is too quick for the endorphine rebound effect to have happened? My understanding was that LDN acts as an antagonist but that it takes 2-4 hours before more endorphines are produced? This makes me think that the TLR4 or some other mechanism not yet researched may be playing a significant role in the drug's action...
ABarnett I'm not trying to nitpick here but Tom Gilhouly seems to think it is the levo rather than the dextro side of the drug that acts on the TLR's. In the article that Viewpoint has just posted Tom Gilhouly writes: "The more interesting part regards the left handed molecule, which acts on the Toll-like 4 receptors on the surface of immune cells and acts as an immune modulator...The left handed (levo) naltrexone binds to these receptors and reduces the inflammatory chemicals that are pouring out of these cells". Is this disparity between what is the levo and dextro side of the drug significant? i.e. Is there some disagreement as to what consists of the levo/dextro side of the drug?
You both say the science backs the opiate hypothesis; that it is the significant increase in endorphines that accounts for the improvement in peoples symptoms. However, is not the research performend and published by Dr Rachel Allen and Dr Younger just as valid? I get the impression that the research carried out by Ian Zagon is considered more weighty by you both. Why is this?
Finally ABarnett you say that split dosing, if useful at all, will likely be of greater benefit to those with a Th2 rather than Th1 illness. I'm not quite sure what you mean by this. I think a central mechanism in the pathogenesis of ME/CFS is that the Th2 arm of the immune system is elevated whilst the Th1 arm is suppressed. Would this be considered a Th1 or Th2 illness?
Sorry for all the questions but I'd really appreciate both your thoughts...
Best wishes,
12 years ago
ABarnett
After checking, it is the dextro that acts on TLR's and the levo that acts on the endorphins
12 years ago
Viewpoint
I forgot to add Jamison that whatever it is you're doing, it does sound like there's some movement going on in your immune system that is helping you and this in itself great news to hear. Please continue to keep us posted on your dosing and how you feel. I always find it interesting how different people respond to LDN.
Great news if Dr G can get a CFS/LDN trial going - fingers crossed to that one - thanks for sharing and being so open. LDN is one of those medications where we can all learn from each other hence the interest I have in your posts. You also sound well versed in what you're doing so I have no doubt you have researched this yourself and long may the journey to better health continue!
Great news if Dr G can get a CFS/LDN trial going - fingers crossed to that one - thanks for sharing and being so open. LDN is one of those medications where we can all learn from each other hence the interest I have in your posts. You also sound well versed in what you're doing so I have no doubt you have researched this yourself and long may the journey to better health continue!
12 years ago
Viewpoint
I have just put out a bulletin - LDN and TLRs by Dr Tom Gilhooly which I hope explains his thinking for getting people to as high of a dose as possible and then perhaps splitting the dose. I know he is getting a lot of his patients on as high of a dose as possible which is something Dr Zagon feels this is an extremely bad idea and is quite worried about future outcomes.
When I have contacted Dr Zagon about LDN and TLR4s he pretty much dismissed this - here's his response:-
Forget about the TLR4 story - LDN works in tissue culture without any TLR4 or immune system, as well as in animals without an immune system. Once again, LDN is a decoy. It causes the body to compensate for a failure of the opioids and opioid receptors to interact because of the blockade between these two molecules. So, more opioids and receptors are produced, and this gives you what you want - an enhanced opioid-receptor exchange of information. But you need sufficient time for the body to allow the good things to happen. Using LDN twice daily or more often takes what is a 4-6 hour blockade and a window of 18-20 hr/day and makes you have two 4-6 hour blockades and essentially allows only a 6 hour window at best twice daily (12 hours total) for the good opioids to act on the good receptors. If you start to have too much time with the blockade, you are going to allow the natural repression of cell proliferation to be restricted - hence, you get more cells produced. Now this is great if you want more cells (e.g., wound healing), but terrible if you have cancer. As for an autoimmune disease, LDN works through the OGF-OGFr axis to inhibit replication of T and B lymphocytes - the very cells that heighten an immune response. If LDN elevated immune response in these autoimmune diseases (e.g., multiple sclerosis) you would get an exacerbation of the symptoms!!!
This all comes down to understanding the biology of opioids and naltrexone and LDN. And, again, we have performed the science to prove the point.
One more little item. We have a paper in press that nicely shows that if you knockdown OGFr (in other words you are diminishing the receptor for OGF), and add LDN, you do not get the effect of LDN. This means that LDN requires the OGF receptor - if it is not present, LDN has no inhibitory action on cell proliferation.
I know this is a tremendous amount of complicated material (and I haven't even begun to tell you about all the past studies - and present investigations - we are talking 150 or more scientific papers published). Remember, we discovered LDN and have been devoted to this for 30 years. And we are scientists with the indepth knowledge needed to integrate the stories. It has led us to an understanding of how LDN works, and we have uncovered a basic, fundamental biological system that is involved: OGF and OGFr.
So it's a case of playing safe and going with what has already been proven by a man who has been working with LDN for 30+ years, or participating in Dr Gilhooly's trial. I know many who are dosing twice a day and don't feel much different from taking LDN once a day (these take a daily dose of no more than 4mg). However I also know of a lady with fibro who takes 4.5mg in the morning and 4.5mg in evening and has done so for a year and still feels great. Who knows? Dr Tom may have seen something from Dr Younger's trial with fibro and is now hoping to find out more. The only way he can do this is by trying it out on his patients. I can understand this protocol for controlling inflammation but I wouldn't think it's a good idea to be on this protocol long term. However, it would be great if this is does prove as beneficial as Tom believes. Wishing you luck with this.
When I have contacted Dr Zagon about LDN and TLR4s he pretty much dismissed this - here's his response:-
Forget about the TLR4 story - LDN works in tissue culture without any TLR4 or immune system, as well as in animals without an immune system. Once again, LDN is a decoy. It causes the body to compensate for a failure of the opioids and opioid receptors to interact because of the blockade between these two molecules. So, more opioids and receptors are produced, and this gives you what you want - an enhanced opioid-receptor exchange of information. But you need sufficient time for the body to allow the good things to happen. Using LDN twice daily or more often takes what is a 4-6 hour blockade and a window of 18-20 hr/day and makes you have two 4-6 hour blockades and essentially allows only a 6 hour window at best twice daily (12 hours total) for the good opioids to act on the good receptors. If you start to have too much time with the blockade, you are going to allow the natural repression of cell proliferation to be restricted - hence, you get more cells produced. Now this is great if you want more cells (e.g., wound healing), but terrible if you have cancer. As for an autoimmune disease, LDN works through the OGF-OGFr axis to inhibit replication of T and B lymphocytes - the very cells that heighten an immune response. If LDN elevated immune response in these autoimmune diseases (e.g., multiple sclerosis) you would get an exacerbation of the symptoms!!!
This all comes down to understanding the biology of opioids and naltrexone and LDN. And, again, we have performed the science to prove the point.
One more little item. We have a paper in press that nicely shows that if you knockdown OGFr (in other words you are diminishing the receptor for OGF), and add LDN, you do not get the effect of LDN. This means that LDN requires the OGF receptor - if it is not present, LDN has no inhibitory action on cell proliferation.
I know this is a tremendous amount of complicated material (and I haven't even begun to tell you about all the past studies - and present investigations - we are talking 150 or more scientific papers published). Remember, we discovered LDN and have been devoted to this for 30 years. And we are scientists with the indepth knowledge needed to integrate the stories. It has led us to an understanding of how LDN works, and we have uncovered a basic, fundamental biological system that is involved: OGF and OGFr.
So it's a case of playing safe and going with what has already been proven by a man who has been working with LDN for 30+ years, or participating in Dr Gilhooly's trial. I know many who are dosing twice a day and don't feel much different from taking LDN once a day (these take a daily dose of no more than 4mg). However I also know of a lady with fibro who takes 4.5mg in the morning and 4.5mg in evening and has done so for a year and still feels great. Who knows? Dr Tom may have seen something from Dr Younger's trial with fibro and is now hoping to find out more. The only way he can do this is by trying it out on his patients. I can understand this protocol for controlling inflammation but I wouldn't think it's a good idea to be on this protocol long term. However, it would be great if this is does prove as beneficial as Tom believes. Wishing you luck with this.
12 years ago
ABarnett
hi jamison. Whilst I don't argue with Dr Gilhoolys thoughts, the science just doesn't support the idea that the levo effect is dominant. Dr Zagon, who disovered LDN and gave it to Bihari has shown that the met enkephalin stimulated to 300% by LDN is significant in modulating the immune system, so if you heed that response then the dextro is the one to use. We know that restoring homeostasis also restores a full and proper immune response to pathogens, something that is lost with chronic sickness (ssickness is cytokine driven). However, the levo effect needs more study before we can say for sure that it is effective and the clinical view is not science. It is legitimate if the observations support it but Dr Gilhooly cannot say which effect is resonsible for the results he observes at this point. So the study he is trying to get done will be important in answering some questions as long as it does seperate the two effects.
Since I have MS, I would never try twice a day. am trying to avoid further relapses more than trying to control a TLR4 response and I have found this to be very effective.
I cannot advise people to experiment with the unknown when they are at risk of it being erroneous and the science to date suggests that the TLR4 effect is not strong, though that may change. Dr Gilhooly has been interested in this side of LDN for some time and I wish him luck, but as far as I am aware, he uses it for Th2 type immune problems rather than Th1 ones, so I am ken to keep these 2 seperate. I wish you luck with your experimentation.
One question, if the TLR4 effect is the one to use, why not go for 50mg a day and really stimulate it? This can only be because the endorphins are so important that it is unwise to stope them completely, but I'm not convinced you can have both via twice a day. I get both dosing once a day and I make sure the met enkephalin has enough time to give me an overall positive effect, but then again I have an autoimmune disease to control so I would say that.
Since I have MS, I would never try twice a day. am trying to avoid further relapses more than trying to control a TLR4 response and I have found this to be very effective.
I cannot advise people to experiment with the unknown when they are at risk of it being erroneous and the science to date suggests that the TLR4 effect is not strong, though that may change. Dr Gilhooly has been interested in this side of LDN for some time and I wish him luck, but as far as I am aware, he uses it for Th2 type immune problems rather than Th1 ones, so I am ken to keep these 2 seperate. I wish you luck with your experimentation.
One question, if the TLR4 effect is the one to use, why not go for 50mg a day and really stimulate it? This can only be because the endorphins are so important that it is unwise to stope them completely, but I'm not convinced you can have both via twice a day. I get both dosing once a day and I make sure the met enkephalin has enough time to give me an overall positive effect, but then again I have an autoimmune disease to control so I would say that.
12 years ago
jamison
A quick update. I had an appointment with Dr Tom Gilhouly the other day which overall was very informative. He said that he is aiming to start a CFS LDN trial which is great news for us patients.
The main thing to come from the consultation is that Dr Gilhouly is increasingly pro split dosing because he believes that the levo (active) side of the drug works directly on the toll like rereceptors and LDN modulates the immune system that way. He seems to believe that the increased endorphin levels that are a result of the other (dextro) side of the drug are not as significant in leading to improved health. Dr Gilhouly pointed out that lots of things increase endorphin levels such as chocolate and exercise but these do not have the same powerful therapeutic effects as LDN does. He therefore believes that it is LDN's impact on the toll like receptors that is the main mechanism which leads to clinical improvement. In order to maximise this effect he is increasingly recommending that patients titrate their dose upwards until they reach opiate blockade and then lower the dose by 1mg. This is the maximum dose that can be tolerated by a patient and therefore maximises the impact on the toll like receptors and the immune system. The maximum dose varies from individual to individual but one of his patients is on 25 mgs a day! When you reach opiate blockade, apparrently it is obvious because you feel horrible and flat as a pancake within 1 hour.
I am still currently on 3mgs taken once a day. My glandular fever symptoms are not as strong and unfortunately I have had some ME symptoms return. It is almost as if I have become tolerant to this dose as I seem to be getting diminishing returns from the LDN. Having said I have been unusually active over the last few days as it has been my birthday and my girl friend took me to Cornwall for a holiday so I am going to see how I fair on my usual routine before upping my dose. My gut feeling is that I may suit the split dosing more but I am going to systematically exhaust the single dose option first.
The main thing to come from the consultation is that Dr Gilhouly is increasingly pro split dosing because he believes that the levo (active) side of the drug works directly on the toll like rereceptors and LDN modulates the immune system that way. He seems to believe that the increased endorphin levels that are a result of the other (dextro) side of the drug are not as significant in leading to improved health. Dr Gilhouly pointed out that lots of things increase endorphin levels such as chocolate and exercise but these do not have the same powerful therapeutic effects as LDN does. He therefore believes that it is LDN's impact on the toll like receptors that is the main mechanism which leads to clinical improvement. In order to maximise this effect he is increasingly recommending that patients titrate their dose upwards until they reach opiate blockade and then lower the dose by 1mg. This is the maximum dose that can be tolerated by a patient and therefore maximises the impact on the toll like receptors and the immune system. The maximum dose varies from individual to individual but one of his patients is on 25 mgs a day! When you reach opiate blockade, apparrently it is obvious because you feel horrible and flat as a pancake within 1 hour.
I am still currently on 3mgs taken once a day. My glandular fever symptoms are not as strong and unfortunately I have had some ME symptoms return. It is almost as if I have become tolerant to this dose as I seem to be getting diminishing returns from the LDN. Having said I have been unusually active over the last few days as it has been my birthday and my girl friend took me to Cornwall for a holiday so I am going to see how I fair on my usual routine before upping my dose. My gut feeling is that I may suit the split dosing more but I am going to systematically exhaust the single dose option first.
12 years ago
jamison
Hi Maff,
Yes I have been getting up the last few mornings and there has been no brain fog whatsoever. This is the first time in 10 years! I feel tired sometimes but in a viral/ washed out way. So I have to say that I think this LDN is extraordnarily powerful stuff and worth giving a go at some point.
I have found that when I undergo treatments that are aimed at rebalancing the immune system back into a Th1 pattern, I start to get real benefit. I suspect that an immune system shift induced by a bout of glandular fever when I was 16 is at the core of my troubles. This caused a biochemical cascade leading to mitochondrial dysfunction, methylation cycle blocks, gut dysbiosis, adrenal exhaustion - what we call CFS/M.E. LDN addresses the imbalance imbalance and this is why I think it so effective. I have got an appointment with Dr Gilhouly on Thursday and will be sure to post about the outcome of this consultation.
Yes I have been getting up the last few mornings and there has been no brain fog whatsoever. This is the first time in 10 years! I feel tired sometimes but in a viral/ washed out way. So I have to say that I think this LDN is extraordnarily powerful stuff and worth giving a go at some point.
I have found that when I undergo treatments that are aimed at rebalancing the immune system back into a Th1 pattern, I start to get real benefit. I suspect that an immune system shift induced by a bout of glandular fever when I was 16 is at the core of my troubles. This caused a biochemical cascade leading to mitochondrial dysfunction, methylation cycle blocks, gut dysbiosis, adrenal exhaustion - what we call CFS/M.E. LDN addresses the imbalance imbalance and this is why I think it so effective. I have got an appointment with Dr Gilhouly on Thursday and will be sure to post about the outcome of this consultation.
12 years ago
Maff
Great to hear you are doing so well on the LDN jamison! I am really happy for you and appreciate you sharing your experiences here so others can benefit. I had been thinking about giving LDN a trial for a while now and your experience with it has only enhanced my feeling that it is an avenue definitely worth investigating. It must be odd to be experiencing all the viral symptoms again. I have not had symptoms like that for about 14 years (been ill 20). No colds or flu in that time. I suspect I would react in a similar way to you on LDN as the antiviral immune pathways came back online. Anyway, I hope you continue to see improvements and can begin to enjoy life once again. Keep us updated!
ABarnett - Thank you for sharing your wealth of knowledge. I have seen very little mention of the direct immunological mechanism proposed for LDNs action via TLR4. It will be interesting to read more about this given jamison's seemingly postive results with twice daily dosing. Thanks for the lead on Dr. Rachel Allen.
ABarnett - Thank you for sharing your wealth of knowledge. I have seen very little mention of the direct immunological mechanism proposed for LDNs action via TLR4. It will be interesting to read more about this given jamison's seemingly postive results with twice daily dosing. Thanks for the lead on Dr. Rachel Allen.
12 years ago
jamison
ABarnett,
Thank you for your reply. That is really useful information to have. I am going to drop down to single dosing again (2mgs in the evening) to see how I get on.
Today I woke up and had my best day in years. I feel clear headed and excited that I may not be forced to live in a perpetual fog for the rest of my life! I still think I have some viral issues to clear up and I am not back to full health yet but I think that with LDN and the other interventions I am making, there is a good chance I can get there...
The work you are doing at LDNNow is really important. This drug has the potential to help thousands of people and, as you say, trials are needed to establish the best way to use it.
Good luck with this endeavour and very best wishes,
Nick
Thank you for your reply. That is really useful information to have. I am going to drop down to single dosing again (2mgs in the evening) to see how I get on.
Today I woke up and had my best day in years. I feel clear headed and excited that I may not be forced to live in a perpetual fog for the rest of my life! I still think I have some viral issues to clear up and I am not back to full health yet but I think that with LDN and the other interventions I am making, there is a good chance I can get there...
The work you are doing at LDNNow is really important. This drug has the potential to help thousands of people and, as you say, trials are needed to establish the best way to use it.
Good luck with this endeavour and very best wishes,
Nick
12 years ago
ABarnett
The academic doing the TLR4 work is Dr Rachel Allen, do contact her if you have questions, she is very responsive.
12 years ago
ABarnett
I have talked a lot about the levo and dextro effects. My concern at the moment with this is that the direct effect is thought to be quite small and I believe there are other ways to achieve this result. If someone would seperate the two forms, life would be easier, but we have been well informed that the endorphin effect is the most important and significant for autoimmune conditions and critically, for cancer. Opioid growth factor, or metenkephalin is a fundamental endorphin which is also a constituent part of other endorphins and provides the immune modulation. Unfortunately, twice a day dosing will lose this aspect.
We need the direct effect research to produce results. We are in contact with all the people you mention and know that the twice a day dosing is clinically legitimate but has unanswerd questions and we know it also loses the endorphin effect, so while people are using it for Th2 related conditions, it seems innapropriate for Th1 type problems.
Dr Gilhooly seems to be getting results from his method but he is selective about it's use.
So I am just trying to mirror the choices we make to try and beat our various sicknesses with the science we know. Much of our choices have to come down to personal gambling, but we at LDNNow feel that we need to keep clear in our minds about what is scientific and what is clinical opinion. Only then can patients make informed choices and avoid the internet's great capacity to disinform.
There is one big difference between LDNNow and LDN research trust of note, and that is that LDNNow is not a charity and not interested in collecting money. We believe the way to get the research done is to tackle the systemic issues of research and get the academics to do the research because patients are making choices without a clinical trial. We need the trials so we can stop arguing with each other about LDN and get down to using it with the full support of the medical community.
The trial should be publicly funded because the research must be done and the existing public funded research systems can therefore do this work. We just need to get them, NIHR and other funding bodies, to accept this trial and set it in motion. I don't believe any charity will succeed in raising the amount of funds to pay for a trial for LDN but I wish LDN research trust all the luck they can get. LDN is not profitable and is of minority interest which is why it hasn't been accepted.
The one thing that can compel this research is the fact the we sick people are choosing it and we want to know the truth because our lives depend on it!
Good luck wih your chosen protocol and do keep us informed of the progress. LDN is certainly a fascinating drug, and I look forward to the results of the research project.
Here is a useful link on this matter too ajpgi.physiology.org/content/296/6/… this is useful
We need the direct effect research to produce results. We are in contact with all the people you mention and know that the twice a day dosing is clinically legitimate but has unanswerd questions and we know it also loses the endorphin effect, so while people are using it for Th2 related conditions, it seems innapropriate for Th1 type problems.
Dr Gilhooly seems to be getting results from his method but he is selective about it's use.
So I am just trying to mirror the choices we make to try and beat our various sicknesses with the science we know. Much of our choices have to come down to personal gambling, but we at LDNNow feel that we need to keep clear in our minds about what is scientific and what is clinical opinion. Only then can patients make informed choices and avoid the internet's great capacity to disinform.
There is one big difference between LDNNow and LDN research trust of note, and that is that LDNNow is not a charity and not interested in collecting money. We believe the way to get the research done is to tackle the systemic issues of research and get the academics to do the research because patients are making choices without a clinical trial. We need the trials so we can stop arguing with each other about LDN and get down to using it with the full support of the medical community.
The trial should be publicly funded because the research must be done and the existing public funded research systems can therefore do this work. We just need to get them, NIHR and other funding bodies, to accept this trial and set it in motion. I don't believe any charity will succeed in raising the amount of funds to pay for a trial for LDN but I wish LDN research trust all the luck they can get. LDN is not profitable and is of minority interest which is why it hasn't been accepted.
The one thing that can compel this research is the fact the we sick people are choosing it and we want to know the truth because our lives depend on it!
Good luck wih your chosen protocol and do keep us informed of the progress. LDN is certainly a fascinating drug, and I look forward to the results of the research project.
Here is a useful link on this matter too ajpgi.physiology.org/content/296/6/… this is useful
12 years ago
jamison
Hi maff,
Yes sorry for being off the radar lately. I have been away staying with family the last ten days or so and then I have had a fairly manic time chatting to doctors etc as I have had a load of test results back.
Anyway back to the LDN. I have been experimenting with dosing and dosing times. The higher the dose, the more glandular fever type symptoms I get. If I split dose i.e. one dose in morning and one in evening, I also get glandular fever type symptome more severely than if I just single dose. However, I would like to emphasise that whilst these symptoms are quite strong (at times just like having glandular fever) they are not unbearable. Indeed I now feel conventionally ill rather than having ME/CFS which is a welcome change to be honest. I am hoping that it this is my immune system rebalancing the TH1/TH2 shift and allowing me to finally clear out the unresolved viral illness that left me ill 10 years ago. Both Dr Pouria and Dr Myhill think and hope that this is the case and want me to steer a steady course for a while to see if these viral symptoms dissipate.
I am getting sore throats, temperatures, sweats, sore glands (my glands have been swollen for years now but not sore, just like marbles in my neck). I also feel for the most part very calm, grounded, peaceful and positive. I am sleeping a lot more (12+ hours per night). My dreams are more vivid, as has been reported by many, but I do not find this a problem.
Currently I am on quite a high dose of 4mg taken in split doses. I am tolerating this okay. Just taking it easy - watching lots of films and sleeping. All my other test results are looking good - no DNA adducts, Gut is now normal and I know from previous tests that most of the other biochemical pathways implicated in ME have now normalised. This was the result of other treatments (not LDN) but I think it has put me in quite a good place to tolerate a high dose.
About the split dosing. Due to ABarnetts post which suggested that it was not beneficial to split dose, I have done some research on this. The LDN research trust basically seem to think it is okay. I spoke to a nice lady, Linda, who set up the charity after being helped tremendously by LDN for her MS. She is not medically qualified but clearly very knowledgeable about LDN and up to date on the latest research. She said that she personally knows numerous ME patients who have been helped by split dosing. She also mentioned some recent research (sorry can't remember the name of the researcher) that suggested it could be more beneficial to split dose rather than single dose.
Dr Tom Gilhouly who is one of the main proponents for LDN in the UK also thinks it may be beneficial to split dose. He wrote this on the subject:
"I have no doubt that LDN is one of the most useful and effective drugs available today. It has a remarkable safety profile and can be used to treat wide immune related conditions from MS to Chronic Fatigue Syndrome to Inflammatory Bowel Disease. We now know a lot more about the action and mechanism of LDN which can be used to our advantage as we try and squeeze even more out of the drug. The knowledge that the drug has a dual action, opiate blockade on one hand and direct immune action on the other opens up new possibilities.
Rather than start at 3mg and stopping at 4.5 mg, we titrate the dose from 1mg to the maximum tolerated dose. The maximum tolerated dose of LDN is determined by complete opiate blockade which makes most patients feel mentally and physically tired. This effect usually happens on the day of a dose increase and lasts for 6 – 8 hours. Reducing the dose by half a milligram will normally result in these effects easing or in most cases ceasing altogether.
Knowing that the opiate blockade lasts for this relatively short time allows the use of opiate based painkillers 12 hours after the dose of LDN, which we usually recommend in the morning. The standard advice to take LDN after 10 pm is based on the fact that this produces a larger increase in endorphins but even Dr Ian Zagon from Penn State University, the world’s foremost authority on the endorphin effect of LDN, suggests this is not necessary. If the main action on the immune system is the direct effect of the levo portion of the drug, then timing of dosing is not important. In fact morning dosing reduces the well known sleep disturbance to almost zero. I have only had one patient complain of vivid dreams with a.m. dosing.
This knowledge did made us wonder if we could increase the effectiveness of LDN by splitting the doses by 12 hours and so avoid the opiate blockade effect but increase the total dose in 24 hours. In theory this should produce an even more profound effect on the immune system which could increase the effectiveness of an already amazing drug !
In the past few months we have started to recommend this to patients and although it is too early to comment on effectiveness, it does appear that split dosing is well tolerated and allow larger doses to be taken in 24 hours. At EHC we are very excited about the possibilities this opens up particularly for patients with inflammatory bowel disease who have been difficult to completely settle with conventional doses. The possibilities with LDN have just expanded dramatically."
I am due a telephone consultation with Dr Gilhouly on July 21st and will be sure to ask him about split dosing etc. However, my overall feeling is that there is enough which IS NOT known about this drug to warrant taking it in a way that feels most beneficial - providing you stay within the limits of safe dosing.
Yes sorry for being off the radar lately. I have been away staying with family the last ten days or so and then I have had a fairly manic time chatting to doctors etc as I have had a load of test results back.
Anyway back to the LDN. I have been experimenting with dosing and dosing times. The higher the dose, the more glandular fever type symptoms I get. If I split dose i.e. one dose in morning and one in evening, I also get glandular fever type symptome more severely than if I just single dose. However, I would like to emphasise that whilst these symptoms are quite strong (at times just like having glandular fever) they are not unbearable. Indeed I now feel conventionally ill rather than having ME/CFS which is a welcome change to be honest. I am hoping that it this is my immune system rebalancing the TH1/TH2 shift and allowing me to finally clear out the unresolved viral illness that left me ill 10 years ago. Both Dr Pouria and Dr Myhill think and hope that this is the case and want me to steer a steady course for a while to see if these viral symptoms dissipate.
I am getting sore throats, temperatures, sweats, sore glands (my glands have been swollen for years now but not sore, just like marbles in my neck). I also feel for the most part very calm, grounded, peaceful and positive. I am sleeping a lot more (12+ hours per night). My dreams are more vivid, as has been reported by many, but I do not find this a problem.
Currently I am on quite a high dose of 4mg taken in split doses. I am tolerating this okay. Just taking it easy - watching lots of films and sleeping. All my other test results are looking good - no DNA adducts, Gut is now normal and I know from previous tests that most of the other biochemical pathways implicated in ME have now normalised. This was the result of other treatments (not LDN) but I think it has put me in quite a good place to tolerate a high dose.
About the split dosing. Due to ABarnetts post which suggested that it was not beneficial to split dose, I have done some research on this. The LDN research trust basically seem to think it is okay. I spoke to a nice lady, Linda, who set up the charity after being helped tremendously by LDN for her MS. She is not medically qualified but clearly very knowledgeable about LDN and up to date on the latest research. She said that she personally knows numerous ME patients who have been helped by split dosing. She also mentioned some recent research (sorry can't remember the name of the researcher) that suggested it could be more beneficial to split dose rather than single dose.
Dr Tom Gilhouly who is one of the main proponents for LDN in the UK also thinks it may be beneficial to split dose. He wrote this on the subject:
"I have no doubt that LDN is one of the most useful and effective drugs available today. It has a remarkable safety profile and can be used to treat wide immune related conditions from MS to Chronic Fatigue Syndrome to Inflammatory Bowel Disease. We now know a lot more about the action and mechanism of LDN which can be used to our advantage as we try and squeeze even more out of the drug. The knowledge that the drug has a dual action, opiate blockade on one hand and direct immune action on the other opens up new possibilities.
Rather than start at 3mg and stopping at 4.5 mg, we titrate the dose from 1mg to the maximum tolerated dose. The maximum tolerated dose of LDN is determined by complete opiate blockade which makes most patients feel mentally and physically tired. This effect usually happens on the day of a dose increase and lasts for 6 – 8 hours. Reducing the dose by half a milligram will normally result in these effects easing or in most cases ceasing altogether.
Knowing that the opiate blockade lasts for this relatively short time allows the use of opiate based painkillers 12 hours after the dose of LDN, which we usually recommend in the morning. The standard advice to take LDN after 10 pm is based on the fact that this produces a larger increase in endorphins but even Dr Ian Zagon from Penn State University, the world’s foremost authority on the endorphin effect of LDN, suggests this is not necessary. If the main action on the immune system is the direct effect of the levo portion of the drug, then timing of dosing is not important. In fact morning dosing reduces the well known sleep disturbance to almost zero. I have only had one patient complain of vivid dreams with a.m. dosing.
This knowledge did made us wonder if we could increase the effectiveness of LDN by splitting the doses by 12 hours and so avoid the opiate blockade effect but increase the total dose in 24 hours. In theory this should produce an even more profound effect on the immune system which could increase the effectiveness of an already amazing drug !
In the past few months we have started to recommend this to patients and although it is too early to comment on effectiveness, it does appear that split dosing is well tolerated and allow larger doses to be taken in 24 hours. At EHC we are very excited about the possibilities this opens up particularly for patients with inflammatory bowel disease who have been difficult to completely settle with conventional doses. The possibilities with LDN have just expanded dramatically."
I am due a telephone consultation with Dr Gilhouly on July 21st and will be sure to ask him about split dosing etc. However, my overall feeling is that there is enough which IS NOT known about this drug to warrant taking it in a way that feels most beneficial - providing you stay within the limits of safe dosing.
12 years ago
Maff
Jamison - How are things going on the LDN? It's been a couple of weeks since you checked in so I'm thinking either you've seen a big improvement and are busy enjoying yourself, or things have taken a turn for the worst. I really hope it's the former. Of course you might just have got fed up of posting here! Would be good to hear how you're doing if you are able to post a quick update. All the best.
12 years ago
Maff
I will let ABarnett reply to this more fully as he is clearly more knowledgeable than I am on the specifics of LDN pharmacology!
I do know however that if naltrexone binds quickly to opioid receptors and prevents endogenous endorphins from binding to them - you would likely experience a change in symptoms quickly also. This could be independent of upregulation of endogenous endorphin production (at 2-4 hours) and the associated immune modulating effects. Perhaps this would be a likely explanation? Do you experience a further change in symptoms at 2 hours+?
Mostly guessing here but I'm sure ABarnett or maybe Viewpoint will give a more concrete explanation.
I do know however that if naltrexone binds quickly to opioid receptors and prevents endogenous endorphins from binding to them - you would likely experience a change in symptoms quickly also. This could be independent of upregulation of endogenous endorphin production (at 2-4 hours) and the associated immune modulating effects. Perhaps this would be a likely explanation? Do you experience a further change in symptoms at 2 hours+?
Mostly guessing here but I'm sure ABarnett or maybe Viewpoint will give a more concrete explanation.
12 years ago
jamison
ABarnett,
Thank you for your reply. You are clearly very knowledgeable about LDN and I appreciate you taking your time to explain some the technicalities which I find it difficult to get my head round.
The reason I started taking LDN twice a day is because I could feel its effects very quickly within 10 minutes of taking it (a calm, relaxing heaviness, sore throat, flu symptoms etc). These symptoms wore off when I was dosing once a day and the familiar ME Symptoms returned. I felt this was a bad thing as I thought I was healing when I had the fluey symptoms by eliminating viruses etc.
My understanding is that LDN blocks opiod receptors for 2-4 hours. It acts as an antagonist to increase endorphin levels and opiod growth factor after this initial 2-4 hour period. It is this mechanism you say that modulates the immune system. However, I can't help wondering why I feel the effects of the LDN so quickly? Surely, I would need to wait 2-4 hours to feel the beneficial effects of the LDN if it were the endorphins and OGF that were modulating my immune system? Instead I am feeling significantly different 10 minutes later. Is it possible that some of the mechanisms by which LDN works arn't fully elucidated yet?
Or being a lay person am I not understanding something? As I said it is quite technical stuff so that is entirely possible. I would really appreciate your thoughts.
Thank you for your reply. You are clearly very knowledgeable about LDN and I appreciate you taking your time to explain some the technicalities which I find it difficult to get my head round.
The reason I started taking LDN twice a day is because I could feel its effects very quickly within 10 minutes of taking it (a calm, relaxing heaviness, sore throat, flu symptoms etc). These symptoms wore off when I was dosing once a day and the familiar ME Symptoms returned. I felt this was a bad thing as I thought I was healing when I had the fluey symptoms by eliminating viruses etc.
My understanding is that LDN blocks opiod receptors for 2-4 hours. It acts as an antagonist to increase endorphin levels and opiod growth factor after this initial 2-4 hour period. It is this mechanism you say that modulates the immune system. However, I can't help wondering why I feel the effects of the LDN so quickly? Surely, I would need to wait 2-4 hours to feel the beneficial effects of the LDN if it were the endorphins and OGF that were modulating my immune system? Instead I am feeling significantly different 10 minutes later. Is it possible that some of the mechanisms by which LDN works arn't fully elucidated yet?
Or being a lay person am I not understanding something? As I said it is quite technical stuff so that is entirely possible. I would really appreciate your thoughts.
12 years ago
ABarnett
The twice a day dosing regime has important disadvantages. Met enkephalin is the prime mover of LDN therapy and it is blocked by the LDN while it is blockading the receptors. So twice a day severely reduces the time available for the met enkephalin - aka OGF or opiod growth factor - in the 24 hours and reduces the beneficial effect of taking LDN for immune regulation. This is supported by the research, but currently some are dosing twice a day believing the action on Toll Like Receptor 4 is of value, but it appears to be minimal in effect.
So, if you want immune regulation via endorphins, once a day maximum is recommended and also seek the lowest dose that works, because this still ramps up the receptor count and then the endorphins.
So, if you want immune regulation via endorphins, once a day maximum is recommended and also seek the lowest dose that works, because this still ramps up the receptor count and then the endorphins.
12 years ago
jamison
Hi Maff - thanks for the encouragement. I have to say I am really hopeful and positive about LDN and think it has huge potential. I wouldn't be surprised if it becomes standard protocol to prescribe LDN to CFS patients in the not too distant future.
I'm still experimenting with dosing. I've increased my dose from 1.5mgs to 2.0 mgs. Unconventionally I am dosing myself twice a day - 1mg in the morning and one at night. I find I am more steady doing this. At 1.5mgs I was still getting some ME symptoms. 3mgs resulted in fluey symptoms that at times were a bit overpowering. My feeling is that the LDN is causing a herxheimer reaction. My aim is to maintain this reaction but at a level I can manage. I hope this will allow me to improve the quickest. So far 2mgs seems to be a good compromise. I'm getting low grade glandular fever/ fluey type symptoms but no ME symptoms which I think is a good thing...
The liquid came through today and I noticed the fluey symptoms within 10 minutes of taking it. So I suspect it is directly modulating the immune system quite quickly. I have also noticed my stools have a darker colour to them and are better formed. Again my intuition is telling me this is a good sign. So here's hoping...
I'm still experimenting with dosing. I've increased my dose from 1.5mgs to 2.0 mgs. Unconventionally I am dosing myself twice a day - 1mg in the morning and one at night. I find I am more steady doing this. At 1.5mgs I was still getting some ME symptoms. 3mgs resulted in fluey symptoms that at times were a bit overpowering. My feeling is that the LDN is causing a herxheimer reaction. My aim is to maintain this reaction but at a level I can manage. I hope this will allow me to improve the quickest. So far 2mgs seems to be a good compromise. I'm getting low grade glandular fever/ fluey type symptoms but no ME symptoms which I think is a good thing...
The liquid came through today and I noticed the fluey symptoms within 10 minutes of taking it. So I suspect it is directly modulating the immune system quite quickly. I have also noticed my stools have a darker colour to them and are better formed. Again my intuition is telling me this is a good sign. So here's hoping...
12 years ago
Maff
WindingDown - Glad to hear you have got a group going for LDN on Facebook and thanks for your comments about this group here on EiR. I hope others will share their experiences as jamison is kindly doing.
Jamison - So happy that you are doing well on the LDN and better to take things easy rather than have to endure severe flu-like symptoms for who knows how long. From what I've read and what Viewpoint has confirmed, 1.5mg is a common dose, so it's not like you are being overly cautious and won't get the full benefits. I hope the flu-like symptoms are manageable and don't persist for too long and that you start to see some real improvement in symptoms as your immune system starts to act as it should!
Jamison - So happy that you are doing well on the LDN and better to take things easy rather than have to endure severe flu-like symptoms for who knows how long. From what I've read and what Viewpoint has confirmed, 1.5mg is a common dose, so it's not like you are being overly cautious and won't get the full benefits. I hope the flu-like symptoms are manageable and don't persist for too long and that you start to see some real improvement in symptoms as your immune system starts to act as it should!
12 years ago
jamison
Hi Viewpoint,
Thanks for clearing that up. That's really useful information to have. Yesterday I halved my dose to 1.5 mgs. Although I wasn't too bad on 3 mgs, some of the viral symptoms were very strong at times and I thought rather than push through, I would give myself a break and make life a little easier. I also started dosing myself last thing at night rather than in the morning. First signs are that this dose suits me more. I'm still getting the viral symptoms but they're not as severe.
I agree that Dr Myhill doesn't need any more trouble with the GMC. I am due to see both her and Dr Pouria in early July. I will be sure to mention LDN dosing for CFS patients and suggest they consult with the LDN Research Trust. I will also ask them about being on the LDN doctors list as you suggest.
I am taking the capsules obtained from the Dickson pharmacy in Scotland. I have, however, just ordered the liquid as I want to be able to modulate my dose more easily.
Thanks again for your response. It was really useful.
All the best,
Thanks for clearing that up. That's really useful information to have. Yesterday I halved my dose to 1.5 mgs. Although I wasn't too bad on 3 mgs, some of the viral symptoms were very strong at times and I thought rather than push through, I would give myself a break and make life a little easier. I also started dosing myself last thing at night rather than in the morning. First signs are that this dose suits me more. I'm still getting the viral symptoms but they're not as severe.
I agree that Dr Myhill doesn't need any more trouble with the GMC. I am due to see both her and Dr Pouria in early July. I will be sure to mention LDN dosing for CFS patients and suggest they consult with the LDN Research Trust. I will also ask them about being on the LDN doctors list as you suggest.
I am taking the capsules obtained from the Dickson pharmacy in Scotland. I have, however, just ordered the liquid as I want to be able to modulate my dose more easily.
Thanks again for your response. It was really useful.
All the best,
12 years ago
Viewpoint
Hi Jamison,
I am aware of Dr Myhill and am pleased she is prescribing LDN for CFS/ME patients. I know she recommends LDN for MS on her website (which I believe has been or is being updated). I have been in touch with a couple of staff members at her office re LDN as her website mentioned getting 50mg tablets from India and making your own. With LDN being a prescription only drug in the UK, I suggested she take this down (we all know how much trouble she was in with the GMC last year largely due to her advice on her website). I suggested instead they could list E-Med for those who had difficulty in getting a prescription where they could have a phone consultation with a Dr there who if satisfied LDN could help you, would write you a prescription, and also a link to LDN Research Trust.
I believe Dr Myhill and Dr Pouria are going on the recommended dosing from the 'old days'. Until these last couple of years, people were advised to start on 3mg and if all is going well, increase to 4.5mg - that seemed the protocol at the time. However this was mostly for those with MS. When looking at Dr Myhill's website which I refer to often as it holds a wealth of information, I suggested she may want to put a link to Dr Bob Lawrence who introduced LDN into the UK and also Dr Tom Gilhooly (two main LDN prescribing Drs here). I got a response saying she hadn't heard of them. The office recently came back to me saying they couldn't find anything about dosing on the LDNNow website or LDN RT to which I responded it was usually up to the prescribing Dr to do this and dosing differed for each person depending on their illness - there is no 'one size fits all'.
I'm so pleased to hear that LDN is working well for you at 3mg - this is great news and would indicate you are metabolizing LDN rather quickly which is what you want, hence some of the side effects you are now experiencing from starting at what is considered a high dose for CFS/ME. This is not a bad thing as this shows your body is readjusting itself and your immune system is responding. As you say, everything else now appears to be functioning at 'normal' levels from working with the two Drs you mention - good stuff!
Out of interest, can you let me know are you taking the capsules or liquid LDN and where do you get it from?
Also, Crystal Nason holds a list of prescribing Drs worldwide. Would you mind asking Dr Myhill and Dr Pouria if they wouldn't mind having their names added to this list?
Look forward to following you on your journey to better health.
I am aware of Dr Myhill and am pleased she is prescribing LDN for CFS/ME patients. I know she recommends LDN for MS on her website (which I believe has been or is being updated). I have been in touch with a couple of staff members at her office re LDN as her website mentioned getting 50mg tablets from India and making your own. With LDN being a prescription only drug in the UK, I suggested she take this down (we all know how much trouble she was in with the GMC last year largely due to her advice on her website). I suggested instead they could list E-Med for those who had difficulty in getting a prescription where they could have a phone consultation with a Dr there who if satisfied LDN could help you, would write you a prescription, and also a link to LDN Research Trust.
I believe Dr Myhill and Dr Pouria are going on the recommended dosing from the 'old days'. Until these last couple of years, people were advised to start on 3mg and if all is going well, increase to 4.5mg - that seemed the protocol at the time. However this was mostly for those with MS. When looking at Dr Myhill's website which I refer to often as it holds a wealth of information, I suggested she may want to put a link to Dr Bob Lawrence who introduced LDN into the UK and also Dr Tom Gilhooly (two main LDN prescribing Drs here). I got a response saying she hadn't heard of them. The office recently came back to me saying they couldn't find anything about dosing on the LDNNow website or LDN RT to which I responded it was usually up to the prescribing Dr to do this and dosing differed for each person depending on their illness - there is no 'one size fits all'.
I'm so pleased to hear that LDN is working well for you at 3mg - this is great news and would indicate you are metabolizing LDN rather quickly which is what you want, hence some of the side effects you are now experiencing from starting at what is considered a high dose for CFS/ME. This is not a bad thing as this shows your body is readjusting itself and your immune system is responding. As you say, everything else now appears to be functioning at 'normal' levels from working with the two Drs you mention - good stuff!
Out of interest, can you let me know are you taking the capsules or liquid LDN and where do you get it from?
Also, Crystal Nason holds a list of prescribing Drs worldwide. Would you mind asking Dr Myhill and Dr Pouria if they wouldn't mind having their names added to this list?
Look forward to following you on your journey to better health.
12 years ago
WindingDown
I have been taking LDN for almost 3 months for my Fibro/CFS, BIG bonus, my mood and knee arthritis was helped as well, had some tummy issues first few weeks on LDN, and only one day of cramps, only lasted 5 minutes, not even sure if it was from LDN.. I started out on 1.0, couldnt go higher for 5-6 weeks, Ill take the few weeks of tummy issues LDN gave me to save the pain relief was better than my daily motrin and no fuzzy headed vico needed. After a few months even my IBS got 75% better, I can eat summer fruits with out paying the price in the bathroom now. I added this People's personal Experience on LDN group to my facebook support group I started on LDN called GOT ENDOPRHINS? LDN so hopefully you will have a lot more people coming in leaving their exp. GOT ENDOPRHINS? LDN group is closed and you need to ask to join, its private, no one can see your posts unless they belong to it. SO HAPPY TO SEE THIS started on here too!!!
12 years ago
jamison
Viewpoint and Abarnett - thank you for your posts. Indeed I had read myself that a 3mgs starting dose was certainly towards the high end and after your posts I was concerned enough to ring the LDN research trust. I spoke to a nice lady on the phone (not medically qualified but clearly very knowledgeable about LDN) and she also said that 3mgs was very high for someone with CFS/ME.
However, after I explaned that by and large I was tolerating the dose quite well, she said it was fine to carry on. I have taken my 4th dose this morning. Since taking LDN, what I would call my ME/CFS symptoms (brain fog, light sensitivity, spacey feeling, cognitive deficit) have all but gone and been replaced by viral, fluey symptoms. These vary in intensity but come on strongest immediately after taking LDN. My intuition is telling me that this is no bad thing as a viral insult (probably EBV) was my trigger point for CFS. I don't think I ever properly resoved that viral infection and I am hoping that the LDN is rebalancing my immune system sufficiently so I can finally resolve the glandular fever. I won't increase my dose though until a lot of these viral symptoms have died down and I feel sufficiently strong to do so.
I have to say I do find this discrepancy in what is considered a normal starting dose for CFS a bit strange and worrying. Both Dr Pouria and Dr Myhill prescribed 3 mgs very readily to me when I asked to be prescribed LDN. Both prescribed me LDN separately without the others knowledge and there was no discussion of dose. Both simply gave me a prescription for 3 mgs. These are very experienced ME/CFS doctors who have clearly prescribed LDN many times before. Though having said that the LDN research Trust clearly know what they are talking about too. So what's going on?
I think I may be able to tolerate a higher starting dose than normal because I am taking LDN off the back of a significant number of other treatments for CFS that have successfully normalised a lot of the biomedical markers for CFS/ME. My ATP profile, thyroid, methylation cycle are all now functioning normally. I have also cleared all my DNA adducts, corrected vitamin and mineral deficiencies and appear to have resolved my candida and leaky gut issues too. So I believe I am at the core of what is causing my CFS which is the immune disturbance and the unresolved glandular fever. Perhaps if you started LDN on 3 Mgs dose without having successfully treated the above, this would be a too bigger jolt for the body to handle and this is why a lot of CFS patients have to start on a smaller dose?
However, after I explaned that by and large I was tolerating the dose quite well, she said it was fine to carry on. I have taken my 4th dose this morning. Since taking LDN, what I would call my ME/CFS symptoms (brain fog, light sensitivity, spacey feeling, cognitive deficit) have all but gone and been replaced by viral, fluey symptoms. These vary in intensity but come on strongest immediately after taking LDN. My intuition is telling me that this is no bad thing as a viral insult (probably EBV) was my trigger point for CFS. I don't think I ever properly resoved that viral infection and I am hoping that the LDN is rebalancing my immune system sufficiently so I can finally resolve the glandular fever. I won't increase my dose though until a lot of these viral symptoms have died down and I feel sufficiently strong to do so.
I have to say I do find this discrepancy in what is considered a normal starting dose for CFS a bit strange and worrying. Both Dr Pouria and Dr Myhill prescribed 3 mgs very readily to me when I asked to be prescribed LDN. Both prescribed me LDN separately without the others knowledge and there was no discussion of dose. Both simply gave me a prescription for 3 mgs. These are very experienced ME/CFS doctors who have clearly prescribed LDN many times before. Though having said that the LDN research Trust clearly know what they are talking about too. So what's going on?
I think I may be able to tolerate a higher starting dose than normal because I am taking LDN off the back of a significant number of other treatments for CFS that have successfully normalised a lot of the biomedical markers for CFS/ME. My ATP profile, thyroid, methylation cycle are all now functioning normally. I have also cleared all my DNA adducts, corrected vitamin and mineral deficiencies and appear to have resolved my candida and leaky gut issues too. So I believe I am at the core of what is causing my CFS which is the immune disturbance and the unresolved glandular fever. Perhaps if you started LDN on 3 Mgs dose without having successfully treated the above, this would be a too bigger jolt for the body to handle and this is why a lot of CFS patients have to start on a smaller dose?
12 years ago
Viewpoint
Having read the below, I am surprised someone with CFS has been prescribed to take 3mg of LDN to start off with. I have found from talking to numerous people, that those who are living with CFS are sensitive to meds so it is common to start at 1.5mg increasing every 2 weeks by 0.5mg. Some stay at 2mg whereas others feel they need to get what was one 'thought' to be the optimal dose of 4.5mg. Please do be careful with trying to get to a higher dose than 3mg. Dr Ian Zagon and I have exchanged numerous emails who has been explaining to me that after some time, those taking 4.5mg tend to have a build up of LDN in their bodies and feel LDN is no longer working for them. At this point, he has advised them to cut back to 3mg and they then started reaping the benefits of LDN.
It is his opinion after 30 years plus of research to not go higher than 3mg. Please do bear this in mind with LDN as it is potent and very effective when you get the dose right. Some times, less is more - I'm sharing with you a blog from LDNNow which explains this better
www.ldnnow.co.uk/… this helps.
It is his opinion after 30 years plus of research to not go higher than 3mg. Please do bear this in mind with LDN as it is potent and very effective when you get the dose right. Some times, less is more - I'm sharing with you a blog from LDNNow which explains this better
www.ldnnow.co.uk/… this helps.
12 years ago
ABarnett
I have done a lot of work on how LDN works, including talking to Dr Zagon and most of the LDN scientists and doctors and pharmacists. Dr Zagon explains that LDN stimulates a range of endorphins, but one in particular - OGF (Opiod Growth Factor) or metenkephalin - is most important. It attaches to the OGFr (receptor) and LDN causes the proliferation of this receptor. OGF is what had the effect of regulating the immune system, diretly by inhibiting the proliferaion of the T cells and of cancer cells. The OGF-OGFr axis works directly into the nucleus and thus has the effect of eliminating the residual immune system activation that accompanies chronic illness and causes severe cytokine imbalances that make us feel sick.
This chronic low level immune activation also prevents the immune system responding to infections, so correcting this will restore a normal immune function, hence the impression that LDN results in a boosting of the immune system. In fact, we are tackling the effects of chronic sickness which results in proper immune function and hence improvements in autoimmune conditions. Cancer is controlled by the effect of OGF to stop tumour cells growing via the zeta receptor.
The exact dose which is correct is difficult to determine but Dr Zagon says to take the lowest dose that works. That makes sense to me.
This chronic low level immune activation also prevents the immune system responding to infections, so correcting this will restore a normal immune function, hence the impression that LDN results in a boosting of the immune system. In fact, we are tackling the effects of chronic sickness which results in proper immune function and hence improvements in autoimmune conditions. Cancer is controlled by the effect of OGF to stop tumour cells growing via the zeta receptor.
The exact dose which is correct is difficult to determine but Dr Zagon says to take the lowest dose that works. That makes sense to me.
12 years ago
jamison
Hi Maff,
Yes - I think you are right. The LDN is switching on some dormant anti-viral pathways (at least that's what I'm hoping). I took my 3rd dose this morning and feel like I have got a very heavy cold so I'm just going to run with that for a while. In many ways its not so bad - it makes a pleasant change from CFS symptoms (feels like more of a conventional immune response) and I just want to sleep all the time which I think must be quite healing and restorative.
I had read the same thing about the LDN dosing but interestingly both Dr Pouria and Dr Myhill (who prescribed me LDN separately) both suggested starting on 3mgs so I went with that. The plan is then to push it up to 4.5 mgs in a months time.
Good luck with your other treatment route. I might be following suite. I was positive for a hydrogen sulphide urine test this morning so although the rest of my gut tests have been good I am far from convinced my problems are fully resolved in that department. I noticed Redo has done the first HPI already. Fascinating stuff! I shall be watching keenly...
Take care,
Yes - I think you are right. The LDN is switching on some dormant anti-viral pathways (at least that's what I'm hoping). I took my 3rd dose this morning and feel like I have got a very heavy cold so I'm just going to run with that for a while. In many ways its not so bad - it makes a pleasant change from CFS symptoms (feels like more of a conventional immune response) and I just want to sleep all the time which I think must be quite healing and restorative.
I had read the same thing about the LDN dosing but interestingly both Dr Pouria and Dr Myhill (who prescribed me LDN separately) both suggested starting on 3mgs so I went with that. The plan is then to push it up to 4.5 mgs in a months time.
Good luck with your other treatment route. I might be following suite. I was positive for a hydrogen sulphide urine test this morning so although the rest of my gut tests have been good I am far from convinced my problems are fully resolved in that department. I noticed Redo has done the first HPI already. Fascinating stuff! I shall be watching keenly...
Take care,
12 years ago
Maff
Hi, jamison and thanks for creating this discussion. As you know I also have long-term CFS and had exactly the same thoughts as you when learning of LDN. I am going another treatment route first (faecal transplant/HPI) but still have LDN in mind at some point.
Fantastic to hear your impressions of LDN treatment, even at this early stage. I thought it's effects would be potent based on its mechanism of stimulating endorphin production. Also I was a bit surprised you went straight for a dose of 3mg. I had read that half of that was a typical starting dose? Anyway, great to hear that it had such a positive impact on your symptoms and functioning so soon. I would give anything to have a clear head and stable positive moods! The fluey feeling is probably to be expected if the LDN has started modulating your immune response and switching on dormant antiviral pathways. You might be in for a rough ride for a while with that but it will be worth it in the end won't it! I've heard many ex-CFS patients and doctors who treat CFS patients say that when they started getting colds and flu again was when they knew they were recovering and starting to respond normally to infections.
Take care and keep us updated...
Fantastic to hear your impressions of LDN treatment, even at this early stage. I thought it's effects would be potent based on its mechanism of stimulating endorphin production. Also I was a bit surprised you went straight for a dose of 3mg. I had read that half of that was a typical starting dose? Anyway, great to hear that it had such a positive impact on your symptoms and functioning so soon. I would give anything to have a clear head and stable positive moods! The fluey feeling is probably to be expected if the LDN has started modulating your immune response and switching on dormant antiviral pathways. You might be in for a rough ride for a while with that but it will be worth it in the end won't it! I've heard many ex-CFS patients and doctors who treat CFS patients say that when they started getting colds and flu again was when they knew they were recovering and starting to respond normally to infections.
Take care and keep us updated...
12 years ago
jamison
Well my first impressions of this drug are that it is very potent indeed! Within 2 hours of my first dose yesterday I experienced improved mood followed by clearer thinking, more energy, greater assertivness and improved word finding and substitution. In short I felt much more like my old self. I had my second dose this morning and have begun to feel a bit fluey (just woken up from a nap). I think this is no bad thing as I am sure I have unresolved viral issues (swollen glands etc) and if the LDN is modulating my immune system it makes sense to me I could feel a bit rough whilst my immune system begins to attack remnant infections. Here's hoping....Although still very early days I feel this is a very promising treatment.
12 years ago
