6 replies to this topic

[experimenting]

Warrior gene. And it describes me perfectly. Low motivation and enjoyment of life, but excellent function under stress, when you need it.

This made me a superb student (largely by being a great test taker) but my proactivity is poor. So low ability to be entrepreneurial etc etc.

Long story short...any treatments for this? Sounds like COMT inhibitors are in order. I'd note that when I megadose vit D and don't take K, I get hypercalcemia, but feel good mentally-because calcium inhibits COMT. So does iron but that has dangers.

One thought was p5p. Not much literature on this though.

[MankindRising]

I have the same, comt warrior. On top of that I also have 60% efficiency in processing folate. Please note that pretty much all methyl donors (MSM, TMG, 5mhtf cause rage, agression, irritability and hyperactivity in me), only SAM-E seems to help me, along with magnesium, vitamin c, p5p, panax ginseng, nadh and biogaia gastrus.

 

And believe it or not SAM-E helps FUCK LOTS, I believe that we have low adrenalin this is due to comt normally enhancing noradrenalin breakdown not into adrenalin but in some crappy unneeded metabolyte.

Try SAM-E you will be impressed, it gives me outlook in life, socializing, excited to try new stuff in life.

I will tell you it has to do with methylation and sam-e/sah/homocysteine and the ratios between them also it has to do with acetaldehyde processing in which the methylation cycle takes place (acetaldehyde is high reinforcing, it makes nmda receptors on vta dopamine neurons more sensitive and increases burst fireing). Also SAM-E is needed for proper function of receptors, including dopamine and nmda (it enhances both phospholipid and polyamine synthesis).

 

Heres some papers to chew on, rest you can dig up yourself:

Influence of S-adenosyl-l-methionine on chronic mild stress-induced anhedonia in castrated rats

https://www.ncbi.nlm...les/PMC1566059/

Abstract

1. S-adenosyl-l-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons is involved in the therapeutic mechanisms of antidepressants.
2. The effect of SAMe in an animal model of ‘depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats.
3. Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg−1daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg−1 daily i.p.) produced a similar effect after a 3 week treatment.
4. Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg−1 daily i.m.)- and in imipramine (10 mg kg−1 daily i.p.)-treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats.
5. Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test.
6. While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment.
7. These results show that SAMe reverses an experimental condition of ‘depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects.

  Oral S-adenosylmethionine (SAM) Administration Increases Whole Brain Concentrations of Dopamine and Norepinephrine in Rats

https://www.fasebj.o...upplement.134.3

" Oral SAM supplementation increased the intracellular concentration of SAM in the liver and brain approximately 2- and 4-fold respectively. S-adenosylhomocysteine (SAH) concentrations were significantly elevated by oral SAM treatment in the brain, but were not affected in liver tissue. For whole brain tissue, SAM also markedly increased the concentration of dopamine and norepinephrine 15-fold and 50%, respectively, whereas it did not have a statistically significant impact on serotonin concentrations. Moreover, SAM administration was without effect on the concentrations of the transporters for dopamine, norepinephrine, or serotonin. Therefore, oral daily provision of SAM to rats at a dosage recommended for humans dramatically increased the intracellular concentrations of specific neurotransmitters, dopamine in particular. The significant increase in brain SAH concentrations may result in the allosteric inhibition of a number of SAM-dependent methyltransferases that function to metabolize dopamine and norepinephrine, thereby elevating their tissue concentrations."

 

So as you can see SAM-E increased not only SAM-E but also SAH levels in the brain, now SAH altered sam-e and sah levels and their ratios have been linked to mania.

Now bare with me. As I think anhedonia is basically the oposite of mania, so a little SAM-E would put you in the 'normal zone'.

 

Trust me btw that when I say SAM-E is powerfull stuff, treat it with respect 200-400mg on an empty stomach ONCE per day to start with, even skipping a dose a few days later and you can still feel effects ~1-2 days later.

 

Also I should say that im one of those 'weirdos' that both a hangover and sleep deprivation makes me feel normal, I believe this is due to homocysteine buildup being recycled into sam-e and this is what causes the antidepressant effect.

Edited by MankindRising, 02 January 2019 - 01:05 AM.

[experimenting]

I have the same, comt warrior. On top of that I also have 60% efficiency in processing folate. Please note that pretty much all methyl donors (MSM, TMG, 5mhtf cause rage, agression, irritability and hyperactivity in me), only SAM-E seems to help me, along with magnesium, vitamin c, p5p, panax ginseng, nadh and biogaia gastrus.

And believe it or not SAM-E helps FUCK LOTS, I believe that we have low adrenalin this is due to comt normally enhancing noradrenalin breakdown not into adrenalin but in some crappy unneeded metabolyte.
Try SAM-E you will be impressed, it gives me outlook in life, socializing, excited to try new stuff in life.
I will tell you it has to do with methylation and sam-e/sah/homocysteine and the ratios between them also it has to do with acetaldehyde processing in which the methylation cycle takes place (acetaldehyde is high reinforcing, it makes nmda receptors on vta dopamine neurons more sensitive and increases burst fireing). Also SAM-E is needed for proper function of receptors, including dopamine and nmda (it enhances both phospholipid and polyamine synthesis).

Heres some papers to chew on, rest you can dig up yourself:
Influence of S-adenosyl-l-methionine on chronic mild stress-induced anhedonia in castrated rats
https://www.ncbi.nlm...les/PMC1566059/
Abstract

• S-adenosyl-l-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons is involved in the therapeutic mechanisms of antidepressants.
• The effect of SAMe in an animal model of ‘depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats.
• Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg−1daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg−1 daily i.p.) produced a similar effect after a 3 week treatment.
• Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg−1 daily i.m.)- and in imipramine (10 mg kg−1 daily i.p.)-treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats.
• Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test.
• While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment.
• These results show that SAMe reverses an experimental condition of ‘depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects.

Oral S-adenosylmethionine (SAM) Administration Increases Whole Brain Concentrations of Dopamine and Norepinephrine in Rats
https://www.fasebj.o...upplement.134.3
" Oral SAM supplementation increased the intracellular concentration of SAM in the liver and brain approximately 2- and 4-fold respectively. S-adenosylhomocysteine (SAH) concentrations were significantly elevated by oral SAM treatment in the brain, but were not affected in liver tissue. For whole brain tissue, SAM also markedly increased the concentration of dopamine and norepinephrine 15-fold and 50%, respectively, whereas it did not have a statistically significant impact on serotonin concentrations. Moreover, SAM administration was without effect on the concentrations of the transporters for dopamine, norepinephrine, or serotonin. Therefore, oral daily provision of SAM to rats at a dosage recommended for humans dramatically increased the intracellular concentrations of specific neurotransmitters, dopamine in particular. The significant increase in brain SAH concentrations may result in the allosteric inhibition of a number of SAM-dependent methyltransferases that function to metabolize dopamine and norepinephrine, thereby elevating their tissue concentrations."

So as you can see SAM-E increased not only SAM-E but also SAH levels in the brain, now SAH altered sam-e and sah levels and their ratios have been linked to mania.
Now bare with me. As I think anhedonia is basically the oposite of mania, so a little SAM-E would put you in the 'normal zone'.

Trust me btw that when I say SAM-E is powerfull stuff, treat it with respect 200-400mg on an empty stomach ONCE per day to start with, even skipping a dose a few days later and you can still feel effects ~1-2 days later.

Also I should say that im one of those 'weirdos' that both a hangover and sleep deprivation makes me feel normal, I believe this is due to homocysteine buildup being recycled into sam-e and this is what causes the antidepressant effect.

Odd that one but not any other methyl donor helps you.
I do want to make clear that my goal is primarily motivation based. Want to get into that flow state to actually get things done.

[MankindRising]

"Low motivation and enjoyment of life, but excellent function under stress, when you need it. "

 

The above you write are core symptoms of anhedonia and adhd.

 

So this means your environment isnt stimulating enough for you to have any motivation or desire to do so.

Now this is exactly what adrenalin does, it triggers excitement and is extremely motivating.

What do you think coffee does? thats right it jolts up cortisol and adrenalin. This is the shit that will help you get up on the morning. You need some form of 'stress' to have motivation. Trust me man ive been there, I barely flinched when a truck was about to hit me, this is low adrenalin/improper cortisol secretion issues.

 

Thing is when you got high com-t activity at baseline, your noradrenalin is going down into improper pathways and you will end up with LOW adrenalin!

Feeding SAM-E will increase ADRENALIN : NORADRENALIN ratio.

[experimenting]

"Low motivation and enjoyment of life, but excellent function under stress, when you need it. "

The above you write are core symptoms of anhedonia and adhd.

So this means your environment isnt stimulating enough for you to have any motivation or desire to do so.
Now this is exactly what adrenalin does, it triggers excitement and is extremely motivating.
What do you think coffee does? thats right it jolts up cortisol and adrenalin. This is the shit that will help you get up on the morning. You need some form of 'stress' to have motivation. Trust me man ive been there, I barely flinched when a truck was about to hit me, this is low adrenalin/improper cortisol secretion issues.

Thing is when you got high com-t activity at baseline, your noradrenalin is going down into improper pathways and you will end up with LOW adrenalin!
Feeding SAM-E will increase ADRENALIN : NORADRENALIN ratio.

Yes OK, but I had a horrid time on methyl donors.

Anyone have a solution that doesn't touch the methylation cycle (which of course may be quack science anyway)...

[MankindRising]

I had some weird side effects from SAM-E which led me to discontinue, you should read through my posts on it.

Otherwise I would say it was very effective for giving meaning to basic things in life and not needing an enormous stimulus to get some form of motivation.

 

My next plan is to move foward to either bupropione or aripipazole. I seem to do well with nicotinic antagonism (seems to calm down my over-cognition and this seems to bring back some of my empathy, basically I need a pill that makes me stupid, so I can be social).

[experimenting]

I had some weird side effects from SAM-E which led me to discontinue, you should read through my posts on it.
Otherwise I would say it was very effective for giving meaning to basic things in life and not needing an enormous stimulus to get some form of motivation.

My next plan is to move foward to either bupropione or aripipazole. I seem to do well with nicotinic antagonism (seems to calm down my over-cognition and this seems to bring back some of my empathy, basically I need a pill that makes me stupid, so I can be social).

OK so you repeatedly shilled SAM-E despite my reservations and hijacked the thread without responding to my concerns. Now you say you've quit it.


Moving on, anyone try rhodiola for this effect?