Thoughts on why dopamine drugs like ablify or others might poop out

xebex

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Of course this is only based on my own experience and I really have very little scientific understanding, but thought it was atleast worth mentioning/discussing.

I have not tried ablify but I did experience poop out with ritalin.

It seems fairly established that ME causes some kind of low dopamine state (or maybe the low dopamine state causes the ME? Who knows)

BUT what about COMT gene status?

I have COMT met/met mutation which means I generally have a high dopamine (as I can’t break it down well) and can perform very well if not under stress - this might explain why cognitively I’m better off than many.

If you had COMT Val/Val this will likely contribute to the low dopamine state potentially making you iller than the met/met type.

My thoughts are that if you have COMT met/met like me you are constantly swinging between high and low dopamine which would mean dopaminergic drugs may not be as effective and could actually build too high levels of dopamine causing issues like rage (which I get) it could also be the cause of poop out because we end up with too high dopamine levels causing us to push too hard and crash then reducing the positive action of the drug.

But if you have the COMT Val/Val maybe the drugs were less likely to poop out because your dopamine wouldn’t get too high causing you to push and ruin the positive effect of the drug?

Any thoughts?
 

Judee

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I also think dopamine is one of the keys to this puzzle.

I am COMT V158M (Val/Met?). Is that what you meant by COMT?

Edit: I haven't used Abilify or any ADHD meds but I do think I have some ADHD tendencies.
 

xebex

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Yes that’s what I mean by COMT. So you are Val/met which means your dopamine as a nonME person would be fairly balanced and I’m imagining as a pwME you’d likely fall in the lower dopamine category. Have you ever experienced drug poop out?
 

Judee

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Not drugs so much especially since I haven't tried any of the drugs that affect that. (Sorry, I think I edited after you read my post.)

However, things do "poop out" for me very quickly and I do think I tend to run low dopamine. Dopa mucuna has helped but it doesn't seem to anymore even though I only tried it once in a while. :(
 

xebex

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Not drugs so much especially since I haven't tried any of the drugs that affect that. (Sorry, I think I edited after you read my post.)

However, things do "poop out" for me very quickly and I do think I tend to run low dopamine. Dopa mucuna has helped but it doesn't seem to anymore even though I only tried it once in a while. :(
Interseting so that kind of puts my theory out the window. My other theory is that the ME body/brain likes homeostasis so for some reasons will always revert back to its baseline. How it remembers what it’s baseline was after feeling better I don’t know. Such a messed up illness.
 

ljimbo423

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Thoughts on why dopamine drugs like ablify or others might poop out
I'm not sure that Abilify helps people with ME/CFS by affecting dopamine, although it could be. I thought that at first but there is evidence that it affects inflammation in the body too.

As to why it stops working for some, I'd really like to know the answer to that but don't have a clue.:)

Results: We observed high clinical efficacy in aripiprazole linked to a 2.7% weight loss.

There were statistically significant reductions in PANSS scores and body parameters (p<0.001). After 28 days we detected a significant reduction in hsCRP (p<0.001), insulin (p<0.001), IL-1β, IL-6, TNF-α, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4 (p<0.001), IFN-γ (p<0.05) and a significant elevation of IL-10 (p<0.001).

There was a significant negative correlation between IL-10 levels and PANSS positive, negative and total scores after the study (p=0.022, p=0.003, p=0.008, respectively).


Conclusions: Aripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling. Aripiprazole also reduces the risk of metabolic abnormalities.
Link to study
 

Boba

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I don't understand what Val/Met is? I have the Warrior Gene, means I'm low on dopamine and good in stressful situations. I have an ADHD diagnosis. Dopamine was always a problem for me. I took Ritalin for a year and it never pooped out on me. Abilify worked after one day for me and gave me a lot of energy.
 

xebex

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I don't understand what Val/Met is? I have the Warrior Gene, means I'm low on dopamine and good in stressful situations. I have an ADHD diagnosis. Dopamine was always a problem for me. I took Ritalin for a year and it never pooped out on me. Abilify worked after one day for me and gave me a lot of energy.
Hmm you confirm my theory lol.

Val/met is a balance between the two states. I’m met/met (I can’t break down dopamine very well so I get build up resulting in lack of stress resilience) Judy is Val/met and you are Val/Val. All states can have ADHD but it seems Val/Val would be more severe because they breakdown dopamine fast and end up with very low dopamine.
 

Boba

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Makes sense. I breakdown dopamine supporting drugs very fast. I tried coke and I wasn’t able to enjoy it because the effect was gone very fast leaving me frustrated while all others were partying.
 

xebex

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Makes sense. I breakdown dopamine supporting drugs very fast. I tried coke and I wasn’t able to enjoy it because the effect was gone very fast leaving me frustrated while all others were partying.
Intersting this totally fits my theory!
 

ljimbo423

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“Importantly, different lines of evidence have shown dopamine as a major regulator of inflammation”
I think you're right. I did a quick google search and found several studies that say Dopamine affects the immune system.

So the question I have now is, how is Abilify helping people with ME/CFS? Through working within the brain by increasing Dopamine and lowering neuroinflammation, changing the immune system in the body by increasing Dopamine (which could also effect the brain) or is it working by doing both?

However it's working, it seems like it's altering the immune system somehow. As complex as the immune system is, maybe the immune system finds ways to get "around" the increased Dopamine. Which stops Abilify from working in some of us.
 
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Alvin2

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Dopamine drugs are essentially stimulants and the body adapts over time to counteract their effects (outside of ME).
 

xebex

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@ljimbo423 i’d say it was both, but in many people it eventually poops out and this is where my COMT theory comes in maybe the Val/Val people it’s less likely to poop out. I’d love to know if the non poopers are all Val/Val.
 

godlovesatrier

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This is really interesting. Is it just me or does it feel like recently we've had loads of posts on PR that feel like there working at collective root causes.

Anyway I've always had issues with rage. Literally going off in a fit of rate when taking most things combined usually with anxiety and insecurity as part of the rage. Now you've said about dopamine it's got me to wondering. On the herpes veridai protocol tho I'm not experiencing any of that compared to usual. So it doesn't seem like lion's mane or reishi effects dopamine.

I always did very well in stressful situations pre ME and was quite resilient even in incredibly stressful situations. Didn't throw up or really have any of those issues. Unless the stress was sort of protracted over many years.

Gets me to wondering though if my dopamine is normally high as well. I wonder if this would effect sex drive too? I've always felt mine was above average.

I also like your Abilify theory. Could well be a reason for it not always working long term.
 

xebex

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@godlovesatrier

have you had you genome sequenced? You can get it read at https://geneticgenie.org/ to see what your COMT status is.
If you work well under stress you likely have Val/met or Val/Val

I have met/met which means I can function at an exceptionally high level as long as I’m not under stress the problem is it also can cause a lack of stress resilience due to it not breaking down dopamine and other catechols fast enough.

High dopamine does increase sex drive but as you function well under stress I’d make a good guess that you were Val/met which means that essentially you should be able to maintain a good balance.
 

xebex

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So the AA or TT are the "bad ones" so you have GG and CC for your COMT genes (Val/val) which is not a mutation but does mean you are more likely to have lower dopamine - which would explain your ability to work well under stress. (But then add ME on top of that and it could cause issues)

Here's my results.
Screen Shot 2021-06-04 at 4.24.18 PM.png


This may or may not be of further interest to you

https://www.seekinghealth.com/collections/dirty-genes-comt-fast-support
 
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