"Homeostatic Plasticity Drives Tinnitus Perception in an Animal Model"

The uc berkley scientist who headed the study published sept 2011 tht i believe has been linked at TT before received some interesting reporting in scientific american as the article includes somee information not available in the abstract (full publication behind pay wall) and some graphs and quotes

and heres one money quote

"So. We know the rats’ brains remapped. We know that the individual neurons are more excitable. We know the rats have tinnitus. The question is, can they BLOCK the effect? The idea is that if individual neurons are more excitable, they lack inhibition. Inhibition is usually provided by the neurotransmitter GABA. So if, after hearing loss, you have less GABA signaling, you have excitatory signaling that is uninhibited, and you might get tinnitus. But you don’t KNOW this unless you block the effect.
And it worked! When the authors gave drugs to the deafened rats that increased GABA signaling and tested them on conditioned place preference again, the rats began to prefer the dark side, suggesting they weren’t hearing the high pitched tones in their head anymore."

http://blogs.scientificamerican.com.../13/tingling-neurons-titillate-your-tinnitus/

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heres how the research was published at the UC berkley neewspaper and if you read the article there is reference to a comapany called "possit science" that appears to be moving in a commercial direction with the findings

http://newscenter.berkeley.edu/2011...y-could-lead-to-new-ways-to-stop-the-ringing/

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the original published research paper behind the pay wall is at the Proceedings of the National Academy of Sciences,

http://www.pnas.org/content/108/36/14974.abstract

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and here is dr shaowen bao's site at uc berkley

http://baolab.org/

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im trying to get a line on what possit science is about , i found their web site and it looks very commercial (so im not leaving a link) and kinda put me off but im diggin into it

seems like what they are doing is like neuromonics...no?

Interesting, the ANM T30CR is programmed to produce 4 tones One at T level and 3 up and bellow, if the tones are successful enough to travel through the ear and to the auditory cortex, this would give inhibition to the missfiring neurons, hence that's why alot of people have success with it. however if you have hearing loss the frequency or neuron that may need stimulating may not be reached

Hmmmmmmmmmmmm

Wait minute

Lets look at this the other way round; like DR Bao has, he mentioned that there's a deficiency of GABA after hearing loss which make the neurons excitable and lack inhibition ( hence Tinnitus) so what if we increase GABA and give the neurons the inhibition. Drugs that increase GABA, " Valium, Xanax, Zoloft " they increase or imitate GABA

People who have taken Xanax for long periods and have discontinued the drug instantly, instead of doing so gradually experience Tinnitus, this must me role reversal, going from sufficient GABA, to not enough hence the neurons start firing.

We all know that Drugs such as Valium are quite addictive, I would personally try a different approach for now, and this has actually just solved another mystery hopefully, we all get good and bad days of our Tinnitus, this maybe because of foods that increase GABA, these would be foods that are rich in glutamic acid (glutamate) forms glutamine, precursor to GABA. So this maybe happening to us daily in our diets when we consume the following.

Almonds
Bananas
Beef Liver
Broccoli
Brown Rice
Halibut
Lentils
Oats, whole grain
Oranges, Citrus Fruits
Rice Bran
Spinach
Walnuts
Whole wheat, Whole Grains

I hope I got my theory right !!

Mock Turtle , Markku, and Jim what you think?

Joe

i personally experience a reduction in the perceived loudness of tinnitus when taking clonazepan a GABA agonist...but interestingly enough i dont get as significant effect from lorazepan or some of the other benzos ...strange; (btw, i never tried xanax)

i measure this effect by noting what kind of noise and at what volume it takes to mask the T

i agree with you that as a concern, benos are habit forming and likely lead to dependency, so it seems we need something other than a gaba agonist ,

something that increases the natural production of GABA may be a better approach...and you gave a great food list that i agree is a good way to go...and i would add yoga (and meditation) because research indicates yoga increaes the bodys natural production of GABA !!

Markku

i think you are on to something as you explore the gaba related meds that have anticonvulsant activity (while some researchers see T as similar in some ways to phantom limb syndrom... OTHERS.... see tinnitus as kinda like an epileptic storm in the auditory cortext where there is synchronous firing in the absence of real sound stimuli...curious)

but i would add , that as you, we look at gaba and anti convulsant drugs, we should also consider that the GABA ligand has more than one sub unit ... there is more than one kind of GABA receptor. for example straight gama amino butyric acid targets the alpha ligand, but beta phenyl gamma amino butaric acid (phenibut) targets the beta gaba ligand...one that is also targeted by some benzos and even alcohol

this might explain why L-glutamine has less or no impact for some manifestations of T..depending on the ligand involved

you make some insightfull observations about the different apporaches and side effects to managing levels of gaba in the body

your points about vigabatrin are very interesting...heres a drug that rather than agonizing gaba receptros or artificially adding synthetic gaba to the system, instead, block or down regulates the enzymatic destruction of the bodies natural production and supply of GABA (like a reuptake inhibitor does for serotonin?)

if we could find a drug like this with less or fewer negative side effects...wow

thanks Joe and Markku for your response to the article i talked about

Markku You targeted the Beta Ligand GABA with Phenibut this may have not made the connection required to complete synapses. You come very close well done!!

The Alpha Ligand GABA is what we need to build on!!!!!!! as this is where there may of been complete elimination of Tinitus.. Vigabatrin is the only drug I can find that has the structure to do it. Is there someone out there that can help us... we have come so close there must be some way of doing it.. Mock Turtle any Ideas?? Markku anyone, out there

Hmmm there all benzo's that target beta ligand.. Is there anyone taken viabatrin? Its the only one that targets the alpha ligand... Darn sideffects!!! I would take it myself if I could get my hands on it here in the uk

you guys (and gals) want to have a good laugh...or a cry.... about the side effects of vigabatrin that Markku talked about above ?...well get this one

Pramipexole, which was on the ATA list some time ago of promising tinnitus control medications...

it has possible side effects of gambling, hyper sexuality, compulsive shopping, and yes you guessed it.... cross dressing !!

that stuff makes vigabatrin not look so bad, dont cha think?!

(ya know i spent some time in my youth in greenwich village nyc in the 60s...i bet i could handle them side effects)

(snark meter pinned)

Side Effects all drugs have side effects, some people are more effected than others, some people are more resistant to them some are not, Vigabatrin or Sabril is the only GABA T drug.... It prevents the breakdown of GABA resulting it staying in the brain for longer.

The other point I want to make is, this: Its often mentioned that Tinnitus is worse on days when the sufferer is under stress or anxiety, GABA's main role is calming nerve activity, so were using more of our stock if were anxious, it seems theres not much of this stock to go around and it breaks down quickly. Vigabatrin stretches it out for longer less breakdown

This could also answer the placebo effect too Heres how

were fooled were getting better, = LESS ANXIETY = MORE GABA in the brain for longer = Reduction in Tinnitus

I'm convinced if we increase GABA and hold it down for longer we can alleviate Tinnitus.

Heres our BABY

Vigabatrin

Systematic (IUPAC) name

(RS)-4-aminohex-5-enoic acid

Clinical data

Trade names Sabril

Markku -
In the Winter 2011 issue of "Tinnitus Today", there is a letter, "My Tinnitus Cure" describing how gabapentin helped one person's tinnitus:

"For many years, I had serious tinnitus...I visited an academic neurologist specializing in epilepsy and electricity in the brain. His diagnosis was a lesion on my brainstem that caused a rare form of reflex epilepsy...He prescribed gabapentin....As I left his office that day, he also made the comment that the gabapentin would likely also cure my tinnitus. Within a day, my tinnitus had decreased in severity and frequency by 90%. I have taken 1,500 mg gabapentin daily these last few years and my tinnitus remains abated."

Karl
interesting point, and heres an NIH Pub Med reported study which indicates that between 15 and 25% of people with tinnitus treated with gabapentin demonstrated significant improvement...people whos hearing was damaged by noise trauma seemed to do better than those suffering from tinnitus due to other causes
"CONCLUSION:

"Gabapentin is effective in reducing subjective and objective aspects of tinnitus in some individuals, with the best therapeutic response obtained in individuals with associated acoustic trauma."

"Gabapentin is effective in reducing subjective and objective aspects of tinnitus in some individuals, with the best therapeutic response obtained in individuals with associated acoustic trauma."

read the abstract here:
http://www.ncbi.nlm.nih.gov/pubmed/16652071
Effect of gabapentin on the sensation and impact of tinnitus.

Bauer CA, Brozoski TJ.

Source

Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9662, USA. cbauer@siumed.edu

Campral (acamprosate calcium), its a double edge sword

we cant use vigabatrin

but whats to say we cant use Campral enhance the GABA Tranmission??

Joe,

several comments above you asked what we can take to target the apha ligand of the gaba receptors to control tinnitus

and also you questioned whether or not benzos are effective at the GABA alpha ligand

let me say that ethanol (alcohol), benzos, barbiturates, kava, valerian, l-theanine and many other meds and supplements are indeed gaba alpha agonists (active at the gaba a ligand) and they are agonists(which means they act like more gaba or support gaba as opposed to antagonists which block the action or inhibit gaba)

as you look for meds that target GABAa (alpha) keep in mind, as you know, we could just use GABA itself except it does not pass the blood brain barrier (BBB) very well if at all

a possible way to get by this here in the us (EU has different supplement regs so i dont know) is to take picamilon which is a chemical combination (not a mixture) of niacin and gaba, which gets the gaba across the BBB

as we disused up-thread phenibut passes the BBB but seems to target the beta ligand of the gaba receptor

Markku indicated that phenibut (beta-phenyl-gamma-amino-buteric-acid) was not noticeably effective in turning down the volume on his tinnitus

so lets assume that it IS the alpha ligand that needs to be targeted to help us,.... if so, ....then benzos, or alcohol, or some of the others listed above should be effective...and indeed, at least for me.... these have helped ...problem is a person cant drink every day for the rest of their life nor can they take benzos long term

vigabatrin looks like a vey interesting medication as it halts the elimination of GABA and only acts in the brain as opposed to peripheral systems tht rely on GABA, however there are questions about side effects especially damage to eye sight

i suspect that targeting GABAa is paliative, gives us a break, eases the pain...but is not a true remedy and does not get at... nor does it fix... the source of tinnitus...just guessing here as im half smart and half the fool

i like your ideas about caroverine better

best wishes

Joe

i seem to remember acamprosate was tested (funded in part by ATA) several years ago and there was a brazilian study before that

both studies inidcated a good degree of positive results...but then...poof..nothing

kinda like the neramexame fiasco...seems like things look good and then for some reason, i dont know, maybe its the 60% success rate where patients report only (ONLY!) a 50% reduction in the perception of T loudness that causes investors... or whom ever... to say, hey, never mind ? ! ...... i just dont know

I keep hitting a stumbling block everytime I come close, hmm ?? With caroverine they go iv with it as it needs to cross BBB, I think the cochlear is only reachable this way or through the round window.

Any effective treatment is going to have to cross the BBB. Or maybe its not the cochlear that needs the shot its the Brain....... Hmmm I have sent an email to the guys in Austria that carried out the trial for caroverine, to see if they will give me an infusion, I am trying to avoid going to India for it.

Joe...i agree with your idea about austria...i may be next in line

i like your preference for caroverine because it seems to be "remedial"... as in, fixing the problem.... rather than palliative or perception dulling, like the drugs that suppress some part of the brain

lets hope they get back to me, I think I need to act fast, as this drug might go on demand in Austria

picamilon, yes very interesting supplement

since brain over activity in regions devoted to auditory function are implicated in tinnitus ,it makes sense that if we can boost brain gaba then tinnitus should be decreased

Picamilon, qute easily obtained on ebay, UK, USA, upto 150mg, quite interesting to hear its good result with you markku, although from the same family of nootropics as piracetam which had no effect in previous experiments, Picamilon goes in hand with our understanding of Gaba, Good.

Markku

i went to two large supplement stores here in the northwest and could not ind picamilon

guess its order online or nothing...have you been able to get picamilon by itself yet?

best wishes
mock turtle

Mock, Hope your well !!! get it on Ebay,

Joe ,
yes i will,
thanks,
best wishes to you
mock turtle

Markku,

Are you still taking the Picamilon? What were the side effects? My hearing aids helped a lot, but for the past few days I'm spiking as the day progresses. Overnight, I reset and wake up great. (Better than before the hearing aids.)

That said, I was glad to find this thread on Picamilon, for it is something I've never tried. I know my tinnitus is GABA sensitive.

Markku,

Are you still experiencing some relief with this product? I might pick up a bottle online and try it myself.

Do you think it will have any adverse effects with the buspirone that I take, or should I consult the pharmacist about that?

Thanks

Hmm I'll give it a shot. Think I'll order some today. Thanks for the write up!

Thanks Markku for the information and links!!

I wonder how the Picamilon compares to PharmaGABA? I was taking PharmaGABA for awhile, and it had a mild calming effect on me. It didn't really help my tinnitus very much, but it did help with anxiety. It looks as if the main difference is that Picamilon contains niacin. Is that correct?