450 replies to this topic

[Kingsley]

The downside to the whole thing is that it's verging onto hypo-mania territory. I become ultra excitable and passionate (which is a breath of fresh air) and though i get a bit too outrageous at times, I somehow find the will to contain myself.

 

 

By the way, this is not what you want.  Could it be that you are overdoing the sarcosine or other NMDA agonist?  I read some case study somewhere written by a doctor treating some one with sarcosine who, like you, had almost too-good results and became a bit hypo-manic.  The doctor lowered the sarcosine dosage and the issue resolved.  Hypomania may feel good but it is not a sustainable or healthy state, and is usually followed by a crash.  Unless you're Charlie Sheen and have Tiger Blood!

 

Just something to consider. 

[Apprentice_Bob]

 

 

 

As to my symptoms, I have a diagnosis of ADHD-PI, though the emerging concept of Sluggish Cognitive Tempo (SCT) is probably more applicable.  It is nothing recent--I've had lifelong issues with attention, focus, working memory, mental fatigue, sluggish processing, malaise, amotivation, asociality, etc.  It runs in my family, too, so seems as genuine a case of ADHD-PI/SCT as you could find.

 

I am now interested in the idea that I may have had life-long low or borderline low iron, maybe a genetic predisposition to such, though I'm not going to assume anything.  In some ways it would make sense: I've always had extra pale skin, fatigue easily, out of breath easily, etc.  I remember distinctly having a lot less stamina than my friends as a child.  In more recent years I have also noticed a tendency to bruise, and there are times when physical activity causes me to feel dizzy or generally unwell.  These things seem in line with some of the iron deficiency symptoms I've read about.  And, there are at least a couple of studies showing a strong association between ADHD and low iron status. 

 

When I began iron supplementation, the effects were quite rapid.  I feel more energetic, less fatigued, though time will tell on that.  Also, my coloring appears affected.  My hands for example seem to have a deeper and more reddish hue than normal. 

 

I'm skeptical, and am prepared to be disappointed.  It wouldn't be the first time.  However, it is an interesting turn of events, worth exploring.

 

Your comment about the potential effect of free radicals is interesting.  What are the signs that this would be the case?  Is it at least feasible that my life-long issues could be related, at least in part, to iron status?

 
 

 

 

This was more than half a year ago. With your supplementation, are many of those symptoms you described fading?

 

Also, the mania bit you mention is confusing. Often mania seems okay with me because my base state is so low. But then, afterwards, it's of course that divide between the mania state and sober state that brings regret.

Edited by Apprentice_Bob, 08 February 2016 - 03:55 PM.

[Kingsley]

 

 

This was more than half a year ago. With your supplementation, are many of those symptoms you described fading?

 

Also, the mania bit you mention is confusing. Often mania seems okay with me because my base state is so low. But then, afterwards, it's of course that divide between the mania state and sober state that brings regret.

 

 

 

That's funny, I forgot that I mentioned the iron issues earlier on this forum.  At the time I speculated that I may have had a life-long borderline iron deficiency, maybe due to an underlying state of inflammation.  I still consider this a possibility.  In hindsight, I think it more likely that my low-iron issues were brought on by heavy and prolonged supplementation with grape seed extract, a well known inhibitor of iron absorption, in an attempt to treat my cognitive issues.  I have since replaced grape seed extract with quercetin and longvida curcumin (though I may revisit it), both of which are also known to interfere with iron metabolism.  I recently started having low-iron symptoms again, and sure enough, I added some iron supplementation back into the mix and my energy has come roaring back.  I will continue to take quercetin and curcumin with perhaps an iron booster here and there. 

 

To answer your question: yes, with my current stack most of my symptoms described in my other posts have dwindled to an astonishing degree.  I'm going to keep an updated version of my stack in my profile for ease of reference.

 

As to your other point, by its definition hypomania is a pathological state that is neither healthy nor sustainable, and should not be the goal of anyone seeking long-term mental health.  Again, I'm no expert, but my understanding is that hypomania is characterized by compromised judgment, increased risky or impulsive behavior, unrealistic or grandiose ideas, unstable mood, etc.  To the extent that someone with our issues is simply bringing themselves up to baseline, or perhaps experiencing excitement or optimism about making some progress with their issues, then this wouldn't be hypomania.      
 

[ExtrinsicFalsehood]

Hey guys, I haven't posted in this thread in a while. I originally boosted it back up in the forum. 

 

Bob what's your take on my experience with the hangover is it anything like yours?

 

I'm only 20 so at this stage of my life I don't know how I'd really feel about starting to take some nootropics but who knows.

 

When I read your post Bob I could very much relate. I do sometimes feel like I reach almost controllable state of mania. To me i'm just happy and will express myself in any way I see fit, the social anxiety becomes unwinded and being more relaxed brings this inner state out.

 

Someone also stated the correlation between creativity and sleep deprivation.. To me the lower amount of sleep i'm running on the more creative my ideas. It's so strange, as well as getting more energy when I have less sleep. It's like backwards then most people. I don't get tired at night and end up sleeping at like 4-5 because I forget i'm supposed to sleep haha.

 

Anyways rambling hope it works out. I'll stay in tuned with the thread.

 

 

 

EDIT: Noots i'm currently looking at:     Sulbutamine, Tianeptine , Caffeine + L-Theanine ( Need to re-order) , also was looking into trying Mr.Happy Stack (lol)

Edited by ExtrinsicFalsehood, 09 February 2016 - 07:24 PM.

[Apprentice_Bob]

Quick note: sarcosine has affected me very positively today. My first dose.

[Helllllo]

Tried experementing with sarcosing dosing and 2gs is perfect. Definitely one of the best in my stack. As for the creativity while sleepless. Happens to me as well, almost as close as the holy grail itself, the hangover. I think it's from a surge of ampa signalling.

Got my glycine this
Morning and mixed it with my stack. I know most people have it at night. It made me feel strange + gave me brain fog at 5gms.

[oneshot]

Don't these papers suggest that supplementing with BH4 may be harmful to dopamine cells and thus we should avoid this route?  I'm sort of confused since at the same time BH4 is required for dopamine synthesis, yet at the same time is said to be harmful to dopamine cells.

 

http://www.ncbi.nlm....pubmed/10953058
http://www.ncbi.nlm....pubmed/12807434

 

Edited by oneshot, 10 February 2016 - 08:48 AM.

[Kingsley]

Don't these papers suggest that supplementing with BH4 may be harmful to dopamine cells and thus we should avoid this route?  I'm sort of confused since at the same time BH4 is required for dopamine synthesis, yet at the same time is said to be harmful to dopamine cells.

 

http://www.ncbi.nlm....pubmed/10953058
http://www.ncbi.nlm....pubmed/12807434

 

Thanks for studies.  My two cents (having only read the abstracts):

 

First, both studies appear to have been performed in vitro (i.e. in a test tube), so their relevance to BH4's effect in the actual environment of the body is questionable.  You can show plenty of harmful effects of a substance on cells in a test tube that aren't ultimately a concern since the body may have protective mechanisms preventing such, i.e. the anti-oxidant system.  Case in point: the toxic effect of BH4 discussed in these studies, which was based on oxidative stress, was prevented or at least highly inhibited by the addition of anti-oxidants.  This could suggest that it is advisable to take extra anti-oxidant supplements (NAC is specifically mentioned) if supplementing BH4.  Or, it could mean nothing; the anti-oxidant status of the average person may be more than enough to prevent the effects observed in vitro.  Further, we don't know if supplementing BH4 even results in enough of an increase of BH4 in the applicable brain areas to make a difference.  Finally, the purpose of these studies is to speculate concerning the mechanism of neuro-degeneration in Parkinson's disease, and they don't appear to come to any firm conclusions regarding such, much less BH4's effects in normal individuals. 

 

Personally, I wouldn't have any concerns about BH4 based on these two studies, beyond maybe making an effort to support anti-oxidant status.        

[Apprentice_Bob]

Just an update. I hope this lasts. I feel more confident and comfortable around others, using the sarcosine at 2 grams per day. This could be the placebo effect. One reason I think that my cognition may actually be increased is because of a few tests I like to run on myself. One is, can I understand the Coriolis effect working in the East/West direction. With sarcosine, I think I can. If hangtroped, I obviously can. But I am comfortable with this more stable enhancement. My ability to visualize seems strengthened... It's hard to tell. 

 

To those who understand the finer points of sarcosine's effect in the brain, what might it be correcting in my brain and does this mean that I have some schizoid-personality-disorder symptoms, or a similar brain structure to one who does? 

 

Also, can someone point me to our reasoning behind using N-A-G? 

 

Last, Kingsley, you said that you eventually grew a tolerance to sarcosine? How long did this take and is there any way that you've found to avoid building tolerance? How does prenenolone effect you? What part of your stack is most valuable? I haven't begun using methyldonors, should I expect to see even more enhancement when I do?

 

 

Edit: Also, I notice that my facial expressions are much stronger and... natural than they usually are. My eyebrows have become much more active. When hangtroped, I sometimes can express entire paragraphs with my eyebrows alone. I think that's part of the magic of hangover paradise time. There is so little thinking involved. Everything becomes intuitive. It's magical. And I personally become completely immersed in the now. So I think meditation might help us retrieve that state. 

Edited by Apprentice_Bob, 10 February 2016 - 08:13 PM.

[Kingsley]

Glad you are getting a positive response to sarcosine.  In response to your numbered paragraphs quoted below . . .

 

1) Sarcosine is a glycine transporter inhibitor, which means that it increases the level of glycine in the brain, resulting in more stimulation of the NMDA receptors.  Based on your description of your symptoms and your response to sarcosine, we can probably speculate with some confidence that your issues are related to NMDA hypo-function.  When we think NMDA hypo-function, we automatically think schizo-spectrum disorders since that cluster of disorders is so closely linked to NMDA hypo-function.  The most mild schizo-spectrum disorder that I am aware of is probably schizotypal personality disorder, and my pet theory is that those with our symptoms may have a subclinical version of it.  However, whatever label we put on our symptoms is probably not relevant; the point is to find what works for you.

 

2) I am the one who initially brought up NAG based on my success with it.  The reasoning is that NMDA hypo-function is linked to brain inflammation, and current research is pointing to a major role for anti-inflammatories in treating schizo-spectrum disorders.  The reason I focused on NAG in particular is because of the need for a powerful anti-inflammatory supplement that efficiency passes the blood-brain barrier, which NAG appears to be.   

 

3) No, I didn't necessarily develop a tolerance to sarcosine.  I would say that it became a less important part of my stack once I began focusing on anti-inflammatories, but I can't say that tolerance was an issue.  Whether sarcosine builds tolerance is an open question.  I find the effect of pregnenolone very similar to sarcosine, which isn't surprising since it too results in increased stimulation of the glycine site of the NMDA receptor.  As for what part of my stack is the most valuable, I think it is probably the anti-inflammatories.  If I am having a bad day cognitively, nothing increases my mental clarity like popping an ibuprofen, a NAG and maybe a quercetin.

 

As for methyl donors, I wouldn't expect too much.  Personally, I have the double mutation of the MTHFR gene affecting folate metabolism, and this is considered probably the most significant methylation defect.  So, I need methylfolate in a sense because I have trouble producing it on my own.  However, much of what you read about methylation on the internet is pseudo-science, and most people likely won't benefit in a huge way unless they have significant methylation defects.

 

4) Not surprising--blunted facial expression is one of the symptoms of NMDA hypo-function.  This is a good sign that you are successfully treating your issue. 

 

Keep us posted on your progress!

 

Just an update. I hope this lasts. I feel more confident and comfortable around others, using the sarcosine at 2 grams per day. This could be the placebo effect. One reason I think that my cognition may actually be increased is because of a few tests I like to run on myself. One is, can I understand the Coriolis effect working in the East/West direction. With sarcosine, I think I can. If hangtroped, I obviously can. But I am comfortable with this more stable enhancement. My ability to visualize seems strengthened... It's hard to tell. 

 

[1] To those who understand the finer points of sarcosine's effect in the brain, what might it be correcting in my brain and does this mean that I have some schizoid-personality-disorder symptoms, or a similar brain structure to one who does? 

 

[2] Also, can someone point me to our reasoning behind using N-A-G? 

 

[3] Last, Kingsley, you said that you eventually grew a tolerance to sarcosine? How long did this take and is there any way that you've found to avoid building tolerance? How does prenenolone effect you? What part of your stack is most valuable? I haven't begun using methyldonors, should I expect to see even more enhancement when I do?

 

 

[4] Edit: Also, I notice that my facial expressions are much stronger and... natural than they usually are. My eyebrows have become much more active. When hangtroped, I sometimes can express entire paragraphs with my eyebrows alone. I think that's part of the magic of hangover paradise time. There is so little thinking involved. Everything becomes intuitive. It's magical. And I personally become completely immersed in the now. So I think meditation might help us retrieve that state. 

 

[Apprentice_Bob]

 

Glad you are getting a positive response to sarcosine.  In response to your numbered paragraphs quoted below . . .

 

1) Sarcosine is a glycine transporter inhibitor, which means that it increases the level of glycine in the brain, resulting in more stimulation of the NMDA receptors.  Based on your description of your symptoms and your response to sarcosine, we can probably speculate with some confidence that your issues are related to NMDA hypo-function.  When we think NMDA hypo-function, we automatically think schizo-spectrum disorders since that cluster of disorders is so closely linked to NMDA hypo-function.  The most mild schizo-spectrum disorder that I am aware of is probably schizotypal personality disorder, and my pet theory is that those with our symptoms may have a subclinical version of it.  However, whatever label we put on our symptoms is probably not relevant; the point is to find what works for you.

 

2) I am the one who initially brought up NAG based on my success with it.  The reasoning is that NMDA hypo-function is linked to brain inflammation, and current research is pointing to a major role for anti-inflammatories in treating schizo-spectrum disorders.  The reason I focused on NAG in particular is because of the need for a powerful anti-inflammatory supplement that efficiency passes the blood-brain barrier, which NAG appears to be.   

 

3) No, I didn't necessarily develop a tolerance to sarcosine.  I would say that it became a less important part of my stack once I began focusing on anti-inflammatories, but I can't say that tolerance was an issue.  Whether sarcosine builds tolerance is an open question.  I find the effect of pregnenolone very similar to sarcosine, which isn't surprising since it too results in increased stimulation of the glycine site of the NMDA receptor.  As for what part of my stack is the most valuable, I think it is probably the anti-inflammatories.  If I am having a bad day cognitively, nothing increases my mental clarity like popping an ibuprofen, a NAG and maybe a quercetin.

 

As for methyl donors, I wouldn't expect too much.  Personally, I have the double mutation of the MTHFR gene affecting folate metabolism, and this is considered probably the most significant methylation defect.  So, I need methylfolate in a sense because I have trouble producing it on my own.  However, much of what you read about methylation on the internet is pseudo-science, and most people likely won't benefit in a huge way unless they have significant methylation defects.

 

4) Not surprising--blunted facial expression is one of the symptoms of NMDA hypo-function.  This is a good sign that you are successfully treating your issue. 

 

Keep us posted on your progress!

 

 

I know people like you, so informed and so clear in their language. Thanks for the quick response. 

 

1.) Putting a label on what's wrong with us does not solve our problem. It helps to know what might be going on, but there's no reason to attach a stigma to what's wrong.

 

Just one more question. My stack so far includes

 

Prenenolone

Sarcosine

Tianeptine (wiki says it affects the glutamate system, I'm only 2 days in so I cannot say yet)

NAG

Magnesium Bisglycinate 

 

Because of money constraints, I only want to add one or two more supplements. What do you think would help most?

 

Edit: Note: I find this very important. Since I've seemed to have found a stack that has dramatically improved my cognitive and emotional state, I feel regretful for all the times that I used the hangover to achieve the same thing. I would caution anyone out there who has yet to see improvement to stop using the hangover effect to bring the temporary enhancement. It's my feeling that doing so will just lower the baseline that you can potentially reach through safe means (like sarcosine et. al.). While I am extremely happy to have finally found a potential solution to my cognitive difficulties, I can't help but feel that the baseline I've now reached through sensible medication is lower than what it might have been, before the alcohol abuse. 

 

Is there anyone who knows how alcohol affects the brain? Will I one day recover from the binge drinking of the past year?

Edited by Apprentice_Bob, 11 February 2016 - 06:10 PM.

[Kingsley]

1) Yes of course you are right.  What I mean is that the clinical label (ADHD, schizotypal, depression, etc.) is a lot less important than focusing on the actual mechanism (NMDA hypofunction), though the two do go hand-in-hand.

 

2)  First, based on a quick search it appears that tianeptine is actually an NMDA antagonist, which is the opposite of what we're going for here.  See http://www.ncbi.nlm....pubmed/22358100.  According to this study the effects of tianeptine are inhibited by D-serine, which is a glycine-site agonist.  This suggests that tianeptine would actually directly oppose sarcosine and pregnenelone.  Though, to complicate things, tianeptine might have other positive mechanisms that outweigh this: who knows?  Nothing wrong with trying it but be alert to the possibility that it might interfere with the sarcosine and pregnenelone.

 

As to adding one more supplement, that is a tough question.  You probably have the NMDA agonism pretty well covered with the pregnenolone and sarcosine, so I would probably add another anti-inflammatory.  To be honest, I am finding that no anti-inflammatory supplement can quite compare to good old ibuprofen, which is affordable and probably safe even long-term at low doses.  Beyond that, Longvida brand curcumin is very good.  It is specially formulated to cross the blood-brain barrier and is much better than any other type of curcumin out there, though more expensive.  Mileage may vary.

 

*Edit:  I forgot to mention NAC (n-acetyl-cysteine)!  NAC is one of the most well-researched and respected supplements for the schizo-spectrum disorders. Won't go too much into it but it increases glutathione, which for various reasons is particularly beneficial to NMDA receptor function.  Plus, glutathione can be depleted by alcohol abuse.  So NAC is probably my number one recommendation at this point.

 

I can't really comment on the alcohol question though I wouldn't underestimate the brain's capacity to heal if you treat it right.  I'd be surprised if the effects were truly long-term but again, haven't researched it.

 

Anyway, I am thrilled that sarcosine is so effective for you.  Keep us updated!   

 

 

 

1.) Putting a label on what's wrong with us does not solve our problem. It helps to know what might be going on, but there's no reason to attach a stigma to what's wrong.

 

Just one more question. My stack so far includes

 

Prenenolone

Sarcosine

Tianeptine (wiki says it affects the glutamate system, I'm only 2 days in so I cannot say yet)

NAG

Magnesium Bisglycinate 

 

2) Because of money constraints, I only want to add one or two more supplements. What do you think would help most?

 

 

 

Edited by Kingsley, 11 February 2016 - 07:49 PM.

[Helllllo]

Big thanks for everyone's contributions. Small update. The anti-inflammatories don't seem to be doing anything but I ran out of sarcosine yesterday and I'm back to feeling like my old self. Sarcosine definitely saved me. Still waiting on my pregnenolone and re-order of sarcosine to see if they synergise. Psyched.

Tianeptine definitely made me a bit happier but worsened other forms of cognition. Kinda excacerbated my adhd-Pi.


Has anyone considered adding noopept to their stack? Works through the nmda/glycine route and definitely looks like it could aid people like us. The lady that synthesised it 20 years ago has taken it since then with three months worth of breaks every year so it seems relatively safe. Ordered some and will keep you guys posted.

Edited by Helllllo, 15 February 2016 - 06:30 AM.

[Kingsley]

Big thanks for everyone's contributions. Small update. The anti-inflammatories don't seem to be doing anything but I ran out of sarcosine yesterday and I'm back to feeling like my old self. Sarcosine definitely saved me. Still waiting on my pregnenolone and re-order of sarcosine to see if they synergise. Psyched.

Tianeptine definitely made me a bit happier but worsened other forms of cognition. Kinda excacerbated my adhd-Pi.


Has anyone considered adding noopept to their stack? Works through the nmda/glycine route and definitely looks like it could aid people like us. The lady that synthesised it 20 years ago has taken it since then with three months worth of breaks every year so it seems relatively safe. Ordered some and will keep you guys posted.

 

Interesting that you respond more to the sarcosine than the anti-inflammatories; tends to be the opposite for me though both help. 

 

Not surprised about your response to tianeptine.  My understanding is that it boosts dopamine but is an NMDA antagonist, which would explain why it boosted your mood yet hurt your cognition.

 

Never tried noopept personally.  I've tried piracetam, aniracetam, and fascoracetam, with varying levels of success and no consistency. 
 

[Apprentice_Bob]

 

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!!

I took me two years of medical school as well as a lot of thinking and reading on my own to figure out what my own problem really was. And now than I've done that and learned how to treat it, I can tell you that it was so, so worth it. I changed my life for the better, and I would be glad if I could help other people with similar problems to do the same.

I'm curious about how you see your problem subjectively - is it lack of motivation, depression, fatigue, or how would you describe them?

23and me will tell you some basic information about disease risks, but if you want to find out about you're genes relating to neurotransmission I'm afraid you'll have to download the raw data and analyze it yourself. The easiest way to do this is to use Promethease (https://promethease....ondemandlicense) which is an easy analytic tool, GeneticGenie Methylation Analysis (https://geneticgenie...ation-analysis/) which will give some info about genes relating to methylation, and SNPedia (http://www.snpedia.c...dex.php/SNPedia) which is a wiki-site that explains various genes. The easies ways to see your polymorphisms (gene variations) is to download your raw data from 23andme and upload it to Promethease, and then download the files you get from them. In the "report_ui2.html" file you can then search for certain SNPs (point mutations), that have names like Rs123456 and so on below. For the genes with many important SNPs you can just search for the gene name in Promethease and it will tell you if it finds something unusual.

These are the genes and SNPs I believe are the most important to look at when it comes to dopamine:

MTHFR - A gene involved in producing the active form of folate, which is needed to make several neurotransmitters.
Rs1801133 aka C677T. C is good to have, T is bad.
Rs1801131 aka A1298C. A is good, T is bad.

DHFR - Another gene involved in folate metabolism AND BH4 recycling. Not quite as important but still relevant. It's not know which SNPs are important here. Personally I'm homozygous Rs1650697 which is somewhat uncommon. C is good to have here, and T is bad.

GCH1 - Involved directly in BH4 synthesis. Many SNPs that are important, see http://snpedia.com/index.php/GCH1.

PCBD1 - Involved in BH4 synthesis. Many SNPs, see http://snpedia.com/index.php/PCBD1.

PTS - Involved in BH4 synthesis. Many SNPs, see http://snpedia.com/index.php/PTS.

QDPR (aka DHPR) - Involved in BH4 synthesis. This enzymes uses NADH, which I believe is the reason that NADH can raise BH4. Many SNPs, see http://snpedia.com/index.php/QDPR.

SPR - Involved in BH4 synthesis. Many SNPs, see http://snpedia.com/index.php/SPR.

TH (tyrosine hydroxylase) - Converts tyrosine to L-DOPA, which then is used to make dopamine. TH is an iron-containing enzyme, which is the reason that iron deficiency can lead to lower dopamine levels. Many importants SNPs, see http://snpedia.com/index.php/TH

DDC (aka AADC, dopa decarboxylase) - Turns L-DOPA into dopamine, and 5-HTP into serotonin. Several important SNPs, see http://www.snpedia.com/index.php/DDC.

COMT - Breaks down dopamine and other neurotransmitters.
Rs4680 aka the warrior/worrier SNP. The Met version (A) will give you lower COMT activity and therefore more dopamine. This will lead to higher pleasure response and higher extraversion, but also lower threshold for stress. The Val version (G) will give you higher COMT activity and therefore less dopamine. This will lead to lower pleasure response, lower extraversion but also higher threshold for stress. Val will make you calm and collected while Met will make you motivated and outgoing.

MAO - Breaks down dopamine and several other neurotransmitters.
Rs6323 - G will lead to higher enzyme activity and lower dopamine, and T to lower activity and higher dopamine.

DAT (aka SLC6A3, dopamine transporter) - removes dopamine from the synapse so it can't bind its receptors.
Rs27072 is onvolved in alcohol withdrawal as well as ADHD. C increases risk for ADHD and alcohol withdrawal, T lowers it.

DRD1 (dopamine receptor D1) - Involved in neuronal development and various behavioural responses. Several semi-important SNPs, see http://www.snpedia.com/index.php/DRD1.

DRD2 (dopamine receptor D2) - Involved in social functioning, extraversion and social status. Low D2 binding correlate with social phobia.
Rs1800497 aka Taq1a polymorphism. C is good to have, T is bad.

DRD3 (dopamine receptor D3) - Low activation is involved in cognitive problems and depression. See http://www.snpedia.com/index.php/DRD3.

DRD4 (dopamine receptor D4) - Links to lots of psychiatric conditions, including ADHD.
Rs1800955 is linked to personality. T is the normal variant, and C increases novelty seeking.

DRD5 (dopamine receptor D5)http://en.wikipedia.org/wiki/DRD5 - Not sure if it's involved in anything unique. See http://en.wikipedia.org/wiki/DRD5.

If you're main focus is how low dopamine connects to social phobia or lack of social drive/motivation, I believe that MTHFR, DHFR, MAO, COMT and DRD2 are the most important. And yeah - I personally have bad versions of them all.

If you wanna do more reading I suggest this article. Also if you want pictures explaining the reactions connecting folate metabolism with BH4 and dopamine, you can check this out.

 

 

 

Could you please tell us where you found BH4 or tetrahydrobiopterin ? PLEASE?

[Helllllo]

I posted a link of someone selling it earlier on the page. Scroll up. Made a thread on reddit that found a bit of traction. Will compile the convincing responses soon. https://www.reddit.c...hat_have_adhdi/

[oneshot]

I have some extra BH4 capsules from Ecological Formulas if anyone is interested.  I'm selling it for a little below retail at $1/mg plus the cost of shipping with ice packs.  PM me for more details.

[Kingsley]

I posted a link of someone selling it earlier on the page. Scroll up. Made a thread on reddit that found a bit of traction. Will compile the convincing responses soon. https://www.reddit.c...hat_have_adhdi/

 

Nice reddit thread.  So many responses, it's hard to tell if anyone has contributed anything of value.  Let us know if you learn anything interesting.

 

I still believe the mechanism underlying the hangover effect is the acute NMDA-receptor upregulation that accompanies alcohol washout.  See study http://www.ncbi.nlm..../books/NBK5284/: discussing "rebound potentiation of NMDA Receptor Activity"; "The activity of the [NMDA] channel is greatly potentiated upon ethanol washout." 

 

By the way, I've been in touch with the guy you referenced who was selling BH4.  He had a couple Ecological Formulas bottles left over, but he has now placed an order with a laboratory for a batch of bulk BH4 and plans to sell it.  I will let people know when he makes it available.

[.Moose.]

I'm not going to recommend that anyone take l-glutamic acid, simply because there is so much doubt out there as to its safety.  It is well known that glutamate is neurotoxic under certain circumstances, though it is also absolutely key to cognitive function and is one of the primary neurotransmitters.  Personally, I accept the risk in light of how effective it is for me and because there appears to be no evidence that it is harmful at reasonable doses.  The closely related substance MSG has been extensively studied, and a panel of experts recently concluded that doses up to 16,000mg/kg are safe, which is an astronomical number.  I have been dosing between 1,000 mg and 2,000 mg per day.  I am sure that glutamic acid would be exactly the wrong supplement for some, particularly those suffering from more of an over-active mind, but for me it feels right.   

 

Kingsley, a couple of us are looking at the moment into glutamic acid, but I was under the assumption that it would be to counter glutamate neurotoxicity through facilitating GABA production. You mentioned that it might be bad for an over-active mind - you think that it would be boosting glutamate instead of GABA?

[medievil]

Dealing with exact issue as OP, but with the addition of social anxiety and delusional thinking. Tried A-Z, B complex, B6, P5P, zinc, Mfolate, MB12 etc. etc. etc. without any effect. I'm not a drinker. If the NMDA upregulation by alcohol theory is true, then it could explain why the people I grew up with (weekend alcoholics) are so far ahead of life than me (in terms of success).

 

There are rare occasions when I achieve a dopa high with the same diet I'm on for months now. It might be a sleep quality issue. With the high I'm much more talkative; infact, overly talkative. Anxiety lessens and my thinking becomes sharp and instant. It also makes me want to be spiritual.

Going to try Phenibut and report back. It's supposed to have the exact effects of alcohol without the nasty crap. Should lower acetylcholine and boost dopamine in theory...

Why would nmda upregulation cause succes? what you achieve in life is largely modulated by the pfc, impulsivity modulated by dopamine and GABAB, for example baclofen shifts decission making towards the positive angle and so forth.

 

Piracetam dramatically upregulates nmda, even causing ketamine to be inefective,

[medievil]

 

 

2)  First, based on a quick search it appears that tianeptine is actually an NMDA antagonist, which is the opposite of what we're going for here.  Seehttp://www.ncbi.nlm....pubmed/22358100.  According to this study the effects of tianeptine are inhibited by D-serine, which is a glycine-site agonist.  This suggests that tianeptine would actually directly oppose sarcosine and pregnenelone.  

Glycine antagonism is cognitively enhancing, also it wouldnt counteract pref as it does a ton of things and is mostly involved with the glutaminergic excitacitory mechanism, not the inhibitory neurotransmitter glycine.

 

Take in mind that everyone is differened, there wont be a certain direction to go into achieving "what we are trying to do here" due to individual neurochemistry.

[medievil]

 

 

When we think NMDA hypo-function, we automatically think schizo-spectrum disorders since that cluster of disorders is so closely linked to NMDA hypo-function.  

In many cases, ppl suffering from adhd, ocd, depression, social anxiety, the avoidant personality disorder kind relate to ocd and simular treatment for the negative symptions, eg amphetamine.

 

Also in shizo there is overmethylation, aps and hdac inhibitors counteract this.

[medievil]

i ment they relate to shizophrenia and respond to simular treatments, adhd and avpd are mini shizophrenia conditions in many ways responding to amphetamine like the negatives in shizo, also stimulants when i used to suffer from extreme ocd years ago completely removed my ocd leaving my not understand my ocd and thinking at all, unlike things that improve it which leave you still able to relate.

[Kingsley]

 

I'm not going to recommend that anyone take l-glutamic acid, simply because there is so much doubt out there as to its safety.  It is well known that glutamate is neurotoxic under certain circumstances, though it is also absolutely key to cognitive function and is one of the primary neurotransmitters.  Personally, I accept the risk in light of how effective it is for me and because there appears to be no evidence that it is harmful at reasonable doses.  The closely related substance MSG has been extensively studied, and a panel of experts recently concluded that doses up to 16,000mg/kg are safe, which is an astronomical number.  I have been dosing between 1,000 mg and 2,000 mg per day.  I am sure that glutamic acid would be exactly the wrong supplement for some, particularly those suffering from more of an over-active mind, but for me it feels right.   

 

Kingsley, a couple of us are looking at the moment into glutamic acid, but I was under the assumption that it would be to counter glutamate neurotoxicity through facilitating GABA production. You mentioned that it might be bad for an over-active mind - you think that it would be boosting glutamate instead of GABA?

 

 

My understanding is that l-glutamic acid boosts both glutamate and GABA, since glutamate is transformed into GABA.  When I first tried it I found it both mentally stimulating and calming--a very smooth stimulation totally unlike dopamine-boosters.  However, I'm sad to say that tolerance seems to be a big issue.
 

[Kingsley]

 

 

 

2)  First, based on a quick search it appears that tianeptine is actually an NMDA antagonist, which is the opposite of what we're going for here.  Seehttp://www.ncbi.nlm....pubmed/22358100.  According to this study the effects of tianeptine are inhibited by D-serine, which is a glycine-site agonist.  This suggests that tianeptine would actually directly oppose sarcosine and pregnenelone.  

Glycine antagonism is cognitively enhancing, also it wouldnt counteract pref as it does a ton of things and is mostly involved with the glutaminergic excitacitory mechanism, not the inhibitory neurotransmitter glycine.

 

Take in mind that everyone is differened, there wont be a certain direction to go into achieving "what we are trying to do here" due to individual neurochemistry.

 

 

Glycine has a dual role: it is inhibitory in the central nervous system (thus its use as a sleep aid) but excitatory at the NMDA receptor since it is a co-agonist along with glutamate.  Without glycine, glutamate cannot activate the NMDA receptor. 

 

Agreed that everyone is different, and NMDA antagonism might be just what some people need, though this forum has been focusing on NMDA agonism since many of us suspect that we are suffering from NMDA hypo-function.  This has been validated in part by the success some of us are experiencing with sarcosine.  However, I say, when in doubt, try it out! 
 

[medievil]

I dont think the forum focusses on agonism looking at all the memantine threads man.

[Kingsley]

I dont think the forum focusses on agonism looking at all the memantine threads man.

 

I mean this thread, not the forum as a whole.

[Helllllo]

Have you guys ever considered that we have some rare polymorphism dysregulating a calcium channels and hence it makes sense why gabapentin helps us considerably?

[Helllllo]

CACNA1C Gene disrupts l type calcium currents. Ethanol regulates this.
CACNA1C Gene disrupts l type calcium currents. Ethanol regulates this.

[medievil]

Have you guys ever considered that we have some rare polymorphism dysregulating a calcium channels and hence it makes sense why gabapentin helps us considerably?

Calcium channel thread, therapeutic potential and implications and disorders with roles in cognition and more thread coming up, thx for mentioning this, good idea for a research project.

 

 

Gabapentin isnt a calcium channel agonist it acts on that subtype thing, which may be related but everything in the brain is related, so therapeutic implications of that warrents its own thread, phenibut acts on it too.