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

Martin aka paused||M.E.

Senior Member
Messages
2,291
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?
Interesting read. Drugs that act on the nervous system poop out for me after some time (Insidon, Vagantin...) . Didn’t make a COMPT test?! Is it expensive?
 

godlovesatrier

Senior Member
Messages
2,372
Location
United Kingdom
Right I thought we just wanted what I have above. The ones I screenshotted are 23andme.

If you want the whole genome it costs about £600. I think Dante still do WGS whole genome sequencing. £600 is a 30x pass so that would get you a decent level of accuracy for all genes.
 

Martin aka paused||M.E.

Senior Member
Messages
2,291
Right I thought we just wanted what I have above. The ones I screenshotted are 23andme.

If you want the whole genome it costs about £600. I think Dante still do WGS whole genome sequencing. £600 is a 30x pass so that would get you a decent level of accuracy for all genes.
Is it saliva? Because that’s again a factor for artefacts
 

godlovesatrier

Senior Member
Messages
2,372
Location
United Kingdom
They've taken pricing and methods off there website. There touting some sort of new technology. Looks like it's 130x pass. Would be dead interesting to know if it still costs £600. As the price of genomics is meant to be going down every year anyway.
 

hapl808

Senior Member
Messages
1,844
I haven't taken a lot of drugs that I would think play with dopamine levels, but I have noticed in recent years that my mental PEM crashes became just as bad and similar to my physical ones, and the crash is the same whether I have enjoyable mental exertion or stressful. Makes no difference.

I've generally avoided drugs that would change neurotransmitter levels as I don't think I've had any particular issues with depression. I'm always concerned about some of the drugs that doctors say have no long term effects when discontinued, but patient reports are drastically different and often filled with regret for taking them in the first place.

I have wondered about beta blockers as my heart rate can be all over the place, but sometimes my heart rate is very low during an enjoyable mental activity - and yet the next day PEM still hits. I didn't even notice the correlation initially, but I try to track what I do each day carefully and once I realized, it was pretty close to 100% of the time.

Screen Shot 2021-06-05 at 9.32.26 AM.jpg
 

xebex

Senior Member
Messages
840
so you have the COMT mutation (met/met) which means you are naturally higher in dopamine - less prone to depression and can excel without stress - but you would struggle to perform well under stress. The val/val tend to excel in stressful situations but are prone to depression and lack of focus.

with the met/met mutation you also struggle to break down catechols which is why dopamine and estrogen can get too high. My theory is that met/mets are more likely to experience poop out on dopamine enhancing drugs.
 

hapl808

Senior Member
Messages
1,844
That makes some sense. I used to deal with stress better (pre-ME), but now it definitely can affect me a lot. Although only some types of stress seem really damaging - the worst is when mental stress is combined with physical stress or injury.

Other than minimizing stress, would there potentially be interventions that might be helpful here based on genotypes? I've researched neurotransmitters more often lately because of the mental PEM crashes, and I've tried to adopt a low free-glutamate diet based on some of that research. It seems moderately helpful, but that's about it as I was already eating a pretty healthy diet.
 

xebex

Senior Member
Messages
840
i'm very similar to you and yes I find that low glutamate diet is very helpful. I have attached a link from seeking health - I'm not sure how valid it is BUT I have found some small help in balancing my dopamine by using SAMe - the DIM and CDG don't seem to do much.

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

My theory is that us met/mets will experience dopamine swings, (which could be why we experience poop out) whereas as val/val is more likely to experience more consistently low dopamine. This is all just theory so take with a pinch of salt.
 

hapl808

Senior Member
Messages
1,844
Haven't tried CDG. SAMe has been somewhat helpful in the past, but only while taking it - then benefit disappears as soon as I discontinue. Also couldn't tell if it made me a bit wired. I recently have looked into lithium orotate - I took it a couple times but didn't notice anything huge. Haven't trialed it regularly, though. DIM I don't think I tried, but might have some around that I bought - can't remember on that one. Magnesium is helpful, but also seems to make my reflux worse, so that's a balancing act.
 

xebex

Senior Member
Messages
840
yes SAMe is is def something you need to take continuously, I think it made me feel a bit wired to start but not anymore. I'm also considering upping it to 400mg a day, I think many people take around 600mg but you also need to take cofactors like b vits - b12 in particular, though i haven't found any issues with that yet, fingers crossed!

I have been considering lithium orotate too but not got round to it yet.

its all such a minefield - and I hate the thought of throwing other things out of whack. But needs must!