450 replies to this topic

[Reiher Allendi]

English isn't my main language - so it make difficult to explain what I have learned in theory and practice. The guy in the first post seems to me to have symptoms of anhedonia (I would bet he have some kind of dysthymia). I'm really tired because of a unknown disease that I had in the last year, but if anyone want some information useful about any mood or anxiety disorder I can try to help. I learned a bit in the last 10 years, but I wont write before I'm sure that it's going to be read by someone that need some kind of help right now.

[Reiher Allendi]

Hey guys. This is my first post. I'v been trying to find information about this for a while and have only just found this thread. Honestly, I feel like crying. The fact that there are other people with similar issues is beyond comforting.

I'm new too nootropics and have been trying to take supplements to combat this but to no avail. So far Iv tried ashwaganda, fish oil, theanine, magnesium and b complex. I'v noticed close to no drastic changes in my moods from these supplements.

A little background, I'm 24 and have noticed from a young age that I really enjoy a hangover. The reason being is that I'm slightly neurotic, ruminate a lot, am extremely stiff and boring, struggle to smile or laugh, have depression and anhedonia. During a hangover, literally all these symptoms are gone. I'm in a carefree state, extremely creative and wordy. I work efficiently and more
Logically. I feel connected to people and can relate to close to anyone. I feel like I actually have a personality and it comes out when I'm hungover.

After a day or two, Its back to same old me. Anxious, tense and over thinking and being depressed over things I shouldn't be. It's kind of ruining my life to be honest and I'd love some advice. I feel like I have so much potential and that my life doesn't have to be constant hell.

Chadwick, you're a godsend. Anymore advice on what I should do or take?

 

Mood and anxiety anxiety disorders usually bring (among a lot shitty symptoms) some kind of cognitive dysfunction (usually too weak to be noted).

Analyzing your words I would assume that's your case. So I would bet that the best way to improve your cognitive function is first to treat your depression/anhedonia.

I usually approach depression from neuroscience point of view. Using drugs prescribed by my doc (well... usually I suggest my medication) and some dietary supplement/herbal/OTC (over-the-counter) drugs.

I can be more specific about it in my next post.

[Kingsley]

Hey guys. This is my first post. I'v been trying to find information about this for a while and have only just found this thread. Honestly, I feel like crying. The fact that there are other people with similar issues is beyond comforting.

I'm new too nootropics and have been trying to take supplements to combat this but to no avail. So far Iv tried ashwaganda, fish oil, theanine, magnesium and b complex. I'v noticed close to no drastic changes in my moods from these supplements.

A little background, I'm 24 and have noticed from a young age that I really enjoy a hangover. The reason being is that I'm slightly neurotic, ruminate a lot, am extremely stiff and boring, struggle to smile or laugh, have depression and anhedonia. During a hangover, literally all these symptoms are gone. I'm in a carefree state, extremely creative and wordy. I work efficiently and more
Logically. I feel connected to people and can relate to close to anyone. I feel like I actually have a personality and it comes out when I'm hungover.

After a day or two, Its back to same old me. Anxious, tense and over thinking and being depressed over things I shouldn't be. It's kind of ruining my life to be honest and I'd love some advice. I feel like I have so much potential and that my life doesn't have to be constant hell.

Chadwick, you're a godsend. Anymore advice on what I should do or take?

 

I will chime in here, as I relate to your symptoms in a lot of ways.  You say you have tried b-vitamin supplements without much effect, but I'd be curious to hear how you respond to Chadwick's regimen of relatively low dose methylfolate and moderate hydroxo-b12, which could be effective if any of your issues relate to faulty b-vitamin metabolism / methylation mutations. 

 

I'm paraphrasing, but Chadwick's situation is essentially a success story about treating issues with mood, energy, and social drive with supplements targeting the methylation cycle, i.e. methylfolate and hydroxocobalamin, with remarkably long-term success.  I think that one of Chadwick's key insights is the importance of not overdoing the methyl donors. That is, he takes low dose methylfolate and zero methyl b12, after having observed that too much of either causes their benefits to diminish. 

 

This runs directly counter to so much of what you read on the internet about methylation support, which often recommends fanatic levels of methylfolate and methyl B12.  There are forums where people suffering from various health and cognitive issues are convinced that huge doses of methyl folate and methyl b12 are the solution to their problems, yet you hardly ever hear of anyone having long-term success.  It is often the same story: exciting results in the beginning that are eventually lost.  And somehow they always think the solution is MOAR METHYLFOLATE/METHYL B12. 

 

This was exactly the case for me, but like Chadwick, I am now getting much more consistent results by vastly reducing my methyl donor intake.  Despite having the homozygous C677T mutation greatly reducing my ability to metabolize folate into methylfolate, I find that significant doses of methylfolate just end up putting me into a stupor and making me feel worse.  The best approach for me so far has been high-dose non-methyl b12 (cyano or hydroxo), low dose methylfolate or moderate folic acid, along with a balance of the other b vitamins and other vitamins and minerals.

 

Chadwick's position is, I believe, that the problem with high dose methyl donors is that they route folate away from BH4 production at the expense of dopamine production and/or they overdrive the COMT enzyme, causing the breakdown of too much dopamine.  Another possibility, which I suspect is the case for me and which I think Chadwick talks about, is that too much methylfolate ends up using up the available b12 causing the so-called "methyl trap," paradoxically causing folate to be expelled from cells and mimicking a deficiency or at very least losing the benefits.  My understanding is that b12 from most supplements is only absorbed in very small amounts, compared to folate which is much better absorbed, so it would not be surprising if b12 supplementation simply can't keep up with the methylfolate supplements for some people.  It's a bit confusing because methyl donors are apparently involved both in production and breakdown of neurotransmitters. 

 

In sum, I don't have much to add except to suggest that, if you do try a methyl donor regimen, keep in mind that less is more and don't over-supplement.  And please let us know your results.

 

 

 

 

Edited by Kingsley, 22 July 2015 - 05:28 PM.

[Apprentice_Bob]

Would one of the posters who has found success through playing with methyl donors and B vitamins post explicitly the supplements they have turned to?

 

I was doing really well using a B-complex and fish-oil, better than my whole use history of exotic and promising nootropics, and then went on a bender for three days. Since then, I've had brain fog. I've switched over to an Activated B complex, by Swanson, and I cannot say that I feel at the level that I felt I was at before the bender.

 

I'm also curious to see whether those who have experienced the hangtropic effect also have positive nootropic experience with phenibut.

 

 

[Kingsley]

Would one of the posters who has found success through playing with methyl donors and B vitamins post explicitly the supplements they have turned to?

 

I was doing really well using a B-complex and fish-oil, better than my whole use history of exotic and promising nootropics, and then went on a bender for three days. Since then, I've had brain fog. I've switched over to an Activated B complex, by Swanson, and I cannot say that I feel at the level that I felt I was at before the bender.

 

I'm also curious to see whether those who have experienced the hangtropic effect also have positive nootropic experience with phenibut.

 

My take on this is constantly evolving, but I am in a very good spot right now in terms of managing my cognitive complaints.  Currently I am doing well taking one or two 800 mcg Solgar methylfolate tablets per day, along with a lot of b-12 as 2mg cyanocobalamin and 2mg methyl-b12. 

 

In previous posts I speculated on the need to keep methylfolate/methylb12 doses low, and described how too much of either makes me feel stupid and sick. This appears to mirror Chadwick's experience.  It never made much logical sense to me since, in my case, I am homozygous for the C677T MTHFR mutation which indicates a critical need for methylfolate and/or methyl-b12.   

 

I had read a lot of speculation and anecdotal accounts on other forums that methyl donors can increase the need for potassium, a shortage of which can cause issues with fatigue, mood, etc.  After having a bit of success with adding a few potassium tabs and a banana here and there, I decided to go all out.  After all, the daily recommended dose of potassium for adults is about 3.5 grams, and many of us fall woefully short of this.  So, I began purchasing V-8 Low Sodium, which contains 900 mg of potassium per serving, and drinking probably 3-5 servings per day with some 99mg potassium tabs thrown into the mix.  BINGO.  I no longer have ANY mal-effects from methylfolate or methyl-b12, no matter how much I take.  Not to mention I am feeling healthier all around and I'm pretty sure my blood pressure has come down.  Bottom line: if you are among those who react negatively to methyl donors, try upping your potassium intake significantly.

 

I have had another breakthrough as well by adding calcium supplements.  In another post on this or another thread, I commented that I was having great success from magnesium.  I was actually taking calcium/magnesium pills and just assumed the effect was from the magnesium.  However, after switching to just straight magnesium for a while I found that the benefit was subsiding.  I just recently added calcium back in and the cognitive gains are staggering.  This makes some sense considering that I speculate that my issues are related to the glutamate-receptors and calcium-signaling, though why such a dramatic effect I am not sure.  Don't know if I was deficient or what was going on.

 

For the first time in a long time I feel like a fully functioning human being, and am praying that these gains hold.  My current regimen looks like this:

 

Vyvanse:  40mg first thing in the morning. Helps get my ass out of bed and benefits mood and motivation.  Less so cognition.  I am hoping to ultimately get off of it.

Methylfolate: 1 or 2 800 mcg Solgar tablets per day.  I often break tablets in twos or fours and spread my dosage throughout the day.

Cyanocobalamin: 2mg per day spread out.  For some reason I seem to benefit from cyanocobalamin no matter how much methyl-b12 I take.  I suspect that you need some non-methyl b12 (either cyano or hydroxo) for the methylfolate to really do its job, since methyl-b12 already has its methyl group and doesn't need methylfolate)

Methyl-b12: 2 1mg Jarrow sublingual tabs per day.

Potassium: Hard to get enough through diet, and potassium pills are limited by law to 99mg since potassium can be dangerous to some subset of the population with certain conditions.  So, I chug V-8 Low Sodium like there's no tomorrow (900mg potassium per serving).

Calcium.  1 gram+ throughout the day.  Should be balanced with magnesium at 2:1 ratio.

NAC:Jarrow 500mg 2-3 times per day

Sarcosine: about 4 grams per day.  (I have noticed acute benefits from it though not sure if such benefit is consistent.  May try going without it).

Tyrosine & 5-htp: I take as needed for a boost to mood and cognition.  I try to maintain a 10 to 1 balance as is typically recommended.  Some days I take none, some days up to 3000mg tyrosine/300mg 5-htp.  Less needed with my recent gains from methyls, potassium and calcium.

Other key vitamins/minerals: all other b-vitamins, zinc, magnesium, iodine, etc.  A good multivitamin will do.

 

So, that is where I am at right now, subject to further tweaking.  Would be curious to hear if anyone else makes any consistent gains.

 

 

Edited by Kingsley, 29 July 2015 - 01:33 PM.

[.Moose.]

Currently I am doing well taking one or two 800 mcg Solgar methylfolate tablets per day, along with a lot of b-12 as 2mg cyanocobalamin and 2mg methyl-b12. 

 

Kingsley, do you notice the effects of a single dose? I've tried a couple of methyl donors and a comprehensive methyl factor and see no effects - negative or positive - at all. Being only hetero c677t, i'm sure i don't need too much. I don't understand why others do so well on it, even though I share the original symptons Chadwick listed as well as the reactional to alcohol.

 

Sorry for the self-indulgant post 

 

PS interesting about the calcium supp'ing. Again, do you notice fairly immediate benefits from that?

Edited by MH Moose, 03 August 2015 - 02:07 PM.

[Kingsley]

Sorry for the self-indulgant post 

 

 

Hah, I always feel that my posts are self-indulgent.  Feels like I'm going on and on and on about myself . . .  But what's a forum like this for if not to compare notes and experiences.

 

I do notice acute effects from single doses of methylfolate and methyl-b12, even cyano-b12.  However, the acute effects are becoming less and less aparent over time while the overall benefits remain.  Your experience is probably the most common.  I suspect that you have to have some level of deficiency to feel a strong acute effect from a vitamin or mineral.  Though the methyls are particularly strong for vitamin supplements and many seem to feel them. 

 

Same with calcium--strong acute effects at first but less so over time.  I am almost certain I had a least a border-line calcium deficiency.  I have had almost no dairy in my diet for a while, and was experiencing some muscle spasms in my hands and calves that resolved upon adding calcium, along with the strong cognitive benefit I described in a previous post, which, knock-on-wood, appears to be holding.  

 

Again, if your levels of b-vitamins or calcium are already solid, I wouldn't expect any kind of acute reaction, and I have no doubt that my experience is idiosynchratic.  The idea of feeling each dose of calcium as if it's a nootropic seems so silly, and yet it's what I have experienced.  The next step for me is to figure out why I seem to be prone to vitamin and mineral deficiencies.  I suspect poor absorption potentially due to digestive issues/inflammation. 

[.Moose.]

Thanks, that's helpful. Yeah, unfortunately this all seems about trial and error - finding what helps and what doesn't and theorising as to why. Unfortunately nothing has seemed to work for me so far, but the experience you guys have is the next best thing to go on. Very interesting about calcium, I'll have a look into that.

[Chadwick]

I had read a lot of speculation and anecdotal accounts on other forums that methyl donors can increase the need for potassium, a shortage of which can cause issues with fatigue, mood, etc.  After having a bit of success with adding a few potassium tabs and a banana here and there, I decided to go all out.  After all, the daily recommended dose of potassium for adults is about 3.5 grams, and many of us fall woefully short of this.  So, I began purchasing V-8 Low Sodium, which contains 900 mg of potassium per serving, and drinking probably 3-5 servings per day with some 99mg potassium tabs thrown into the mix.  BINGO.  I no longer have ANY mal-effects from methylfolate or methyl-b12, no matter how much I take.  Not to mention I am feeling healthier all around and I'm pretty sure my blood pressure has come down.  Bottom line: if you are among those who react negatively to methyl donors, try upping your potassium intake significantly.

 

I've been away for the last seven weeks so I haven't replied to any posts in this thread or PMs, sorry for this. Regarding potassium I agree that it might be a problem for people using high doses of *methyl B12* in combination with methylfolate. People doing this should pay attention to symptoms such as cramps or muscle spasms. This should not be aproblem if you use hydroxocobalamin. The methylation experts over at http://forums.phoenixrising.me/ knows much more about this.

 

The reason why American potassium supplements are limited to 99 mg is that to much potassium in the same place in the GI tract can cause local damage to the mucosa. This is avoided by taking several small pills (< 100 mg) instead of a single larger one.

[Duchykins]

OTC potassium caps are limited because of them getting stuck in too many people's throats, and from some people really hurting themselves by self-diagnosing and overdoing the potassium, which can be very dangerous.

 

Prescription potassium still comes in the pills (or liquids) and are typically hundreds of milligrams of potassium (usually as KCl).

 

But I also had some issues with the methyl and had mysterious and scary random potassium crashes over a period of a few months last year (a few of which required an ambulance trip to the ER because of arrhythmia) until I started deliberately adding hundreds of mg of K to my daily routine, both as food (fresh spinach, baby carrots, soymilk) and Albion potassium pills.  Everything's just fine now.  Docs never figured out why that happened, the only thing that came up was hypokalemia, other blood tests for a bunch of shit came back normal, chest x-ray and MRI, and 2 week heart monitor all came back showing normal healthy heart.  I've never had any trouble with electrolytes before.

 

After some reading, it looks like it could be my starting methylcobalamin (5 mg sublingual) and Quatrefolic (400 mcg in a B complex).  I'm not about to drop these though, because I've done so much better aside from the K issue.

Edited by Duchykins, 04 August 2015 - 04:01 PM.

[NeuroNootropic]

I started taking methylfolate back in June and at that time I was taking Dr's Best Quatrefolic which has 400 mcg of methylfolate per capsule. Just taking 2 capsules would increase my energy, focus, motivation, and mood to a great extent, but I ran out and had to order more. I ordered Life Extension's methylfolate which also has Quatrefolic, i.e. methylfolate in the glucosamine salt, but life extension's is cheaper and has 1000 mcg of methylfolate per tablet. After it arrived I started taking it and while I noticed some benefits it felt like it wasn't working as well as it did when I was taking the Dr's best brand. Specifically, I still got the benefits that Dr's Best gave me but they were a lot weaker. No longer could I sleep 8 hours and wake up refreshed, my focus wasn't as good, and my motivation only increased a tiny bit.

 

Why would this happen?

 

I noticed that on the label Dr's Best lists (6S)-5-MethylTetraHydroFolate (MTHF) (elemental, as 800 mcg (6S)-5-methyltetrahydrofolic acid, glucosamine salt (vegetarian source)) whereas Life Extension's does not list the elemental dosage: Folate [as (6S)-5-Methyltetrahydrofolic acid, glucosamine salt]. Could Life Extension's methylfolate only be providing 500 mcg of elemental folate and not 1000 mcg?

 

On a side note, I take Life Extension's two-per-day capsule multivitamin which has methylcobalamin and coenzymated b-complex. Here's the thing, normally I only take 1 capsule every other day, but if I'm taking methylfolate and I skip taking my multivitamin, on the 3rd day I get a very noticeable mood and motivation boost. This does not happen if I don't take methylfolate. What does this mean? I'm guessing that I don't need methylb12 and I'm only benefiting from the increased BH4 production and not from methylation.

 

TMG at 1000 mg used to boost my focus and learning ability, but gave me brain fog and short-term memory problems. It also caused weight gain.

 

What do all these things mean? Am I an undermethylator or overmethylator?

[Kingsley]

NeuroNootropic:

 

Interestingly, I tried Life Extension brand methylfolate a while back, and I distinctly recall feeling that it was less effective than other brands that I had tried.  Why this would be, I am not sure.  Poor quality perhaps?  I don't think the amount of "elemental" folate would be any different between two equivalent doses of quatrefolic.

 

The other experiences you describe appear consistent with my own experiences.  I find that modest doses of methylfolate and methylcobalamin can be beneficial in terms of mood and cognition, but after a certain threshold my mood and energy take a nose dive.  I tend to think it is due to excess SAM-E overdriving the COMT enzyme and breaking down too much dopamine and norepinephrine in the prefrontal cortex, though I can't say for sure.  It appears that moderation is key for benefitting from methyl donors, at least for some people. 

 

I think personal experimentation is key, and I question how constructive it is to get too hung up on labels like "undermethylator" vs. "overmethylator" that you see bandied around by the so-called methylation authorities (like Amy Yasko) out there on the internet.    

[NeuroNootropic]

Yeah, I'm not sure either. I even contacted Life Extension and they assured me that the 1000 mcg in each tablet is elemental folate. That aside, I've noticed Life Extension's methylfolate gives me a lot of side effects, but with the Dr's Best I barely had any. In fact, with Dr's Best the only side effect I can remember happening is overstimulation. With Life Extensions's brand I get:

• Irritability
• Fatigue and poor sleep quality (how?)
• Brain fog
• Anxiety
• Dizziness
• Headache
• Poor focus

Maybe the dosage is too high? I was taking 800 mcg with Dr's Best and didn't have these side effects so could a 200 mcg increase really make a huge difference?

[Kingsley]

This does not happen if I don't take methylfolate. What does this mean? I'm guessing that I don't need methylb12 and I'm only benefiting from the increased BH4 production and not from methylation.

 

TMG at 1000 mg used to boost my focus and learning ability, but gave me brain fog and short-term memory problems. It also caused weight gain.

 

 

Looking a bit more closely at your post, it also appears that you are suggesting that you get a benefit from methylfolate but not methylcobalamin, and speculate that it could be due to BH4 production.  It was always my understanding that huge doses of methylfolate were needed to produce a significant effect on BH4 production, thus the reason why Deplin contains such a ridiculously large dose of methylfolate.  However, this is an interesting idea, and I'd be happy for some one with more knowledge than me to chime in and explain the relationship between methylfolate and BH4.  I intend to take a closer look at the studies when I get a chance.

 

As for me, I get similar effects from methylfolate, methylcobalamin, TMG, and SAM-E: great benefit up to a point, but terrible brain fog if I overdo it.

[Kingsley]

Yeah, I'm not sure either. I even contacted Life Extension and they assured me that the 1000 mcg in each tablet is elemental folate. That aside, I've noticed Life Extension's methylfolate gives me a lot of side effects, but with the Dr's Best I barely had any. In fact, with Dr's Best the only side effect I can remember happening is overstimulation. With Life Extensions's brand I get:

• Irritability
• Fatigue and poor sleep quality (how?)
• Brain fog
• Anxiety
• Dizziness
• Headache
• Poor focus

Maybe the dosage is too high? I was taking 800 mcg with Dr's Best and didn't have these side effects so could a 200 mcg increase really make a huge difference?

 

Interesting.  The side effects you describe mirror the effects I get from taking too much methylfolate.  But it would seem unlikely for 200mcg to make such a difference.  Maybe it's due to a cumulative effect over time.  It would be interesting to see if you now experience bad effects from Dr.'s Best brand.

 

You could try opening up the capsule and dumping a portion of the powder into your mouth to reduce the dosage.  I do this frequently.

 

By the way, you may want to try adding more potassium to your diet.  There is a lot of anecdotal evidence out there, consistent with my own experiences, that methylation can increase the body's need for potassium and result in a drop in potassium levels.  This can cause dizziness, brain fog, etc., and I personally benefitted greatly from upping my potassium.

[Chris_T_Malta]

 

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.

 

 

Hi Chadwick,

 

I am a 35 year old male who feels lack of motivation (low dopamine?) despite being very motivated in the past.

 

I have searched through my Promethease report for these SNPs you mentioned and found only 3:

 

rs1801131(C;C) - MTHFR (good).

 

rs27072(C;C) - DAT - remove dopamine the sybaose so it can't bind its receptors

rs1800497(C;T) - DRD2 - social functioning, extraversion and social status

 

What kind of supplementation would you recommend?

[ExtrinsicFalsehood]

The thing about me is that throughout the days and weeks I'll be normal. Just a stable person with nothing noticeable about them, maybe more social then most people. I get slight anxiety and depression at random times throughout the year. But the one thing I lack is any sort of motivation. Growing up I was filled with ideas, always working on something new. Now I just feel clouded in a light brain fog that never truly allows me to reach my full potential. I can't describe it at all.

 

Anyways, everything gets reversed the day after drinking like other posters have stated. But to me I highly doubt I have any sort of mutation in those genes, I just feel like I have a lack of dopamine upregulation...

 

As stated from my other forum post,

I'll wake up from let's say a party with all my other friends they'll be dreading waking up and I will already be so happy just walking around and ready to take on the day (VERY UNUSUAL)

From there my verbal fluency increases tenfold, creating and sustaining a very intelligent conversation I otherwise never would. I don't get where it comes from, I actually give people the attention of day and want/am interested in them. I feel like I build meaningful connections and I honestly blew my parents away because of how deep our conversations were going. I never really care about conversations and just reply in pretty simple sentences but after drinking I actually want to keep a discussion going. I feel like I become a perfect image of myself.

 

Now onto motivation, I will think of something and without thinking execute the task. I would always struggle to do anything. It's so strange. Everything interests me, I have a sudden appreciation for the world around me and start notice the smaller things and cherish it.... From this new found motivation and my new cognition of formulating amazing ideas and thoughts my productivity sky rockets it's amazing. I can literally go on and on. My mind feels like it finally opens up and I can see the whole picture at once. I'm so confused. 

 

And then the days after it crashes and i'm back to the start.

I honestly am scared to mess around with Nootropics due to me only being 19. It's scary to me messing with my brain while it is still developing so I have just stuck with L-Theanine.

 

Can go way more in depth but I just summarized how it feels...

[Helllllo]

Mr. Extrinsic falsehood. If there's any consolation, I'm 24 and feel the exact same way. I've made it my mission to find out what's up with me/us. I'll keep you guys posted.

[ExtrinsicFalsehood]

Mr. Extrinsic falsehood. If there's any consolation, I'm 24 and feel the exact same way. I've made it my mission to find out what's up with me/us. I'll keep you guys posted.

 

Have you made any progress at all?

[Kingsley]

 

And then the days after it crashes and i'm back to the start.

I honestly am scared to mess around with Nootropics due to me only being 19. It's scary to me messing with my brain while it is still developing so I have just stuck with L-Theanine.

 

Can go way more in depth but I just summarized how it feels...

 

I think you have done a good job summarizing your struggles, which many of us can relate to.  I also think that your wariness or skepticism of nootropics is wise.  While I wouldn't be too worried about detrimental effects from most nootropics, most people find them disappointing, especially if trying to treat an underlying issue like we are.

 

It is interesting how many people are chiming in about the beneficial hangover effect.  I too have experienced a positive cognitive response after nights of heavy drinking. 

 

I have speculated in my layman kind of way that the effect comes down to upregulation of the NMDA receptor, and I just stumbled upon a fascinating article that appears to support this view.  See "The NMDA Receptor and Alcohol Addiction" at http://www.ncbi.nlm..../books/NBK5284/.  The article discusses the effect of alcohol as an acute NMDA inhibitor resulting in "rebound potentiation and long-term facilitation of NMDA receptor activity."  The activity of the NMDA channel is "greatly potentiated upon ethanol washout."  

 

This suggests to me that those of us who benefit most from a hangover may also benefit from supplements that enhance NMDA receptor function.  This is certainly true for me, as I find NAC and sarcosine indispensable.  I also benefit from occasional use of l-glutamic acid and l-glutamine, though the safety of those two (particularly the former) has been called into question by some (not convincingly in my opinion).

 

It would be interesting to see if any of you also benefit from NAC, sarcosine, or other NMDA-enhancing substances.  

[Helllllo]

Mr Kingsley, I'll shoot you a pm tonight.

Just out of curiosity, have you tried memantine?

[Kingsley]

Mr Kingsley, I'll shoot you a pm tonight.

Just out of curiosity, have you tried memantine?

 

Funny thing about memantine. . . I actually have about 60 tabs of it but have never tried it.  A while back I ordered a bunch after reading some glowing reviews on this and other sites about its ability to prevent amphetamine tolerance, as well as cognitive benefits of memantine in its own right.  I also read a couple of studies citing success treating negative symptoms of schizophrenia.

 

However, I chickened out after reading some inconsistent anecdotal reports, and reports that an acclimation period is necessary to get past initial negative effects on cognition, which I am hesitant to risk since I have to be on the ball at work.  Plus, I just couldn't square in my mind how an NMDA antagonist would be beneficial for me.  Granted that NMDA antagonists can cause rebound upregulation of NMDA receptors (i.e. as seen in study I cited in previous post), but it is my understanding that such benefit occurs after the antagonist wears off or leaves your system, whereas I believe memantine has a long half life and is taken daily thus continually antagonizing the receptor.

 

That said, I am still fascinated by memantine and suspect based on my limited reading that its effects may be more multi-faceted than straightforward NMDA antagonism.  It is definitely something I am interested in trying when the time is right.  Would be nice if anyone could weigh in with experiences. 
 

[Chadwick]

I thought I should give you an update as I've progressed somewhat more in all of this. Methylfolate and hydroxocobalamin has helped me a lot over the years but somehow I've still felt that I've only been able to get rid of my symtoms by 85% or so, and I've been longing to get to 100%. The protocol I've described before (200 mcg methylfolate 3 times a day and only small amounts of hydroxocobalamin) helps with dopamine is seems but it also increases methylation, which breaks down dopamine. The net effect is noticeable and good but not really perfect. 

 

Two and a half weeks ago I stopped using both of these supplements and switched to pure BH4/tetrahydrobiopterin/sapropterin (three words for the same thing) instead. BH4 is what the methylfolate protocol aims to increase and getting that without the methylation should in theory be even more effective for increasing dopamine. 

 

I use 0,5 mg of BH4 twice a day, which is a much much lower dose than what is used in Kuvan which the pharmaceutical version of the substance. Kuvan is used for treating some versions of the disease phenylketonuria and the doses used then are not really applicable for me. 0,5 mg has a pronounced effect which sets in about 30 minutes after oral consumption and it lasts for about 8 hours, hence the two doses a day. Higher doses than that can give me headaches.

 

BH4 is a whole new game for me and so far I can say it's easily the best supplement I've ever used. All the symtoms I described in the first post of this thread are 100% gone now. I could use very big words to describe it but I think you get the point.

 

There are a few ways to get BH4. It's sold as a supplement called Pteridin-4 from Ecological Formulas, which I use, but it seems like it's out of stock often and for long periods. It can also be purchased from several suppliers in China at Alibaba. If you try that, then the form of BH4 you want is 6R-5,6,7,8-tetrahydro-L-biopterin (cas no 69056-38-8). 

[Kingsley]

Very interesting.  It's such a shame that BH4 is so hard to get ahold of.  I'm open minded but buying bulk from Chinese suppliers turns me off.

 

I agree that the methyl supplements are a mixed bag.  For me, taking just enough can be energizing and can help clear brain fog, but if I take even a little bit too much my mood INSTANTLY tanks and I feel more stupid than ever.  Low dose is key, but it's still hard to find the right balance. 

 

Please keep us updated and let us know if your effects with BH4 are consistent.

[Helllllo]

Hey guys, 

I posted in this thread earlier about the hangover phenomenon and have gotten significantly worse. The hangovers been my lifeline for a while now. Anytime i'd get in this extremely depressed, confused, awkward, cognitively fried mood, i'd drink to experience a hangover and get on with my next couple of days really well. I'd self medicate to feel normal. That is until about a month and a half ago when I pooped it out. I tried a few times getting drunk but for the first time in my life, i'd have the typical hangover regular people experience. I'd vomit (which i never used to do), I would be slightly negative and extremely lethargic.

So since about a month ago, I've stopped drinking entirely. I've gone from professional to professional and was finally diagnosed with ADHD-PI. The psychiatrist described it as ethanol igniting my neurons to fire up and that other people have different catalysts such as marijuana etc. I started my introductory dose of adderal and it felt really strange. I became really quiet and dysphoric. This is off two doses of 5mg dexamphetamine, four hours apart. I tried supplementing tyrosine a couple of weeks prior to my diagnosis and that made me feel really irritable. Also, it's worth noting that smoking makes me dysphoric too?

Oh and I wanted to experiment with DXM to see if that did anything and 80mg literally put me in this strange, hypnotic and mute state. I was in a dysphoric mood where I brain fog, a mental block and wasn't talkitive. I think I got the rebound effect because I was in an okay mood the next day but that could've been placebo. I tried again the next week and had 30mgs. Same hypnotic, strange and untalkative mood. On second thought, I think it was after the whole experience with experimenting with DXM where I stopped experiencing those hangovers where I feel normal. 

I'm finding it harder to regulate thoughts, feelings and emotions. I've become rigid and awkward. Can hardly look at people in the eye. Short terms memory has tanked. I feel really trapped, I know this isn't me and i'm a really light and easy going person but something in my cns is happening that's making me extremely depressed and stupid. Above all, I feel really dumb at the moment. 

I'm in a really dark place. I'm a stones throw away from handing myself over to a clinic. But i doubt they'll take me or even know whats going on. 

My country subsidizes BH4 if you can prove through some pretty expensive testing that you're deficient. Could my cns fuckups be a product of a bh4 deficiency? 
Could I just have an extremely hypo-active nmda neurotransmitter? What could potentially be causing this? 
Could it be a faulty glu neurotransmission?

I'm extremely lost. I've quit my job and studies, living a dormant life till I become functional again. Any help would be an absolute god send. Please.

Edited by Helllllo, 23 December 2015 - 04:28 PM.

[Kingsley]

I really feel for you and can strongly relate to almost every single symptom you describe: ADHD-PI diagnosis, dysphoria, lethargy, bad short-term memory, rigidity/awkwardness, "cognitively fried," significant cognitive boost from alcohol consumption, trouble with eye contact, the feeling that all this does not reflect who you really are, ALL OF IT.  One minor difference is that where you experience dysphoria from dexamphetamine, I experience a marked mood boost.  In any event, it does not sound like a dopamine issue.

 

It all sounds like the hallmarks of NMDA/glu receptor dysfunction to me, maybe with some added effects from chronic alcohol consumption.  I believe you stated that you don't benefit from NAC, though I wonder if you'd see a benefit from continued use or upping your dosage.  I also wonder if you'd benefit from glycine, which has become a staple of my stack.  Glycine can be beneficial for NMDA-receptor hypofunction in two ways: 1) required (along with the cysteine from NAC) for synthesis of glutathionine, which has been shown to benefit compromised NMDA-receptor function; and 2) glycine is a co-agonist (along with glutamate) for the NMDA receptor and directly stimulates it.  I have read some fairly convincing arguments that the modern diet may not contain enough glycine for optimum health, and maybe it could be depleted further by alcohol consumption?  Not sure.  In any event it is very cheap and 10 grams a day gets me one step closer to where I want to be. 

 

Also, alcohol consumption can deplete glutathione which can contribute to NMDA receptor dysregulation, so supplements that increase it could be a reasonable approach to explore (the trifecta is NAC, glycine, glutamine, though NAC is the most important). 

 

Other potentially beneficial supplements could include sarcosine (blocks the re-uptake of glycine and enhances NMDA-receptor stimulation), and anything that is beneficial for inflammation (hell, I get a mental boost from ibuprofen).  BH4 may not be a viable option since it seems almost impossible to get your hands on though I would absolutely love to try it.

 

Again, I feel for you.  It is a crime that so many of us have to turn to internet forums for help.  We really are in the dark ages of mental health in some ways. 

 

 

Edited by Kingsley, 23 December 2015 - 06:15 PM.

[PalmAnita]

I really feel for you and can strongly relate to almost every single symptom you describe: ADHD-PI diagnosis, dysphoria, lethargy, bad short-term memory, rigidity/awkwardness, "cognitively fried," significant cognitive boost from alcohol consumption, trouble with eye contact, the feeling that all this does not reflect who you really are, ALL OF IT.  One minor difference is that where you experience dysphoria from dexamphetamine, I experience a marked mood boost.  In any event, it does not sound like a dopamine issue.

 

Me too - especially the emotional things, rigidity and social anxiety but also lethargy, chronic dysphoria and restlessness (this is awful when you're tired at the same time), also have inattentive adult ADD diagnosed ... but the strange thing is that I get great relief from NMDA antagonists. Sometimes that antidepressant afterglow ketamine has become so famous for works, but usually it's really that I feel just better while actually being on the dissociative. So I heavily suspect a NMDA dysfunction too, but with overactive and/or too many receptors. 

 

I've tried AMPAkines, both sunifiram and unifiram, despite that uni is said to be gentler, I found the suni to be better but both were intensifying the tension and somewhat speedy. So more AMPA activity is a part (antagonizing NMDA actually leads to more glutamate output, I suspect because of auto receptor antagonism, and this glutamate will then preferably bind to the AMPAR's which aren't blocked) but less NMDA is more crucial.

 

Currently I'm using ketamine daily (threshold dosages, 2-3x 10mg's or so). This is not sustainable, because of laws and money, but I also fear of tolerance and long-term toxicity. 

 

 

 

We really are in the dark ages of mental health in some ways. 

 

This is so sad and so true. We have this very promising riluzole out there for example, but getting a script for it is impossible despite of a shitload of well done studies. The same for ketamine. And I have one of the best doctors in town, next to all my other experiences were disappointing to say the least. I've heard repeatedly that taking memantine when you don't have Alzheimer's is like 'taking smarties' - they forced me to go off it cold turkey and wanted to start fucking antipsychotics. They know shit about their matter and get such high salaries.

[.Moose.]

To the recent posters here, I really think we are really getting closer to being on exactly the same page here, so take hope. I also have adult inattentive ADD diagnosed. Of the last 4 posts of here, three of us have the same diagnosis and one suspects having it. I also know another poster who is diagnosed similarly. THIS IS HUGE NEWS GUYS!! There is an ever growing amount of research on ADD which will undoubtedly be of help, and the fact that we have identified such a common link between us in extremely good news. 

 

I believe strongly that this is a dopamine problem, which holds true to the ADD diagnosis and my research, as well as Chadwick's position (though seemingly a different dopamine system). However, I have recently read about a guy who fixed his believed ADD through NMDA agonist (think that's the right word, will check when it's no longer christmas day haha) and am open to different interpretations. Ive been doing a lot of reading recently and think I'm making a lot of headway, If we have 4 of us doing this, we could make so much more. Myself and 'helllllo' have been chatting a bit recently but expanding the group would only be beneficial, for anyone interested. 

 

In the terms of 'dark ages', maybe relatively little is still known about this but the fact that we have the internet for research and to find others in the same position is a luxury afforded only in the last 10/15 years or so, making this the best time to be alive and able to rectify this problem. so lets get this sorted.

 

Chadwick, many thanks again for the thread and informative last post. 

 

Merry christmas all, if applicable....

 

 

Edited by MH Moose, 25 December 2015 - 12:44 AM.

[.Moose.]

From there my verbal fluency increases tenfold, creating and sustaining a very intelligent conversation I otherwise never would. I don't get where it comes from, I actually give people the attention of day and want/am interested in them. I feel like I build meaningful connections and I honestly blew my parents away because of how deep our conversations were going. I never really care about conversations and just reply in pretty simple sentences but after drinking I actually want to keep a discussion going. I feel like I become a perfect image of myself.

 

Now onto motivation, I will think of something and without thinking execute the task. I would always struggle to do anything. It's so strange. Everything interests me, I have a sudden appreciation for the world around me and start notice the smaller things and cherish it.... From this new found motivation and my new cognition of formulating amazing ideas and thoughts my productivity sky rockets it's amazing. I can literally go on and on. My mind feels like it finally opens up and I can see the whole picture at once. I'm so confused. 

 

This precisely sums up how i have felt on the rare occasion when I get this alcohol afterglow!! It's the best feeling, I just want to shake people like "see how I'm not actually socially/ generally retarded?!" And then I sink back into that state, which can only be described as general retardation. 

[Helllllo]

Same. It's a bit of a nightmare seeing your full potential and saying bye to it a day or two later. Dedicating a lot of time to find out what the glitch in our system is. My physch is quite knowledgable and I've told her about this thread. She's looking into it for me which is a breath of fresh air considering every professional I've told has never cared.