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alcohol vs chronic NMDA receptor upregulation

depression alcohol nmda anxiety

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#1 jack black

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Posted 14 July 2017 - 03:19 PM


I noticed a few recent threads where people selfmedicated with alcohol. While those people are urged to stop (common sense and empirical evidence of what happens to chronic alcoholics), little explanations were provided for mechanisms.

Up to recently I only knew about etoh effects on dopamine and GABA signaling. I though D receptor downregulation and GABA receptor upregulation account for the depression that follows repeated etoh consumption (that made me almost stop using etoh at all).

Now, there is evedence that etoh has a rapid and profound anti-NMDA effects (dissociation, memory lapses, impairment, etc), followed by chronic NMDA receptor upregulation that can lead to depression and anxiety when a person stays sober. Even worse, combined with low magnesium, low zinc, and low thiamine (all natural NMDA modulators), common in alcoholics, that can produce brain damage via excitotoxicity.

There are many papers on this topic including this: http://journal.front...2013.00014/full

This shows how it's dangerous to chronically use any psychoactive substances, and etoh is amoung the worst, IMHO.

There is more. There is some evidence that stress has similar effect on NMDA: http://journals.plos...al.pone.0037916

Combine stress with alcohol (that is commonly used by countless as anti stress remedy), add genetic predisposition and you get the perfect storm. I believe that's exactly the source of my problems that started in University.

Unfortunately, countless young people (including members of my own family) go through the same path and damage brains in the process.

Edited by jack black, 14 July 2017 - 03:33 PM.


#2 medievil

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Posted 14 July 2017 - 11:39 PM

Psychoactive substances have tremendous therapeutic potential when chronically consumed in therapeutic doses, also you can prevent tolerance off ethanol as off all other drugs with memantine or DXM.
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#3 jack black

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Posted 15 July 2017 - 12:48 PM

True, memantine prevents excitotoxicity in some alcohol experiments.

#4 Galaxyshock

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Posted 15 July 2017 - 02:14 PM

I would take Ginseng  

 

Red ginseng relieves the effects of alcohol consumption and hangover symptoms in healthy men: a randomized crossover study.

 

Heavydrinking causes hangover symptoms, because the action of alcohol dehydrogenase forms acetaldehyde, which is metabolized by acetaldehyde dehydrogenase into acetate. Red ginseng shows positive effects on alcohol metabolism in animal studies. We investigated the effects of red ginseng on relieving alcohol and hangover symptoms in 25 healthy men in a randomized crossover study. At each visit (0, 1, and 2 weeks), the subjects drank 100 mL whiskey (40% alcohol) and either 100 mL water or 100 mL of a 0.321 mg mL(-1) red ginseng anti-hangover drink (RGD). We took blood samples periodically until 240 min after alcohol consumption, and we investigated the blood profiles, alcohol levels, and acetaldehyde levels. We also measured anthropometric parameters, expiratory air-alcohol levels, and hangover symptoms. The plasma alcohol concentrations within the RGD group were significantly lower than those within the placebo group after 30 min (p = 0.002), 45 min (p = 0.016), and 60 min (p = 0.009); the areas under the response curves revealed a positive effect of RGD (p = 0.051). Furthermore, the expiratory alcohol concentration was significantly lower after 30 min (p = 0.005) and 60 min (p = 0.065), and the areas under the response curves (p = 0.058) likewise revealed a positive effect of RGD. The plasma acetaldehyde level was significantly elevated at 120 min (p = 0.020), but the areas under the response curves showed a similar trend (p = 0.054). While the plasma acetaldehyde concentration slightly increased, the RGD showed positive effects on hangover symptoms. Considering the reduction of plasma alcohol levels, expiratory concentrations, and hangover severity, we conclude that red ginseng relieves the symptoms of alcohol hangover.

→ source (external link)


Edited by Galaxyshock, 15 July 2017 - 02:15 PM.


#5 jack black

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Posted 26 July 2017 - 10:33 PM

I see this thread is going nowhere. Let me make my last point. When I drink, even small amounts, 3 days in a row or longer, depression follows next week or two. My mood is better when i stay away from alcohol. coincidence? anyone else noticed that?



#6 normalizing

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Posted 28 July 2017 - 05:18 AM

jack black thank you for making this thread my friend, thank you! i have a severe problem going on here. i have been binge drinking for 1 year with almost no days off and recently i stopped but i feel so fucking strange. i feel like schizophrenic, a lot of anxiety and depression and weird visions and ideas flow in my head. im still trying to stay sober but im so confused and sad i dunno what to do really. i have been taking benzos to sedate myself to a point and also some antipsychotics as i go crazy at times. i have really hard time perceiving reality now since all i was seeing was the world through alcohol induced state for one year.

please my friend, tell me any ideas how to continue with this, i really dont wanna go back to drinking but if this continues I HAVE TO, because im going psycho!

 

let me describe in better detail how i feel. now, the lack of sleep thats expected  i combat it with benzos and various sleep meds i kind of deal with it, but its the days that really bang me with a hammer kind of. i feel very dissociated, strange ideas and psychotic rush of thoughts i cant control or know how to stop. i dont really feel calm, always anxious, speedy and need to move and do things and i have to always drinking fluids, juices or waters at this point, as if to replace the constant bottle handling of alcohol in the past. now, if it wasnt for some meds, i would have cut my head off long ago, but so far i have managed to stay afloat, barely! so anyway, as i continue throughout the day, i feel schizophrenic at times. somehow i observe my actions and my communication with people as out of loop and being strange and im being paranoid around people how they react and respond to me. NOW, those are several difficult psychological states im experiencing all at once, BUT the worst is the fucking depression and the apathy and lack of any damn fucking feeling or pleasure!!! all the feelings, and excitement i ever had were on alcohol, so you can imagine, im a stone now. so.... thats just brief explaination thus far, i can keep going with examples with how horrible and shitty i feel, but its no use to bore people, honestly people in my state probably already figured out how it is.

so jack black, please man, what do i do, recommend ideas please!!! and yes, i do use few meds currently that kind of take the edge off for a bit, and also i tried shitload of herbal stuff that doesnt work! i even read ashawagandha helped alcoholics,but all it did to me is just give me morning boost and then slap me in the face and ill get anxiety later in the day, bah

 

any help will be greatly appreciated!!! :(:(:(


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#7 jack black

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Posted 28 July 2017 - 07:20 PM

hazy,

as I said in my first post, magnesium, zinc, and thiamine are essential to prevent excitoxicity. Take good B complex. if that's not enough, tianeptine or memantine are good options. tianeptine is OTC and cheap in this country. also, NAC and milk thistle wouldn't hurt. Litihium is also a good option. if I were you, i would take all of those (i'm taking most of those myself).

more reading: https://en.wikipedia...Neuroprotection



#8 normalizing

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Posted 28 July 2017 - 07:50 PM

im taking tianeptine but it lasts about 1-2 hours then it makes me like crashing out, even more anxious. i tried to combine it with various things to take the comedown off, but im not sure which is good interaction as it can have worse effects like the time i mixed it with some downers or other antidepressants which felt like serotonin syndrome like weird feeling. i guess IF i can find a way to make tianeptine last longer and have something to counteract its comedown, tianeptine is actually a good anti-alcohol drug

 

i was wondering, maybe mix it with memantine? i have had mixed results with memantine by itself. on days it will make me more chilled out but most times i wont notice it. i think its a good combination type of drug, i just cannot figure out the precise combo with it. no clue which works best with it and im again worried for side effects depending which combination i use...


Edited by hazy, 28 July 2017 - 07:52 PM.


#9 jack black

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Posted 29 July 2017 - 07:48 PM

buy free acid tianeptine that absorbs slowly and can be taken once a day rather the more popular sodium salts that has short half-life and needs to be taken 3xday.

https://newmind.com/...e-acid-5-g.html



#10 normalizing

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Posted 29 July 2017 - 08:10 PM

i was thinking, is it a good idea to dose with the sodium and free acid same time, get rapid boost the first hour from the sodium and as it falls the free acid will come through. or could that be an overkill... im not sure. and i wonder if free acid and sulfate forms work the same?



#11 jack black

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Posted 29 July 2017 - 09:29 PM

It's my understanding that free acid and sulfate forms work similar.

Another drug you might want to look into is naltrexone and acamprosate.

And of course everyone knows about disulfiram.


Edited by jack black, 29 July 2017 - 09:31 PM.


#12 Eryximachus

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Posted 29 July 2017 - 11:02 PM

Drinking alcohol is in general not the best idea.  Consuming to combat some kind of disorder is profoundly unwise. 

 

If you really need this, take Klonopin.  But, whether alcohol or benzos - the withdrawals will be hell should you decide to quit someday.  


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#13 jack black

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Posted 31 July 2017 - 04:45 PM

Drinking alcohol is in general not the best idea.  Consuming to combat some kind of disorder is profoundly unwise. 

 

If you really need this, take Klonopin.  But, whether alcohol or benzos - the withdrawals will be hell should you decide to quit someday.  

 

benzos are not that great either. between dulling ones memories and habit forming, it's not suitable for longer term use.

IMHO, Buspar, Atarax and cyproheptadine are much better options for dealing with anxiety as they directly deal with 5HT2aR.



#14 normalizing

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Posted 01 August 2017 - 05:31 AM

i have been using hydroxyzine (atarax) for anxiety, but is it also not addictive, meaning you stop it, you get worse than before? i know its not a benzo, but i think anything temporary relieving anxiety is going to cause rebound effect after discontinuation



#15 Eryximachus

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Posted 01 August 2017 - 01:00 PM

 

Drinking alcohol is in general not the best idea.  Consuming to combat some kind of disorder is profoundly unwise. 

 

If you really need this, take Klonopin.  But, whether alcohol or benzos - the withdrawals will be hell should you decide to quit someday.  

 

benzos are not that great either. between dulling ones memories and habit forming, it's not suitable for longer term use.

IMHO, Buspar, Atarax and cyproheptadine are much better options for dealing with anxiety as they directly deal with 5HT2aR.

 

 

I have only researched Buspar, but it is my understanding it is nowhere near as effective as benzos are.  A significant proportion of people do no respond to Buspar, whereas virtually all respond to benzos. 

 

At the end of the day, I would rather someone be addicted to a mild benzo like Klonopin than be a drunk.  Just saying.  


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#16 normalizing

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Posted 02 August 2017 - 05:56 AM

i didnt react well to buspar. it made me kind of sedated and dizzy but feeling unpleasant, definitely not good for depression or anxiety honestly. i believe thats a good reason its not that popular and its not even asian or european drug, those usually are underrated because US has its own market, but not with buspar. the main reason i believe is unpopular here is definitely not a great drug.



#17 jack black

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Posted 02 August 2017 - 02:40 PM

i didnt react well to buspar. it made me kind of sedated and dizzy but feeling unpleasant, definitely not good for depression or anxiety honestly. i believe thats a good reason its not that popular and its not even asian or european drug, those usually are underrated because US has its own market, but not with buspar. the main reason i believe is unpopular here is definitely not a great drug.

 

fair enough. a family member was on buspar for a while for GAD and she liked the improvements.

I took atarax just once and it gave me insomnia and tiredness next day. cyproheptadine is sedating alright.

everyone is different.
 


Edited by jack black, 02 August 2017 - 02:43 PM.


#18 normalizing

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Posted 02 August 2017 - 07:41 PM

atarax works for 12 hours which sucks. it makes everyone tired the next day, including me, therefore i have to be careful when i take it and how much. but what about the insomnia, the next night you cant sleep because of it or what? i didnt think it will cause insomnia on discontinuation after just one time



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#19 jack black

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Posted 03 August 2017 - 12:45 PM

atarax works for 12 hours which sucks. it makes everyone tired the next day, including me, therefore i have to be careful when i take it and how much. but what about the insomnia, the next night you cant sleep because of it or what? i didnt think it will cause insomnia on discontinuation after just one time

It was insomnia after taking it. It's a rare side effect. It made my mind calm and clear and I sort of liked that, but it was middle of the night and the next day was trashed.





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