Ketamine Relieves Depression by Restoring Brain Connections

[Nic B]

Lately there has been a lot of hype around Ketamine for the treatment of depression. There has also been some discussion regarding NMDA receptor agonists and tinnitus. Ketamine is a powerful NMDA receptor agonist. I have read comparisons between tinnitus and phantom limb pain. I know that Ketamine, and also one of its analogues, Methoxetamine has been used to treat phantom limb pain.

A recent study has showed that it looks like Ketamine is actually restoring brain connections.

I'm very curious to know how this would apply to tinnitus.

Ketamine Relieves Depression By Restoring Brain Connections

 

[erik]

Nic B, it is possible this could work for T along with other similar drugs. See this below and link for more info

Summary:
The invention relates to methods for preventing and/or treating tinnitus induced by cochlear excitotoxicity in a human. The methods include administering to a human a therapeutically effective amount of a pharmaceutical composition comprising an NMDA receptor antagonist. In a method for treating tinnitus, the NMDA receptor antagonist administered is effective to suppress or reduce NMDA receptor mediated aberrant activity of the auditory nerve in the human in need of such treatment. In a method for preventing tinnitus, the NMDA receptor antagonist administered is effective to prevent NMDA receptor mediated aberrant activity of the auditory nerve in the human in need of such treatment. The tinnitus to be prevented and/or treated may be provoked by acoustic trauma, presbycusis, ischemia, anoxia, sudden deafness, or other cochlear excitotoxic-inducing occurrence.

Methods for the treatment of tinnitus induced by cochlear excitotoxicity

 

[calin]

I don't want to be the guinea pig on this one! lol

 

[Nic B]

I kinda do lol

 

[mock turtle]

Nic B, thanks for the information and the link

very interesting stuff restoring brain connections

btw, i believe ketamine is not an agonist...but rather an nmda antagonist ( but hey i could be wrong cause....

i get confused, often between neurotransmitter receptor agonists and antoagonists...its easy to get confused because for example, neurotransmitters such as GABA are inhibitory and when we inhibit or antagonize an inhibitor...what have we got is kinda like a double negative......my head spins from double negatives

what i find so fascinating about all this, is that MSG is clearly bad stuff for many many tinnitus sufferers, and of course the G in msg is for glutamate and excitatory neurotransmitter

glutamate, i believe...(remember i get easily confused) is an nmda agonist, so ketamine being an nmda antagonist would (could?) counter act glutamate and "quiet things down in our ears"

( and of course the quiet we are looking for probably needs to happen somewhere between the ear and the auditory cortex, but who knows where T comes from for sure, as the debate rages on)

best wishes
mt

 

[mock turtle]

from CBS news

http://www.cbsnews.com/8301-18563_1...of-drugs-could-offer-depression-breakthrough/

"Jim Staples, 58, has suffered from depression since his twenties.

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"I tried to commit suicide, and it wasn't a hearty attempt," Staples says. "It was just screaming out for help." snip​

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"The medicines that I had been taking over the years, they only work for two to three years and then they just fizzled out," Staples adds.​

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In depressed patients such as Jim Staples, brain cell communication breaks down. Current medications target a chemical called serotonin to help brain cells talk to each other. But it's present in just five percent of those cells. snip​

These new drugs target a different chemical called glutamate, present in 80 percent of brain cells. Researchers believe these new drugs restore the lost communication better than older drugs, which can take months to kick in.​

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"The exciting part of some of these newer medications is that they might, in fact, produce very rapid antidepressant effects, within hours or days," says Dr. Gerard Sanacora of Yale University, who is leading one of the trials.​

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The new approach was discovered by accident, when doctors noticed that an anesthesia drug -- ketamine, which targets glutamate -- relieved depression. But it also caused symptoms that mimicked schizophrenia...."​

ketamine blocks the nmda receptor at the allosteic site and is a glutamate antagonist​

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from wikipedia heres a snip but hey check out the entire wikipedia article...amazing stuff​

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http://en.wikipedia.org/wiki/Ketamine#Research​

tamine is a noncompetitive NMDA receptor (NMDAR) antagonist. More specifically, ketamine binds to the allosteric site of the NMDA receptor, effectively inhibiting its channel. The S(+) and R(-) stereoisomers bind with different affinities: Ki = 3200 and 1100 nM, respectively.[41] NMDAR antagonism effects analgesia by preventing central sensitization in dorsal horn neurons; in other words, ketamine's actions interfere with pain transmission in the spinal cord.[27] Ketamine also inhibits nitric oxide synthase, inhibiting production of nitric oxide, a neurotransmitter involved in pain perception, and hence further contributing to analgesia.[42] Ketamine also interacts with sigma and opioid receptors, but with lower affinity and without significantly contributing to analgesia.[43]
Ketamine also interacts with a host of other receptors to effect analgesia. It blocks voltage-sensitive calcium channels and depressessodium channels, attenuating hyperalgesia; it alters cholinergic neurotransmission, which is implicated in pain mechanisms; and it acts as a noradrenergic and serotonergic uptake inhibitor, which are involved in descending antinociceptive pathways.[27][44]
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very interesting drug.... reminds me of tianeptine that louise was talking about on another thread

 

[Louise]

Was just thinking the same

 

[Aisling]

Is this not what is in AM101 drug? I think someone posted this

 

[mock turtle]

i dont remember the formula name for am-101

but yes i believe that both ketamine and am 101, are nmda antagonists

i must confess

i dont know what "non competitive" , in the lead article, means, but i will research it

best wishes
mt

 

[Deep]

I'll try it for you this weekend and get back to you, I never really take it but a "source" has pure so will let you know. I am the guinea pig people have been looking for haha.

Obviously I do my research and take suitable amounts. I will also try to evaluate the situation whilst under the influence as much as possible to consider an actual reduction in volume, placebo, or anti-depressive state.

 

[Steve]

Deep you are indeed a selfless individual, to give your body to scientific study is a noble cause. Though you may need an assistant to take notes and help evaluate, it's difficult to do that whilst spannered in the corner. I suppose the 'medical' dose will be a fair bit less than the 'clubbing' dose.

 

[Aisling]

Good on ya deep! I also think this is a good one to try. They say that AM101 is based on ketamine. please make sure you report back to us deep on how you get on. Thanks!

 

[exodus]

Hi all

if this is the same ketamine we are talking about,please be careful

http://www.channel4.com/news/ketamine-drugs-bladder-damage-health-video

 

[Deep]

Right guys I have completed the task.

I went into this experiment with spiking T and hypercausis (5/10 which is bad for me), although people must note that I usually have a week of my T behaving and during that week my hypercausis pretty much disappears, this always happens after I have had a bad spike so this might effect the results of this experiment. (Basically I might of just moved into a good week, during these numerous tests).

I would also recommend this experiment for someone with severe Tinnitus that doesn't really fluctuate in level. 1. So that you can monitor the changes more accurately. 2. Obviously you are hammered whilst under the influence so it isn't a very practical every day solution for T.

1st day, took a small amount - no real change, although it worked as an anti-depressant, so this allowed me to really tune out of the T whenever I wished and focus my mind on something else, just like when you read a book for example and during a paragraph you could of sworn you experienced complete silence.

2nd day, took slightly more - again no real change but my hypercausis was completely gone! In addition when in complete silence I could really work on turning down the volume mentally.

3rd day - hypercausis still vanished along with a general sense of my ears not having to work as hard (a pressure variance sensation if you will) like my central nervous system was in less shock.

4th day - woke up with very quite Tinnitus, the quietest it's been in a while, maybe a 1.75 / 10, and this was tested whilst plugging my ears! Hypercausis still completely diminished and T has somewhat remained at a very quite level during the day, maybe slightly louder now but only about a 2.5 / 10.

Yes very unprofessional experiment but I was obviously having a lot of fun during this so tried to make notes the best I could. Please if you have any other questions I would be more than happy to answer them.

Yes Kitamine does cause bladder damage but this is from heavy everyday use for years, so please do not warn me as I rarely take the drug, but thanks for the heads up! I recommend everyone must research Kitamine individually and come up with their own personal decision on whether they might like to try it or not, instead of people getting scared away buy some horror article on the net about how it messed someones life up after years of addiction.

Thanks

Deep

 

[Esko]

I'd like an update Deep. Did the tinnitus stay away?

 

[Hudson]

I am interested in this as well. How long have you had your T and did it stay at low levels? AM-101 is basically Ketamine if I remember correctly, or very similar. They just locally apply it to the ear instead of a systemic application.

 

[Deep]

Still pretty low in volume, hypercausis still diminished / gone depending on the day. Yes a systemic application would be better.

 

[yonkapin]

How have you been doing since your little experiment?! I may be doing my own little experiment soon, have had some ketamine lying around for a while that I still have yet to try, bit scared of going too deep but my friends seemed to have a blast on it - if it has any positive effect on my tinnitus/hyperacusis I will be well happy!

 

[Deep]

Its not a permanent cure, but I did find relief for a week or two after. Any drug that works to prevent central sensitization will give most some type of relief.

 

[erik]

Deep, did you only find relief when you took Ketamine and how many consecutive days did you take it? Thx

 

[Deep]

3 consecutive days, had relief after the ketamine, not necessarily during. Other things give me relief but that's off topic, I see ketamine as a kind of reset.

 

[Golly]

Is Ketamine available in the US? Is it in fact FDA-approved to treat anything yet? In any case, Deep, I am happy to hear that three days of this drug has brought you extended relief.

Deep: You acknowledge that your experiment was not exactly scientific (i.e. you did not control for various factors). I am curious as to whether your tinnitus comes and goes on its own. If so, can you elaborate on such a pattern in the absence of Ketamine?

-Golly

 

[jazz]

Is Ketamine available in the US? Is it in fact FDA-approved to treat anything yet? -Golly

Ketamine is known as a dissociative anesthetic. A popular clubbing drug, its official use is an anesthetic in veterinary and dental procedures. Below is the wikipedia article on ketamine, and another one on its anesthetic properties:

https://en.wikipedia.org/wiki/Ketamine​

http://ceaccp.oxfordjournals.org/content/7/2/59.full​

Here's the reference to ketamine's cousin that is in drug development, though not for tinnitus. Still, the drug could be exciting for us and is moving through the clinical trial process:

https://en.wikipedia.org/wiki/GLYX-13​

http://www.news-medical.net/news/20...om-GLYX-13-Phase-IIa-trial-on-depression.aspx​

http://www.naurex.com/html/glyx13.html​

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Here is a reference to several clinical trials with GLYX-13:

http://www.clinicaltrials.gov/ct2/results?term=GLYX-13&Search=Search​

 

[Golly]

Thanks Jazz---very helpful! (I won't ask where Deep acquired his treatment.) -G

 

[Deep]

Again I apologize for a very amateur experiment. I could execute a scientific one if everyone's down? ie. measure mg taken, how many doses until relief, side effects, how long it lasts, etc. I was with friends at the time and couldn't exactly write things down!

The main benefit I noticed was a decrease in hypercausis and for me T and hypercausis come hand in hand, when my T behaves so does my hypercausis.

 

[erik]

Deep, we appreciate the information. So much of having T is being the human guinea pig. Only do what you are comfortable with and thanks

 

[Golly]

Again I apologize for a very amateur experiment. I could execute a scientific one if everyone's down? ie. measure mg taken, how many doses until relief, side effects, how long it lasts, etc. I was with friends at the time and couldn't exactly write things down!

The main benefit I noticed was a decrease in hypercausis and for me T and hypercausis come hand in hand, when my T behaves so does my hypercausis.

Hi Deep:

Just to be clear, when you say "hyperacusis", are you referring to an inability to tolerate normal sounds? Or, like many of us, are you describing the aggravation that particular sounds give to your tinnitus? In my case, the sound of and air conditioner, for example, makes me more aware of my tinnitus. This, in turn, gives rise to what can be characterized as "misophonia": the hatred of particular sounds.

-Golly

 

[Deep]

It's like sound that is in the frequency of my T (quite high) so clangy plates or treble heavy low quality in-built iphone speakers sound to me slightly distorted. My hyperacusis is very strange because it only happens with a certain frequency and that frequency has to be at a certain volume in order to cause discomfort.

It feels slightly like a contraction of the ear drum. Again I have good weeks and slightly annoying weeks, this fluctuation in behavior makes it hard for me to do a fair experiment.

 

[Deep]

Deep, we appreciate the information. So much of having T is being the human guinea pig. Only do what you are comfortable with and thanks

No problem. I appreciate no one is telling me to do this and I know that Kitamine is a class C drug in the UK, no-one on the forum has forced me to do this, let me make that clear. I have decided to conduct a proper experiment. Well a proper experiment needs to be spread between many people, BUT I will do the best I can and space out the experiment over 3 doses of 30mg per week for 2 weeks.

I'll start within the month.

 

[Steve]

If I was closer to Bristol I would probably join in (not the kind of thing we can do via royal mail), it's intriguing to know how it works with the T especially given its relationship to current trial treatment. In years past I have had substances with Ketamine in so I can imagine how it may help, definitely in a psychological sense if no other. The disassociation would probably be very helpful, kind of like instantly going to the end of a successful CBT / TRT combo program. The key is in getting a dose that will help whilst letting you still function normally.

What does 30mg equate to in relation to a 'clubbng dose'?