Preprint Low Dose Naltrexone for Post-COVID Fatigue Syndrome: A Randomized Controlled Trial, 2026, Naik, Nacul+

jonathan_h said:
That it’s floating around all these different disease communities doesn’t inspire confidence in me.
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If you thought that review was bad, this one even contains studies with null results but the conclusion still says that it’s compelling….

Therapeutic Uses and Efficacy of Low-Dose Naltrexone: A Scoping Review - PMC

Low-dose naltrexone (LDN) has been suggested as a novel treatment option for several conditions and is of increasing interest due to its potential ability to address certain medical conditions that lack effective treatments or frequently rely on the ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

“examining the treatment of fibromyalgia, multiple sclerosis, complex regional pain syndrome (CRPS), various gastrointestinal conditions (including Crohn’s disease), dermatological conditions (such as Hailey-Hailey disease), and certain cancers [4]. However, studies continue to emerge that analyze the effect of LDN against a variety of conditions, even extending beyond chronic painful and autoimmune conditions. The clinical use of LDN remains off-label, with no standardized, regulatory-approved treatment protocols.”

“These articles provide a compelling argument for future clinical usage and observation of LDN while also helping to establish areas where there is still room for further research and understanding”

This is hodge podge of throwing things at the wall and seeing if they stick then ignoring anything falls on the floor.
 
jonathan_h said:
One fact about LDN which I find dispiriting is how many diseases it’s been claimed to treat.

Jared Younger was lead author on a 2014 review which said LDN has been shown to reduce symptom severity in these conditions:

Fibromyalgia
Crohn’s Disease
Multiple Sclerosis
Complex Regional Pain Syndrome

And obviously there are more:
ME/CFS
ALS
MCAS
POTS
etc.

That it’s floating around all these different disease communities doesn’t inspire confidence in me.
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LDN also seems to be popular with people with Hashimoto's thyroiditis. I discovered this when I told my sister about LDN. She is in some Hashi online groups and knew immediately what I was talking about. It does indeed float around in various disease communities.
 
They did try a subgrouping of male vs female. This is just misinformed. The “works for me” mental gymnastics is something I regrettably have taken part in when I was taking mestinon. It is very easy to warp your own perception with placebo, I’ve done it. However I didn’t hold a position of power for scientific testing.

The “works for me” mindset is no better than GET people saying exercise works for them and there are subtypes that would respond to exercise.

I want to ask what subtyping? They always say subtyping but never explain. It’s such a catch all

 
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I think some people will come around in time, but not on day 1 of the first trial in ME/CFS, and perhaps not in public.

It's understandable that if you have been taking something for years, invested money and energy into it, and been open about thinking it helps you, it would not be easy to wrap your head around this. When all the negative trials were starting to stack up in fibro, there was still room for people to think that they/we might be different.

But there will be some change, in time, particularly as more trials with different protocols get published.
 
Evergreen said:
I think some people will come around in time, but not on day 1 of the first trial in ME/CFS, and perhaps not in public.

It's understandable that if you have been taking something for years, invested money and energy into it, and been open about thinking it helps you, it would not be easy to wrap your head around this. When all the negative trials were starting to stack up in fibro, there was still room for people to think that they/we might be different.

But there will be some change, in time, particularly as more trials with different protocols get published.
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Yes, this is hard to handle for any human.

I think the first focus should now go towards researchers and practitioners. They have to be made aware of these type of result and they also have to understand evidence and trials better. No matter what you believe, the evidence undoubtedly shows that a GP who usually sees patients at most a handful of times, cannot possible conclude that he sees "responders", if in a study of 160 people there is no measurable difference between placebo and drug. If myths amongst researchs and practitioners can die out, a lot would already be won. I think some researchers that advocate for looking at the actual evidence in ME/CFS have become more prominent recently and I believe that is a path that leads out of a hole.
 
I saw Jack’s tweet from Amatica Health, and I have to say I was pretty disappointed.

A bit off-topic, but I paid quite a lot of money for a really comprehensive RNA analysis wirh Amatica, with tens of thousands of values grouped into different categories. But how meaningful are these results, really? Can the medications we take significantly affect them? I have quite a few questions about all this.

What struck me was that when we compared our results with other patients on Twitter, those with mild or moderate ME/CFS seemed to have much better results. Mine were honestly terrible, with a huge number of values way below the median. But it's hard to know what conclusions we can actually draw from that.

Anyway, back to Jack. I'm obviously in favour of identifying subgroups, but his tweet leaves me puzzled. Claiming he can guarantee it wasn't a placebo effect simply because LDN worked so well for him, when we're talking about a negative randomised trial, is pretty strange coming from someone who presents himself as a scientist.
 
Kitty said:
Not sure, but some women with ME/CFS or long Covid feel so terrible during the luteal phase (and so much better after it) that trials based on subjective questionnaires need to control for it specifically. If they don't and some of the women haven't yet spotted the pattern, they're likely to report feeling better if they have to report symptoms just after the bad week, or worse if they're asked within it.
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Yeah and with a mean age of 45, things are starting to get unpredictable for some
 
Trish said:
I think the biggest cults at at the moment are probably brain retraining and LDN.

For me it removes the self imposed 'ought to try', and the guilt for not suggesting my daughter should try it.
No more.
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Well done on protecting her.

I feel like you’d get a big well done if you pushed her to try and it had helped, so equally you should get a bigger one for taking the right approach and protecting her from the worsening it would probably have caused.
 
neophyte32 said:
Claiming he can guarantee it wasn't a placebo effect simply because LDN worked so well for him, when we're talking about a negative randomised trial, is pretty strange coming from someone who presents himself as a scientist.
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This sums up my Fb feed today - science-oriented groups attracting people who claim to be scientifically literate disputing the study with comments which blew my mind (all the usual already mentioned on this thread).
 
Wyva said:
LDN also seems to be popular with people with Hashimoto's thyroiditis. I discovered this when I told my sister about LDN. She is in some Hashi online groups and knew immediately what I was talking about. It does indeed float around in various disease communities.
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I have a friend with Lupus who gets LDN prescribed on private prescription. Swears by it.
 
neophyte32 said:
Claiming he can guarantee it wasn't a placebo effect simply because LDN worked so well for him, when we're talking about a negative randomised trial, is pretty strange coming from someone who presents himself as a scientist.
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He’s an aerospace engineer grad, but I do not think he got a chance to work in industry as he got long covid sadly right at graduation if I remember. He has it in his bio:

www.amaticahealth.com

Amatica Health

Building the world's largest chronic disease research database to advance understanding of ME/CFS, Long COVID, and other complex conditions.
www.amaticahealth.com www.amaticahealth.com

Discussed elsewhere but batch effects, shipping handling, and no open verification or methods of their testings makes the results useless. They also don’t have any verification of CFS, anyone can send samples so you have no idea what you’re actually testing against.
 
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ChronicallyOverIt said:
He’s an aerospace engineer grad, but I do not think he got a chance to work in industry as he got long covid sadly right at graduation if I remember. He has it in his bio:

www.amaticahealth.com

Amatica Health

Building the world's largest chronic disease research database to advance understanding of ME/CFS, Long COVID, and other complex conditions.
www.amaticahealth.com www.amaticahealth.com

Discussed elsewhere but batch effects, shipping handling, and no open verification or methods of their testings makes the results useless. They also don’t have any verification of CFS, anyone can send samples so you have no idea what you’re actually testing against.
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Just had a look at their website…I know paying out of pocket for healthcare related things tends to be expensive but…are they having a fucking laugh.
 
ChronicallyOverIt said:
I want to ask what subtyping? They always say subtyping but never explain. It’s such a catch all

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I apologize if this has been discussed elsewhere, but I don’t quite understand how this sub typing argument works.

If a drug did work for a subtype of people, wouldn’t a signal show up in this trial, assuming that the proportions of people in that subgroup are the same in the placebo and drug arms of the study?
 
wingate said:
If a drug did work for a subtype of people, wouldn’t a signal show up in this trial, assuming that the proportions of people in that subgroup are the same in the placebo and drug arms of the study?
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Long discussion here, but overall its impossible with the current ME/CFS knowledge and criteria we have


Jonathan Edwards

Post in thread 'Why are patient pleas about subtyping and stratifying in studies seemingly falling on deaf ears?'

Liface said:
The endpoints would be pre-specified.
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Maybe you are unaware that this does not solve the power problem, @Liface ?
The more analyses you do the weaker your statistics. If you analyse 5 subgroups your power to detect any significant result is reduced by a factor of 5 (roughly). I have designed and run many trials. You simply cannot afford to do this. If you think a drug will work on a more limited population you do your trial on that population, you do not stratify. You can post-hoc stratify for interest but not to get an efficacy result.

The subsetting craze is almost...
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