"Homeostatic Plasticity Drives Tinnitus Perception in an Animal Model"

[mock turtle]

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/

---

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/

----

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


----

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?

 

[joe]

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?

 

[Markku]

The findings aren't exactly new. Check the link below. I noticed this new study used the same drug as the previous study: vigabatrin.

http://www.ncbi.nlm.nih.gov/pubmed/17221143

It was hypothesized that vigabatrin would decrease the evidence of tinnitus by restoring central inhibitory function through increased GABA availability.
Vigabatrin completely and reversibly eliminated the psychophysical evidence of tinnitus at both doses. Although vigabatrin has serious negative side effects that have prevented its clinical use in the USA, it is nevertheless a potentially useful tool in unraveling tinnitus pathophysiology.

I dunno. Gabapentin (Neurontin) itself hasn't helped many tinnitus cases. If you google for neurontin tinnitus or gaba tinnitus, you'll find that there are people with tinnitus who've got neurontin for other conditions and it hasn't helped their tinnitus at all. Then again, vigabatrin isn't the same thing as gabapentin and doesn't have the same mechanism of action and also has way more serious adverse effects.

Gabapentin:
Gabapentin was initially synthesized to mimic the chemical structure of the neurotransmitter gamma-aminobutyric acid (GABA), but is not believed to act on the same brain receptors.
One possible mechanism of action, reported by Ben Barres of Stanford University and colleagues in Cell in 2009, was that gabapentin halts the formation of new synapses.[40] Gabapentin binds to the α2δ subunit (1 and 2) and has been found to reduce calcium currents after chronic but not acute application via an effect on trafficking[41] of voltage-dependent calcium channels in the central nervous system.[42] This effect on calcium channel trafficking is another possible mechanism of action of gabapentin, but the exact mechanism remains in dispute.

Vigabatrin:
Vigabatrin is an irreversible suicide inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of GABA, which increases the level of GABA in the brain.[1][8] Vigabatrin is a racemic compound, and its -enantiomer is pharmacologically active.[9],[10]


My tinnitus, by the way, doesn't react to glutamine at all. I've even taken L-Glutamine as a supplement (5-10 grams a day) with no effect whatsoever.

It doesn't mean, however, that Vigabatrin couldn't reduce my tinnitus. No doctor is going to prescribe vigabatrin for tinnitus tho. The possible side effects are kind of huge. Similar drug to vigabatrin with fewer side effects could be just what at least some tinnitus patients needed.

From Wikipedia I can find that vigabatrin is sometimes used for treating epilepsy. It would be interesting to find someone who has/had tinnitus and took vigabatrin. Did they notice reduction (or even complete elimination) in their tinnitus...

 

[mock turtle]

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]

Yeah, speaking of Phenibut, I've tried that too. It's hard to say did I notice improvements in T, probably a little, but the little improvement could be attributed to the effects mentioned below...

Phenibut does have a very nice relaxing and calming effect, makes me sleep like a baby & wake up refreshed. The only problem is that tolerance builds up quickly. Continual use isn't suggested and at least cycling is recommended (i.e. 3 days on, 3 days off, or something).

I still have some phenibut left (I use the brand Primaforce), so will need to take note of my tinnitus next time I use it.

Re: vigabatrin, yes, it's interesting that the study I linked to and the study by Dr. Shaowen Bao used the same drug, vigabatrin. And both times with great results... Of course not on humans, but animal models anyhow. I'm sure there are people who have taken vigabatrin for other conditions and who also has tinnitus, but finding those people is tough, especially because vigabatrin is not widely used...

Taking one or two vigabatrin pills just to test the drug out might interest me. From what I can find I likely wouldn't drop dead...

The adverse effects of vigabatrin are bad, for example:
Visual field defects had been reported as early as 1997 by Tom Eke and others, in the UK. Some authors, including Comaish et al. believe that visual field loss and electrophysiological changes may be demonstrable in up to 50% of Vigabatrin users.

Huh...

And...

Out of 2,081 subjects, somnolence (12.5%), headache (3.8%), dizziness (3.8%), nervousness (2.7%), depression (2.5%), memory disturbances (2.3%), diplopia (2.2%), aggression (2.0%), ataxia (1.9%), vertigo (1.9%), hyperactivity (1.8%), vision abnormalities (1.6%), confusion (1.4%), insomnia (1.3%), impaired concentration (1.2%), personality disorder (1.1%).[1] Out of 299 children, 33 (11%) became hyperactive.[1]
Some patients develop psychosis during the course of vigabatrin therapy,[11] which is more common in adults than in children.[12] This can happen even in patients with no prior history of psychosis.[13] Other rare CNS side effects include anxiety, emotional lability, irritability, tremor, abnormal gait, and speech disorder.[1]


But I think one would need to be very unlucky to develop some of these things if only taking one or two doses.

I'd just like to test it out to see the effects on tinnitus. I guess that effect can be seen starting from the first dose? So it doesn't need to build up like SSRIs etc...


I'd also like to point out that I used to have epilepsy. Benign rolandic epilepsy. I had two-three seizures when I was about 7-8 after which I was prescribed Oxcarbazepine (Trileptal). During the medication I was seizure-free. At the age of 15 I quit the drug and never had seizures after that either. I'm very happy about that. Because I know how tough of a hardship epilepsy can at the worst be (I used to have one friend who had very bad epilepsy, one that seemed like untreatable because he had gone through the most rigorous treatments and still got daily seizures).

Anyway, I think it's definitely possible my history of epilepsy might have made me more susceptible to tinnitus... Who knows.
I went through EEGs and MRIs before, during and after the treatment (Trileptal). After I had stopped the drug, been off of it for about a year, I went in for a set of these tests one last time. The neurologist told me that he couldn't find any abnormalities of any kind and said I'm healthy as could be.
Still, I have a feeling my brain is more prone to things like epilepsy, perception of tinnitus, etc.

 

[joe]

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

 

[Jim]

Oh man, you guys are way over my head here!

Drugs that increase GABA, " Valium, Xanax, Zoloft " they increase or imitate GABA

The only thing I can add is I have taken all 3 of the above for short periods to relieve anxiety. I never noticed any effect on the T.

 

[joe]

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

 

[mock turtle]

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)

 

[joe]

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​

 

[Karl]

....
I dunno. Gabapentin (Neurontin) itself hasn't helped many tinnitus cases.

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."

 

[mock turtle]

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

 

[joe]

Campral (acamprosate calcium), its a double edge sword

we cant use vigabatrin

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

 

[mock turtle]

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

 

[mock turtle]

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

 

[joe]

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.​

 

[mock turtle]

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

 

[joe]

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

 

[Markku]

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

Interesting. I just today received a package and amongst other items it contained Labrada Nutrition's Charge!

It says on the bottle that it contains 20mg of Pikatropin (Picamilon), and quite soon after I took the suggested serving of 2 capsules I noticed a reduction in my tinnitus. It's like it went way more to the background than usual and actually seems like it's capable of reducing the volume / annoyance of my tinnitus.

Maybe placebo, but then again I have tried a ton of stuff (incl. ginkgo that didn't have any effect) to reduce my tinnitus and nothing has made such a difference as this 20mg of picamilon.

I couldn't find plain Picamilon on iHerb's site, I wonder where I could order it online. The "Charge!" product does give a nice energy boost, but I'd rather not use it as often as I could use Picamilon. And I could also test higher dosages of picamilon if I had a product that contained only it.

 

[mock turtle]

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

 

[joe]

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.

 

[mock turtle]

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

 

[joe]

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

 

[mock turtle]

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

 

[jazz]

Interesting. I just today received a package and amongst other items it contained Labrada Nutrition's Charge!

It says on the bottle that it contains 20mg of Pikatropin (Picamilon), and quite soon after I took the suggested serving of 2 capsules I noticed a reduction in my tinnitus. It's like it went way more to the background than usual and actually seems like it's capable of reducing the volume / annoyance of my tinnitus.

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]

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.

I did experience no adverse effects whatsoever. I read on "Longecity" (the previous Imminst) quite a bit about Picamilon before taking it. I haven't taken it for a long while, but it's one substance I'd like to test out again.

e.g. http://www.longecity.org/forum/topic/44565-unexpected-possible-effect-from-picamilon/

Le Magazine, July 1997 - Late Breaking New: How And Why Picamilon Works

Too bad it isn't available through my favorite supplement sites iHerb & Vitacost.
These two companies sell Picamilon though:
http://smart-drugs.net/info-picamilon.htm
http://supplements.relentlessimprovement.com/picamilon-p282.aspx

Some other threads about supplements & tinnitus in general on Longecity:
http://www.longecity.org/forum/topic/19113-tinnitus/?q=forum/topic/19113-tinnitus/
http://www.longecity.org/forum/topi...pic/18594-nootropics-that-alleviate-tinnitus/
http://www.longecity.org/forum/topi.../6411-what-are-some-good-things-for-tinnitus/

 

[Hudson]

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

 

[Juice564]

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

 

[jazz]

Thanks Markku for the information and links!!

 

[Karen]

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?