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Can anything help Dopamine and GABA receptors regenerate?

brain damage dopamine gaba receptors panic attacks anxiety neural pain regeneration biochemical

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#1 BioInfinite

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Posted 21 April 2013 - 10:04 PM


I ask because I have a dopamine receptor/neuronal injury which is being made worse by my feeling stimulated during my more energetic and speedy periods. This means a very good mood can turn into a nightmare past a certain threshold of stimulation. The injury was caused 1.5 years ago by an accidental Dopamine reuptake inhibitor OD and this system has been super sensitive ever since (things keep on happening that delay its recovery or make it worse but I have nearly recovered a couple of times).

To give you an idea of how serious it is, just a sip of tea or nibble of chocolate throws me into the most irritable, agitated and anxious mood so I've steered clear. But this happens naturally without triggers.

I've been thinking, is there a supplement or nootropic that increases MAO-B enzymes? That would help enormously. Or what about DA transporter enhancement... or anything that can downregulate dopamine?

Antipsychotics are a nightmare, seroquel completely destroyed my recovery over 3 months by constantly binding to and rapidly dissociating from D2 receptors causing me major panic attacks in the process. I don't know quite how I'd react to one that binded much longer, but it would have to be long enough to not cause gradual deterioration and instead allow gradual healing. And thats not even considering the horrendous potential side effects.

To top it all off I can't have the usual GABA-related calmants any more, not even chamomile. The same thing has basically happened there too. Chamomile, valerian, alcohol, and of course benzos all make me agitated and anxious and can put me in pain. It was getting better for quite a while and I was able to tolerate chamomile and the occasional drink very well, then I foolishly thought it'd be ok to use valerian to help me quit my doxylamine sleep aid which had escalated to 75mg, and it worked just fine for 3 nights after which I crossed the threshold again and had neural pain for 3 days after (I imagine them being bombarded and shrivelling up, just like with the dopamine). Only DHC + acetaminophen helped. Now its in the process of recovering again.

I was planning to try Tegretol with my psychiatrist, but that potentiates GABA receptors, isn't that a bad thing in my case? And I presume upregulation is not something I want either. Instead I need something to help renew, regenerate or promote new growth.

Right now the only things that are helping when I get too stimulated are the antihistamine doxylamine for rapid relief, glycine helps, and in general I take magnesium glycinate and Omega 3s. I read the anxiety advice thread here too and think Relora is worth a shot, as my adrenaline and cortisol is rather high.

Any help would be greatly appreciated,

Thankyou

Alex

Edited by BioInfinite, 21 April 2013 - 10:06 PM.


#2 Olon

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Posted 22 April 2013 - 06:27 AM

Depolarizing mode of GABA receptors is physiologically (in utero and in early childhood) caused by the shifted balance of inward/outward chloride transport. The inwardly-directed transporter NKCC1 is inhibited by bumetanide. Would be an experimental treatment, however, should be hard to get.
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#3 BioInfinite

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Posted 22 April 2013 - 02:40 PM

Depolarizing mode of GABA receptors is physiologically (in utero and in early childhood) caused by the shifted balance of inward/outward chloride transport. The inwardly-directed transporter NKCC1 is inhibited by bumetanide. Would be an experimental treatment, however, should be hard to get.


So that would make the natural actions of GABA more effective, without increasing GABA concentrations or through agonism, sounds promising. Thats not out of my reach, I may try it after more research. Just the kind of suggestion I was hoping for!

#4 BioFreak

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Posted 22 April 2013 - 03:12 PM

I am not sure about your problem with gaba, however, raising serotonin might be an idea to lower dopamine levels. Through an ssri or 5-htp.

Did you consider acetylcholine to be a problem, too? Antihistamines can inhibit it, and maybe that is part of your problem.

Do you have any idea what the actual problem is? What kind of injury is it exactly? I am curious.

#5 Olon

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Posted 22 April 2013 - 03:12 PM

It is already in trials for newborn epilepsy. Here its temporarily switches the brain into "adult mode" (hyperpolarization by GABA), and I assume that it could also help adult people with paradox reaction to gabaergic drugs.

#6 BioInfinite

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Posted 22 April 2013 - 04:56 PM

I am not sure about your problem with gaba, however, raising serotonin might be an idea to lower dopamine levels. Through an ssri or 5-htp.


Alas I already tried that with Moclobemide, a reversible MAO-A inhibitor. Results were initially highly positive, but I eventually realised it was probably prolonging the condition overall by partial dopamine increases and I was having more GABA-ergics to compensate, so I tried to reduce it and quit, and being out of my mind in withdrawal supplemented with too much tryptophan. This led to two lucky escapes from serotonin syndrome. Since then I've had a kind of cyclothymia, which has gotten less pronounced and more mixed over the last 6 months. Now I have stimulated highs (sometimes with agitation/dysphoria developing), good days, occasional normal days and some depressive days but it seems to be normalising. I'm hesitant to try anything else serotonergic as its already been messed with but I'm open to suggestions. I suspect the antagonist actions of seroquel were instrumental in stabilising my mood, but it could just be the antihistamine action. If only I had tried Tianeptine an SSRE instead of an MAOI.

Did you consider acetylcholine to be a problem, too? Antihistamines can inhibit it, and maybe that is part of your problem.


I used to take DMAE for energy and memory but after a few months it ended up just making me really anxious and nervous so I had to stop it. I see your point, but I don't want to lose much cognitive ability. What would you suggest in relation to this?

Do you have any idea what the actual problem is? What kind of injury is it exactly? I am curious.


Well, I only know what happened, everything else is my theory and I'm hardly educated in this field. No professional I've talked to so far understands what I'm on about, but I expect people here will have more insight. I suspect this was the beginning of my dopamine related troubles: 7 years ago I was smoking too much weed, after a few years I very gradually developed intolerance (reverse tolerance). Clearly my body had enough. I had to quit altogether when I started getting panic attacks from the tiniest amounts. Then the same thing happened with dextro-amphetamine for my ADD - I got a reverse tolerance until eventually I had to stop altogether. Fast forward to 2 years ago, and I had found Methoxetamine (MXE) which is a dissociative similar to ketamine but with much stronger Dopamine reuptake inhibitor activity, as well as NMDA antagonist. As I was using it for as an anti-depressant and for ADD, I was having very small amounts daily with weekly breaks. I noticed after some months that I was developing an intolerance to this also, the nice dissociative, antidepressive and anxiolytic effects were diminishing, and the speedyness/potential anxiety was increasing way beyond how it was when I started. I also began doing escapist sessions with a friend every week or two, a large component of that was my worsening depression due to lack of progress in life. I was beginning to have a rollercoaster of mood swings that echoed bipolar and became worrying.

One day I foolishly let my friend give me too much and I OD'd, after I'd been so careful up to that point. At some point I crossed a threshold, a very distinctive barrier (from the over-flooding of dopamine I presume) when I suddenly realised something had gone horribly wrong. I had the worst anxiety and frightening perspective hallucinations, I was afraid I was going crazy (things were giant then tiny, then tall and squashed vertically, then fat and squashed horizontally etc). After it, I had this severe mental pain/agitation/anxiety recurring very frequently and very gradually reducing over the next 6 months, during which I found occasional GABA agonists like baclofen, phenibut, and gabapentin worked at the worst times. The feeling itself felt like a black hole in my stomach. I still get that a little to this day, both with too much dopamine/sugar in mornings or sometimes at night when I lie down. I had to cut out caffeine as that was the worst trigger. After 6 months of that, I tried the Moclobemide with amazing results initially.

It is already in trials for newborn epilepsy. Here its temporarily switches the brain into "adult mode" (hyperpolarization by GABA), and I assume that it could also help adult people with paradox reaction to gabaergic drugs.


From what I read about it, it allows chloride ions to leave cells more easily, and reducing the chloride inside brain cells may help GABA neurons’ inhibitory functions work better. In theory, this may well be effective for me.

Its strange, I didn't see this intolerance coming. It happened exactly at the same time of my first partial serotonin syndrome. I wondered whether they were somehow memory-linked events. I had anxiety one day and as soon as I popped an etizolam (which I later found out has additional SNRI activity), my energy drained and I became weak so fast I panicked hard, vision converged and lost consciousness in front of a friend for 4 mins, after which my heart raced at 90-120 bpm for 24h. Since then my GABA has been messed up. I first noticed when I tried alcohol, it was a real weird feeling, especially red wine which contains GHB. It was worsened extremely by Seroquel, just 2 light beers threw me into the worst nightmare of anxiety and depression for days.

2-3 years ago I was also using GHB almost nightly (1.5-2g) to combat my chronic insomnia. I didn't realise it could lead to problems down the line, I just thought as long as a tolerance doesn't develop I'll be fine. Boy was I wrong. In retrospect, its possible that I developed a reverse tolerance to this as well, as I noted I wasn't having to take 3g for maximal effects. I remember when I was first introduced to it 3.5g was my sweet spot for occasional social use, 4g was just unpleasant. But when I started using it for insomnia 1 or 2 years later (perhaps the fact I made it myself with perfect pH) 2.5g got me maximal effects, so mostly used 1.5-2g. I ran out of it 2 years ago thankfully.

Edited by BioInfinite, 22 April 2013 - 05:00 PM.


#7 Thorsten3

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Posted 23 April 2013 - 10:42 AM

L-lysine might help with psychotic symptons.
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#8 BioInfinite

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Posted 23 April 2013 - 02:46 PM

L-lysine might help with psychotic symptons.

Thanks Thorsten, thats very helpful. Thats actually one of the few aminos I never looked at. I will try it.

I know the post above was a rather huge amount of info. Thats all in the past, I was young and thought I was smart but actually pretty naive about most of it and I can see the absurdity of the whole thing in retrospect. I can feel myself normalising over time, and I never want to go back to any of that. I just want to be able to lead a stable, enjoyable life. I've chosen to start fresh down under at the end of this year, so I have real incentive to get well enough so that I can survive out there on my own. So I just want to say thankyou to anyone who has any insight or ideas to speed my recovery. :)

#9 jakord

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Posted 27 April 2013 - 10:22 AM

Your situation sounds pretty messed up. As gaba-action is no option for you, you might want to look into something like this to treat your anxiety. The 2,3-Benzodiazepines completly lack gaba-related effects, though their anxiolytic properties are well documented. I hope you'll recover soon, don't give up!

#10 BioInfinite

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Posted 27 April 2013 - 06:14 PM

Yeah it has been pretty messed up, but lately I've been feeling better all the time. Closer to normal as time goes on. I'm also changing my diet to stabilise sugar levels, and not eating as much protein. I would really like to find a chart of foods that list the levels of amino-acid content so I could more tightly regulate it. As life situations are improving as well, my focus is on wellness so that seems to be helping a lot too.

I looked into Tofisopam, but looking at its studies I see it provides dopaminergic stimulation so its not suitable. Thanks for the suggestion though.

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#11 Flex

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Posted 16 February 2014 - 02:25 PM

I am not sure about your problem with gaba, however, raising serotonin might be an idea to lower dopamine levels. Through an ssri or 5-htp.


Alas I already tried that with Moclobemide, a reversible MAO-A inhibitor. Results were initially highly positive, but I eventually realised it was probably prolonging the condition overall by partial dopamine increases and I was having more GABA-ergics to compensate, so I tried to reduce it and quit, and being out of my mind in withdrawal supplemented with too much tryptophan. This led to two lucky escapes from serotonin syndrome. Since then I've had a kind of cyclothymia, which has gotten less pronounced and more mixed over the last 6 months. Now I have stimulated highs (sometimes with agitation/dysphoria developing), good days, occasional normal days and some depressive days but it seems to be normalising. I'm hesitant to try anything else serotonergic as its already been messed with but I'm open to suggestions. I suspect the antagonist actions of seroquel were instrumental in stabilising my mood, but it could just be the antihistamine action. If only I had tried Tianeptine an SSRE instead of an MAOI.

Did you consider acetylcholine to be a problem, too? Antihistamines can inhibit it, and maybe that is part of your problem.


I used to take DMAE for energy and memory but after a few months it ended up just making me really anxious and nervous so I had to stop it. I see your point, but I don't want to lose much cognitive ability. What would you suggest in relation to this?

Do you have any idea what the actual problem is? What kind of injury is it exactly? I am curious.


Well, I only know what happened, everything else is my theory and I'm hardly educated in this field. No professional I've talked to so far understands what I'm on about, but I expect people here will have more insight. I suspect this was the beginning of my dopamine related troubles: 7 years ago I was smoking too much weed, after a few years I very gradually developed intolerance (reverse tolerance). Clearly my body had enough. I had to quit altogether when I started getting panic attacks from the tiniest amounts. Then the same thing happened with dextro-amphetamine for my ADD - I got a reverse tolerance until eventually I had to stop altogether. Fast forward to 2 years ago, and I had found Methoxetamine (MXE) which is a dissociative similar to ketamine but with much stronger Dopamine reuptake inhibitor activity, as well as NMDA antagonist. As I was using it for as an anti-depressant and for ADD, I was having very small amounts daily with weekly breaks. I noticed after some months that I was developing an intolerance to this also, the nice dissociative, antidepressive and anxiolytic effects were diminishing, and the speedyness/potential anxiety was increasing way beyond how it was when I started. I also began doing escapist sessions with a friend every week or two, a large component of that was my worsening depression due to lack of progress in life. I was beginning to have a rollercoaster of mood swings that echoed bipolar and became worrying.

One day I foolishly let my friend give me too much and I OD'd, after I'd been so careful up to that point. At some point I crossed a threshold, a very distinctive barrier (from the over-flooding of dopamine I presume) when I suddenly realised something had gone horribly wrong. I had the worst anxiety and frightening perspective hallucinations, I was afraid I was going crazy (things were giant then tiny, then tall and squashed vertically, then fat and squashed horizontally etc). After it, I had this severe mental pain/agitation/anxiety recurring very frequently and very gradually reducing over the next 6 months, during which I found occasional GABA agonists like baclofen, phenibut, and gabapentin worked at the worst times. The feeling itself felt like a black hole in my stomach. I still get that a little to this day, both with too much dopamine/sugar in mornings or sometimes at night when I lie down. I had to cut out caffeine as that was the worst trigger. After 6 months of that, I tried the Moclobemide with amazing results initially.

It is already in trials for newborn epilepsy. Here its temporarily switches the brain into "adult mode" (hyperpolarization by GABA), and I assume that it could also help adult people with paradox reaction to gabaergic drugs.


From what I read about it, it allows chloride ions to leave cells more easily, and reducing the chloride inside brain cells may help GABA neurons’ inhibitory functions work better. In theory, this may well be effective for me.

Its strange, I didn't see this intolerance coming. It happened exactly at the same time of my first partial serotonin syndrome. I wondered whether they were somehow memory-linked events. I had anxiety one day and as soon as I popped an etizolam (which I later found out has additional SNRI activity), my energy drained and I became weak so fast I panicked hard, vision converged and lost consciousness in front of a friend for 4 mins, after which my heart raced at 90-120 bpm for 24h. Since then my GABA has been messed up. I first noticed when I tried alcohol, it was a real weird feeling, especially red wine which contains GHB. It was worsened extremely by Seroquel, just 2 light beers threw me into the worst nightmare of anxiety and depression for days.

2-3 years ago I was also using GHB almost nightly (1.5-2g) to combat my chronic insomnia. I didn't realise it could lead to problems down the line, I just thought as long as a tolerance doesn't develop I'll be fine. Boy was I wrong. In retrospect, its possible that I developed a reverse tolerance to this as well, as I noted I wasn't having to take 3g for maximal effects. I remember when I was first introduced to it 3.5g was my sweet spot for occasional social use, 4g was just unpleasant. But when I started using it for insomnia 1 or 2 years later (perhaps the fact I made it myself with perfect pH) 2.5g got me maximal effects, so mostly used 1.5-2g. I ran out of it 2 years ago thankfully.



It seems, You got nearly the same Issues as I.
Too much Coffeine triggers Mental Pain and "the Blackhole" in my stomach.

In my case mao-a inhibitors like passionflower do relieve the pain to some extend but may elevate it sometimes a bit.
Hordenine a mao-b inhibitor gave me the same euphoria back as I felt it once.

I would give tofiospam a try because it do help for me against the black hole in the stomach
( I the case we have really the same Issue).
Unfortunaetly it didnt modulate anything. So if You stop taking it, the depression comes back. Therefore I stopped it for myself.


In my case the bad mood is accompanied with cognitive/Intelligence decline and concetration, memory, strong anhedonia
+ lack of emphaty problems. It has recovered to a extend. So, I´m not allways depressed but the mood does swing. Therefore I concluded that my Dopamine storage is damaged. And the best possible explanation is a decrease in Vmat2 due Synaptic damage which causes a leackage of Neurotransmitters So hence the moodswings during the day(which imho didnt match to bipolar).
Given the mentioned issues it seemed to me that rather the Striatum, more precisely, the Caudate is damaged instead the Nucleus Accumbens. But it seems for me also that it does compesate the mood turbulences caused by the Striatum.

This are my Issues and my possible explanation to that. Maybe it could help You.





Also tagged with one or more of these keywords: brain damage, dopamine, gaba, receptors, panic attacks, anxiety, neural pain, regeneration, biochemical

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