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GABA-a Receptor Damage and Repair


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#31 irz

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Posted 12 February 2009 - 10:48 AM

Great I'm not alone. I stumbled upon this quite accidentally and wanted to add to the notion, that ciprofloxacetin problems are indeed very real.
I was taking these drugs for a couple of weeks and it was easily the worst time of my life. One day I was awoken by vertigo. You can imagine how fast my head was spinning. I couldn't sleep and it kept getting worser. The vertigo wouldn't stop for MONTH and it was paired with intense physical anxiety symptoms and constantly upcomming panic attacks. My doctoc wasn't beliving me so I had to "ride it out". It took me half a year on the couch and another year with somehow uncomfortable symptoms. I thought it would never get any better.

But it did. Now I'm somewhat sensitive to vertigo but ..well...I'm happy that my anxiety got away.

I wish I would have known a treatment. It sure is one hell of a drug.

#32 Matt

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Posted 14 February 2009 - 07:33 PM

Theres probably still some time to recover then. Most people i personally talk to recovered fully within 18 - 36 months. Only severe persons take 5 years or more.

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#33 yoyo

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Posted 20 February 2009 - 09:26 PM

i think the biggest problem is knowing just what the exact damage is that 'floxing' does. its not that i'm saying it doesn't exist, but that i don't know what it is other than 'getting damage from certain drugs'

assumingi gaba deficiency, it might be worth trying an antiglutamatergic anticonvulsant, like lamotragine, might help.

ketogenic diet could be worth trying too

tianeptine helps alcohol withdrawl. i think i posted some other things that help in another thread

Acute and chronic tianeptine treatments attenuate
ethanol withdrawal syndrome in rats

ABSTRACT

The effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.

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#34 comeva14

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Posted 05 March 2009 - 03:16 AM

A little background: about 3 weeks ago, I was floxed, which, for those of you who don't know, is a severe negative reaction to a quinolone antibiotic (ciprofloxacin in my case). Ciprofloxacin acts as a competitive antagonist at GABA-a receptors, which, acutely, can cause seizures. However, as a rare allergic case, I am still experiencing symptoms of GABA-a antagonism 3 weeks after discontinuation - difficulty sleeping, nonrestorative sleep, anxiety, tinnitus, shaking fingers. This leads me to believe that cipro is somehow still bound to my receptors (is this even possible?) or that it has destroyed many of my GABA-a receptors.

So, I'm wondering if anyone has any insight into whether the GABA system regenerates/repairs itself with time, and if there's anything (chemically) that I can do to expedite this process.

For teh brains, I currently supplement:
1. 100 mg choline citrate
2. 5g fish oil
3. 5 mg lithium aspartate.


Any knowledge or suggestions are greatly appreciated.


How are your symptoms now, about 5 or 6 weeks later?

#35 comeva14

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Posted 05 March 2009 - 04:40 AM

To help with the tendons you might consider a nicotine patch. Nicotine has been shown to increase angiogenesis.

Lithium Orotate also causes growth of the prefrontal cortex (thus neurons??)


Lithium is widely cited as having very favorable brain cell growth characteristics. Some people use small doses everyday. Probably would help to SLOWLY repair some of the brain damage discussed in this thread, especially by those that were damaged by chemo or quinolone drugs.

#36 Matt

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Posted 12 March 2009 - 04:29 AM

A person named John who was floxed 3+ years ago recently just got on the radio on various stations including sean hannity, and have a lot of publicity for the support forum and reactions to quinolones. Now unfortunately a group that existed for over 10 years and had over 60,000 messages have been wiped out *poof* and no one can get answers why. I don't want to sound paranoid but, are there any legal reasons why a group could be shut down where thousands of people documented their symptoms? Now 5 minutes ago I checked another quinolone forum and that has been shut down too.

Spooky lol.


And any improvement in your symptoms yet?

Edited by Matt, 12 March 2009 - 04:32 AM.


#37 VespeneGas

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Posted 12 March 2009 - 04:49 AM

The tinnitus only shows up when it's really quiet now, thank science. I thought that symptom alone might drive me crazy. Sleep is a bit better, but that's because I'm taking 75mg trazodone before bed time, and treating myself to one night of ambien-induced sleep per week (any more than that builds tolerance/dependence ;) ). So not really sure if sleep quality sans medication is improving.

My caffeine tolerance is totally in the toilet, which is crazy, because I used to take 2 no-doz just to stay up for three hours (freshman year of college). Now my green tea extract pill (New Chapter, containing 12-17mg caffeine) is way to racy, and I get a substantial buzz from raw cacao in my morning smoothie.

The joints and tendons I can handle, the pain is annoying but not intrusive, and I remind myself that I'll be able to exercise again some day. The really frustrating thing right now is the "prostatitis" for which the cipro was originally prescribed - now the doctor isn't sure it ever even WAS prostatitis, after months of antibiotics, and wants to refer me to a neurologist to test for neuromuscular disorders ("don't worry, just want to get you tested for huntingtons and MS") so he appears to be completely incompetent, given that this urine retention and constant throbbing abdominal pain comes at the heals of a documented UTI. Pure coincidence, in his senile mind. So I have no treatment for that and it hurts like hell :(

Thanks for the concern! Some days are hopeless, but usually I can remind myself that life will slowly get better.

that's terrible about the forums getting shut down. Smells like a rat, no?

#38 Matt

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Posted 12 March 2009 - 04:59 AM

Thanks for the update. Well I just learned that 5 websites on quinolone toxicity have been shut down. Hmmm

#39 Matt

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Posted 12 March 2009 - 05:06 AM

The caffeine intolerance thing goes away mostly after about 4-5 months. I found that much of our symptoms might be related to neuropathy, interestingly I could say that I had most of these symptoms listed here; http://www.patient.c...owdoc/40000795/

I had all the feet symptoms, all the gastro symptoms, all of the vision symptoms, and the sweating symptom. Also sometimes respritory but rarely. Plus teh CNS side effects from mechanisms we already know, and then you have the connective tissue problems which is already documented. Seems to me that this could be largely an issue that stems from generalized neuropathy that is accounting almost all symptoms. And also the cycles or long term nature of the disease could be explained because there is a delay on a lot of symptoms. Which is also quite common for chemotherapies and radiation therapy and other toxicities. Typically neuropathy can appear weeks, months to years later.

It's a long journey but you'll get there in the end!

Edited by Matt, 12 March 2009 - 05:06 AM.


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#40 VespeneGas

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Posted 21 March 2009 - 06:44 PM

I just found this WRT tendons, for any current and future floxed imminsters:

The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells.
Lowes DA, Wallace C, Murphy MP, Webster NR, Galley HF. Division of Applied Medicine, School of Medicine & Dentistry, University of Aberdeen, UK.

Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles' tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles' tendons were exposed to 0-0.3 mm antibiotic for 24 h and 7 days in the presence of 1 microm MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture.

PMID: 19235604 [PubMed - as supplied by publisher]

#41 raja

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Posted 09 December 2009 - 07:36 PM

Off-label use of this medication has been a boon

I have suffered horribly ... megadoses of b-complex ( i suspect b6 in my case) caused partly irreversible neuropathy 14 years ago. .. life in hell .. but turned to regular aerobics to keep me healthy and sane as far as possible.

Then i was floxed early this year. two days of cipro and.... joint pains , tinnitus, numbness, disturbed sleep, nighmares...tried almost everthing
baclofen, benzos, GABA this GABA that, off label use of antideps, homeopathy, naturopathy, body flushing, green tea, biochemistry

finally...... finally one things and given me back good quality of life. The way things have shaped in the the last 5 days that i have been taking it.. i have hopefull that it will repair my nerves to a fully healthy state.

here it is

http://www.himalayah...UCTS/mentat.htm

I take one large table spoon just before going to bed

Go through the research papers as well. is very interesting.

I hope this helps everyone. PS: if it benefits anyone Pls post this message to other similar boards to help others as well.

God! help all and show us the way. Peace

Raja Sen

#42 Logan

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Posted 24 September 2010 - 01:28 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja

#43 bobman

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Posted 24 September 2010 - 02:12 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.

#44 Logan

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Posted 24 September 2010 - 02:31 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.

#45 bobman

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Posted 24 September 2010 - 03:17 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.


LOL, again with this. Just no, there is nothing that even remotely suggests valporate is good for the brain at any dose. It's flatly nonsense, this is a substance with well documented neurotoxicity, and having this idea that at some low, but still therapeutic dose a neurotoxin suddenly becomes healthy is crazy. I'm sorry, it's just idiotic. With lithium I could see some very, very theoretical benefit based on some positive cognitive studies, although even that has more evidence of damaging cognition than benefiting it by a country mile.

#46 Logan

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Posted 24 September 2010 - 04:11 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.


LOL, again with this. Just no, there is nothing that even remotely suggests valporate is good for the brain at any dose. It's flatly nonsense, this is a substance with well documented neurotoxicity, and having this idea that at some low, but still therapeutic dose a neurotoxin suddenly becomes healthy is crazy. I'm sorry, it's just idiotic. With lithium I could see some very, very theoretical benefit based on some positive cognitive studies, although even that has more evidence of damaging cognition than benefiting it by a country mile.


Call it what you want. I equate it to drinking a glass of red wine as opposed to drinking 2 bottles. I think it is possible that someone could benefit from a lower dose of something that is toxic at higher doses. Toxicity with substances like valproic acid and lithium are dose dependent, and the same goes with many other substances, natural or synthetic.

While Rol82 is taking many risks with many pharmaceutical drugs, I believe he is a very bright individual that has done his research. He is another person that believes valproic acid may have some benefits. I'm sure he can give you some good reasons for taking a low dose of valproic acid. Just go over to the regimens forum and check out his.

Also, Vincent Giuliano has done quite a bit of research on valproic acid and possible anti-aging benefits- http://anti-agingfir...g-arises-again/

Here's some studies on Pubmed showing some promise in the use of valproic acid for health issues other than bipolar mania:

http://www.ncbi.nlm....pubmed/20160205

http://www.ncbi.nlm....pubmed/20021450

http://www.ncbi.nlm....pubmed/19628741

http://www.ncbi.nlm....pubmed/18640245

http://www.ncbi.nlm....pubmed/17398106

http://www.ncbi.nlm....pubmed/18649067

http://www.ncbi.nlm....pubmed/20530048

I'm not saying that we should all be using valproic acid, but I do think that it may have many applications as a fairly safe drug. I really see no reason for not trying a small dose of valproic acid to try to stimulate GABA neurogenesis, which is what the OP was trying to do.

#47 Yearningforyears

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Posted 24 September 2010 - 09:42 PM

I´m really into taurine right now and a study says that it might be able to treat brain damage caused from seizures. no harm in trying. It works like wonders for me (even though I have a history of seizures and a mood disorder on top of that).
Well at least it could be much worse.



#48 Yearningforyears

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Posted 24 September 2010 - 09:44 PM

Oh and one more thing. I work in a pharmacy and one of my clients (who is bipolar 1) said that she had a manic reaction after starting ciprofloxacine (or was it cefadroxile... i can´t really remember). You´re sure it´s not just temporary destabilization that will go away with time?

#49 bobman

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Posted 26 September 2010 - 01:40 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.


LOL, again with this. Just no, there is nothing that even remotely suggests valporate is good for the brain at any dose. It's flatly nonsense, this is a substance with well documented neurotoxicity, and having this idea that at some low, but still therapeutic dose a neurotoxin suddenly becomes healthy is crazy. I'm sorry, it's just idiotic. With lithium I could see some very, very theoretical benefit based on some positive cognitive studies, although even that has more evidence of damaging cognition than benefiting it by a country mile.


Call it what you want. I equate it to drinking a glass of red wine as opposed to drinking 2 bottles. I think it is possible that someone could benefit from a lower dose of something that is toxic at higher doses. Toxicity with substances like valproic acid and lithium are dose dependent, and the same goes with many other substances, natural or synthetic.

While Rol82 is taking many risks with many pharmaceutical drugs, I believe he is a very bright individual that has done his research. He is another person that believes valproic acid may have some benefits. I'm sure he can give you some good reasons for taking a low dose of valproic acid. Just go over to the regimens forum and check out his.

Also, Vincent Giuliano has done quite a bit of research on valproic acid and possible anti-aging benefits- http://anti-agingfir...g-arises-again/

Here's some studies on Pubmed showing some promise in the use of valproic acid for health issues other than bipolar mania:

http://www.ncbi.nlm....pubmed/20160205

http://www.ncbi.nlm....pubmed/20021450

http://www.ncbi.nlm....pubmed/19628741

http://www.ncbi.nlm....pubmed/18640245

http://www.ncbi.nlm....pubmed/17398106

http://www.ncbi.nlm....pubmed/18649067

http://www.ncbi.nlm....pubmed/20530048

I'm not saying that we should all be using valproic acid, but I do think that it may have many applications as a fairly safe drug. I really see no reason for not trying a small dose of valproic acid to try to stimulate GABA neurogenesis, which is what the OP was trying to do.



Lol, morgonator, how about you actually post studies, not some out of context abstracts. I know that you didn't read those studies, since they require a paid account and ncbi offers no university access. You have no idea what you're talking about, that is a fact.

Here is a primer on valporate: http://ukpmc.ac.uk/a...&tool=pmcentrez

Since you're a lover of excerpts:

"At therapeutically relevant concentrations, valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34). Inhibition of histone deacetylase may underlie the ability of valproic acid to reduce proliferation of C6 glioma cells and may correlate to its teratogenicity, as alterations in the normal proliferation rate of these cells can result in an embryo with a neural tube defect (35). Exposure to subteratogenic doses of valproic acid can cause microcephaly and behavioral changes (i.e., deficits in spatial learning tasks and altered locomotor activity) in rodents (30,36). In utero exposure of rats to valproic acid (at peak blood levels of 99–134 mg/mL) causes cerebellar anomalies (36)."

Please don't reply to this telling me that this is somehow unique to fetal exposure. It isn't, whatever dose, whatever stage of development, the drug has the exact same biochemical effect. Even if the damage is subclinical, it is happening. There isn't a dose where suddenly it changes mode of action and becomes neurologically beneficial.

Why? Because this is what valporate does: "valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34)."

If you had any knowledge of neurology you wouldn't dare post this level of bs.


Please in the future, stick with being an arm chair commentator, and stay away from giving medical advice. Your profligate demonstration of grade school search engine use is awesome in the original meaning.
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#50 Temp

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Posted 26 September 2010 - 02:18 AM

A little background: about 3 weeks ago, I was floxed, which, for those of you who don't know, is a severe negative reaction to a quinolone antibiotic (ciprofloxacin in my case). Ciprofloxacin acts as a competitive antagonist at GABA-a receptors, which, acutely, can cause seizures. However, as a rare allergic case, I am still experiencing symptoms of GABA-a antagonism 3 weeks after discontinuation - difficulty sleeping, nonrestorative sleep, anxiety, tinnitus, shaking fingers. This leads me to believe that cipro is somehow still bound to my receptors (is this even possible?) or that it has destroyed many of my GABA-a receptors.

So, I'm wondering if anyone has any insight into whether the GABA system regenerates/repairs itself with time, and if there's anything (chemically) that I can do to expedite this process.

For teh brains, I currently supplement:
1. 100 mg choline citrate
2. 5g fish oil
3. 5 mg lithium aspartate.


Any knowledge or suggestions are greatly appreciated.



Most SSRI's will cause increase in GABA receptors AFTER few MONTHS as your brain is attempting to regulate the extra seratonin flood....main reason why SSRI's take 8 weeks to fully work and also a reason why many of them "pooop out" after few months to years.

#51 Logan

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Posted 26 September 2010 - 04:57 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.


LOL, again with this. Just no, there is nothing that even remotely suggests valporate is good for the brain at any dose. It's flatly nonsense, this is a substance with well documented neurotoxicity, and having this idea that at some low, but still therapeutic dose a neurotoxin suddenly becomes healthy is crazy. I'm sorry, it's just idiotic. With lithium I could see some very, very theoretical benefit based on some positive cognitive studies, although even that has more evidence of damaging cognition than benefiting it by a country mile.


Call it what you want. I equate it to drinking a glass of red wine as opposed to drinking 2 bottles. I think it is possible that someone could benefit from a lower dose of something that is toxic at higher doses. Toxicity with substances like valproic acid and lithium are dose dependent, and the same goes with many other substances, natural or synthetic.

While Rol82 is taking many risks with many pharmaceutical drugs, I believe he is a very bright individual that has done his research. He is another person that believes valproic acid may have some benefits. I'm sure he can give you some good reasons for taking a low dose of valproic acid. Just go over to the regimens forum and check out his.

Also, Vincent Giuliano has done quite a bit of research on valproic acid and possible anti-aging benefits- http://anti-agingfir...g-arises-again/

Here's some studies on Pubmed showing some promise in the use of valproic acid for health issues other than bipolar mania:

http://www.ncbi.nlm....pubmed/20160205

http://www.ncbi.nlm....pubmed/20021450

http://www.ncbi.nlm....pubmed/19628741

http://www.ncbi.nlm....pubmed/18640245

http://www.ncbi.nlm....pubmed/17398106

http://www.ncbi.nlm....pubmed/18649067

http://www.ncbi.nlm....pubmed/20530048

I'm not saying that we should all be using valproic acid, but I do think that it may have many applications as a fairly safe drug. I really see no reason for not trying a small dose of valproic acid to try to stimulate GABA neurogenesis, which is what the OP was trying to do.



Lol, morgonator, how about you actually post studies, not some out of context abstracts. I know that you didn't read those studies, since they require a paid account and ncbi offers no university access. You have no idea what you're talking about, that is a fact.

Here is a primer on valporate: http://ukpmc.ac.uk/a...&tool=pmcentrez

Since you're a lover of excerpts:

"At therapeutically relevant concentrations, valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34). Inhibition of histone deacetylase may underlie the ability of valproic acid to reduce proliferation of C6 glioma cells and may correlate to its teratogenicity, as alterations in the normal proliferation rate of these cells can result in an embryo with a neural tube defect (35). Exposure to subteratogenic doses of valproic acid can cause microcephaly and behavioral changes (i.e., deficits in spatial learning tasks and altered locomotor activity) in rodents (30,36). In utero exposure of rats to valproic acid (at peak blood levels of 99–134 mg/mL) causes cerebellar anomalies (36)."

Please don't reply to this telling me that this is somehow unique to fetal exposure. It isn't, whatever dose, whatever stage of development, the drug has the exact same biochemical effect. Even if the damage is subclinical, it is happening. There isn't a dose where suddenly it changes mode of action and becomes neurologically beneficial.

Why? Because this is what valporate does: "valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34)."

If you had any knowledge of neurology you wouldn't dare post this level of bs.


Please in the future, stick with being an arm chair commentator, and stay away from giving medical advice. Your profligate demonstration of grade school search engine use is awesome in the original meaning.


Fair Enough...You do realize the study you quoted said "therapeutically relevant concentrations". You say valproic acid is not neurologically beneficial at any dose. What about people with specific neurological illnesses? What about people with Huntington's that benefit from valproic acid treatment?

I realize may not have made a very thoughtful or thorough post. Still, I don't think valproic acid the poison you're making it out to be. Is this temporary new account name you created, deletethisaccount, meant for me? Really?

I wasn't exactly giving medical advice, I just posted an abstract saying that valproic acid promoted GABA neurogenesis, something I thought might be relevant to this thread. I may not have the mental capacity at the moment to make as thorough a post as I would like, so maybe I should not attempt them at all. At least I'm not a miserable spineless prick.

Hey bobmann, why couldn't you just come on here and make a post under your normal account instead of creating a new one just to make a distasteful attempt to rip me a new asshole.

Edited by morganator, 26 September 2010 - 05:06 AM.

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#52 bobman

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Posted 26 September 2010 - 05:55 PM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.


LOL, again with this. Just no, there is nothing that even remotely suggests valporate is good for the brain at any dose. It's flatly nonsense, this is a substance with well documented neurotoxicity, and having this idea that at some low, but still therapeutic dose a neurotoxin suddenly becomes healthy is crazy. I'm sorry, it's just idiotic. With lithium I could see some very, very theoretical benefit based on some positive cognitive studies, although even that has more evidence of damaging cognition than benefiting it by a country mile.


Call it what you want. I equate it to drinking a glass of red wine as opposed to drinking 2 bottles. I think it is possible that someone could benefit from a lower dose of something that is toxic at higher doses. Toxicity with substances like valproic acid and lithium are dose dependent, and the same goes with many other substances, natural or synthetic.

While Rol82 is taking many risks with many pharmaceutical drugs, I believe he is a very bright individual that has done his research. He is another person that believes valproic acid may have some benefits. I'm sure he can give you some good reasons for taking a low dose of valproic acid. Just go over to the regimens forum and check out his.

Also, Vincent Giuliano has done quite a bit of research on valproic acid and possible anti-aging benefits- http://anti-agingfir...g-arises-again/

Here's some studies on Pubmed showing some promise in the use of valproic acid for health issues other than bipolar mania:

http://www.ncbi.nlm....pubmed/20160205

http://www.ncbi.nlm....pubmed/20021450

http://www.ncbi.nlm....pubmed/19628741

http://www.ncbi.nlm....pubmed/18640245

http://www.ncbi.nlm....pubmed/17398106

http://www.ncbi.nlm....pubmed/18649067

http://www.ncbi.nlm....pubmed/20530048

I'm not saying that we should all be using valproic acid, but I do think that it may have many applications as a fairly safe drug. I really see no reason for not trying a small dose of valproic acid to try to stimulate GABA neurogenesis, which is what the OP was trying to do.



Lol, morgonator, how about you actually post studies, not some out of context abstracts. I know that you didn't read those studies, since they require a paid account and ncbi offers no university access. You have no idea what you're talking about, that is a fact.

Here is a primer on valporate: http://ukpmc.ac.uk/a...&tool=pmcentrez

Since you're a lover of excerpts:

"At therapeutically relevant concentrations, valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34). Inhibition of histone deacetylase may underlie the ability of valproic acid to reduce proliferation of C6 glioma cells and may correlate to its teratogenicity, as alterations in the normal proliferation rate of these cells can result in an embryo with a neural tube defect (35). Exposure to subteratogenic doses of valproic acid can cause microcephaly and behavioral changes (i.e., deficits in spatial learning tasks and altered locomotor activity) in rodents (30,36). In utero exposure of rats to valproic acid (at peak blood levels of 99–134 mg/mL) causes cerebellar anomalies (36)."

Please don't reply to this telling me that this is somehow unique to fetal exposure. It isn't, whatever dose, whatever stage of development, the drug has the exact same biochemical effect. Even if the damage is subclinical, it is happening. There isn't a dose where suddenly it changes mode of action and becomes neurologically beneficial.

Why? Because this is what valporate does: "valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34)."

If you had any knowledge of neurology you wouldn't dare post this level of bs.


Please in the future, stick with being an arm chair commentator, and stay away from giving medical advice. Your profligate demonstration of grade school search engine use is awesome in the original meaning.


Fair Enough...You do realize the study you quoted said "therapeutically relevant concentrations". You say valproic acid is not neurologically beneficial at any dose. What about people with specific neurological illnesses? What about people with Huntington's that benefit from valproic acid treatment?

I realize may not have made a very thoughtful or thorough post. Still, I don't think valproic acid the poison you're making it out to be. Is this temporary new account name you created, deletethisaccount, meant for me? Really?

I wasn't exactly giving medical advice, I just posted an abstract saying that valproic acid promoted GABA neurogenesis, something I thought might be relevant to this thread. I may not have the mental capacity at the moment to make as thorough a post as I would like, so maybe I should not attempt them at all. At least I'm not a miserable spineless prick.

Hey bobmann, why couldn't you just come on here and make a post under your normal account instead of creating a new one just to make a distasteful attempt to rip me a new asshole.



Read it again. It has the same effects at < therapeutic doses. The damage shows up at "therapeutically relevant doses" yes, but that does not mean its mode of action changes, and if the mode of action hasn't changed it's still having potentially deleterious effects, in fact very likely, it would just be sub clinical, meaning you don't see a nystagmus, or gait issues, and it can't be detected on an iq test, which is notoriously insensitive to neurological damage.

edit: This is the same account, I was in conversation with maxwatt about deleting it, if you couldn't tell.

edit2: My point is that abstracts give you no real information. They are meant to prepare the reader for the information in the study, and do not provide enough information to make some tenuous connection to "low-dose" use, which again, means nothing, since you would first have to demonstrate the substance changes mode of action at that lowered does. What I'm telling you is that valporate does not. It will just cause less genetic damage at a lower dose.

Edited by deletethisaccount, 26 September 2010 - 06:11 PM.

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#53 Logan

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Posted 27 September 2010 - 03:39 AM

Did anyone mention Valproic Acid?

http://www.google.co...Fi2YXUA&cad=rja


I don't think valporate is very safe, it has a horrible cognitive profile, and is linked to permanent cognitive damage in zygotically exposed children. It has many effects other than upregulating GABA receptors, some of which you don't want; on balance it is more likely to decrease his mental state.


I should have mentioned a low dose. Again, just like lithium, valproic acid will unlikely have the same side effects at much lower doses than those given to control mania. Sometimes we have to take risks in order to discover benefits. It all really depends on individual brain chemistry as to whether something adversely affects or improves one's mental state. A good trial of a low dose is well worth it and I seriously doubt it will have any unwanted long term side effects.


LOL, again with this. Just no, there is nothing that even remotely suggests valporate is good for the brain at any dose. It's flatly nonsense, this is a substance with well documented neurotoxicity, and having this idea that at some low, but still therapeutic dose a neurotoxin suddenly becomes healthy is crazy. I'm sorry, it's just idiotic. With lithium I could see some very, very theoretical benefit based on some positive cognitive studies, although even that has more evidence of damaging cognition than benefiting it by a country mile.


Call it what you want. I equate it to drinking a glass of red wine as opposed to drinking 2 bottles. I think it is possible that someone could benefit from a lower dose of something that is toxic at higher doses. Toxicity with substances like valproic acid and lithium are dose dependent, and the same goes with many other substances, natural or synthetic.

While Rol82 is taking many risks with many pharmaceutical drugs, I believe he is a very bright individual that has done his research. He is another person that believes valproic acid may have some benefits. I'm sure he can give you some good reasons for taking a low dose of valproic acid. Just go over to the regimens forum and check out his.

Also, Vincent Giuliano has done quite a bit of research on valproic acid and possible anti-aging benefits- http://anti-agingfir...g-arises-again/

Here's some studies on Pubmed showing some promise in the use of valproic acid for health issues other than bipolar mania:

http://www.ncbi.nlm....pubmed/20160205

http://www.ncbi.nlm....pubmed/20021450

http://www.ncbi.nlm....pubmed/19628741

http://www.ncbi.nlm....pubmed/18640245

http://www.ncbi.nlm....pubmed/17398106

http://www.ncbi.nlm....pubmed/18649067

http://www.ncbi.nlm....pubmed/20530048

I'm not saying that we should all be using valproic acid, but I do think that it may have many applications as a fairly safe drug. I really see no reason for not trying a small dose of valproic acid to try to stimulate GABA neurogenesis, which is what the OP was trying to do.



Lol, morgonator, how about you actually post studies, not some out of context abstracts. I know that you didn't read those studies, since they require a paid account and ncbi offers no university access. You have no idea what you're talking about, that is a fact.

Here is a primer on valporate: http://ukpmc.ac.uk/a...&tool=pmcentrez

Since you're a lover of excerpts:

"At therapeutically relevant concentrations, valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34). Inhibition of histone deacetylase may underlie the ability of valproic acid to reduce proliferation of C6 glioma cells and may correlate to its teratogenicity, as alterations in the normal proliferation rate of these cells can result in an embryo with a neural tube defect (35). Exposure to subteratogenic doses of valproic acid can cause microcephaly and behavioral changes (i.e., deficits in spatial learning tasks and altered locomotor activity) in rodents (30,36). In utero exposure of rats to valproic acid (at peak blood levels of 99–134 mg/mL) causes cerebellar anomalies (36)."

Please don't reply to this telling me that this is somehow unique to fetal exposure. It isn't, whatever dose, whatever stage of development, the drug has the exact same biochemical effect. Even if the damage is subclinical, it is happening. There isn't a dose where suddenly it changes mode of action and becomes neurologically beneficial.

Why? Because this is what valporate does: "valproic acid alters the expression of certain homeobox genes and inhibits histone deacetylase, which is involved in the repression of gene expression (34)."

If you had any knowledge of neurology you wouldn't dare post this level of bs.


Please in the future, stick with being an arm chair commentator, and stay away from giving medical advice. Your profligate demonstration of grade school search engine use is awesome in the original meaning.


Fair Enough...You do realize the study you quoted said "therapeutically relevant concentrations". You say valproic acid is not neurologically beneficial at any dose. What about people with specific neurological illnesses? What about people with Huntington's that benefit from valproic acid treatment?

I realize may not have made a very thoughtful or thorough post. Still, I don't think valproic acid the poison you're making it out to be. Is this temporary new account name you created, deletethisaccount, meant for me? Really?

I wasn't exactly giving medical advice, I just posted an abstract saying that valproic acid promoted GABA neurogenesis, something I thought might be relevant to this thread. I may not have the mental capacity at the moment to make as thorough a post as I would like, so maybe I should not attempt them at all. At least I'm not a miserable spineless prick.

Hey bobmann, why couldn't you just come on here and make a post under your normal account instead of creating a new one just to make a distasteful attempt to rip me a new asshole.



Read it again. It has the same effects at < therapeutic doses. The damage shows up at "therapeutically relevant doses" yes, but that does not mean its mode of action changes, and if the mode of action hasn't changed it's still having potentially deleterious effects, in fact very likely, it would just be sub clinical, meaning you don't see a nystagmus, or gait issues, and it can't be detected on an iq test, which is notoriously insensitive to neurological damage.

edit: This is the same account, I was in conversation with maxwatt about deleting it, if you couldn't tell.

edit2: My point is that abstracts give you no real information. They are meant to prepare the reader for the information in the study, and do not provide enough information to make some tenuous connection to "low-dose" use, which again, means nothing, since you would first have to demonstrate the substance changes mode of action at that lowered does. What I'm telling you is that valporate does not. It will just cause less genetic damage at a lower dose.


I understand the mode of action probably does not change much. You have some very good points. It is not a drug I would ever want a developing brain to be exposed to. I'm still skeptical of whether lower doses, or higher "therapeutic" doses will do any real permanent damage. All psychiatric drugs change gene expression in one way or the other. Unfortunately, at this stage in the game, we don't have many options for therapeutic drugs that don't have potential for negative side effects like altering of gene expression in some manner. I will stick by my belief that valproic acid may have some real therapeutic benefit for some conditions aside from bipolar disorder.
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#54 bobman

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Posted 27 September 2010 - 05:46 AM

Read [the abstract] again. It has the same effects at < therapeutic doses. The damage shows up at "therapeutically relevant doses" yes, but that does not mean its mode of action changes, and if the mode of action hasn't changed it's still having potentially deleterious effects [...]

My point is that abstracts give you no real information. They are meant to prepare the reader for the information in the study, and do not provide enough information to make some tenuous connection to "low-dose" use ... What I'm telling you is that valporate does not [change mode of action at that lowered doses.]. It will just cause less genetic damage at a lower dose.


I understand the mode of action probably does not change much. You have some very good points. It is not a drug I would ever want a developing brain to be exposed to. I'm still skeptical of whether lower doses, or higher "therapeutic" doses will do any real permanent damage. ... Unfortunately, at this stage in the game, we don't have many options [...] [V]alproic acid may have some real therapeutic benefit for some conditions aside from bipolar disorder.


I guess we'll just have to agree to disagree. I also agree that it's possible that a sufficiently low dose would not cause permanent changes which would be noticeable, but I contend that at those doses the patient would experience no benefits either, as the effect & mode of action are intrinsically linked, and the overall effect is not only negative but mutagenic or epigenetic in nature. You're right, we don't have many options, and so I suppose valporic acid could be beneficial to someone whose major problem was a depletion of GABA, although I'd suggest exploring healthier options first, as this one is potentially dangerous.

Edited by Michael, 23 February 2012 - 02:41 PM.

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#55 Logan

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Posted 27 September 2010 - 11:23 PM

I guess we'll just have to agree to disagree. [...] You're right, we don't have many options, and so I suppose valporic acid could be beneficial to someone whose major problem was a depletion of GABA, although I'd suggest exploring healthier options first, as this one is potentially dangerous.


I completely understand and respect your concern. Cheers brotha.

Edited by Michael, 23 February 2012 - 02:36 PM.


#56 Lufega

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Posted 28 September 2010 - 03:05 AM

Metronidazole causes vertigo by binding to GABA/diazema receptors and preventing it's function there. This can be reversed by giving a couple of injections of diazepam to displace the drug. Maybe there's a similar mechanism involved with Cipro. ?

#57 Ark

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Posted 06 October 2010 - 05:35 AM

lemon balm-

#58 Steve_86

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Posted 09 March 2012 - 01:26 PM

Stole this from ScienceGuy's "TREATING ANXIETY SAFELY & EFFECTIVELY" thread: http://www.longecity...ly-effectively/

BACOPA MONNIERI:

BACOPA MONNIERI in fact might prove very helpful, since this has been shown in studies firstly to NOT be a GABA RECEPTOR AGONIST, but has in fact be shown to upregulate down-regulated GABA receptors, which means it could prove highly useful in helping to treat recovery from GABA RECEPTOR AGONIST ADDICTION:

Epilepsy Behav. 2010 Apr;17(4):441-7. Epub 2010 Feb 11.

Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A.

Mathew J, Peeyush Kumar T, Khan RS, Paulose CS.

Source
Department of Biotechnology, Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Kerala, India.

Abstract
In the present study, the effects of Bacopa monnieri and its active component, bacoside A, on motor deficit and alterations of GABA receptor functional regulation in the cerebellum of epileptic rats were investigated. Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the cerebellum of epileptic rats revealed a significant decrease in B(max) compared with control. Real-time polymerase chain reaction amplification of GABA(A) receptor subunits-GABA(Aalpha1), GABA(Aalpha5,) and GABA(Adelta)-was downregulated (P<0.001) in the cerebellum of epileptic rats compared with control rats. Epileptic rats exhibit deficits in radial arm and Y-maze performance. Treatment with B. monnieri and bacoside A reversed these changes to near-control levels. Our results suggest that changes in GABAergic activity, motor learning, and memory deficit are induced by the occurrence of repetitive seizures. Treatment with B. monnieri and bacoside A prevents the occurrence of seizures thereby reducing the impairment of GABAergic activity, motor learning, and memory deficit.

PMID: 20153260


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#59 bernard

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Posted 05 July 2012 - 01:45 AM

Heres one article on Quinolones and GHB as a treatment
http://aac.asm.org/c.../40/11/2573.pdf


I'd be happy to try it out [GHB is actually neuroprotective],


Neurotoxicity

In multiple studies, GHB has been found to impair spatial and working learning and memory in rats with chronic administration.[37][38][39][40] These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.[37]
Pedraza et al. (2009) found that repeated administration of GHB to rats for 15 days drastically reduced the number of neurons and non-neuronal cells in the CA1 region of the hippocampus and in the prefrontal cortex. With doses of 10 mg/kg of GHB, they were decreased by 61% in the CA1 region and 32% in the prefrontal cortex, and with 100 mg/kg, they were decreased by 38% and 9%, respectively. It is interesting to note that GHB has biphasic effects on neuronal loss, with lower doses (10 mg/kg) producing the most neurotoxicity, and higher doses (100 mg/kg) producing less.
Pretreatment with NCS-382, a GHB receptor antagonist, prevents both learning/memory deficits and neuronal loss in GHB-treated animals, suggesting that GHB's neurotoxic actions are mediated via activation of the GHB receptor.[40] In addition, the neurotoxicity appears to be caused by oxidative stress.[40][41][42]


No It's not...

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#60 mycotheologist

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Posted 20 July 2012 - 03:14 PM

Floxing sounds pretty horrific. To the OP and Matt, have you both made a full recovery? I hope so since its been over 3 years now.

EDIT: Yeah, GHB is definitely not neuroprotective. When it wears off, theres a flood of glutamate.

Edited by mycotheologist, 20 July 2012 - 03:16 PM.





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