450 replies to this topic

[iseethelight]

I've now stopped all b12 and folate supplements. Since starting megadosing these 2 vitamins, I've become more depressed, foggy, and my anhedonia became worse than ever. I do get a nice mood boost for 30 minutes after taking folic / folinic acid which then turns into deep depression hours later. Luckily I bought them from amazon, so I'm returning them all. I'm experimenting with antifolates like calcium etc.

[iseethelight]

THIS IS AN EXCESS GLUTAMATE ISSUE. THANK ME LATER...

[Cube]

I've just been looking into that myself! Interestingly noopept increases glutamate also and i felt horrible brain fog ect taking it as i did on most nootropics so i gave up. Excess ach or excess glutamate can cause grief.

[ThreeKings12341]

THIS IS AN EXCESS GLUTAMATE ISSUE. THANK ME LATER...

 

so u recommend....?

[Helllllo]

There's not really a whole lot that can help unfortunately. I'm with him and say that it's probably excess Glutamate. We probably need to wait for the new age Glutaminergic drugs like NRX-1074 to get into the market to properly resolve this issue and even that lasts for about a week so lifetime redosing will be inevitable. The best and only thing you can really do right now is get on route for anti-depressant treatment. You will need a polypill. Go to Ken Gillmans depression algorithm. Something along the lines ol Parnate and Nortriptyline. There's someone on socialanxietyforum who's taking something along the lines of Wellbutrin, Parnate, Nortritpyline, Ketamine, Agmatine and a couple of others to reach his desired dopamine level. That and reducing neuronal inflammation with Galantamine and Ibudilast are virtually our only options (I believe) . Right now I'm on an ssri and nortriptyline and it's working okay but I'm thinking i'm going to change to something else sometime soon. Wish you guys all the best.

[ThreeKings12341]

There's not really a whole lot that can help unfortunately. I'm with him and say that it's probably excess Glutamate. We probably need to wait for the new age Glutaminergic drugs like NRX-1074 to get into the market to properly resolve this issue and even that lasts for about a week so lifetime redosing will be inevitable. The best and only thing you can really do right now is get on route for anti-depressant treatment. You will need a polypill. Go to Ken Gillmans depression algorithm. Something along the lines ol Parnate and Nortriptyline. There's someone on socialanxietyforum who's taking something along the lines of Wellbutrin, Parnate, Nortritpyline, Ketamine, Agmatine and a couple of others to reach his desired dopamine level. That and reducing neuronal inflammation with Galantamine and Ibudilast are virtually our only options (I believe) . Right now I'm on an ssri and nortriptyline and it's working okay but I'm thinking i'm going to change to something else sometime soon. Wish you guys all the best.

 

thx for your reply!

 

1)ahh ok so you are on jaihos / gillmans recommendation - notryp + ssri.  ,: have u experienced any emotional blunting before the meds  and if yes did it improve while on your current meds? and other improvements on this med?

 

2)would you be so kind and send post me the links of the guy whos posting about wellbutrin, parnate.... would interest me to read .. please (maybe have read it in the last 2 weeks but maybe not - sounds familiar)

 

3)why do you think that stuff like nrx-1074 etc. would only work for a week?

 

4)and last question sorry^^ : what does galantamine else do,  is galantamine for those people who have a big antidepressent state on a hangover day? i mean do these people have big neuronal inflammation?

 

thanks!!

Edited by ThreeKings12341, 22 July 2017 - 12:43 PM.

[jack black]

it just occurred to me that since people are posting here, there is alcohol drinking involved. as I discovered recently, alcohol upregulates glutamate signaling long term while producing short term down regulation:  http://www.longecity...r-upregulation/

this may be of interest for some of you looking into glutamate.

BTW, the OP mentioned that too in his very first post (point #1).

Edited by jack black, 22 July 2017 - 04:11 PM.

[ThreeKings12341]

it just occurred to me that since people are posting here, there is alcohol drinking involved. as I discovered recently, alcohol upregulates glutamate signaling long term while producing short term down regulation:  http://www.longecity...r-upregulation/

this may be of interest for some of you looking into glutamate.

BTW, the OP mentioned that too in his very first post (point #1).

 

sorry for not gettin things always, but does it mean that exess glutamate is good and i should focus on that or not?

[jack black]

 

it just occurred to me that since people are posting here, there is alcohol drinking involved. as I discovered recently, alcohol upregulates glutamate signaling long term while producing short term down regulation:  http://www.longecity...r-upregulation/

this may be of interest for some of you looking into glutamate.

BTW, the OP mentioned that too in his very first post (point #1).

 

sorry for not gettin things always, but does it mean that exess glutamate is good and i should focus on that or not?

 

 

did you read the link I posted?

[ThreeKings12341]

 

 

it just occurred to me that since people are posting here, there is alcohol drinking involved. as I discovered recently, alcohol upregulates glutamate signaling long term while producing short term down regulation:  http://www.longecity...r-upregulation/

this may be of interest for some of you looking into glutamate.

BTW, the OP mentioned that too in his very first post (point #1).

 

sorry for not gettin things always, but does it mean that exess glutamate is good and i should focus on that or not?

 

 

did you read the link I posted?

 

 

ok now i read it slowly, so that means it is upregulated.. so avoiding diary is a first good step? , what else?
 

[iseethelight]

Excess glutamate is BAD and it's the reason for the issue being discussed in their thread. It causes anhedonia, depression, poor memory, loss of intelligence, anxiety, etc. Keep it high long enough and it starts killing brain cells, making you literally dumber as time goes on. Alcohol greatly reduces glutamate by partially blocking the receptors and by also converting some of the excess glutamate to GABA. The issue with this temporary alcohol treatment is that once the alcohol's effect diminishes, glutamate shoots up again and you're hit with worse depression...So you have to keep drinking..And you know what that means.. 

 

The treatment for this is to avoid all sources of MSG and only consume foods low in glutamic acid. This will gradually reduce the excess glutamate floating around. Normal people can get rid of the excess glutamate fine but not us... 

There are no supplements that can cure this. Taking some b12 will help reduce excess glutamate if you're deficient in it so it can help but won't make difference unless you're deficient. A low glutamate diet along with moderate drinking is the most promising treatment.. 

 

Here is a good base list to start with. http://www.dramyyask...oprovokers8.pdf

Edited by iseethelight, 22 July 2017 - 05:41 PM.

[ThreeKings12341]

Excess glutamate is BAD and it's the reason for the issue being discussed in their thread. It causes anhedonia, depression, poor memory, loss of intelligence, anxiety, etc. Keep it high long enough and it starts killing brain cells, making you literally dumber as time goes on. Alcohol greatly reduces glutamate by partially blocking the receptors and by also converting some of the excess glutamate to GABA. The issue with this temporary alcohol treatment is that once the alcohol's effect diminishes, glutamate shoots up again and you're hit with worse depression...So you have to keep drinking..And you know what that means.. 

 

The treatment for this is to avoid all sources of MSG and only consume foods low in glutamic acid. This will gradually reduce the excess glutamate floating around. Normal people can get rid of the excess glutamate fine but not us... 

There are no supplements that can cure this. Taking some b12 will help reduce excess glutamate if you're deficient in it so it can help but won't make difference unless you're deficient. A low glutamate diet along with moderate drinking is the most promising treatment.. 

 

Here is a good base list to start with. http://www.dramyyask...oprovokers8.pdf

 

nice thanks a lot!,  but will there be an effect to it also? since it kills brain cells and i dont feel that well as i used to. will it just stay and not get worse or will i notice maybe an antidepressive state?

 

and do u recommend avoiding dairy also? didnt find that one on the list

 

edit: i think "caseinate" answerd my last qeustion then...

Edited by ThreeKings12341, 22 July 2017 - 06:05 PM.

[jack black]

A low glutamate diet along with moderate drinking is the most promising treatment.. 

 

 

I don't agree with the drinking part. that was my point in the first place.

[iseethelight]

 

Excess glutamate is BAD and it's the reason for the issue being discussed in their thread. It causes anhedonia, depression, poor memory, loss of intelligence, anxiety, etc. Keep it high long enough and it starts killing brain cells, making you literally dumber as time goes on. Alcohol greatly reduces glutamate by partially blocking the receptors and by also converting some of the excess glutamate to GABA. The issue with this temporary alcohol treatment is that once the alcohol's effect diminishes, glutamate shoots up again and you're hit with worse depression...So you have to keep drinking..And you know what that means.. 

 

The treatment for this is to avoid all sources of MSG and only consume foods low in glutamic acid. This will gradually reduce the excess glutamate floating around. Normal people can get rid of the excess glutamate fine but not us... 

There are no supplements that can cure this. Taking some b12 will help reduce excess glutamate if you're deficient in it so it can help but won't make difference unless you're deficient. A low glutamate diet along with moderate drinking is the most promising treatment.. 

 

Here is a good base list to start with. http://www.dramyyask...oprovokers8.pdf

 

nice thanks a lot!,  but will there be an effect to it also? since it kills brain cells and i dont feel that well as i used to. will it just stay and not get worse or will i notice maybe an antidepressive state?

 

and do u recommend avoiding dairy also? didnt find that one on the list

 

edit: i think "caseinate" answerd my last qeustion then...

 

 

This list doesn't include foods with naturally high glutamic and aspartic acid content. You will need to avoid those. That includes almost all high protein foods.

[Cube]

http://forums.phoeni...in-state.44269/

Not sure how good the recommendations are but interesting ideas on glutamate

[Cube]

Oxaloacetate, oxaloacetic acid
https://universityhe...an-protect-you/

[chipdouglas]

I'm merely sharing in case some might find this to be informative, as it is somewhat connected to the original topic : https://chrismasterj...ealth-dopamine/

[Tim76]

I am posting to this thread in case someone like myself finds it in the future and my added experience might be helpful to them. I am homozygous for c677t MTHFR gene variant. I have struggled with depression, anxiety, and general bipolar-ish symptoms for my entire adult life (I'm 41). 3 years ago I started on my journey to find a solution for what, to me, were problems that were clearly caused by some sort of faulty biological process. I quit drinking, took up yoga, minimized refined sugar intake, stopped using marijuana, tried gluten free, and anything else I could think of to resolve my issues. Nothing seemed to work, but I was having the occasional moment of zen. I noticed that multi-vitamins were making me aggressive and irritable. After some research I decided it was one of the B-vitamins causing this. That led me to the MTHFR variant/mutation and I got my DNA sequenced. I was ecstatic to see that I did indeed have a homozygous variation because it meant that I was most likely not crazy. I started taking methy-B12 at high doses and I felt pretty good for a few months, but then I became angry and aggressive again, perhaps even a little psychotic. I didn't even think/realize it was the methyl-b12 at first, but it was. I hypothesize that as my levels got higher and higher my mood got worse. So, I added a low dose of methylfolate and things got better for few days before I returned to my shitty disposition. That's when I came across this thread and it all came together for me. I cut the methyl-b12 all together and started taking high dose methylfolate (15mg) and I now feel normal for the first time ever! This is not placebo and I am not overstating the effect. I have also added hydroxocobalamin to support my b12 levels without any problems. I owe Chadwick a world of thanks! And, I hope the addition of my experience to the thread might help others in the future. Best of luck to everyone!

Edited by Tim76, 10 January 2018 - 07:28 PM.

[jack black]

Good to know, did you have that clarity after ETOH drinking? I don't remember if Chadwick had that c677t MTHFR gene variant. i'm sure high dose methylfolate is beneficial outside that mutation, too. I don't have that mutation and find methylfolate quite stimulating. the highest dose i tried was 3x1.6mg and it was short term only. maybe i should try a higher dose than that. where do you get it at that high dose?

[Tim76]

Chadwick stated that he is heterozygous for MTHFR C677T and A1298C, which from my understanding is similar to being homozygous for C677T. I did experience a similar effect after drinking but I always felt so hungover that I didn't take much notice because I was consumed with the discomfort of being hungover. High dose methylfolate is prescribed as an antidepressant (Deplin) and a lot of people seem to have positive results from what I can find and they are usually people  that get no benefit from common anti-depressants. It definitely has benefits outside of MTHFR mutations. I also found lower doses to be too stimulating, but I cannot say for sure if it was the methylfolate, methyl B-12, or a combination of the two that was causing it. It's odd that the higher dose provides clarity and calm while the lower dosage seems to be over-stimulating to a lot of people. I'm using 5,000mcg/5mg L-Methylfolate pills from Life Extension that I bought on Amazon for $45 (120 pills) and I take 3 in the mornings.

[Chadwick]

That's when I came across this thread and it all came together for me. I cut the methyl-b12 all together and started taking high dose methylfolate (15mg) and I now feel normal for the first time ever! This is not placebo and I am not overstating the effect. I have also added hydroxocobalamin to support my b12 levels without any problems. I owe Chadwick a world of thanks! And, I hope the addition of my experience to the thread might help others in the future. Best of luck to everyone!

 

I'm very happy to hear someone has shared my symptoms and has benefited from the same treatment!

 

I have a compound MTHFR mutation, which means I'm heterozygous for both c677t and a1298c. The effect of this is somewhat less pronounced than a homozygous c677t. Most people with these mutations do not get any symptoms, and the reason I get the symtoms is probably the combination of my MTHFR mutations and several polymorphisms related to low dopamine production and high breakdown (COMT, MAOA etc). 

 

I'm still using 10 mg MTHF per day, in combination with 1 mg hydroxocobalamin orally every third day (a very small dose). This still works great for me. 

[Galaxyshock]

Dopamine deficiency my ass

[Golodnyy]

 

That's when I came across this thread and it all came together for me. I cut the methyl-b12 all together and started taking high dose methylfolate (15mg) and I now feel normal for the first time ever! This is not placebo and I am not overstating the effect. I have also added hydroxocobalamin to support my b12 levels without any problems. I owe Chadwick a world of thanks! And, I hope the addition of my experience to the thread might help others in the future. Best of luck to everyone!

 

I'm very happy to hear someone has shared my symptoms and has benefited from the same treatment!

 

I have a compound MTHFR mutation, which means I'm heterozygous for both c677t and a1298c. The effect of this is somewhat less pronounced than a homozygous c677t. Most people with these mutations do not get any symptoms, and the reason I get the symtoms is probably the combination of my MTHFR mutations and several polymorphisms related to low dopamine production and high breakdown (COMT, MAOA etc). 

 

I'm still using 10 mg MTHF per day, in combination with 1 mg hydroxocobalamin orally every third day (a very small dose). This still works great for me. 

 

 

Chadwick, what brand of MTHF do you use? And what form: L-Methylfolate or 5-MTHF ?

[Chadwick]

 

Chadwick, what brand of MTHF do you use? And what form: L-Methylfolate or 5-MTHF ?

 

 

I use Metabolic Maintenance L-methylfolate (which is the same thing as MTHF, 5-MTHF, L-5-MTHF and levometofolic acid - just different names for the same substance).

[katzenjammer]

@Chadwick & Tim76 - did you guys go on a low Glutamic Acid diet as well, or was the L-methylfolate supplement sufficient?  I'd hate to have to give up meat and eggs 

[Chadwick]

@Chadwick & Tim76 - did you guys go on a low Glutamic Acid diet as well, or was the L-methylfolate supplement sufficient?  I'd hate to have to give up meat and eggs 

I haven't had any reason to go on any special diet, no. 

[greyfox]

 

@Chadwick & Tim76 - did you guys go on a low Glutamic Acid diet as well, or was the L-methylfolate supplement sufficient?  I'd hate to have to give up meat and eggs 

I haven't had any reason to go on any special diet, no. 

 

 

Chadwick, have you ever tried using low-dose Amisulpride before? Or GHB/GBL/1,4-butanediol?

 

I'm simply curious due to the fact that a particular user on reddit (reddit.com/u/Yoyomamahh who is a.k.a. reddit.com/u/Nedzilla55 , I believe) found GABA-B receptor agonism fixed his Asperger's issues of low sociability/social anxiety and NMDA receptor hypofunction... initially he made this discovery due to Phenibut being incredibly useful for his symptoms, leading to his now-current Baclofen usage rather than Pheni.

 

My issues seem to suspiciously align much with yours, and in addition I had my genetic results done via 23andMe, which shows the following (all of these are the SNPs/genes you yourself shared as being critical for dopamine relevancy):

 

-------------------

 

 

MTHFR:  RS1801133 aka C677T: A;G

 

                RS1801131 aka A1298C: T;T

 

 

DHFR:     RS1650697: G;G

 

GCH1 -    I do not appear to have any mutations... according to SNPedia, the below are part of a three SNP haplotype, and it appears I have the 'normal' haplotype.

 

                                                                                 RS8007267: C;C

                                                                                 

                                                                                 RS10483639: G;G

 

                                                                                 RS3783641: T;T

 

PTS -      RS3819331: T;T 

 

COMT -  RS4680: A;G

 

MAO -    RS6323 -  T;T

 

DAT (aka SLC6A3, dopamine transporter) - I have the bad 'C' homozygous mutation!

 

                                                                                 RS27072: C;C

 

DRD1 (dopamine receptor D1) - RS4532: T;T

 

                                                      RS265981: G;G

 

 

DRD2 (dopamine receptor D2) - RS1800497: G;G

 

                                                       RS6275: T;T --->  I have the ‘bad’ (T;T) allele! - MY RISK FOR SCHIZOPHRENIA, ((due to this phenotype along with the (A;G) phenotype for COMT Val158Met)), ACCORDING TO THE STUDY ‘Genetic susceptibility to schizophrenia: role of dopaminergic pathway gene polymorphisms’—> ‘Ratio of cases to controls: 2.54’, and ‘Association with schizophrenia: High risk’

 

 

DRD3 (dopamine receptor D3) - RS6280: T;T

 

 

-------------------

 

What are your thoughts on my genes/SNPs...? I'm not sure what to make of it, although the RS6275 SNP seems a little troubling, as I match VERY similarly to the 'negative' symptoms of schizophrenia, which I guess would really in that case be more similar to 'Schizotypal' personality, or 'Avoidant personality'. (Both of which also seem creepily applicable to me)

 

 

Currently, I am on the MAOI medication 'Nardil' (generic name 'Phenelzine'), and for the first year or so it worked pretty well for my Atypical depression symptoms but also my social phobia/avoidance.

Now, though, it seems that much of the benefit has gone away, except for still receiving a pretty good effect from it on my social phobia/avoidant ways, and also my overall ability to think & focus.

 

The fact that Nardil was one of the only things to work for me also makes me think my issues are dopaminergic in nature, because I've done some reading of studies over the past couple of months, one which seems to indicate it's antidepressant effect and overall benefit are derived from it's effect of increasing catecholamines, according to this study --> https://www.ncbi.nlm.../pubmed/2418010 :

 

"It seems that phenelzine acts more through catecholamine release phenomenon than by inhibition of MAO."

 

Also, in addition to this, the other major effect of Nardil is to increase hypothalamic-pituitary-adrenocortical activity --> http://press.endocri...10/en.2004-0650

 

Lastly, I have the MAO-A SNP which actually appears to indicate my MAO-A is already underactive!

 

 

 

Since I'm trying to quit Nardil and ultimately solve my issues by other means, and REALLY get at the root of the problem, do you have any advice for what might be best used?

 

I should also mention I've been using Kratom since about 2 years into my Nardil usage, due to the fact that I need something stimulating/dopaminergic... however, it is at a dose of about 1 to 1.5 grams, and only up to 3 times a day spaced out (so I believe it should mostly be the stimulating effects rather than delta-opioidergic agonism or u-opioidergic), and always drink a cup of coffee alongside it.

 

 

 

I'm debating everything between Methylfolate, Uridine, Fasoracetam, NSI-189, Sarcosine, low-dose Amisulpride, BH4 (aka Tetrahydrobiopterin), Noopept, Tianeptine sulfate, Baclofen, Pantogam active, GHB/GBL/1,4-butanediol, SAM-e (perhaps alongside Betaine to increase it's beneficial effects as stated in research papers?), microdosing of a psychedelic like 4-AcO-DMT, Nigella sativa (black seed oil), Low-dose naltrexone, Pregnenolone, DHEA............ could really use some advice at this point obviously! Hahah

[Helllllo]

Hey mate. Not Chadwick but I can definitely help. I’ve tried a lot of of the medicines you’ve listed. Memantine, uridine, tianeptine, noopept, methyl folate, sarcosine, amisulride, baclofen, phenibut, pregnenelone, dhea and much more.

The current regimen I’m on has been by far the best. I’m taking 75mg nortriptyline, 20mg escitslopram and 12.5mg amisulpride, 1mg clonidine and 1.5g nac.

Phenibut and baclofen did nothing but make me woozy and I tapered up to pretty high dosages. Nmda agonists like sacorsine and pregnenolone gave me intense anxiety and increased the adhd symptoms. So I think there’s definitely some excitoxicity going on.

I’ve tried a lot of supplements and meds so if you have any questions, feel free to ask.

Edited by Helllllo, 22 January 2018 - 02:25 AM.

[solias]

Has anyone tried Lithium Orotate? It's a NMDA Antagonist. 

[solias]

Hey mate. Not Chadwick but I can definitely help. I’ve tried a lot of of the medicines you’ve listed. Memantine, uridine, tianeptine, noopept, methyl folate, sarcosine, amisulride, baclofen, phenibut, pregnenelone, dhea and much more.

The current regimen I’m on has been by far the best. I’m taking 75mg nortriptyline, 20mg escitslopram and 12.5mg amisulpride, 1mg clonidine and 1.5g nac.

Phenibut and baclofen did nothing but make me woozy and I tapered up to pretty high dosages. Nmda agonists like sacorsine and pregnenolone gave me intense anxiety and increased the adhd symptoms. So I think there’s definitely some excitoxicity going on.

I’ve tried a lot of supplements and meds so if you have any questions, feel free to ask.

 

 

Hey. What symptoms do you take this stack for? What kind of mental state can you replicate with it? 

 

Most of the people in this thread are looking for a solution to the hangtroped state, by which I refer to a state of enhanced cognition experienced during a hangover, following a night of drinking alcohol. Among the many properties, clearheaded, witty, increased verbal fluency and instant memory recall are clues to determine if you are in hangtrope zone.

 

This is unlike the vast majority of people that instead feel sick and bad during a hangover, with their minds feeling foggy and slow. I have run a small poll in my social network and I am the only one that experience the hangtropic state, all the others just feel sick and bad, not enhanced, when hung over.

 

It is also my impression, that depression in everyday life is NOT a core symptom for the people that experience the hangtroped state; I think it's more like 'less congnitively performant ordinarily'. This is just a personal observation based on reading 15-20 internet people describing themselves when hangtroped, and the way they feel during their ordinary life, not hangtroped.

Edited by solias, 22 January 2018 - 02:31 PM.