17 replies to this topic

[xks201]

I have COMT mutations which slow down the COMT enzyme, leaving me with high neurotransmitters like dopamine and the others metabolized by COMT. Is there something I can take that will help utilize these neurotransmitters that are otherwise floating around and otherwise probably downregulating their associated receptors?

[BioFreak]

You could lower your catecholamines by increasing serotonin, for example with 5-htp. I successfully used it to archive exactly this, unfortunately it was not my goal as I was already low on them... So this specific action was useless for me, might be good for you though...

[Reformed-Redan]

Avoid foods that have high tyrosine levels is my only suggestion along with a more extreme route of reserpine.

[darksanity]

Ok.... So how do you know you have a 'COMT muation' resulting in reduced COMT expression?

Even more ridiculous is your assumption that you somehow must use that extra dopamine to avoid inevitable receptor downregulation from 'idle' dopamines....

You have a lot to learn my friend.

I'll just keep it simple because I'm tired and had a few drinks and don't feel like writing a huge rant on "COME ON GUYS WHAT'S UP WITH ALL THE PSEUDOSCIENCE BS?"

So basically even if you happened to have some sort of genetic COMT polymorphism that reduces its activity (which is plausible I guess) and results in greater catecholamines concentration than average, those extra neurotransmitters don't just "float around" downregulatin' yo poor receptors while fucking the dog........ Actually the entire idea is so wrong and a classic example of pseudoscience at work. I understand you're probably learning and everything and that's good but good lord this is the kind of stuff that gives points to them asshole elitists with PhDs' & MDs' who want to regulate, restrict, license everything and be master all-powerful gatekeepers, and basically just make any practical scientific progress in human enhancement and neuroscience advancing in snail mode.....

Alright I admit that degenerated somewhat into a rant but one last thing to the guys who replied the OP: Why the hell would you guys feed his pseudoscietific fantasies with horrible advice?!? Reserpine really??????........ I mean yeah at least that's gonna deplete them catecholamines fo sure no more dopamine fucking the dog and downregulating........ What about Haloperidol now that were at it?... I mean the objective was to counteract the receptor downregulation right??

EDIT: Now that I think about it, we all seem to learn the most from actual experience and trial & error and I know that I used to have some pretty silly and oversimplified concepts about neuroscience a few years ago and I experimented with a wide range a substances and theories some that worked some that didn't.... But anyway I learned the rough way like were meant to learn which is through experimentation. Let's stand up against this pussified uber-risk-averse paradigm and do it like the real pioneers of science from the past! Now that's then spirit! Now go get some reserpine and take a good dose of it to be sure your catecholamines a nicely depleted and it should give you decent cue of what "low dopaminergic neurotransmission" feels like and you should be able to revise your hypothesis and assumptions accordingly.

Edited by darksanity, 04 January 2014 - 09:58 AM.

[BioFreak]

To the one who downvoted my post: Please explain?


darksanity:
He might have the results of a gene test from 23andme for example. Might not be that reliable, though.

High levels of neurotransmitters will make the brain react, thats inevitable. Higher mao activity, less receptors for example. So it is not unreasonable for him to assume that his receptors desensitize. However, that may not be a problem, is a simple regulatory measure. Its not that his dopamine levels raised because of external influences, which would mean withdrawal problems.

As long as there are no mental problems, the only thing he has to worry about is increased oxidative stress because of high levels of dopamine and probably mao is doing more work reducing DA, resulting in more toxic metabolic byproducts.

I also would not go the risperidone route. It's a receptor blocker, meaning that DA levels could even increase while on it, while he would have less effect from dopamine due to receptor blocking. Desensitizing receptors just to desensitize them makes no sense. If he displays signs of schizophrenia however, thats another story.

Edit: "using them up" won't work, reducing them and/or fighting the increased stress makes sense however, as long as there are no psychiatric symptoms.

Edited by BioFreak, 04 January 2014 - 09:43 AM.

[darksanity]

High levels of neurotransmitters will make the brain react, thats inevitable. Higher mao activity, less receptors for example. So it is not unreasonable for him to assume that his receptors desensitize. However, that may not be a problem, is a simple regulatory measure. Its not that his dopamine levels raised because of external influences, which would mean withdrawal problems.

Edit: "using them up" won't work, reducing them and/or fighting the increased stress makes sense however, as long as there are no psychiatric symptoms.

Ok but remember were talking about a genetic issue here so technically the guy had higher-than-average catecholamines concentration for his entire life so you'd assume his receptors to be homeostatically calibrated accordingly.

Edited by darksanity, 04 January 2014 - 09:54 AM.

[BioFreak]

Right, thats what I wanted to say with receptor down regulation is not a problem. You phrased it better, though.

[xks201]

Ok.... So how do you know you have a 'COMT muation' resulting in reduced COMT expression?

Even more ridiculous is your assumption that you somehow must use that extra dopamine to avoid inevitable receptor downregulation from 'idle' dopamines....

You have a lot to learn my friend.

I'll just keep it simple because I'm tired and had a few drinks and don't feel like writing a huge rant on "COME ON GUYS WHAT'S UP WITH ALL THE PSEUDOSCIENCE BS?"

So basically even if you happened to have some sort of genetic COMT polymorphism that reduces its activity (which is plausible I guess) and results in greater catecholamines concentration than average, those extra neurotransmitters don't just "float around" downregulatin' yo poor receptors while fucking the dog........ Actually the entire idea is so wrong and a classic example of pseudoscience at work. I understand you're probably learning and everything and that's good but good lord this is the kind of stuff that gives points to them asshole elitists with PhDs' & MDs' who want to regulate, restrict, license everything and be master all-powerful gatekeepers, and basically just make any practical scientific progress in human enhancement and neuroscience advancing in snail mode.....

Alright I admit that degenerated somewhat into a rant but one last thing to the guys who replied the OP: Why the hell would you guys feed his pseudoscietific fantasies with horrible advice?!? Reserpine really??????........ I mean yeah at least that's gonna deplete them catecholamines fo sure no more dopamine fucking the dog and downregulating........ What about Haloperidol now that were at it?... I mean the objective was to counteract the receptor downregulation right??

EDIT: Now that I think about it, we all seem to learn the most from actual experience and trial & error and I know that I used to have some pretty silly and oversimplified concepts about neuroscience a few years ago and I experimented with a wide range a substances and theories some that worked some that didn't.... But anyway I learned the rough way like were meant to learn which is through experimentation. Let's stand up against this pussified uber-risk-averse paradigm and do it like the real pioneers of science from the past! Now that's then spirit! Now go get some reserpineand take a good dose of it to be sure your catecholamines a nicely depleted and it should give you decent cue of what "low dopaminergic neurotransmission" feels like and you should be able to revise your hypothesis and assumptions accordingly.

Okay Mr. 47 posts/Mr. Know It All, have you done any research whatsoever on COMT mutations? Are you just assuming I am making this up? No I'm not. I had 23andme genetic testing that showed not only do I have an underactive COMT enzyme, I also have an underactive MAO B enzyme. Just one of these mutations can permit dopamine and norepinephrine levels to rise 4 times above normal. If you don't think that affects dopamine signaling, I highly doubt you believe in any causality whatsoever when it comes to anything. Have you done any research whatsoever when it comes to these mutations? There are literally decades of research pointing to how these enzymes affect mood disorders. The elevations in neurotransmitters is real. I wish I was making this up.

How this all leads to your conspiracy theory of "the man" increasing regulation I have no idea. You truly are ridiculous. It sounds literally like you hit a crack pipe and then wrote an ad hominem attack without referencing any of the "pseudoscience" I preach. I am talking about enhancing dopamine signaling, not necessarily just depleting dopamine levels. I have messed with MAO B inhibitors and COMT inhibitors and they give me all of the symptoms of excess dopamine. I wish this was purely pseudoscience. But let me guess, you don't believe in drugs that act via mao or COMT inhibition either. They must be psuedoscience as well. You should research Dr. Mariano, a brilliant psychiatrist who has written some on the phenemenon of dopamine resistance. In fact there are tons of doctors who have written on COMT and MAO mutations and their effects. I don't know what cave you crawled out from, but I suggest you do some research before boldly claiming I have full of crap.

Oh let me guess, you don't believe in genetic mutations either? Apparently you don't believe in the concept of receptor downregulation either. Who really is mr. pseudoscience here? I never suggested or agreed to reserpine. I am talking about increasing dopamine signaling, not simply destroying its signaling. It was an idea, and I doubt he expected me to agree to it. That is how suggestions go. People discuss things and don't necessarily come to a conclusion 5 seconds later. Apparently you don't understand that concept either.

Edited by xks201, 04 January 2014 - 02:50 PM.

[golden1]

yay the days are here with more people diagnosing themselves, now with genetics!

[BioFreak]

Have you considered that the 23andme test might not be 100% reliable? After all, that is why the fda shut it down.

Mao and comt inhibitors can induce normal persons with excess dopamine symptoms, so that is no proof that the 23andme test is true.

Do you have dopamine excess symptoms(OCD, extreme sex drive, etc) without comt and mao inhibitors? Do you feel better when you take supplements that decrease dopamine?

Listen I am not saying that you are wrong, but I would let you get tested for the exact mutations by a lab to be sure.

I am sorry but I don't think there is a way to improve dopamine signaling. Why would you do that anyways? If you do have high levels of dopamine already, you'd be inducing psychosis.

If you already have low levels of comt and mao, then your only way out is reducing dopamine by reducing production. You should also consider increasing your antioxidant status, i.e. by NAC, to protect yourself from dopamine toxicity (dopamine and l-dopa themselves can also be neurotoxic if the levels are high enough, not only metabolites)

[xks201]

Yeah I am diagnosing myself based off genetic results. I have had the 23andme results independently tested and they are exactly as they came out as far as the COMT mutations. Assuming the FDA shut them down due to faulty results is a leap. The FDA is full of shit and most of you know that. Scientific papers prove my genetic results and symptoms. And yes I do have extreme sex drive if that means anything. I am not sure which suipplements decrease dopamine. I just didn't appreciate the arrogance from that guy. If he wants to respectfully disagree that is fine but to attempt to make a full of me for making some observations is not what this forum is about and the guy should leave if he is going to act like a toddler.

Edited by xks201, 04 January 2014 - 05:18 PM.

[darksanity]

Yeah I am diagnosing myself based off genetic results. I have had the 23andme results independently tested and they are exactly as they came out as far as the COMT mutations. Assuming the FDA shut them down due to faulty results is a leap. The FDA is full of shit and most of you know that. Scientific papers prove my genetic results and symptoms. And yes I do have extreme sex drive if that means anything. I am not sure which suipplements decrease dopamine. I just didn't appreciate the arrogance from that guy. If he wants to respectfully disagree that is fine but to attempt to make a full of me for making some observations is not what this forum is about and the guy should leave if he is going to act like a toddler.

Buddy calm down don't take it personally I was little tipsy last night and was just making fun of your awfully pseudo-scientific sounding original post lol. And who cares about my "43 posts" lol it's the content that matters genius I came here because everyone apparently bailed M&M but I'm sure not a newbie to the scene.. And honestly if you had posted something like that on M&M a few years ago you would've got destroyed and trolled with far less mercy than I did lol. Just trying to stir up some heightened scientific standards for the forum's credibility's sake.

Anyway I don't know about 23andme and all and really have no qualms with you self-diagnosing based on (purported) genetic results and I definitely hate the FDA as my post rant should've made clear. My problem here is that you basically take for granted that you know for a fact that you have a specific COMT mutation that somehow must lead to debilitating higher catecholamines levels. Then you rationalize this arguing those idle extra neurotransmitters that aren't metabolised by COMT ought to be downregulating their respective receptors and that's a bad thing which must be corrected................ Basically my problem here is that your entire reasoning is basically what gives fuel to such things as the FDA shutting down 23andme or banning this or regulating that...

Now let's assume for a sec that your theory is right because after all I do recall reading some papers on COMT polymorphisms potentially contributing to ADHD, schizophrenia and executive dysfunction, and tolcapone helping executive function deficits. Anyway then like I said you probably should just go ahead and eat some reserpine! That's pretty much as close there is out there as what you seem to be looking for. I think the scientific method is great and direct experimentation a far better teacher than textbooks or data overload from the Internet. Don't forget to report back your experiment.

Edited by darksanity, 05 January 2014 - 02:52 AM.

[BioFreak]

My problem here is that you basically take for granted that you know for a fact that you have a specific COMT mutation that somehow must lead to debilitating higher catecholamines levels. Then you rationalize this arguing those idle extra neurotransmitters that aren't metabolised by COMT ought to be downregulating their respective receptors and that's a bad thing which must be corrected................

He let it doublecheck by another lab, so I would take it for a fact now. In addition if he does also display signs of high dopamine, I would say that no more evidence is needed...

That receptors are downregulated is not important in my view also, but:
The biggest problems with low mao and comt enzyme activity is the potential unwanted psychological symptoms(too extreme sex drive, ocd, psychosis...), and the potential for oxidative damage. Even though inhibiting mao is neuroprotective because of less toxic metabolic byproducts, dopamine and l-dopa within the cell but not stored in the cells vesicle can be neurotoxic as well. So from this point of view also reducing catecholamines would make sense. Receptor sensitivity/density would be of no interest since they should autoadjust to lower levels within reason.

Now let's assume for a sec that your theory is right because after all I do recall reading some papers on COMT polymorphisms potentially contributing to ADHD, schizophrenia and executive dysfunction, and tolcapone helping executive function deficits. Anyway then like I said you probably should just go ahead and eat some reserpine! That's pretty much as close there is out there as what you seem to be looking for. I think the scientific method is great and direct experimentation a far better teacher than textbooks or data overload from the Internet. Don't forget to report back your experiment.

Reserpine works by keeping neurotransmitters where mao and comt can degrade them. If he already has low activity of both, it might do not much good. If I understand it right, it will stop transport into the vesicle. Meaning more free floating neurotransmitters within the presynaptic neuron. Without the ability to get into the vesticle, and without enough comt and mao, a lot of dopamine would accumulate there, and be potentially much more neurotoxic. I would seriously consider NOT trying it out.

Yeah I am diagnosing myself based off genetic results. I have had the 23andme results independently tested and they are exactly as they came out as far as the COMT mutations. Assuming the FDA shut them down due to faulty results is a leap. The FDA is full of shit and most of you know that. Scientific papers prove my genetic results and symptoms. And yes I do have extreme sex drive if that means anything. I am not sure which suipplements decrease dopamine. I just didn't appreciate the arrogance from that guy. If he wants to respectfully disagree that is fine but to attempt to make a full of me for making some observations is not what this forum is about and the guy should leave if he is going to act like a toddler.

Honestly, I would not have liked such a tone either.

What other symptoms of high dopamine do you have? Do you want less dopamine related behavior?
You could also probably decrease production of catecholamines through avoiding foods high in phenylalanine / tyrosine.
Or you could look into ways to increase comt / mao activity(which would fix exactly what your problem is). But the question is how your genetic mutations affect mao and comt, and if it is even possible to increase them.

[BioFreak]

Another thing that came to mind: if you could inhibit tyrosine hydroxylase, or dopa decarboxylase, less dopamine would be produced.

Since l-dopa may be neurotoxic as well if there is an excess in the cell, tyrosine hydroxylase inhibitors may be the best way if you are going down this route. Also because tyrosine is the furthest step in catecholamine synthesis that is covered by nutrition.

Now a tyrosine hydroxylase inhibitor would need to pass the BBB. On wikipedia is a small list, I haven't looked into them yet.

http://en.wikipedia....lase_inhibitors

[protoject]

Avoid foods that have high tyrosine levels is my only suggestion along with a more extreme route of reserpine.

High carb diet might do.

(IIRC high carb should make competition for the amino acid transporter harder for the dopaminergic amino acids, in favor of the serotonergic)

I dont know if thats true for all of the "dopaminergic" amino acids or just some

Also I'm not sure if that's anything more than preventative.

If I come up with any useful idea I'll let you know. I think I have one now but my memory is failing me so I'm having to redo research.

Oh, and , I dont know enough about neurophysiology but if your idea is to "use up" the dopamine, I'm guessing CDP-Choline could help since it upregulates dopamine receptors, but you'll have to check the science on that because I think we are missing a lot of information.

Edited by protoject, 24 January 2014 - 07:38 PM.

[nowayout]

What bothers me is that a lot of people are "abusing" 23andme this way, coming up with wildly elaborate neurophysiological hypotheses based on long chains of reasoning involving very little actual experimental basis. As someone mentioned, this kind misuse of 23andme data is one of the problems the FDA has with their paradigm.

We know where these chains of reasoning lead the best minds in pharmaceutical research - a failure of more than 99% (AFAICR) of therapeutical proposals in clinical trials. There are just too many interdependent variables to expect any naive, or often not so naive, causal chain of reasoning to reflect reality in most biological systems, especially the brain. Humans just are no good at solving nonlinear systems of differential equations with hundreds of variables, many of them unknown, in our heads.

xks201, what makes you think your theories would be among the less than one percent that actually correspond with reality? You are looking for a "treatment" of an ill-defined make-believe condition with no symptoms.

(By the way, high sex drive is not a symptom. It's a gift.)

You do have hypochondria. Could hypochondria have a genetic basis - maybe in part. But there is no repeatable study showing any such connection to date AFAIK.

Edited by nowayout, 24 January 2014 - 08:46 PM.

[Reformed-Redan]

Low doses of amisulpride could be helpful. I find the DA autorecepter rebalancing effect to be of high therapeutic value at lower doses.

[xks201]

Low doses of amisulpride could be helpful. I find the DA autorecepter rebalancing effect to be of high therapeutic value at lower doses.

Interesting to note that amisulpride activates the GHB receptor.