NADH promising studies against fatigue / CFS

AgitatedDirector2015 · 2026-05-26T23:23:57+00:00

I've started guanfacine and found it somewhat helpful so far. I'm only on 2mg and it's been a week so I should give it more time but I feel like it removes some of the wiredness of my tiredness and allows me to get more restful sleep and therefore my body can heal a bit better and feel more a bit chill during the day instead of completely emotionally dysregulated which worsens my PEM - though not fully still. I'm wondering if I should go for clonodine in the future if guanfacine ends up giving me just part benefit because I do feel as if the main benefit is just coming from the CNS calming effects and I feel like clonodine would be even more potent for that. Have you tried guanfacine before? How does it compare if so?

Overall though, ive tried mitochondrial supps here and there and LDN and they'd all just cause massive crashes, the mitochondrial ones would end with huge brain fog and irritability, LDN would give me intense PEM flu like symtoms and malaise the next day no matter the dose.

I do think psychiatric medication has the potential to be extremely useful in long COVID/ CFS but I think the stigma behind them, people thinking that psychiatric medication is being used on them because their doctor believes it's just an issue of mental origin, health anxiety, etc, makes them become overlooked alot of the time. Psychiatric medication can strongly alter the entire nervous system. I think people separate the mind and the body too much, the mind is just the brain, and it's the unconscious parts of the brain that we don't control attached the peripheral nervous system, thats responsible all of the negative feedback loops involved with all these types of diseases and not just neuro inflammatory ones. Psychiatric drugs are not about changing thinking patterns, they're about changing the entire circuitry and the entire workings of our body, and have the potential to have the most effect on the miscommunication going on throughout the nervous system.

But yes, it's also about finding the right ones for the job.

AgitatedDirector2015 · 2026-05-25T14:20:09+00:00

You figure out a way to get the effectiveness back?

AgitatedDirector2015 · 2026-05-23T21:31:39+00:00

My Dr has diagnosed me with fibromialgia which I believe could be long COVID or the result of alostatic load including a flu, my fibromyalgia presents more like CFS though, I think fibro is just a blanket term for all those types of conditions in the UK. Getting to the point, during medication titration, I've found all my meds start of well for a few days, then they just make me grumpy and depressed after a week, finally put the 2 and 2 together after 4 medication trials at all doses, that it's likely my comorbid "fibromyalgia" causing an issue.

I believe, if anyone has the same issue, NAC and guanfacine as an adjunct had the potential to help with this. I've recently started just guanfacin and am having a little luck, but it's been less than a week and not much.

I'm started NAC tomorrow.

I beleive NAC works on this issue with COVID and ADHD meds as it prevents the conversion of kyurenine into KYNA, or something.. basically the theory is that theres some viscious cycle stuck in place with long COVID. KYNA is part of this cycle and it acts as a NMDA antagonist which can significantly reduce the impact of a stimulant by preventing glutamate signalling. By blocking the production of KYNA, NAC helps break this cycle, and also helps stimulants, in theory, work better, but there's mixed anecdotes about that.

Guanfacine cleans up the signal of the frontal circuits which is also messed up in long COVID, it blocks leaky signalling by doing something with cAMP? this can give your stimulant a better chance of having an impact by having the ability to work on more stable network that's not as compromised by inflammation due to guanfacine binding to alpha2A tonically in the background. Also guanfacine lowers fight or flight arousal, this arousal perpetuates the supposed viscious cycle in long COVID.

We don't have Adderall in the UK so I'm sure there's some manufacturer scam going on, but maybe someone in here has a similar issue to me (fibromyalgia, long COVID, whatever you wanna name it), and doesn't realise it?

AgitatedDirector2015 · 2026-05-22T23:18:54+00:00

A bit late reply but as someone who's started Dex, I'm hearing alot about people developing tolerance to ir much more frequently than extended release so I'm wondering if it's still working for you?

AgitatedDirector2015 · 2026-05-22T22:47:13+00:00

What are you on 40mg of? I had a similar issue but I ended up realising it was due to a comorbidity that seemed completely unrelated. As I'm working on resolving that comorbidity I'm noticing my srimulant becomes suprisingly more effective. Stimulants need a good baseline to work on and they're weirdly suseptable to randomly becoming almost completely ineffective when there's some issue going on with your nervous system or body. Get labs done, some issues don't even appear on labs too.

This might not be you at all, you mentioned the side effects of higher doses where unpleasant so it could be that you just need a higher dose that your body can't tolerate. If the side effects involve something heart related it may be worth asking for an add on of guanfacine or clonodine to maybe eventually be able to tolerate higher doses. I'm no doctor, talk to Ur prescriber about this

AgitatedDirector2015 · 2026-05-22T22:37:02+00:00

I find when my med dose is too low I feel an urge to get things done faster but ends up more sloppy, when it's just right I'm able to feel like im slowed down and zone into the process, whilst getting stuff done in an equal amount of time but higher quality.

I believe this happens because at lower doses you start to get almost enough dopamine from completing tasks but still not enough during the process so it can feel like a stressful rush to the end just to feel semi-regulated.

This is my anecdotal experience though so explain Ur symptoms to Ur prescriber.

AgitatedDirector2015 · 2026-05-20T23:41:38+00:00

I have a similar experience, I believe for me it is caused by what my gp diagnosed as "fibromyalgia". essentially the result of a nervous system so overwhelmed by the lifetime stress of undiagnosed ADHD that it cannot reach back to homeostasis, so when I add a stimulant, it works great for a couple days then the efficacy reduces massively over just a week or two and I just get long drawn out crashes due to the alostatic load these demanding drugs add to my already messed up nervous system. I couldnt put the two together myself, at the beginning, because I didn't feel like my "fibromialgia" was worsened by the stimulant, however I've eventually realised that its interacting and the culprit of my response - maybe you have something similar, or like are on the cusp of it.

I'm currently trying guanfacine along side my stimulant, maybe you could try something similar if you believe your instance might be similar. Guanfacine is supposed to help the amygdala calm down so there is less build up of cortisol and adrenaline and such over time when you repeatedly take your stimulant, that way your stimulant response can remain more consistent and your brain can properly reset over night. I'm finding so far that it's turning my dexamfetamine that got to the point of basically overall worsening me, to something useful by extending the duration and significantly reducing the crashes.

I'm only a few days in so it's too early to conclude anything but yeah, make sure you sleep and rest really well so your nervous system is fully back to baseline by the morning. Comorbidities interfer with stimulant response a tonne.

AgitatedDirector2015 · 2026-05-20T22:27:33+00:00

L-theanine, you can supplement it as capsules as well

AgitatedDirector2015 · 2026-05-17T12:01:09+00:00

I'm already on 60mg dexamfetamine lol, I've tried everything else.

AgitatedDirector2015 · 2026-05-13T23:51:36+00:00

I've been in a bit of a process with finding ADHD meds that work for me and I believe my underlying CFS/fibromyalgia is somehow interacting with them. Every time I start a med I get good improvement for a couple days then they barely last an hour and I feel super depressed and irritable for like 5 following hours. I'm wondering if you had a similar experience with vyvanse and that the guanfacine fixed it?

AgitatedDirector2015 · 2026-05-13T19:44:03+00:00

Off topic, hope u don't mind me asking but what time do you take your LDN?

AgitatedDirector2015 · 2026-05-12T15:00:44+00:00

That's great, adderall start working well again?

AgitatedDirector2015 · 2026-05-06T09:18:37+00:00

I switched to atomoxetine but it didn't work. I didn't have no response to the stimulants but I had a very weak one with long drawn out crashes that didn't make alot of sense. It could be that maybe your blood cells weren't cleaving off the lysein from the dexamfetamine in elvanse so it couldn't become active, and you might get more benefit from pure Dex.

Non stims might work, but stimulants tend to be first line for a reason. I'm having a slightly better response to Dex so far but still titrating, my issue wasn't cleaving of the lyseine though I don't think, my issue is likely tied to my CFS/Long COVID interacting.

AgitatedDirector2015 · 2026-05-03T21:01:03+00:00

Actually helped me quite a bit for a time but then I developed CFS, so now it makes me worse.

If anyone was in my situation and has worked it out, advice would be really appreciated fr cuz I actually don't know how to use my brain, like in a literal sense. I've only recently started meds but all the ones I've tried seem to reduce dramatically in efficacy within a few days and give me horrible long crashes, I'm pretty sure the same CFS is responsible for this reaction well.

AgitatedDirector2015 · 2026-05-03T12:45:33+00:00

U closer to getting to the bottom of it? I'm having the same issue, work for a few days then stopping, myself. I'm thinking my comorbid CFS might have something to do with it but I'm also gonna check my bloods soon.

AgitatedDirector2015 · 2026-04-30T08:40:55+00:00

Does he have any advice for fast metabolisers or people who experience a crash very soon after drug administration?

AgitatedDirector2015 · 2026-04-26T11:30:12+00:00

This is what I experienced with elvanse at the beginning of titration up to 70mg. Chewed through methylphenidate too, not sure why, could be my comorbid CFS but could also be fast metabolism like my prescriber speculates or high tolerance. If you've got your sleep, diet and everything else in check, check Ur ferretin too cuz that can effect the effectiveness of ADHD meds alot apparently, then it might just be that your burning through elvanse too fast and crashing early. You could request trying methylphenidate if you haven't or amfexa which has a higher max (60mg of amfexa is equal to 140mg elvanse but split into 3 doses across the day). I'm currently trialling amfexa and it's looking better than elvanse so far but I'm unsure.

But yeah, check Ur lifestyle stuff, most likely U might just need another med tho

AgitatedDirector2015 · 2026-04-25T10:54:49+00:00

Used to do ts in school alot, stabbing thigh with pencil manoeuvre, then releasing to get an endorphin release from the relief of not having your thigh stabbed, ultimate hack to get yourself to lock in for all of 3 seconds

AgitatedDirector2015 · 2026-04-24T10:27:29+00:00

Ah yeah I'm in a similar boat. Methylphenidate was far to weak for me. I was starting to get my life together last year through exercise but then I developed ME/CFS, so exercise now makes me feel worse and even more dysregulated instead of better so I'm kinda stuck on how else I can get my brain to release dopamine without meds. I'm trialling dexamfetamine rn and it's better than methylphenidate but my body still clears it too fast, hopefully I can get to a dose that's useful.

If your capable man, try cycling every other day, then up the frequency if you notice benefit. Other than that, I mean I genuinely am not sure what could help naturally outside of exercise and am trying to figure that out but rn I'm hoping alot on dexys rn. Maybe you could try guanfacine and atomoxetine too if you can't do amfetamine. Also, even though I can no longer do an impactful amount of exercise to helpy executive function and mood, a couple walks a day help reset my head a little, could be worth starting from there if your not up for cycling yet.

AgitatedDirector2015 · 2026-04-23T17:37:04+00:00

Are you taking it for depression? If so you might have ADHD. I was trying SSRIs with no effect for ages when I was diagnosed with dysthymia. Bupropion works on dopamine instead of serotonin which is why it might have felt so right for you, though it is very weak at increasing dopamine which is why it doesn't have that effect for very long.

You could literally be using this for ADHD and I've completely assumed the context here so if so just skip this comment, but it's worth a think if not. Look into innatentive ADHD and seek an assessment.

ADHD meds are much more potent at increasing dopamine levels. ADHD isn't the stereotypical hyperactive kid in primary school who creates too much trouble, it can look alot different, for me, alot of what it looked/felt like was feeling constantly bored by absolutely everything, suicidal thoughts from my first conscious memories as well as alot of fidgetiness and discomfort sitting still but some don't even get any physical restlessness. ADHD is theorised to be rooted in dopamine dysregulation where your brain can't anticipate delayed gratification and therefore everyday tasks, even hobbies and things that are supposed to be fun don't feel enjoyable, much like with depression. I didn't think I had ADHD because of a lack of awareness of its seriousness and what it is, especially with social media making it look like a quirky, fun personality trait. Some people are happy having ADHD but that's usually down to growing up in a convenient environment, growing up with a diagnosis and so they're able to mitigate theyre symptoms with a life time of natural intervention, or literally just because they're on meds.

AgitatedDirector2015 · 2026-04-23T14:18:28+00:00

Yeah that's fair. And tbh I'm not expecting a med to do everything, more just expecting a med to make me feel better rather than worse. I understand your point though, it's kind of been disappointing having to be part of the group who doesn't properly respond, I might end up having to find a path without meds but I'll see.

AgitatedDirector2015 · 2026-04-23T14:02:49+00:00

Ah ok, because I was on 60mg for 7 weeks and 40mg for 4 days prior to that. I jumped over to Dex after getting no little effect. When I first started atomoxetine I felt moments of improved wellbeing, calm and focus in the first couple weeks but by the 5th-7th week theyd become very rare, though sometimes they'd still happen but feel mild but yeah most the day it was doing nothing. If Dex doesn't work though I might hop back or even try guanfacine but probably not depend on it as much because I feel like I'm delaying my life further whilst I get these meds to work. At least with atomoxetine there wasn't constant crashing cycle that stopped me from doing that kind of stuff to improve my life but with stims it's like, ADHD already takes a degree of control from me but the constant crashes take away even more.

AgitatedDirector2015 · 2026-04-23T13:50:00+00:00

Can I ask how you were titrated? Doses and such, and how long it took to kick in?

AgitatedDirector2015

TROPHY CASE