Experience with LDN?

Jonathan's successful trial/pilot re rituximab in arthritis comes to mind. He had a biomarker, but really only at a group level, elevated autoantibodies in arthritis group versus control group.
I'm hoping that DecodeME will provide evidence re pathology and the real win would be off the shelf (re-purposed) drugs i.e. treatments.

But yea, I can think of people who desperately want drug trials now.

 

I haven’t tried LDN and looking forward to a proper randomised placebo control trial.

I have worked in the mental health and it used specifically in alcohol dependency. It might be useful for some people with pain but pretty sceptical on it’s immune modulating effects or any psych drug used for this purpose because of the complexity of neural pathways and thus the propensity for side effects. (even in psychiatry, they are not well understood, so touting they can affect the ME disease process (whatever it is) is highly speculative and personally, unethical.

There is a lack of reasonable scientific reports and studies for LDN, many ME clinicians use LDN, off label, and must have lots of client material they could publish, not just present at conferences. They have a huge influence of the ME community, worldwide, who then have to try and convince their local GP to prescribe it and then they have to self fund it. Many GP’s won’t prescribe as they don’t have this gold-standard study for drug efficacy (imperfect as it may be, it is still a level of evidence higher than what we have now). This would also be required to get funding in my country

(Rather cynically, I am surprised the drug company hasn’t teamed up with them and funded one). I see there is one for long covid starting in Australia, no details if it is placebo controlled, even on the NCNED site for Griffith University, whose researchers are working with a Long Covid clinician in Perth. https://www.abc.net.au/news/2022-12-21/long-covid-treatment-trial-drug-low-dose-naltrexone/101770626.

Researchers have done other placebo controlled RCT’s in ME recently eg. Co-enzyme 10 using various scales of physical and cognitive symptoms and function. It convinced me not to waste my time and money on it for such small gains but having this information was very useful to consider.

The placebo needs to be inert otherwise it is not a placebo. It should be blinded at all levels. The researchers will have to decide on a dosing schedule and a treatment dose (which could be dependent on the individual’s tolerance) and an agreed follow up time etc. Hopefully out of this more data can emerge to inform further trials on bigger and diverse ME populations.

 

I tried low-dose naltrexone (LDN) for a month, but had
constant nausea and several episodes of prolonged severe
nausea, vomiting, delayed gastric emptying, sweating,
diarrhea, and worse IBS.

In one episode, I needed to vomit for about 7 hours but
could not. Strange regurgitating. When finally vomited,
was a large amount.

LDN seems to have caused gastroparesis.

This is the first time I had gastroparesis. In 2016 (a few
years later) I was diagnosed with Gastroparesis.

I eat pureed food and lie on my left side for many hours
every day.


No anti-nausea works for any type of nausea except that
metoclopramide (generic Reglan) helps severe gastroparesis.


I used a compounding pharmacy, who were given strict
instructions to use pure LDN plus acidophilus filler,
immediate release. Not crushed tablets.

However, they admitted later that they used crushed tablets.

I do not know whether the reactions were caused by the
crushed tablets or by LDN itself.

 

LDN included as a recommendation for the treatment of pain, fatigue and neuro symptoms in the review below -

Link to the thread:
Long COVID: major findings, mechanisms and recommendations, 2023, Davis, Topol et al

 

Rambling thoughts (what's new)
Jonathan - "Dose schedules for drugs that have a good evidence base have been worked out."
https://www.s4me.info/threads/experience-with-ldn.31383/page-4#post-455810

If you had a biomarker then OK you could use that to optimise the dose - we don't, so we have to rely on less precise tools like actimetry (FitBit type devices) and questionnaires. If it's well tolerated then why not go high --- not real high, since I'm guessing this would be a maintenance/lifelong drug. If it works high then repeat at half dose ---keep going until confidence levels for control group, and test group, overlap. Suggests, of course, that groups are large enough to generate confidence limits --- how big would the groups need to be?

In case it isn't obvious, I'm way beyond my own confidence levels here! I think the key issue is trying to find out is it helping i.e. versus control group; e.g. do a small group benefit significantly and others (most) do not?

I'm beginning to think I now (thanks to this exercise) have more insight into the challenges in trialling drugs --- maybe DecodeME will help i.e. by indicating pathology and thereby potential treatments (drugs or otherwise)

 

No offence mate but people were saying the same thing about vitamins back in 2011. I've been burned by quack treatments before so may be I'm overly cautious and skeptical as a result. See my previous post here: https://www.s4me.info/threads/experiences-with-alternative-medicine.8320/page-2#post-148181 . I caused my self permanent deterioration due to believing anecdotes from forums.

 

The problem is that ME has individual responses. There are plenty of instances where a certain treatment worked well for one individual, made someone else worse, and did nothing for the majority. I found several anecdotes about LDN for ME, agreed that immunosuppression was a valid experiment, so I gave it a try. I wasn't expecting much, but it was amazingly effective for me, with no nasty side-effects. I don't expect it will work that way for the majority, or even a significant minority, but it will work well for a few, most likely in many different ways rather than one reliable "4.5 mg/day will block pain" or other such response.

I've tried quite a few other anecdotally-supported treatments, and had either no response or a negative response (made my ME worse). So, when something I don't expect much from has a major effect, I'm sure that it's not placebo effect. Also, if it was placebo effect, I wouldn't have pain reminding me that I forgot a dose, and I wouldn't have discovered that I no longer needed it after a couple of years of regular use. My other effective treatments were all complete surprises, with the additional surprise of losing the need for them after different periods of time. I don't have any good theories for why they worked, but they definitely were working. However, if they did a large-scale evaluation of those treatments for PWME, I expect there would only be a couple of people (maybe just me) who would report similar responses. That's just how ME is.

I've been lucky to not get any long-term harm from my experiments. I do know that other PWME have had such negative experiences, some probably have had more than one. I've had enough significant benefits from my experimentation, so I'm a proponent of that. I do recommend trying things you expect will be safe first (common herbs, spices, etc) rather than nasty drugs or mega-dose cocktails that some other person promotes.

I still think that a large-scale study of LDN for ME would likely result in something along the lines of: "LDN at around 4.5 mg/day has 1/430 chance of reducing pain noticeable, and a 1/950 chance of a slight reduction in brainfog, and ... and a 1/125 chance of causing sleep disruption, and a 1/300 chance of gastric upset, and ..." I think it's unlikely that they'd even be able to improve the estimates by identifying sub-groups (has POTS, doesn't have enlarged lymph nodes, etc). They could spend millions on a study, and not provide any more useful data than the poll in this thread. Based on the present poll results, LDN looks like a good risk.

What would be useful is if the medical community supported "trial prescriptions" for drugs such as LDN. Just a few doses, possibly in a form that is easy to vary the amount, so people can start small if they want. I think the minimum I could get a prescription for was for several months worth. If I could get a week's worth for a week's cost, I'd probably try other drugs, herbals, or supplements.

 

As for the study recently discussed, I'm at least slightly biased to accept it, simply because its findings about LDN match my experiences with regards to dosage, duration, etc. If it claimed that doses under 2 mg were more effective, or that it took several days to show an effect, I'd reject the study. If it claimed that it took weeks or months to build up to a noticeable effect, I'd be suspicious of conflict of interest (somehow profiting from increased sales). I'm not qualified to judge the quality of how the study was done, so I'll leave that to experts.

 

Yes, I was disappointed to see that review just copy out anything suggested without apparently any critique.

 

I have voted in this poll - but can remove my vote…
I took LDN for many years - as I found it took the edge off my pain.
I no longer take it - because I cannot easily get a prescription. However, since my new FSHD diagnosis I take gabapentin at night - which I think has a better effect on my pain at night - although I am perhaps more sore in the morning if I have overdone things (which I often have!).

I felt that the LDN effect was small but meaningful for me.

 

Go high first but if that works then try lower doses - an AIDS drug was licensed high then research found it worked lower (1/2) so patients just cut tablet in half ---.

 

This was brought to my attention* anyone looked for/come across an NIH guideline re this study? E.g. dose, how they propose to measure the outcome ---

*
"
---Jared Younger will be doing an LDN trial soon funded by the Patient Led Research Collaborative.
"

1. Clinical trial on Low-dose naltrexone for the treatment of Long-COVID and ME/CFS – Dr. Jarred Younger – University of Alabama at Birmingham’s Neuro-inflammation, Pain and Fatigue Laboratory

​

This project is a clinical trial to determine the efficacy and safety of low-dose naltrexone (LDN) in treating Long COVID and ME/CFS. The hypothesis is that these patients have microglial cells that are continuously producing cytokines and other inflammatory agents. There is evidence that LDN can return microglia to their resting state and reverse neuroinflammation. The study is designed to answer 7 specific questions: 1) Is LDN an effective treatment for Long-COVID? 2) Is LDN an effective treatment for ME/CFS? 3) Do Long-COVID and ME/CFS participants respond similarly or differently to LDN? 4) What is the optimal dosage of LDN? 5) How long does it take for LDN to help? 6) What are the side-effects of LDN? 7) Which symptoms are most impacted by LDN?"

I don't know the NIH time guideline for their study.

 

Any updates on any of this? The working group or Jarred Younger's trial?

 

@josepdelafuente

From the Patient-Led Research Collaborative website referenced above, about Jarred Younger's project funding:

"September 23, 2023 Note: originally the Patient-Led Research Fund had awarded funds to Dr. Jarred Younger at University of Alabama at Birmingham to conduct a clinical trial on low-dose naltrexone for the treatment of Long COVID and ME/CFS. However, due to the institution’s refusal to accept funds that had a cryptocurrency origin, these funds were redistributed.

Prior Request for Proposals:

 

Oh, interesting, that's a shame.