232 replies to this topic

[adamh]

Yes, but I think the conclusion that it works well with opiods is incorrect. It is in fact an opiod antagonist and works against the effect of opiates, not with them. It will block the pain killing effects of an opiate including your endorphins.

It helps with pain because it, perhaps, helps the underlying condition. I've never heard of it being a pain killer by itself.

[viveutvivas]

 

adamh, on 09 October 2010 - 07:11 PM, said:

It helps with pain because it, perhaps, helps the underlying condition. I've never heard of it being a pain killer by itself.

From http://snapl.stanford.edu/ldn/

Quote

At normal doses (50mg – 100mg), naltrexone is a drug used to block the effects of opioids. At low (<5mg) doses, however, the drug may have the reverse effect and actually strengthen analgesia. While the exact mechanism of this action is unknown, it is possible that low doses of naltrexone block the receptors on glial cells that are responsible for fibromyalgia symptoms.

From http://www.medpageto...romyalgia/13785

Quote

Rather than blocking the body's pain relief systems, naltrexone doses of around 4.5 mg modulated activity of glial cells to act as a neuroprotectant and suppressant of proinflammatory cytokines.

From http://drgimbarzevsk...one/index..html

Quote

The idea for using Ultra Low dose Naltrexone (ULDNTX) came after I saw an article in the Medical Post regarding some research that Dr. Jhamandas et al had done in rats using doses in the range of 0.05 femtograms of naltrexone to enhance morphine analgesia and to prolong the actions of morphine. I immediately emailed Dr. Jhamandas and he gave me a number of references involving the use of Naloxone (another opiate antagonist with roughly half the potency of naltrexone) in potentiating morphine in PCA post-operative analgesia.

A PCA pump allows a patient to inject a dose of morphine when they start to experience pain postoperatively. This results in greater patient comfort and decreased nursing workload. As the morphine doses injected are small (1-2 mg) fine titration of pain control is possible without excess sedation. The experiment that Dr. Jhamandas referred me to was a study in which 0.25 micrograms of naloxone/hour was given by continous IV infusion (this normally occurs in PCA as a slow flow of fluid must be maintained to keep iv from clotting), and this miniscule dose decreased the amount of moriphine that patients used by 30%.

Edited by viveutvivas, 09 October 2010 - 08:01 PM.

[adamh]

That's very interesting. In tiny doses (femtograms??) it may have a reverse effect. In humans, who knows? I'm just saying don't rely on it to work exactly the same as morphine or something. They said

"At low (<5mg) doses, however, the drug may have the reverse effect and actually strengthen analgesia."

Notice "may have" and "strengthen analgesia" meaning it works with an analgesic and not on it's own. However I did not know it did that at all and assumed it blocked opiods at any effective dose. I think many on this board may be surprised to hear that too. Good find.

[adamh]

After giving it a fair try I've decided to quit ldn. The only benefit I got for sure was a reduction in allergy symptoms. It has done nothing for nerve discomfort and the sleeplessness is getting worse. I'm tired all day every day even with taking stuff to sleep. Most of the herbs that worked at first for sleep no longer work. Even when I take something that makes me sleepy, I have a hard time getting to sleep and often wake during the night.

Another thing I've noticed is back pain. I've gradually upped the dose to 1.9 mg per day and the sleep problems and brain fog have gotten worse. I use to have back pain that got worse with lying down too long but it hasn't bothered my sleep in a while. I started to notice it again a while back when my dose went over about .5 mg or so. Lately it's gotten worse and when I wake before dawn, it makes it much harder to get back to sleep. Viv reported severe back pain from one 3 mg dose and I saw on the net that its reported side effects can include back pain.

I got some generic lyrica which helps with sleep and is supposed to help with nerve pain. I slept well on it, not sure about the nerve benefit. But I also noticed that I didn't have back pain the morning after I took the lyrica. Very interesting. But the back pain came back the next day and I did not use the lyrica again yet. It's kind of expensive and I don't want to have dependence.

So, I feel I've given it a fair trial and it is doing little to nothing and the side effects are becoming major. Lack of sleep is detrimental to your health all by itself. Plus my mood was not that great, no feeling of well being, possibly because of the lack of sleep. I've been taking st john's lately. I've been on 1.5 mg per day for several weeks and 1 mg or more for about a month and a half. No benefits but lots of problems. I don't need this. Just like benfotiamine, just like lions mane, just like everything else, nothing helps.

I may consider going back to .5 per day later after I evaluate getting off it and have a chance to rest and get back into health. This is not for everyone.

The astragalus doesn't seem to have done anything yet but most of it's purported benefits are for other general health things. I will continue with that and whatever improvements I see later on will be likely due to it and not the ldn.

I have sealed packets of naltrexone tabs if anyone wants to experiment with it. Many people have said it's great but it's not for me. If you have ms, this could be what you need. Or lymes, various other things. I noticed some increase in libido but had no problem with that before. It's great for allergies.

[viveutvivas]

An update:

So I have tried LDN a few times now, dosing down from 3 mg to as low as 0.5 mg.  

I am ending my experiment.

All it does is make me abjectly, utterly miserable for a period depending on dose, with no subsequent benefit.       

[golgi1]

Bump.

Is anyone still on LDN, FunkOdyssey, possibly?

Any updates?

[Logan]

Funk is taking it, but I don't think he's been coming around here much lately.  You might want to get onto M & M and ask him there.

[golgi1]

Thanks. Will do.

[golgi1]

viveutvivas, on 30 October 2010 - 05:41 PM, said:

An update:

So I have tried LDN a few times now, dosing down from 3 mg to as low as 0.5 mg.  

I am ending my experiment.

All it does is make me abjectly, utterly miserable for a period depending on dose, with no subsequent benefit.  

I just want to offer an opinion on the experience put forth in the above quoted post.

First, it sounds like you have moderate withdrawal symptoms at low doses, with no "rebound" effects in the endocrine nor opioid systems that are ostensibly the  objectives of the therapy.

Let me offer that .5 mg, for many candidates, is not as low as you might believe that it is.

In fact, with 'ultra low dose naltrexone' therapy, users take does that are down to 1/500th of the .5 mg "low dose" that this poster describes. When looked at through this lens, "low doses" of 1.5 mg, and even .5 mg, seem very high compared to what could be taken to effect the desired  therapy. Perhaps, between 500 and 1500 times the amount that the poster should be starting with.

It's all about perceived / relative scale, and .5 mg only seems like a small dose when compared to a 1.5-4.5 mg dose. However, it may not be low in reality to this poster's actual needs or what may be effective.

I choose to look at rebound type antagonist-facilitated reactions as similar to the model that is used for the testosterone rebound effect that is effected through anabolic exercise.

That is, higher volumes of the stressor that is facilitating the effect that you want can actually be counterproductive to that effect. For example, over-stressing the system with 30 reps of 200 lbs may not have as an acute a testosterone rebound effect as 10 repetitions. There has to be a sweet spot that is found between intensity and volume to maximize the rebound effect. In weight lifting, the highest intensity, lowest volume (repetition) exercise generally triggers the best testosterone rebound. Fortunately, in weight lifting, intensity and volume directly regulate one another. The more weight (intensity) that you add, the less volume you will be physically able to do.

Hypothetically, when attempting to trigger a rebound effect through antagonist supplementation, the intensity should equal the chemicals ability to fully block the receptor, and volume would equal the dose, with higher dose weights equaling higher volume.

Therefore, hypothetically, a dose that surpasses the users opioid system's ability to rebound (fitness level) may actually just suppress all rebound action. Someone who has a lower opioid fitness level won't be able to tolerate higher doses (relative) and may need to start at much lower doses, similar to a new weight lifter starting out with a less stressful regimen. If a new weight lifter over-does his first workout, he will realize a net testosterone suppressive effect. Similarly, a new LDN user, with compromised opioid fitness, may need to start at microgram (1/1000 of a mg) levels and work his  or her way up to higher levels, if necessary, to avoid suppressing his natural opioid reception without realizing a beneficial rebound effect.

The above poster may well have realized the positive rebound effects that he was after if he had started at a  much lower dose.

Try mixing up a solution where 1 dose will be equivalent to 1 microgram, and go from there. You can also mix another "macro" solution where one dose will equal .050 mg, and perhaps anther that equals .5 mg. Just be sure that when you do the math, keep in mind tht the calibration of the dropper is the most important component in deciding how much liquid to use. For the mcg solution, you will likely have to use 25 uL micropipettes (1/40 of a mL) to take the correct 1 mL amount. As you go higher in terms of the drop volume, you will need more liquid to keep the dose as low as you need it to be. The lowest calibrated dropper that I was able to find was .1 mL, before needing to resort to pipettes to get lower volumes.

Edited by golgi1, 12 October 2011 - 07:54 PM.

[golgi1]

See the attached paper in PDF.

Essentially, it seems that I may be right.
At least if one accepts the premise that LDN likely works against all indicated diseases through "upregulation"(a non-specific over-generalization for what is likely going on, I know). I think that up-regulation is a more likely mechanism than disease mitigation resulting from mere prolonged blocking of receptors that results in no permanent up-regulation nor permanent homeostatic change in signaling. If anyone believes in the likelihood of the same, then the research presented by the attached paper is worth considering.

While the attached paper doesn't address what is generally though of as LDN's effect on disease progression, other than the diseases of addiction and tolerance; it presents, among other critical perspectives, that ULDN is proven to work better as the dose is diminished. If the doses that were found to be most effective are to be believed, then adherents of the standard LDN protocol might be dosing as much as one billion times above the optimal dose.

in my previous post, I was assuming that microgram levels (what seems to be the standard ULDN protocol floating around on the internet) would be adequately small enough to experiment with. According to the attached research for the new opiate/naltrexone combination drug, microgram doses may be too high by up to a million times (milligram doses by one billion times). Instead, the researchers have found that picogram doses seem to have the best effect on conditioning the system to resist and rebound from opioid tolerance, especially when concurrently taking opiates (conjecture: or perhaps consuming natural opiates in food (milk) or otherwise realizing down-regulation through other means, like perhaps sun exposure).  I'm not sure if research has been carried out using femtogram level doses or below. If ULDN works better with an decreasing does, as is claimed by the authors of the paper, then it seems as if further research on smaller doses is warranted.

A last worthy question is if any meaningful research or experimentation has been done with nanogram level doses, or lower, for the broad range of indicated disease states that LDN treats (other than addiction and opiate tolerance). If not, then in light of the success of picogram level ULDN treatment of opiate tolerance, further research into picogram dosing for other disease states shouldn't be ignored. It is very possible that LDN patients are taking over the optimal dose by many orders of magnitude.

I would say to those (no one specific) who might have a knee jerk reaction to such low doses as being "homeopathic" or "too low to be effective" that many people appreciate your comments, but we didn't know that you had such omniscient knowledge of the mechanisms behind neuro-hormonal fitness. In other words, try it. These are not homeopathic doses. When receiving a picogram dose, you are still receiving a dose that contains molecules of the chemical. Anyone's perspective as to how large milligram, microgram, nanogram, or picogram level doses are, relative to the desired effect of the medicine, is based on a learned model of pharmacology that likely doesn't apply here. That is, it likely doesn't apply in a therapy which is attempting to introduce a stressor that will coax the body into finding a new homeostatic baseline. According to the attached research, extremely small doses of potent antagonists seem to work best. I'm looking forward to the further experimentation of others and my own experiences with ultra low doses. While I realize that the same mechanism may not cross over with other drugs, I think that ultra low doses of other antagonists are worth a try. Perhaps, in the future, some of us will try and report back on ultra low doses (nanogram or less) of memantine, other NMDA antagonists, or other monoamine antagonists.

I highlighted what I thought were the relevant sections of the attached paper (although the entirety of the content is instructive). I realize that some might find this annoying, but it draws the eye of others who would otherwise skim the paper. Enjoy.

Attached Files

•  ULDN.pdf   280.09K   12 downloads

Edited by golgi1, 15 October 2011 - 05:28 AM.

[Barry Wheeler]

Does low dose naltrexone increase prolactin levels? I couldn't find the research about endorphins at higher levels in hibiting the prolactin suppressing ability of dopamine but if it is true that endorphins do this that would not likely be a problem with LDN because it only increases receptors not the actual endorphins apparently.

[Logan]

I started LDN 6 days ago.  So far so good.

[Matt79]

Logan, on 23 January 2012 - 05:44 AM, said:

I started LDN 6 days ago.  So far so good.

What you taking it for?

I started LDN about 8 months ago for Rheumatoid Arthritis. I'm really bad at tracking my mood and sleep as I have terrible memory for details. I can only seem to remember concepts.

Anyway, what is the latest thinking on LDN longterm?

Is it good?

I take 4.5mg per day.

[viveutvivas]

Matt79, on 03 February 2012 - 08:59 PM, said:

I started LDN about 8 months ago for Rheumatoid Arthritis.

What are your results, if any?  I have ankylosing spondylitis and have considered trying it again (at a much lower dose than before), although I do seem to be doing well on Enbrel now (touch wood).

[Matt79]

viveutvivas, on 03 February 2012 - 10:08 PM, said:

Matt79, on 03 February 2012 - 08:59 PM, said:

I started LDN about 8 months ago for Rheumatoid Arthritis.

What are your results, if any?  I have ankylosing spondylitis and have considered trying it again (at a much lower dose than before), although I do seem to be doing well on Enbrel now (touch wood).

I tried Enbrel for a brief period a few years ago. While it is effective, I am doing better without it however.

The head of Rheumatology in South Africa said I'd be crippled in a few years without medication. I disagreed and spent the next 3 years researching. Well I haven't taken Enbrel for years and doing better than ever. I exercise, do kitesurfing, snowboarding etc. The biggest effect was changing my diet fundamentally and supplementing with things like EPA/DHA and D3 etc.

Enbrel, has potentially some nasty side effects also you may want to investigate. Look it does work, but it's a drug designed to treat chronic symptoms, not causes.

Enbrel is in the Top 10 biggest revenue generating drugs in the world.
http://www.imshealth...al_Products.pdf

At $6b a year in sales from Enbrel, a "cure" for RA is definitely not considered high on Amgen's priority list.

Chronic treatment is big business.

Edited by Matt79, 03 February 2012 - 11:02 PM.

[viveutvivas]

I am glad to hear of your drug-free remission.  That would have been my first choice.  I kept up with supps, diet and what I could manage of exercise though, and nothing helped during 3 lost years of what my remains of my youth (it didn't help that it took almost 3 years to get diagnosed).  I was suffering badly until starting Enbrel, which has been a lifesaver to me.  I think it is much safer overall than NSAIDs or DMARDs.  Even ibuprofen is in my opinion more dangerous than Enbrel - those side effects you mention are limited to a very small number of patients out of hundreds of thousands.

I'm still curious, tough.  What is your experience on the LDN related to your RA?

I live in the U.S. but I'm also S-African, by the way.  

Edited by viveutvivas, 04 February 2012 - 12:06 AM.

[Matt79]

Matt79, on 04 February 2012 - 12:25 AM, said:

viveutvivas, on 04 February 2012 - 12:05 AM, said:

I am glad to hear of your drug-free remission.  That would have been my first choice.  I kept up with supps, diet and what I could manage of exercise though, and nothing helped during 3 lost years of what my remains of my youth (it didn't help that it took almost 3 years to get diagnosed).  I was suffering badly until starting Enbrel, which has been a lifesaver to me.  I think it is much safer overall than NSAIDs or DMARDs.  Even ibuprofen is in my opinion more dangerous than Enbrel - those side effects you mention are limited to a very small number of patients out of hundreds of thousands.

I'm still curious, tough.  What is your experience on the LDN related to your RA?

I live in the U.S. but I'm also S-African, by the way.  

Howzit

Well I was fine before I took LDN, still fine on it. And been through periods without it. So to be honest, I'm not sure what effect, if any it is having. I might just stop it altogether.

viveutvivas, on 04 February 2012 - 12:05 AM, said:

suffering badly until starting Enbrel, which has been a lifesaver to me.  I think it is much safer overall than NSAIDs or DMARDs.

• Enbrel has pretty good efficacy, so yes, you will most likely feel good on it and it does work.
  
• Enbrel is a DMARD

However remission in my experience, this can be achieved if one is prepared toundergo a radical change in lifestyle. Cut out all grains etc. Consuming lots of fishoils etc

If you in the valley, we can meetup for a chat, if you like.

viveutvivas, on 04 February 2012 - 12:05 AM, said:

I am glad to hear of your drug-free remission.  That would have been my first choice.  I kept up with supps, diet and what I could manage of exercise though, and nothing helped during 3 lost years of what my remains of my youth (it didn't help that it took almost 3 years to get diagnosed).  I was suffering badly until starting Enbrel, which has been a lifesaver to me.  I think it is much safer overall than NSAIDs or DMARDs.  Even ibuprofen is in my opinion more dangerous than Enbrel - those side effects you mention are limited to a very small number of patients out of hundreds of thousands.

I'm still curious, tough.  What is your experience on the LDN related to your RA?

I live in the U.S. but I'm also S-African, by the way.  

Howzit

Well I was fine before I took LDN, still fine on it. And been through periods without it. So to be honest, I'm not sure what effect, if any it is having. I might just stop it altogether.

viveutvivas, on 04 February 2012 - 12:05 AM, said:

suffering badly until starting Enbrel, which has been a lifesaver to me.  I think it is much safer overall than NSAIDs or DMARDs.

• Enbrel has pretty good efficacy so you will most likely feel good on it.
  
• Enbrel is a DMARD

However remission in my experience, can be achieved if one is prepared toundergo a radical change in lifestyle. Cut out all grains etc. Consuming lots of fishoils etc

If you in the valley, we can meetup for a chat, if you like.

Edited by Matt79, 04 February 2012 - 12:26 AM.

[viveutvivas]

Matt79, on 04 February 2012 - 12:25 AM, said:

However remission in my experience, this can be achieved if one is prepared toundergo a radical change in lifestyle. Cut out all grains etc. Consuming lots of fishoils etc

If you in the valley, we can meetup for a chat, if you like.

I wish.   Regrettably I'm stuck living in the cold and dreary Northeast.

Does cutting out grains include oats?  That's the only grain I still eat.  I eat fish every day but fish oil capsules, hmm, every time I try to start taking some I start hurting a few hours after taking a dose.  I've never managed to stick it out long enough to see if this goes away.

[Matt79]

viveutvivas, on 04 February 2012 - 01:45 AM, said:

Matt79, on 04 February 2012 - 12:25 AM, said:

However remission in my experience, this can be achieved if one is prepared toundergo a radical change in lifestyle. Cut out all grains etc. Consuming lots of fishoils etc

If you in the valley, we can meetup for a chat, if you like.

I wish.   Regrettably I'm stuck living in the cold and dreary Northeast.

Does cutting out grains include oats?  That's the only grain I still eat.  I eat fish every day but fish oil capsules, hmm, every time I try to start taking some I start hurting a few hours after taking a dose.  I've never managed to stick it out long enough to see if this goes away.

Try the natural TG form. Bluebonnet stock them, bit more expensive. Also you should always take them with food.

http://www.bluebonne...ormula_Softgels

I was on 20 a day to counter my condition, and cut down to 8 capsules now and am stable.

I cut oat oats, but use Beta Glucans (found in Oats as well as other things eg Shitake mushrooms) as well in my routine. They are excellent. Glucans stimulate macrophage activity.

[Logan]

Matt79, on 03 February 2012 - 08:59 PM, said:

Logan, on 23 January 2012 - 05:44 AM, said:

I started LDN 6 days ago.  So far so good.

What you taking it for?

I started LDN about 8 months ago for Rheumatoid Arthritis. I'm really bad at tracking my mood and sleep as I have terrible memory for details. I can only seem to remember concepts.

Anyway, what is the latest thinking on LDN longterm?

Is it good?

I take 4.5mg per day.

Hey Matt,  I'm taking it for what my doctor and I believe may be fibromyalgia.  I do not experience the usual pain, but I experience every other symptom listed for the condition.

I don't know about taking LDN long term.  I do know there are people that have been on it for years and continue to do very well without any issues.  So far, there does not appear to be any evidence that LDN has any major side effects if taken for a long time, if anything it shoulde be protective and preventative-which is why you should probably continue to take it.  Have you ever thought about going down to 3 mg, just to see if anything changes?

[Matt79]

Logan, on 06 February 2012 - 04:42 AM, said:

Matt79, on 03 February 2012 - 08:59 PM, said:

Logan, on 23 January 2012 - 05:44 AM, said:

I started LDN 6 days ago.  So far so good.

What you taking it for?

I started LDN about 8 months ago for Rheumatoid Arthritis. I'm really bad at tracking my mood and sleep as I have terrible memory for details. I can only seem to remember concepts.

Anyway, what is the latest thinking on LDN longterm?

Is it good?

I take 4.5mg per day.

Hey Matt,  I'm taking it for what my doctor and I believe may be fibromyalgia.  I do not experience the usual pain, but I experience every other symptom listed for the condition.

I don't know about taking LDN long term.  I do know there are people that have been on it for years and continue to do very well without any issues.  So far, there does not appear to be any evidence that LDN has any major side effects if taken for a long time, if anything it shoulde be protective and preventative-which is why you should probably continue to take it.  Have you ever thought about going down to 3 mg, just to see if anything changes?

Thanks for the info.

Hmm 3mg. No, but I think I'll just stop it altogether. I am terribly at noticing effects.

That is actually why am promoting the convergence of realtime blood monitoring with smartphone's and machine learning. I want to be told based on blood levels what I should be eating etc.

In the meantime it's just too much work trying to look for patterns in the data! At least for me, given the way my brain works.

Anecdotes are pretty bad IMHO, and I don't trust myself to spot a real pattern linked to cause and effect unless it's a gross change.

In fact I think this whole space is going to have to rely on AI. I haven't come across a human brain yet that can actually know all the fundamental principles at work and the interrelationships going on with enough competency to make extremely strong predictive judgements.

[Logan]

Well, we can only do what we can with what we have now-it may be more difficult and take more time, but I think we can come to the conclusions we need to.

What are your symptoms?  

LDN could be slowing down the progression.  We don't have to have answers, we just need to feel well-this should be enough for now.

[viveutvivas]

Logan, on 06 February 2012 - 05:19 AM, said:

LDN could be slowing down the progression.  We don't have to have answers, we just need to feel well-this should be enough for now.

I'm similar to Matt - unless the effect of something is really dramatic I never notice it among the usual daily ups and downs in how I feel, which I tend to ascribe, probably wrongly, to whatever I may have started taking that day.  As for slowing down the progression - unfortunately there is no way to anecdotally "notice" a counterfactual.