450 replies to this topic

[Guardian4981]

Well I think there is very much a partnership between chemical makeup and our thought patterns. If a person has been depressed or with dysthmia most of their life improving their chemical makeup may help them feel better a bit especially initially. But the old thought patterns are still there.

I think a goal that is gaining more following in the community is that improving the chemical side can give you a lift that can then be used to improve your thought patterns. If the thought patterns are improved they then can further help the chemical side. This is a self perpetuating process that can go in either direction. This may be why you hear stories of people who hit "rock bottom" and then they start getting better and better and become motivational speakers or what have you.

I read the site you posted. What is interesting is so far my inflamation actually appears to have decreased rather then increased. I have had a sore shoulder for a while. So far with 5-MTHF I feel an almost slight numbness accross my body. This actually is likely the core of the anxiety I felt, when I am anxious the border between my body and matter around me seems to dissolve. I also feel a bit of tingling sensation in my hands and feet. Does folic acid help circulation at all?

I have niacinimide and have used it, seems to help a bit with depression however it tends to zap my libido. I think Niacin boosts serotonin and thus may lower dopamine.

[zaratoo]

This thread made me register, wich I usually don't do (having no will to be social ) But this time I just couldn't watch silently.
I don't really know why, but I started dig into dopamine quite recently, while I've been researching (self-edu I mean) biochemistry and neurophysiology for 10+ years now. Too sporadically I see now..

As for motivation, I'd fit my situation well in Chadwick's description. Thanks for formulating that man, I've never been motivated enough to start do it myself. Though I always saw that problem had it's place.. And well, I have some social anxiety, but it's totally gone, when I need to communicate e.g. officials/bosses (municipal, military, in university etc no matter) for some important (often not for me personally) reason.
Actually when I learned the name of Asperger, I said it's about me! Light form obviously, no one except me would notice my stress and inabilities..

As for ethanol and hangovers.. I often think and say to people that I even drink to get hangover. They laugh thinking it's a joke or just look 0_o this way.
Sorry for being too wordy about myself, I'm just really excite to meet people like myself))
Also hangover and dopamine. No one mentioned (or I missed) the marvelous sex drive in this state. Physical and mental.
And to mention the mentality on the whole it's kinda psychedelic state. Without junkie tail of this term. Wisdom is good suitable word. You think wider and deeper at the same time)
And I enjoyed being drunken too. But most people would say it's like Jekyll and Hyde)) Nothing delirious though, just two really different personalities - from the side view.

Guardian4981, your 5-MTHF experience reminded me thc) Anxiety and sound findings in familiar tracks.

I see Naltrexone talks stopped? It's pretty cheap and can be gotten via local pharmacy (if web doesn't lie to me). Did any of you guys tried? I guess I'm researching effects and dosage as soon as post this entry.
I'll probably order Solgar Metafolin in fiture, but it takes long time to get iherb stuff delivered and I didn't plan to order any soon.
Also won't Mucuna (L-Dopa) do the trick? I was going to try it..

Also abuot metafolin and ch3-group. Most uses before I've read were exactly the methylation and not "our case". So I think we could add some TMG and after being converted into DMG it'll be remethylated by metafolin. Does it work so?
And do excess level of methyl donors make you homocystein-deficit?) So much hype around methylation nowadays.. Couldn't think it'd be a problem..

I guess it's enough of me, too long post not so informative.. Hope I wasn't annoing..
Thanks for thread!

Edited by zaratoo, 26 August 2013 - 05:21 AM.

[zaratoo]

I see Naltrexone talks stopped? It's pretty cheap and can be gotten via local pharmacy (if web doesn't lie to me).

edit: so it _was_ an error in site. it's not cheap at all $20-40 (vendor dependent) per 10*50mg pack..

[nowayout]

I see Naltrexone talks stopped? It's pretty cheap and can be gotten via local pharmacy (if web doesn't lie to me).

edit: so it _was_ an error in site. it's not cheap at all $20-40 (vendor dependent) per 10*50mg pack..

But just one pill will last you months for low dose naltrexone therapy, which is what makes it cheap.

[zaratoo]

Interested again))
Would you please share some detailed info/links about dosage and protocol?

[Guardian4981]

Guardian4981, your 5-MTHF experience reminded me thc) Anxiety and sound findings in familiar tracks.

Also won't Mucuna (L-Dopa) do the trick? I was going to try it..

I personally find Mucuna (L Dopa) gives me headaches and irratibility.


I am on day 5 of 5-MTHF, so far the results overall have been quite positive. The anxiety it brings has slowly diminished. I was out at a beach club yesterday and actually approached some girls with ease a few times which normally is quite a chore. I also am finding that my libido is up, almost to the point of annoyance lol.

I think I need weeks or months longer though to determine how well this will work for me. I will say yesterday I literally felt the best I have in a few years, today I am back to work so not feeling quite as good but still better then usual.

[machete234]

Also hangover and dopamine. No one mentioned (or I missed) the marvelous sex drive in this state. Physical and mental.
And to mention the mentality on the whole it's kinda psychedelic state. Without junkie tail of this term. Wisdom is good suitable word. You think wider and deeper at the same time)

Yes the sex drive is really odd and it happens to ease the headache because apparently when youre at it some more blood gets in you brain and the pain stops for a while.
And psychedelics have nothing to do with junkies, just do your research.

Also won't Mucuna (L-Dopa) do the trick? I was going to try it..

Even if this just gets converted into dopamine and you have more as a result your body decreases the amount of dopamine receptors so that you are back to where you were.

Maybe you dont have to little dopamine but too little dopamine receptors.

Edited by machete234, 26 August 2013 - 04:40 PM.

[nowayout]

Interested again))
Would you please share some detailed info/links about dosage and protocol?

At a starting dose of, say, 1.5 mg, one 50 mg pill of naltrexone will last you more than a month. (You dissolve it in water and drink a measured amount every evening.) Even at the usually recommended upper limit LDN dose of 4.5 mg, the cost per day would be very low.

Some sources recommend much lower doses than this, by the way.

[Chadwick]

This thread made me register, wich I usually don't do (having no will to be social ) But this time I just couldn't watch silently.
I don't really know why, but I started dig into dopamine quite recently, while I've been researching (self-edu I mean) biochemistry and neurophysiology for 10+ years now. Too sporadically I see now..

As for motivation, I'd fit my situation well in Chadwick's description. Thanks for formulating that man, I've never been motivated enough to start do it myself. Though I always saw that problem had it's place.. And well, I have some social anxiety, but it's totally gone, when I need to communicate e.g. officials/bosses (municipal, military, in university etc no matter) for some important (often not for me personally) reason.
Actually when I learned the name of Asperger, I said it's about me! Light form obviously, no one except me would notice my stress and inabilities..

As for ethanol and hangovers.. I often think and say to people that I even drink to get hangover. They laugh thinking it's a joke or just look 0_o this way.
Sorry for being too wordy about myself, I'm just really excite to meet people like myself))
Also hangover and dopamine. No one mentioned (or I missed) the marvelous sex drive in this state. Physical and mental.
And to mention the mentality on the whole it's kinda psychedelic state. Without junkie tail of this term. Wisdom is good suitable word. You think wider and deeper at the same time)
And I enjoyed being drunken too. But most people would say it's like Jekyll and Hyde)) Nothing delirious though, just two really different personalities - from the side view.

I've noticed the increased sex drive too, and I love it. It's uncommon for me to have morning wood, but I often do when I'm hungover. I've also been experienceing the same thing you are describing about having no social anxiety when talking to officials, like job interviews or whatever.

However - after lowering my dose of MTHF to 800 mcg per day and adding 1500 mcg of folic acid I've gotten back the effects I got from MTHF the first week. I'm, feeling great now - all the lack of social interest is gone and I'm out there interracting with lots of energy and a great mood. After digging deeper into my 23andme results I've come to found I have an uncommon homozygous mutation in DHFR, another enzyme involved in the metabolism of folate. I think this has caused a "hidden" deficiency, i.e. blood panels look normal but in reality you have a higher than normal need for folate due to slower conversion to its active forms.

I'm personally feeling cured now, after 22 years, which is absolutely amazing.

It would be interesting to see how you reacted to supplementing higher doses of folic acid (or MTHF if possible) together with iron, which is also important for dopamine production.

[zaratoo]

Nice!
Glad for you pal =)
I'm definitely going with Metafolin and Folinic acid my next order from iherb. Not soon though.
But I've just started taking 2-per-day by LEF (it has standart 400mcg of folate, but it's from lemon peel, not synthetic FA) and am waiting for a bottle of B-Rigth to be delivered soon. It has 400 more mcg per cap (gonna have one per day) from FA (most) and Quartefolic acid (less). Although I don't expect miracle, hope it will do smth within a planned 3-4 moths cycle. Still want to experience metafolic uprise with few mgs daily doses.
Interesting is that folate is always problematic in multis proper form wise. MB12 and p5p are pretty common in decent complexes.. So I realize now I've never took mthf in my life actually.
Also I guess to have pretty high serotonine (as compared to depressed people around me IRL) and lower dopamine (considering all said in this thread). Time for experiments is coming I believe =)

[Psionic]

My first dose of 1mg (1000mcg) MTHF ended with severe anxiety and hindered thinking. I dont know what genetics mutations I can have but the hangover effects is remarkable in me.

So the route should be to lower the dose of MTHF and add some niacin? Chadwick, whats the reason you take MTHF and folic acid at the same time?

[Chadwick]

My first dose of 1mg (1000mcg) MTHF ended with severe anxiety and hindered thinking. I dont know what genetics mutations I can have but the hangover effects is remarkable in me.

So the route should be to lower the dose of MTHF and add some niacin? Chadwick, whats the reason you take MTHF and folic acid at the same time?

The reasoning behind MTHF+folic acid is that they both raise the body's total MTHF levels. Taking a combination is more effective than only taking folic acid, and has less side effects than taking only MTHF.

I'm sorry to hear MTHF produces these effects for you. You could try lowering the dose and combining with niacin, or you could try taking only folic acid (4 mr per day or so, which would be my preffered route).

Edited by Chadwick, 28 August 2013 - 01:19 PM.

[Galaxyshock]

There's a 4 to 5-fold increase in glutamate release during hangovers, of course you are going to feel fucking different.

[Chadwick]

There's a 4 to 5-fold increase in glutamate release during hangovers, of course you are going to feel fucking different.

True. Yet the shift in glutamate release is far from the only thing that happens during a hangover. For me personally, the mood boost was not replicable by using glutaminergics (sarcosine), only dopaminergics (e.g. NADH).

[tritium]

My first dose of 1mg (1000mcg) MTHF ended with severe anxiety and hindered thinking. I dont know what genetics mutations I can have but the hangover effects is remarkable in me.

So the route should be to lower the dose of MTHF and add some niacin? Chadwick, whats the reason you take MTHF and folic acid at the same time?

I also experienced this. I heard that "hindered thinking" is a common detox symptom when starting this regimen as it is kick starting your methylation cycle. Folic acid should be avoided if you have the genetic mutation which reduces the ability to convert it (60% of the world's population have this mutation) as it blocks methylfolate from being absorbed. Instead, B-12 should be brought to normal levels first before starting methylfolate. Here's a good site with more information: http://forums.phoeni...l-basics.10138/

[Absent]

Lol. Here is my 2 cents. I think you are WAY over complicating this. The fact is that when drunk people go to sleep they SLEEP. The best sleeps of my life have been when I had been drunk. This basically means that your "dopamine deficiency" is probably a wide array of things. Getting a more restful sleep will rejuvenate the body in a million different ways.

[lammas2]

Alcohol in no way improves your sleep. What do you mean by the best sleeps of your life? You wake up feeling totally refreshed? Don't be fooled - this isn't because of improved sleep, it is caused by excessive glutamate released after GABA-A agonism caused by ethanol.

[Absent]

Alcohol in no way improves your sleep. What do you mean by the best sleeps of your life? You wake up feeling totally refreshed? Don't be fooled - this isn't because of improved sleep, it is caused by excessive glutamate released after GABA-A agonism caused by ethanol.

While a lot of chemical changes happen when a person has alcohol in their system, one needs to not overlook the fact that alcohol is a DEPRESSANT. This is common knowledge. Depressants slowwwwwwww down the system, and in people who are usually average energetic and hyper, it can cause their systems to slow down beyond their normal states when they sleep, leading to a more restful sleep.

What, do you really think that we all get perfect sleep every night? We age(in terms of getting older/weaker) because our body is not able to heal as fast as it decays. The fact is sleep is never perfectly restorative, and the resulting restfulness can occur in varying degrees. Yes while it is not good to use depressants everynight for sleep because of the other chemical changes that can result, the fact is that they can relax the systems of the body and that relaxation can result in a more restful sleep in some cases.

There is a big problem I've noticed in this community. People get so tied up in very specific chemical processes that they often overlook the total net effect. The body is very complex and no one single chemical is responsible for the functioning of any one single system. Our bodily systems and functions happen as a result of many many different systems interacting with eachother. If it was as simple as one chemical being linked to one single biological function, then we would have discovered a single chemical for photographic memory long ago.

[Mr Serendipity]

Check out a post I put out last year, sounds very similar to my own experience:

http://www.mindandmu...ment-motivation

Hi. So Saturday night I went out, got drunk, but remember around 70% of the night.

Before I went to bed, I downed 2 pints of water, then filled a 3rd pint up to put next to my bed if I get thirsty.

So I woke up pretty much hangover free, in the sense that I don't get headaches, though my cognitive function was slower.

But when showering in the morning, I start contemplating ideas, imaginations, and feeling excited, almost euphoric about them. Like I can do and achieve anything in the world, very motivated to make these ideas happen. It's was an awesome feeling of drive and excitement. As you guessed it it eventually fades, but this has happened to me before after previous nights out with alcohol.

So my question is what causes this, and is it possible to have a continued feeling of this? I think I suffer from low dopamine anyway, so I think this may be the cause. Before this event 2-3 weeks ago, I was recently able to create this feeling using tyrosine and lithium. The problem is lithium dumbs me down during the day, and the euphoric/motivation effects vanished after a day or 2.

To be honest this is the million dollar question with dopamine, keeping it up and preventing downregulation. But to me, that feeling is the feeling I think people should be feeling all the time. It's not a high, more like an excitement of life and to do things. Basically Happy Motivation.

So can anyone make a connection between the aforementioned euphoria:
1.Lithium + tyrosine
2. Alcohol recovering

The last question I have. Is would there be any benefit to a person, if you had 1-2 shots of vodka in the morning, and that's it. Like would this small but significant amount of vodka affect the brain chemistry, or would your liver just get rid of it before hand and there would be no benefit. I know people say you'll become an alcoholic, but why is that? Because your liver would be more efficient to deal with the alcohol, so you need more to create that effect, i.e. tolerance.

Sorry for the long post, I'll be looking forward to your inputs.

1. So Chardwick are you still feeling the effects or have you built up tolerance?

2. Also what supplements are you taking, and which ones did you drop? Are you taking MTHF + folic acid + niacin?

3. Are you still taking them sublingually, or swallowing them?

4. Is 5-MTHF and MTHF the same thing?

5. Is there any point taking NADH, or do you think going the MTHF route is all that's needed?

Edited by manny, 09 September 2013 - 08:16 PM.

[Chadwick]

I’m still taking methylfolate (MTHF), and I doing great on it. Really great. I had dopaminergic problems for the first 22 years of my life, but the last six months or so that I’ve been using this I feel like a different, and much better, person. The social and mental inhibition I’ve felt before is totally gone now, which of course feels amazing.

After some experimenting I’ve found out a simple regimen that works for me, and I also believe I’ve figured out why my previous problems disappeared during hangovers. It’s somewhat complicated, but I’ll try to explain.

The alcohol that we consume is broken down to acetaldehyde, a toxic substance that is responsible for some of the negative effects of a hangover. Acetaldehyde interacts with several enzymes and proccesses in the body, and one of these is methionine synthase, an enzyme in the metabolism of (methyl)folate and B12 that is needed to make methyl groups. It binds this enzyme and blocks it temporarily, reducing the usage of folate and B12 for this purpose. When the folate in our bodies can’t be used for this purpose, it is instead used to create BH4, a cofactor in the synthesis of dopamine, norepinephrine and serotonin.

This, I believe, is my personal problem - that I don’t have enough conversion of inactive forms of folate (such as folic acid or folate from food) to the active form (methylfolate) and therefore not enough to support both the methylation and the BH4 pathways. Lack of methylation can gives rise to a number of problems, such as acne, low immune function, lack of mental and physical energy, and lowered detoxification of heavy metals. Lack of BH4 on the other hand can decrease the production of neurotransmitters. By supplementing methylfolate I can normalize the activity of both of these biological pathways.

I feel a distinct effect from taking methylfolate within an hour, and it lasts for six hours after that. Since I want to have this effect 24/7 I’m taking small doses (200 mcg) every six hours, so four times a day.

The problem that can arise is that too much methylfolate can deplete the body of the active form of B12, methylcobalamin. When B12 gets low inside the cells the usage of methylfolate for it’s two purposes are blocked, and somehow it starts going from the cells to the plasma. So basically we get high folate levels in plasma but we’re unable to use it, so we get a functional deficiency. Taking more methylfolate without B12 will just make the functional folate deficiency worse. This phenomenon is known as methyl trap, folate trap or methylfolate trap. It will take a week or so to develop low intracellular B12 levels when we take high doses of methylfolate, and this is why people (including me) will feel great for a week when starting taking this supplement, but then crash.

This can be avoided by taking B12 with the folate, and there are two main ways to approach this. The first way is to take methylcobalamin - usually sublingually and in doses of >1 mg. This will kickstart methylation and give you all the benefits this might bring, but it won’t leave much folate for the synthesis of BH4, and therefore it won’t help our dopamine problems. The other way to solve the B12/methyl trap issue is to take sublingual hydroxocobalamin, which is an inactive for that converts to methylcobalamin at a steady but low rate. This will prevent methyl trapping as well as preventing all the folate from going down the methylation route.

So, the MTHFR/dopamine regimen I use myself is this:

• 200 mcg of oral methylfolate, every six hours
• 1 mg of hydroxocobalamin once a day

According to my 23andme results I personally have incredibly bad genetics for dopamine - the Val/Val version of COMT, the highly active version of MAO, one Taq1 mutation in the D2 receptor and so on - but it dosen’t seem to affect me that much when I’ve normalised my folate metabolism. I think this might be true for other people as well - that low dopamine levels are mainly caused by a decrease in synthesis, not an increase in breakdown.

[Chadwick]

1. So Chardwick are you still feeling the effects or have you built up tolerance?

2. Also what supplements are you taking, and which ones did you drop? Are you taking MTHF + folic acid + niacin?

3. Are you still taking them sublingually, or swallowing them?

4. Is 5-MTHF and MTHF the same thing?

5. Is there any point taking NADH, or do you think going the MTHF route is all that's needed?

1. Yes, and there is no buildup in tolerance.

2. Hydroxocobalamin and methylfolate (MTHF), nothing else. I don't need niacin when taking ydroxocobalamin as this doesn't cause overmethylation. Methylcobalamin can overdrive the methyl cycle, so if you choose that route niacin may be useful since it can decease methylation in the case of overmethylation.

3. Hydroxocobalamin sublingually, methylfolate orally (just swallowing).

4. Yep. Methylfolate = MTHF = 5-MTHF.

5. No, I don't think NADH is needed.

[Chadwick]

great info, i'll be starting TMG, 5-MTHF, and Methyl B12 today. Chadwick, I don't quite understand your reasoning of the methyl trap. Wouldn't raising the dosage of methylfolate allow it to synthesize BH4 and also methylate other necessary things? I don't see why including Methyl B12 would prevent success when taken together with the 5-MTHF.

I read here: (http://www.ncbi.nlm....les/PMC1574248/) that 5-MTHF has an oral bioavailability 7x higher than folic acid. Though I can't find much info out their on whether or not to take 5-MTHF sublingually. What made you decide to take it orally?

The methyl trap phenomenon is somewhat of a paradox - by taking more methylfolate we lower B12 even more, and more methylfolate is expelled from the cells. Taking more methylfolate without B12 therefore lowers intracellular folate levels while raising extracellular levels. BH4 synthesis takes place inside the cells where folate now is low, and is therefore impaired. I honestly don't fully understand the mechanisms behind this, but it seems to be fairly well documented.

The reason I'm sceptical towards methyl B12 is that it makes us use our folate for production of methionine and in extension methyl groups rather than BH4. Instead of using some folate for methylation (which is regulated by access to methylfolate AND methyl B12) and some for BH4 production there would be a shift towards more methylation and less BH4. Since BH4 is needed to make neurotransmittes and methylation is needed to break down catecholamines, this would lead to lower levels of dopamine.

I take methylfolate orally as it seems to be working very well for me. I've seen various numbers regarding it's bioavailability and it seems like there is no consensus yet, but since it's working as intended I don't see any reason for myself to take it sublingually instead.

Edit: Oh, and I'm not sure if TMG is needed, sine methylfolate and methyl B12 will increase methylation by a fair amount anyway.

Edited by Chadwick, 05 April 2014 - 03:30 PM.

[Chadwick]

I'm still a bit confused, off to do more research lol. I'm actually using TMG, 5-MTHF, and Methyl b12 in order to stimulate Sam-e production. B12 and B9 are cofactors there, so i'm not sure how that fits into the methylation and BH4 cycles. isn't methionine used to produce sam-e?

Yeah, B12 and folate (B9) are used to create methionine, which in turn is used to make SAMe (S-adenosylmethionine). SAMe increases methylation by donating its methyl group to other substances.


Edit: Above pic should say "5-MTHF". MTHFR is the enzyme used to procude 5-MTHF/methylfolate.

Edit 2: regarding the site I liked to earlier, the side effects listed there (increased inflammation, acne, rashes etc) seems to actually be symptoms of methyl trapping - in other words symptoms of LOW folate due to a functional deficiency.

Edited by Chadwick, 05 April 2014 - 05:03 PM.

[Chadwick]

[...]

So why would it be undesirable for folate to be channeled towards methionine production? It seems that at any route 5-MTHF will have some beneficial energy and mood properties.


Also you seem to suggest that b12 is kind of a rate limiting step for BH4 production, meaning that however much b12 is taken, the same amount will be used of b9 for methylation process not neurotransmitter ones. Do you have evidence of this? It seems to make sense since they methylate well together, but I just want to confirm it.

I believe it's important to have a healthy level of methylation going on. The reason methyl B12 can be a problem is that taking large amounts of it can overdrive the methylation cycle, thereby leading to overmethylation and decreased BH4. Normally the body will regulate methyl B12 production on its own, keeping it at a steady and low pace which allows normal levels of methylation.

There are some cases where very high levels of methylation may be beneficial, such as for people with neuropathy (http://www.ncbi.nlm..../pubmed/8021696).

I don't believe B12 is a rate-limiting step for BH4 production or recycling, but some B12 is needed to prevent a methyl trap. B12 is, however, used by methionine synthase, which is the rate-limiting step in the methylation cycle. The statement that methyl B12 decreases BH4 production by re-routing folate usage towards methylation was made by Rich van Konynenburg, an authority in the treatment of chronic fatigue syndrome with methyl B12. It seems to be true in my experience, and somewhat logical.

[golden1]

the liver keeps a years supply of b12

[normalizing]

amazing thread. when i saw the dopamine and alcohol words together in the title, i knew its going to be interesting and boy what a trip it is to read it.

chadwick, i find it amazing how when you started this thread you were still figuring out whats wrong with you and by the end of the thread, not only did you find out and fix yourself, now you are like a teacher to the rest of us! which is amazing. most people start threads and cry all the time asking for answers and usually people cannot give them any. i have noticed no thread ever gives a topic starter their best solutions EVER but its like a road down the thread to find out whats best yourself and you suprised me to do just that contrary to other people on this forum. i must say, you are a pretty smart guy, except mentioning the defects in genes associated with dopamine, did you also see any expression in genes involved in intelligence?

but i have to ask this, its main reason i reply though i love the thread, im not sure i have the same problem to follow your regime and im not sure what problem i have anyway so this is why i reply now to ask this; if order the gene test from 23andMe, how much do they really tell you and explain in detail to you whats wrong and right with you ? i have never done this gene test, i have no clue how to read it! and you are smart enough to have figured it out by yourself without them telling you i assume ? i have to take this test but if they cannot help me with information, ill waste money on something i dont even really understand at all. but i assume you can read those tests and help me out ? i dunno if you self taught yourself all that biochemistry and knowledge on genetical problems, but you know what you are talking about so i put trust in you. perhaps you even have a job related to this ?
anyway any help much appreciated!!