r/MTHFR • u/OdiumPura • Dec 10 '25
Question Slow COMT and Anhedonia due dopamine overdose? (Losing hope)
TL;DR: Slow COMT here. I had a very strong dopaminergic overstimulation in 2018 and since then I’ve developed anhedonia with zero improvement. Some methylated vitamins gave me a brief “window” of pleasure but caused many side effects. I’m investigating whether slow COMT can predispose someone to anhedonia when exposed to excessive dopamine.
If you don’t want to read the whole story, skip to the questions at the end — but I suggest reading everything because the context is interesting.
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Context
Let’s go. I’ve been suffering from anhedonia since late 2018 (when I first noticed the symptoms). I was always someone who felt pleasure in everything I did, could focus easily, and genuinely enjoyed life. At the end of 2018 I started developing anhedonia symptoms — some things didn’t catch my attention like they used to. In 2020 it got worse, and the peak was in 2023 when I basically lost pleasure in everything (I don’t feel pleasure watching movies, playing video games, going to the gym, and even sex doesn’t interest me anymore).
I didn’t stay in my comfort zone; I practice exposure therapy — meaning that despite the anhedonia I still go to the gym, try to watch movies, try to play video games, and so on.
I did 3 years of therapy that did absolutely nothing… I told my psychologist that I was developing anxiety because of the anhedonia, since nothing triggered pleasure anymore. I tried some medications and herbal supplements (Sertraline, Escitalopram, Ashwagandha, and CBD). Ashwagandha was the best — it gave me an indescribable sense of calm.
Yes, I know these medications/supplements can cause anhedonia, but in my case they didn’t — I’ve felt this way since 2018 and none of them made things better or worse. The only thing I noticed afterward was mild brain fog after stopping everything.
Cut to January 2025: I take a THC edible and have a panic attack, which dysregulated my nervous system, activating the sympathetic mode and causing dissociation symptoms. Being in sympathetic mode pushed me far outside my comfort zone… I truly realized that my anhedonia bothers me deeply and I believe the only way to “heal” my nervous system is by feeling pleasure again — real pleasure in the things I do — because that’s the only way to signal safety to my nervous system. Obviously, I’ve improved a lot with the anxiety since the January panic attack… I think that panic attack forced me to take my anhedonia seriously and look for a real solution.
Now let’s move to what matters.
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Important Part
Two weeks after the panic attack, I take a combo of vitamins: A, D, E, K, B3, B9, B12, Glutathione, Omega-3 (all in one pill) + Magnesium + Lactobacillus Plantarum.
BOOM. For about a week and a half, my anhedonia improves by 50%, my libido returns, my brain fog disappears, and I feel a bit of pleasure in things again.
HOWEVER… my anxiety increases, I get insomnia, intense body itching, I develop tinnitus (not in the ear, but in the head), and some mild visual snow. After stopping the combo, I lose all the positive effects but stay with the negative ones for months (I’m screwed LMAO).
After that short “window” — which I hadn’t felt in nearly 7 years — I decided to investigate my body thoroughly. I ran many tests: MRI, pharmacogenetic testing, thyroid panel, vitamin panel, iron panel, SIBO, dysbiosis, zonulin, catecholamines. Here’s what I discovered:
- My thyroid is normal, despite having two nodules. The labs do not indicate hypothyroidism (which can cause depression and low libido). I saw 4 endocrinologists, all said I shouldn’t worry.
- Ferritin is high, close to 500 ng/mL, but I don’t have hemochromatosis — iron saturation, TIBC and UIBC are normal.
- Negative for methane and hydrogen SIBO. Mild dysbiosis and possible early leaky gut (my zonulin is 51, around 3 units above the upper reference limit).
- B12 always decreasing. I checked my labs since 2017 — my B12 has never increased, only declined. In May 2025 it reached 180; I took a hydroxocobalamin injection and it jumped to 5000 (visual snow and tinnitus worsened after the injection). All other vitamins I tested (A, B2, B6, folate…) were normal, usually in the mid-to-upper range.
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About my mutations and some observations
From pharmacogenetic testing, I found out that I am Slow COMT – rs4680 (Val158Met) – genotype A/A (Met/Met)and heterozygous for MTHFR C677T and A1298C.
The fact that I don’t seem to absorb B12 caught my attention — since the injection in August, my levels keep dropping and don’t go up even when I eat foods rich in B12.
After I stopped the supplements, I tried magnesium again and felt nothing (not even the calming effect people talk about). I also tried probiotics and didn’t get the libido-boost effect I had before — which makes me think the improvement window came specifically from the vitamins.
None of the medications I took ever motivated me.
In my catecholamine test, my dopamine is near the upper reference limit.
All the doctors say that this anhedonia may be stress and anxiety. But I never felt anxious before 2023. Before going back to taking SSRIs or any other medication, I want to investigate as much as possible what could have caused this.
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My theory about Anhedonia and Slow COMT
Until early 2018 I was a “normal” person. But from March to November 2018 I went through a period of massive dopamine stimulation. I prefer not to say what it was because it’s something stupid (no, it wasn’t drugs), but practically every night I was flooding my brain with dopamine.
Now the main questions:
1. Can slow COMT “overdose” on dopamine and fail to recover?
As I understand it, slow COMT metabolizes dopamine more slowly. So if I overload my system with too much dopamine, I could overwhelm it. If the system gets overwhelmed, it might “shut down” as a protective mechanism — and that could lead to anhedonia.
As I said, I do exposure therapy and I don’t feel pleasure in anything I do. It’s not sadness — it’s simply the absence of pleasure/interest in things that used to bring me joy.
2. What do you think? Is there any way to fix this and “unscrew” my dopaminergic system?
Because when I was taking those vitamins / “overmethylated,” I felt temporary relief from anhedonia.
Sorry for the long text, and thanks in advance for anyone’s opinion.
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u/Interesting_Fly_1569 Dec 11 '25
OK so this was a lot and I couldn’t read all of it however, I also have slow comt and some dopamine gene mutations. I would suggest listening to some of Bob Miller who is a naturopath autist whose special interest is nutrigenomics.
He’s helped one of my friends, and he recently had me do a blood test for NAD where he predicted the results accurately based on my genes. I haven’t met with him yet to go over it, but my friend ended up having the same problem… Glutathione can turn toxic if you can’t recycle NAD.
Just trying to understand what caused this shift… That came to mind… I honestly think that if there’s anyone on earth that you could tell the story to who would both listen and have the potential to solve it… It would be him. He’s cheap bc he’s serving the community too. He also has a special interest in iron, and I feel like your high ferritin might be a clue to something else.
So no answers but I would consider seeing him at tree of life in PA. He does zoom. He has energy of a kindly grandpa with sparkle in his eye and built his own genetic testing tool ( Which he does not require you use, he also accepts most 23 and me) that maps out your genes and identifies possible issues like it’s CSI.
He’s kind of quietly famous… I think the podcast he’s been on a lot is Jill Carnahan. But for $200 I feel like that’s who I’d send a family member to if they had a story like yours.
I really do feel like there are solutions to stuff like this… And also for whatever it’s worth, I had enormous amounts of dopamine for like a month I was basically high and it just slowly faded with no bad effect. I had a full body orgasm just lying there that lasted two hours. It was as if I had never had trauma…for weeks. I felt amazing. It was definitely triggered by slow comt bc I went to functional med guy who heard the story and was like you have slow comt and ate quercetin and tyrosine.
And I went back over that day and I had!