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    Help needed - long-term gabaergic drug use. 
    #1
    Hi, I've come to Bluelight because of the wealth of valuable experience this forum offers to many.

    My situation is this. I have severe noise-induced tinnitus/hyperacusis which is preventing me working/functioning over last 14 months.

    Research by prof. R.A.Levine at Harvard has suggested loss of gabaeregic inhibition in the auditory pathways and limited studies
    have shown Clonazepam to quieten tinnitus. I experienced a mild but significant improvement with Clonazepam but am concerned
    about tolerance/rebound issues. Some highly reputable people like Levine, Nagler (connected with American Tinnitus Association), etc,
    have recommended taking Xanax daily for life and openly said that the fuss about tapering off is over-blown and can be achieved
    sensibly without repurcussions when the time comes. I am naturally worried because rebound means worse tinnitus. It's difficult to
    know who to trust especially since the dangers of dabbling with benzos has been so warned about by the likes of Dr. Heather Ashton.

    So, some questions.

    1. Is it realistically possible to develop a long-term gabaergic program, cycling say between GabaA and GabaB receptors, in order
    to balance up-regulation? Has anyone ever done this? Anecdotes welcome. How do you think I could do this?
    Has anyone come up with a list that could be cycled (klonopin, baclofen, gabapentin,etc) in such a way to maximise positive effects
    and minimise problems. Suggested dosages?

    2. Much is said of the dangers of constant up-regulation of Gaba receptors....what goes up must come down. But what if one is
    dealing with a Gaba deficiency? Does this this alter the ground-rules in any way, permitting more 'artificial' Gaba production?

    3. What of those guys on Xanax for ten years+? Has the drug lost its efficacy by then for most users? What's going on here?
    Is it possible for the drug to remain potent, carrying out a valuable compensatory role for under-production of gaba in the tinnitus brain?

    4. Non-drug paths. Exercise can increase Gaba naturally. Eventhough I can barely stagger between rooms, I'd be willing to train for a marathon
    to increase any chemical that can suppress tinnitus. Does anyone have figures. How much strenuous exercise exercise required
    to produce x units of Gaba? Also electrical stimulation (Fisher Wallace,etc) has claimed to boost GABA/serotonin by 60%

    A combo-strategy would seem attractive, if it works.

    So you know, I did have very bad 'untreatable' unmaskable noise-induced tinnitus years ago which completely disappeared after
    about 5 years, so even if the hardware is damaged the software is plastic and can fix itself. Enhancing gabaergic inhibition
    may be critical to this process, which is why the answer to these questions will be so important.

    Many thanks for reading my post. Any opinions/ advice will be valued/respected and will prove of benefit to many others.

    Marcus
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    #2
    Hi and welcome to Bluelight.

    Sending your thread over to Advanced Drug Discussion.

    BDD > ADD
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    #3
    Bluelighter FlippingTop's Avatar
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    Quote Originally Posted by marcus77 View Post
    Some highly reputable people like Levine, Nagler (connected with American Tinnitus Association), etc,
    have recommended taking Xanax daily for life and openly said that the fuss about tapering off is over-blown and can be achieved
    sensibly without repurcussions when the time comes.
    Fucking What? Xanax will be less and less effective, doses will be upped Considerably and the withdrawal will be a living hell!

    Can you just make one thing clear, you don't have gaba-induced tinnitus from years of drinking / abusing other Gaba drugs, am I correct?
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    #4
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    My situation is this. I have severe noise-induced tinnitus/hyperacusis which is preventing me working/functioning over last 14 months.
    Have your doctors attempted a differential diagnosis to identify an underlying cause? If so what were their findings?

    I understand that sometimes its untreatable, but have you explored the option of surgery or masking?

    1. Is it realistically possible to develop a long-term gabaergic program, cycling say between GabaA and GabaB receptors, in order
    to balance up-regulation? Has anyone ever done this? Anecdotes welcome. How do you think I could do this?
    It's difficult to cycle between GABA-A and GABA-B agonists since most studies point towards the fact that they share no cross tolerence. For example, if you were to become dependant on Baclofen or GHB and decided to rotate to benzodiazepines, you will be completely resistant to their sedative, hypnotic, and anti-convulsant effect as seen in many cases of GHB or Ethanol withdrawal.

    You might ask, "we'll, if I rotate I won't become dependant."

    Tolerance will always prevail sooner or later irregardless of rotation. Neurototoxicity, excitotoxicity, caused by glutamate up regulation will eventually take place causing a basket of unwanted symptoms. Dysfunctions in neuroadaptation will instigate GABAergic kindling, arousing more severe symptoms between each switch.

    Now, since you mentioned gabapentin, this maybe your salvation. Gabapentin and its more potent successor Pregabalin belong to a glass of drugs called calcium-channel-blockers which are potent neuroprotective inhibitors of glutamate allowing them to effectively halt excitotoxicity and apoptosis (GABAergic withdrawal). Even though these drugs have no direct impact on GABA-A it's well known that through these effects that they impose, they can be cycled with GABA-A agonists or GABA-B agonists without suffering any withdrawal symptoms.

    So, two options could be:

    GABA-A agonist -> Gabapentin -> GABA-B agonist -> Gabapentin etc.

    GABA-A or GABA-B agonist -> Gabapentin etc.

    In theory this cycle should mitigate GABAergic withdrawal to a limited but effective extent.

    2. Much is said of the dangers of constant up-regulation of Gaba receptors....what goes up must come down. But what if one is
    dealing with a Gaba deficiency? Does this this alter the ground-rules in any way, permitting more 'artificial' Gaba production?
    There is no such thing as artificial production of GABA, GABA is synthesized by neurons with the help of a substance called glutamate decarboxylase and the active form of vitamin B6 called pyridoxal phosphate. You can activate/inhibit/agonize or deactivate/excite/antagonize GABA through the use of agonists/antagonists. They merely increase the effeciency of already available GABA.

    I think by dangers of up-regulation you meant down-regulation. The danger would be down-regulation of the BZD receptor coupled with high glutaminergic transmission. This can only recover with time, however Tiagabine is a drug that could theoretically aid in up-regulation since it acts as a GABA reuptake inhibitor allowing increased availability of GABA in the synapses.

    3. What of those guys on Xanax for ten years+? Has the drug lost its efficacy by then for most users? What's going on here?
    Is it possible for the drug to remain potent, carrying out a valuable compensatory role for under-production of gaba in the tinnitus brain?
    Again we go back to glutaminergic activation (due to the brain requiring homeostasis), and GABAergic desensitization requiring higher doses of benzodiazepines to supress this mechanism. For potency to remain the same without increasing the dosage is impossible. However, even as the potency declines a patient can still reap certain benefits from the GABAergic at a consistent dose.

    4. Non-drug paths. Exercise can increase Gaba naturally. Eventhough I can barely stagger between rooms, I'd be willing to train for a marathon
    to increase any chemical that can suppress tinnitus. Does anyone have figures. How much strenuous exercise exercise required
    to produce x units of Gaba? Also electrical stimulation (Fisher Wallace,etc) has claimed to boost GABA/serotonin by 60%
    Here is a study supporting increased GABA synthesis during excercise:

    http://www.ncbi.nlm.nih.gov/pubmed/18801833

    I have read and heard about electrical stimulation causing massive GABA upregulation and increased GABA neurotransmittion, unfortunately it's not at the practical phase in medicine just yet.

    I should also note that GABAergic withdrawal can cause and worsen the symptoms of tinnitus.

    Good luck.
    Last edited by baooozs; 29-01-2013 at 19:04.
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    Thanks mod 
    #5
    Thumbs up
    Quote Originally Posted by debaser View Post
    Hi and welcome to Bluelight.

    Sending your thread over to Advanced Drug Discussion.

    BDD > ADD
    Thanks for the welcome.
    I appreciate your swift transfer of my thread to ADD.
    Hopefully we can get to the bottom of this one.
    Kind regards
    Marcus
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    #6
    This is kind of what i was thinking. So how/why do eminent professors etc hand out advice like this/ Are we missing something. Dr. Jack Vernon famously advised patients of this route with Xanax and many in the tinnitus treatment community see it as respectable, responsible advice.

    My condition is causedspecifically by acoustic trauma. I've never done drugs/drink of any sort, even for treatment. But there's something else valuable you've
    pointed out. Ototoxic side-effects.
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    #7
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    Well I would assume benzodiazepines can be effective in treating tinnitus by reducing oxidative stress, and excitotoxicity.

    Unfortunately, acoustic trauma can actually kill the tiny hair cells, the stereocilia, which are responsible for transducing sound energy into electrical impulses which then travel to the brain for processing. I would assume that benzodiazepines would dampen these electrical impulses by inhibition of action potentials.

    The fact whether the or not the use of GABAergics is neurotoxic is not debatable. I think the altercation would be partly an ethical one, and partly in regards to whether benzodiazepines worsen ototoxicity due to excitotoxicity.

    Have you attempted a masker?

    What was the nature of the acoustic trauma?

    Here is a study that might interest you:

    http://www.tinnitusjournal.com/detal...igo.asp?id=231
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    #8
    Dear Chromophobia,
    your post should be stickied for all to see.
    This is an area where critical, life-changing mistakes can be made.

    I'm impressed by the breadth of your insights, very intrigued by your pregabalin/gabapentin angle.

    A keyword for me is homeostasis, the brain fiercely regulates balance.
    Tinnitus is a form of plasticity gone wrong, like phantom limb pain.
    Sound signals are not received, neurons up their activity in the missing frequency regions, a popular theory.
    The brain in essence thinks all is okay, balanced. tinnitus as an expression of homeostasis if theory is true.

    Some poeple have sworn Xanax has saved their lives, especially if masking not possible. I was hoping I could use this
    gaba-inhibition approach in some safe way.
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    #9
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    Well anticonvulsants such as gabapentin are popular for decreasing electrical impulses (or frequency as you say), hence why they're notorious for giving false EEG results.

    As I mentioned in my first post rotating between benzodiazepine and gabapentin could be relatively safe if executed properly.

    Have you tested gabapentin?

    If so how do you respond to it in comparison to alprazolam, or perhaps in combination?

    Your not getting replies now because ADD is very slow paced and now is not Bluelights busiest time. Many people will pitch in with good advice in time.
    Last edited by baooozs; 29-01-2013 at 23:36.
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    #10
    Quote Originally Posted by Chromophobia View Post
    Well anticonvulsants such as gabapentin are popular for decreasing electrical impulses (or frequency as you say), hence why they're notorious for giving false EEG results.

    As I mentioned in my first post rotating between benzodiazepine and gabapentin could be relatively safe if executed properly.

    Have you tested gabapentin?

    If so how do you respond to it in comparison to alprazolam, or perhaps in combination?

    Your not getting replies now because ADD is very slow paced and now is not Bluelights busiest time. Many people will pitch in with good advice in time.
    Thanks chromophobia, you're opening up new possibilities. I've never tried gabapentin but doctor would happily prescribe.
    I'd be prepared to mix/cycle these groups. I'm aware Gabapentin has helped eliminate hyperacusis, anecdotally on the net.
    It's just a question of timing, dosage, I don't have a precise roadmap at present.
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    #11
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    No problem. I'd be anxious to find out the clinical results.

    With Gabapentin the most probable scenario is your doctor will start you on you on 300 milligrams x 3 daily. I would suggest trying it alone, evaluating the benefit, then doing the same with it mixed with alprazolam. Ideally as I indicated before, the best possible scenario is to cycle to mitigate tolerance and dependance, but if more is gained by combining them then I guess you'll be forced into that route.

    You may also want to look into Tiagabine as in theory it may serve some purpose in tolerance prevention and it can be combined safely with the mentioned pharmaceuticals.
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    #12
    Thanks again Chromophobia, I'm in a pretty desperate situation so your instincts are appreciated. Much food for thought.
    I need to rest right now but will return. looks like the plan is shaping up, thanks. I'm worried about side-effects but
    guess starting low dosage baby-steps will help. Also, considering SSRNIs like effexor (serotonin linked to gaba). Any thoughts?
    Too many chemicals may muddy the water. The exercise solution is fascinating. Any chance of that dropping off in
    effectiveness due to homeostasis? maybe exercise is more interesting than most would think at first.
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    #13
    Hey, as a general rule we don't do medical threads on this forum but so long as the discussion stays interesting and informative I'll let it slide.
    You might want to post this to some subreddits to increase the breadth of people you're drawing from. But, to clarify your condition:

    You had 5 years of tinnitus which vanished prior to this episode, mind providing details on what caused it? Also, how bad was your previous episode and what precipitated this one. You mention acoustic trauma, but I'm unsure if its a new injury or from the previous episode. I'm also assuming you're ~36 years old from your username as well, which might play a role.

    A quick search reveals a lot of research on gabapentin for tinnitus which kind of makes sense regarding the theory that an overabundance of stimulatory inputs relative to inhibitory inputs on the auditory nerve. Of particular interest is how it produces its best effects in individuals who have suffered acoustic trauma, which gives me flashbacks to cramming for lectures on neuropathic pain...
    http://www.ncbi.nlm.nih.gov/pubmed/16652071
    http://www.ncbi.nlm.nih.gov/pubmed/21940981

    But, with all respect intended for the experts in the field you've mentioned have you ever looked at treating it like a neuropathic pain case? You can sidestep the issue of long term gabagenic drugs in some instances then, as several antidepressants have been shown to be fairly effective while also possessing easier though by no means trivial withdrawals.
    http://www.ncbi.nlm.nih.gov/pubmed/22285367
    http://www.ncbi.nlm.nih.gov/pubmed/16415703
    http://www.ncbi.nlm.nih.gov/pubmed/22972065

    Antidepressants and gabapentin might have some shaky trials but are definitely worth considering before going on long term benzodiazapine treatment.
    Keep in mind I'm extremely biased against benzo's so I will try to find a way for you to avoid them unless they're the only thing that works for you.
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    #14
    Thanks for keeping thread alive Epsilon Alpha

    Despite all the tinnitus research, many are still suffering. That's why I've come here, for a fresh perspective.

    My initial tinnitus was noise-induced, hell for years, then went (complete perceptual habituation). Filters
    in the brain shut things down that are no longer interesting or deemed threat, as I understand it.

    My current tinnitus was an entirely separate incident. Loud klaxon. This time tinnitus is sharper,
    higher frequency, louder.

    The plan was to use gaba inhibition two-fold: A) dampen down any rogue neurological hyper-activity
    B)soften my reaction to condition, to break aversion/anxiety/exacerbation loop.

    I don't like idea of benzos either, just reaching out for workable, sustainable concept.
    If there's a way to use benzos, pregabalin,gabapentin, tiagabine, etc, in concert, in a novel responsible way,
    then one of you guys will know how.

    Pretty good guess on my age. But my condition is not deterioration. After my intial recovery, which was supposed to be
    'permanent', I was going to cinemas, listening to music, etc, no problem. No such thing as permanent here. Just because there's
    no official cure or medicine, doesn't mean it can't happen. I believe we already have the tools, we just need the recipe.

    Keeping calm and treating the tinnitus as a neutral entity accelerates habituation/healing. It's tricky if you're stressed
    out by its aversive/painful nature. This may be where pharma comes in. Treating T as neuropathic pain, as you suggest,
    may be a clever approach, thanks.
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    #15
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    I'm pretty sure hypnotism works quite well for conditions like tinnitus. Maybe they call it hypnotherapy in english, I don't know.

    The doctors would now it if there was a regimen of known medicine that helped.
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    #16
    Hyperacousis sounds like living hell, pun not intended.

    Do your symptoms come and go or are they always present, 100% of the time?

    If they come on suddenly and go away only to return later, alprazolam is a reasonable treatment. However, if your symptoms are present 100% of the time with minor fluctuations in intensity, I don't think alprazolam is a responsible treatment.

    A better treatment would be a long acting benzodiazepine like diazepam or clonazepam. I would suggest diazepam, it's exceptionally long duration of action makes it like the methadone of benzodiazepines. As long as you're taking it properly and not abusing it, you should have an easier time tapering off from diazepam than alprazolam. If you're on it daily for years at a dose of 10mg or more per day, I would expect you to have serious problems quitting. It will be much easier than trying to quit alprazolam, though.

    Something you could also consider would be phenobarbital or primidone. These are both GABAergic compounds, and from my limited experience, dependence to them develops far more slowly than you would with a benzodiazepine.



    I'm really surprised that with the (admittedly, fairly limited) reading I've been doing here, all of the suggestions seem to say, "go with alprazolam" online. I'm not sure why that is. It doesn't seem to have any special activity, as all the benzos seem to work.
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    #17
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    Please don't go on Alprazolam. Its one of those drugs which aptly creates the disorder its meant to treat. I've known too many people who had minor anxiety and then suddenly have panic attacks after they try to stop taking it. The only things special about it are its purported (minor) anti-depressant effect and its high affinity for the benzodiazepine receptor sub-type associated with anxiety. If you have tinnitus there are better options available.
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    #18
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    Hi Marcus during a period of extreme stress I developed tinnitus which got unbearable. Never heard of it at that point but must have been pretty extreme as it was influencing my regular hearing among others. Got a lot of shit going at that time anxiety through the roof which I am guessing the tinnitus originated in stress. I opted for Pregabalin for treatment of the anxiety as I hated the effects of benzo's besides the addiction and other possible negatives.


    My tinnitus was gone after that first 75mg dose kicked in after 2 hours, wonderfull side effect I may say. But like I said the tinnitus had its origin in stress/ burn out, don't know how diff people get effected by it. Coming of the pregabalin was easy no withdrawal, although other people get pretty bad withdrawal on it. And the tinnitus stayed gone after quitting, hope you'll find a remedy too.
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    #19
    Quote Originally Posted by emkee_reinvented View Post
    Hi Marcus during a period of extreme stress I developed tinnitus which got unbearable. Never heard of it at that point but must have been pretty extreme as it was influencing my regular hearing among others. Got a lot of shit going at that time anxiety through the roof which I am guessing the tinnitus originated in stress. I opted for Pregabalin for treatment of the anxiety as I hated the effects of benzo's besides the addiction and other possible negatives.


    My tinnitus was gone after that first 75mg dose kicked in after 2 hours, wonderfull side effect I may say. But like I said the tinnitus had its origin in stress/ burn out, don't know how diff people get effected by it. Coming of the pregabalin was easy no withdrawal, although other people get pretty bad withdrawal on it. And the tinnitus stayed gone after quitting, hope you'll find a remedy too.
    Thanks emkee (and thanks chromophobia for alerting me to this post). Yes, I've heard pregabalin can work. If it calms neuronal hyperactivity
    and/or deals with the limbic stress loop that keeps tinnitus alive, it is something very much worth pursuing. i shall share this information with others in need. Appreciate your input. Stay well. Thanks very much for the good wishes.
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    #20
    This is a fantastic reply Chromophobia! Thank you for all of the information. Although I do not suffer from tinnitis, your insight into GABAergic activity has got me thinking about a few things. I will PM you with a separate inquiry as it has nothing really to do with this thread, and more to do with development of a healthy regiment for moderation of my GABA agonists/antagonists as they relate to anxiety.
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    #21
    Quote Originally Posted by TheWikkidOne View Post
    This is a fantastic reply Chromophobia! Thank you for all of the information. Although I do not suffer from tinnitis, your insight into GABAergic activity has got me thinking about a few things. I will PM you with a separate inquiry as it has nothing really to do with this thread, and more to do with development of a healthy regiment for moderation of my GABA agonists/antagonists as they relate to anxiety.
    WikkidOne, please post whatever you learn on this thread. It might be vital information, critical to expanding our understanding.
    Many thanks
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    #22
    One thing I think is worth mentioning is that withdrawal from chronic gabapentin and/or pregabalin can cause some nasty effects if discontinued too quickly. If you intend to cycle it may be worth keeping that in mind, as you would likely need to taper your dose for a week or two before switching to another drug. Antidepressants are in a similar boat, granted at the doses used for neuropathic pain it might not be as much of an issue.
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    #23
    taking benzodiazepine for treating tinnitus is retarded because they are ototoxic by themself, maybe they will mask the tinnitus for the time you take them but they will damage even more your hear!
    i succesfuly treated my tinnitus with high dose piracetam ( 7-10 gr ) daily and high dose vinpocetine ( don't have the exact dosage but it something like half an 0 capsule )
    my tinnitus is now barely present and it manifest himself only when i restart smoking or take ototoxic substances

    I highly recommend you to buy the book "Ototoxic drug exposed 3rd edition " there is A TON of information about ototoxic drug and some good advice
    now every time i want to take a drug i check in this book if it's not ototoxic

    i can say to you both by experience and by the book that alprazolam is toxic to the hear, it cause tinnitus in 6,6% of those whos take it along with other ototoxic effect like Ataxia Dizziness and vertigo

    thoses doctors are just retarded they want you to take a drug to make you shut up

    also
    Gabapentin is extremely toxic to the hear and you will experience hearing loss hyperacusis and tinnitus for sure ! pregabalin has the same toxicity as gabapentin

    please do youself a favor and invest in this book you will save your hear for the better ( AM 101 is coming and spi 5557 is in preclinical trial )
    Last edited by hadora; 13-02-2013 at 12:49.
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    #24
    just to add something
    if you have anxiety disorder maybe you can try Afobazole, its not ototoxic and work good for anxiety after a few weeks i know it because i take now and i don't use garbage benzo anymore

    hope i helped you
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    #25
    ^we prefer evidence based medicine, not saying you might not be on to something. There are a few very weak trials on piracetam with small benefits, but we're talking very small benefits. Also reference for the gabapentin ototoxicity claim?
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