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Kava Kava for Anxiolysis and GABA-a Receptor Upregulation

kava anxiety reverse tolerance gaba

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#31 LazarusMan

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Posted 28 September 2012 - 06:25 PM

Some interesting anecdotal evidence that might lend validity to upregulation of GABA by Kava: http://kavalounge.yu...ce#.UGXqVU3A9n0 Many people report a reverse tolerance to Kava upon taking it over an extended period. Perhaps one Kavalactone is upregulating while another is agonizing the GABA receptor. I have read about this reverse tolerance from multiple sources.

#32 nupi

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Posted 29 September 2012 - 09:40 AM

Very interesting indeed. Does anyone have a view which of the Kava products on iHerb would be worth trying (I know it can be had much cheaper but there's just NFW I will order herbs from eBay or Alibaba ;)?

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#33 Raza

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Posted 29 September 2012 - 09:48 AM

I imagine you'll be buying the same herbs, in the end, but suit yourself.

Venuatu kava is generally highly rated, you'll want to verify that it is only root (and ideally only lateral roots) matter used, and look at the % of kavalactones. Dark Vision is taking 250mg of a 40% extract, which is reportedly effective sublingually for mild anxiolysis but much too little for oral use, so base your choice on that.

Edited by Raza, 29 September 2012 - 09:49 AM.


#34 nupi

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Posted 29 September 2012 - 10:36 AM

That's as much as I thought. Looking at it, http://www.iherb.com...eggie-Caps/2872 seems like a sane choice. They also have http://www.iherb.com...eggie-Caps/2869 but that's probably mostly extreme rip-off

#35 Raza

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Posted 29 September 2012 - 10:54 AM

Freeze dried whole root powder. There's pros and cons to that; don't expect it to work sublingual, you'd get a lot of residue and the doses needed would be uncomfortable, and the % of kavalactones is relatively low so if you respond anything like Dark Vision you'd need at least three (and quite possible more) caps for a noticeable dose... but OTOH, you're getting the full spectrum of active particles, which means its history of local use is more relevant as test data, and there's many reports with kava of some of the better effects being lost in extraction which may not have happened here. If you don't mind the way the costs add up, it's should be a safe approach if not an efficient one.

The juice is interesting enough, and should work sublingually too, if the taste is halfway palatable. Which would most likely give you more bang for your buck than the whole root; if taken sublingually, one capsule would most likely suffice for a dose. A gamble, but quite possibly a worthwhile one.

Edited by Raza, 29 September 2012 - 10:55 AM.


#36 LazarusMan

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Posted 29 September 2012 - 03:40 PM

www.Kavabyrex.com has some amazingly potent Kava

#37 Raza

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Posted 03 October 2012 - 09:30 PM

I just realized that we have some clear precedents for positive allosteric modulators at a receptor site causing upregulation of that receptor with chronic use; the 'racetams all do this for the glutamate receptors they affect. So it's not such an unheard of mechanism after all.

Incidentally with the utmost respect, and please do not take this the wrong way, your argument with regards to KAVA KAVA possibly being a POSITIVE ALLOSTERIC MODULATOR of the GABAA RECEPTOR as opposed to full AGONIST is in fact irrelevant, since in both instances adminstration would be ill advised; wherein I am sure that you surely must realise that if KAVA KAVA were to be demonstrated to be a POSITIVE ALLOSTERIC MODULATOR of the GABAA RECEPTOR then this would mean it is akin to BENZODIAZEPINE DRUGS, and hence you whole argument would be self-defeating ;)



#38 stephen_b

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Posted 04 October 2012 - 09:42 PM

Specifically the problem lies with the fact that whilst those two studies, which do indeed seem to report KAVA KAVA inducing UPREGULATION of the GABA RECEPTORS, specifically via INCREASING RECEPTOR DENSITY, there concomitantly exists just as many (if not more) studies that appear to demonstrate that KAVA KAVA is indeed a GABA RECEPTOR AGONIST.


Maybe the way it increases GABA receptors is by temporarily blockading them, causing upregulation as the body seeks to get back into balance. This mechanism has been suggested for opioid receptor upregulation by low dose naltrexone.

If so, then that might imply that once-a-day dosing would be best. It might also imply a lack of tolerance issues with kava kava (that you see with aminos like tyrosine).

#39 Raza

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Posted 04 October 2012 - 10:36 PM

If it blocked GABA receptors, it'd have an acute anxiogenic effect. The unusual thing is that it doesn't; it's anxiolytic immediately and long term.

And nitpick, but low dose naltrexone doesn't upregulate opiod receptors, but rather endorphin production. Its acute effect is probably mildly unpleasant if it is noticable, but the idea is for you to be asleep when that happens. Different mechanism from Kava on multiple counts.

#40 LazarusMan

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Posted 05 October 2012 - 12:21 AM

This may be sacrilege to some of the purist but if you acquire high grade Kava powdered root you can perform a rather simple Kava extraction via acetone. Fill a container with root powder and top it off with acetone and inch or two above the plant matter. Then shake a few times, let the matter settle and then remove the acetone which you then place in a sheet pan with a good amount of surface area so that it can evaporate quickly. Then you are left with a rather gross looking, put potent tar of kavalactones that you can capsule and use.

Edited by LazarusMan, 05 October 2012 - 12:22 AM.

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#41 xsiv1

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Posted 05 October 2012 - 12:34 AM

I just realized that we have some clear precedents for positive allosteric modulators at a receptor site causing upregulation of that receptor with chronic use; the 'racetams all do this for the glutamate receptors they affect. So it's not such an unheard of mechanism after all.

Incidentally with the utmost respect, and please do not take this the wrong way, your argument with regards to KAVA KAVA possibly being a POSITIVE ALLOSTERIC MODULATOR of the GABAA RECEPTOR as opposed to full AGONIST is in fact irrelevant, since in both instances adminstration would be ill advised; wherein I am sure that you surely must realise that if KAVA KAVA were to be demonstrated to be a POSITIVE ALLOSTERIC MODULATOR of the GABAA RECEPTOR then this would mean it is akin to BENZODIAZEPINE DRUGS, and hence you whole argument would be self-defeating ;)


Sorry to veer off-topic slightly, but if someone was say, in a state where glutamate excitotoxicity was causing anxiety, insomnia, panic-like episodes - would you say that concurrent racetam use would make the problem worsen or would this have more to do with the NMDA receptors? Just a question here regarding abuse of Gaba agonists and the subsequent flood of glutamate upon abrupt cessation of use. I know aniracetam seems to exhibit some anxiolytic effects but was wondering if it'd be counterproductive in cases of withdrawal syndrome.

More in line with this thread, Kava, if it indeed does upregulate gaba receptors would seem a useful adjunct in a Gaba agonist withdrawal regimen. Even if it's specific to Gaba (A) receptors. It has been stated (no source(s) right now) that L-Theanine and Bacopa act in similar ways but L-theanine may have more to do with blocking glutamate excitotoxicity...which I don't understand fully since Gaba is produced from Glutamate isn't it?

Edited by xsiv1, 05 October 2012 - 12:39 AM.


#42 Raza

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Posted 05 October 2012 - 10:22 AM

Sorry to veer off-topic slightly, but if someone was say, in a state where glutamate excitotoxicity was causing anxiety, insomnia, panic-like episodes - would you say that concurrent racetam use would make the problem worsen or would this have more to do with the NMDA receptors? Just a question here regarding abuse of Gaba agonists and the subsequent flood of glutamate upon abrupt cessation of use. I know aniracetam seems to exhibit some anxiolytic effects but was wondering if it'd be counterproductive in cases of withdrawal syndrome.

I wouldn't risk 'racetams during a hyperglutamatergic state. There seem to be a couple of ways by which that could go wrong, of which glutamate receptor upregulation seems relatively minor but also the most certain.

More in line with this thread, Kava, if it indeed does upregulate gaba receptors would seem a useful adjunct in a Gaba agonist withdrawal regimen. Even if it's specific to Gaba (A) receptors. It has been stated (no source(s) right now) that L-Theanine and Bacopa act in similar ways but L-theanine may have more to do with blocking glutamate excitotoxicity...which I don't understand fully since Gaba is produced from Glutamate isn't it?

I think so, yes. It's the first thing I would personally try in that situation.

From reading the study people cited for it, I wouldn't expect GABA receptor upregulation from Bacopa - that only resulted from protection against seizures in epileptic rats, which seems irrelevant to most real-life circumstances. Theanine helps exactly because it encourages GABA production from Glutamate - that means you end up with less Glutamate, which you want.

Edited by Raza, 05 October 2012 - 10:22 AM.

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#43 Raza

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Posted 05 October 2012 - 10:26 AM

This may be sacrilege to some of the purist but if you acquire high grade Kava powdered root you can perform a rather simple Kava extraction via acetone. Fill a container with root powder and top it off with acetone and inch or two above the plant matter. Then shake a few times, let the matter settle and then remove the acetone which you then place in a sheet pan with a good amount of surface area so that it can evaporate quickly. Then you are left with a rather gross looking, put potent tar of kavalactones that you can capsule and use.

Cool. But won't it be full of acetone residue? Isn't that unhealthy?

#44 Dark Vision

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Posted 05 October 2012 - 01:25 PM

This may be sacrilege to some of the purist but if you acquire high grade Kava powdered root you can perform a rather simple Kava extraction via acetone. Fill a container with root powder and top it off with acetone and inch or two above the plant matter. Then shake a few times, let the matter settle and then remove the acetone which you then place in a sheet pan with a good amount of surface area so that it can evaporate quickly. Then you are left with a rather gross looking, put potent tar of kavalactones that you can capsule and use.

Cool. But won't it be full of acetone residue? Isn't that unhealthy?


Completely pure acetone won't leave a residue it will all evaporate leaving not even an odour. Of course in practise it's never completely pure, but the very best stuff won't leave anything worth speaking of.
The kava extracts you can buy on the internet seem to be ethanol extractions, and I don't see why you shouldn't use ethanol instead. All the kavalactones are soluble in ethanol.

Kava continues to exert a good anxiolytic effect on me at the same dosage. I dosed before the premier I attended recently and I felt noticeaby calmer during the socializing before the screening. I was able to think more clearly, remember peoples names and listen to what they were saying properly. Usually this is a problem for me at such events. I can't say yet if the effect has got any stronger though. It certainly hasn't got weaker, and I'm tempted to say it's got stronger, but I'm not sure. It can take several weeks for reverse tolerance to build so it's early days yet.

It gives you very vivid and memorable dreams if taken before bedtime, which I have been enjoying. I had a terrifying nightmare a few nights ago, but on the whole I don't mind these occasionally, like a good horror movie :)

I tried the theanine again a couple of times whilst not on kava and got minimal effects. I guess if a reverse tolerance does emerge and theanine suddenly starts having a larger effect then that will be pretty interesting.

#45 Raza

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Posted 05 October 2012 - 07:41 PM

Good info! But why would the kavalactone extract be a tar, if you started out with dry powder and there are no solvents left?

And I'm glad the kava experiment is working out for you so far. Thanks for keeping us updated!

#46 xsiv1

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Posted 05 October 2012 - 11:37 PM

This may be sacrilege to some of the purist but if you acquire high grade Kava powdered root you can perform a rather simple Kava extraction via acetone. Fill a container with root powder and top it off with acetone and inch or two above the plant matter. Then shake a few times, let the matter settle and then remove the acetone which you then place in a sheet pan with a good amount of surface area so that it can evaporate quickly. Then you are left with a rather gross looking, put potent tar of kavalactones that you can capsule and use.

Cool. But won't it be full of acetone residue? Isn't that unhealthy?


Completely pure acetone won't leave a residue it will all evaporate leaving not even an odour. Of course in practise it's never completely pure, but the very best stuff won't leave anything worth speaking of.
The kava extracts you can buy on the internet seem to be ethanol extractions, and I don't see why you shouldn't use ethanol instead. All the kavalactones are soluble in ethanol.

Kava continues to exert a good anxiolytic effect on me at the same dosage. I dosed before the premier I attended recently and I felt noticeaby calmer during the socializing before the screening. I was able to think more clearly, remember peoples names and listen to what they were saying properly. Usually this is a problem for me at such events. I can't say yet if the effect has got any stronger though. It certainly hasn't got weaker, and I'm tempted to say it's got stronger, but I'm not sure. It can take several weeks for reverse tolerance to build so it's early days yet.

It gives you very vivid and memorable dreams if taken before bedtime, which I have been enjoying. I had a terrifying nightmare a few nights ago, but on the whole I don't mind these occasionally, like a good horror movie :)

I tried the theanine again a couple of times whilst not on kava and got minimal effects. I guess if a reverse tolerance does emerge and theanine suddenly starts having a larger effect then that will be pretty interesting.


Do you know approximately what dose you would take for anxiolytic effects like that? I bought the NOW brand of capsules despite negative reviews because I could buy it locally. Following the label's recommended dosage I get nothing but perhaps a placebo effect that produces subtle calm.

#47 Dark Vision

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Posted 06 October 2012 - 09:20 AM

This may be sacrilege to some of the purist but if you acquire high grade Kava powdered root you can perform a rather simple Kava extraction via acetone. Fill a container with root powder and top it off with acetone and inch or two above the plant matter. Then shake a few times, let the matter settle and then remove the acetone which you then place in a sheet pan with a good amount of surface area so that it can evaporate quickly. Then you are left with a rather gross looking, put potent tar of kavalactones that you can capsule and use.

Cool. But won't it be full of acetone residue? Isn't that unhealthy?


Completely pure acetone won't leave a residue it will all evaporate leaving not even an odour. Of course in practise it's never completely pure, but the very best stuff won't leave anything worth speaking of.
The kava extracts you can buy on the internet seem to be ethanol extractions, and I don't see why you shouldn't use ethanol instead. All the kavalactones are soluble in ethanol.

Kava continues to exert a good anxiolytic effect on me at the same dosage. I dosed before the premier I attended recently and I felt noticeaby calmer during the socializing before the screening. I was able to think more clearly, remember peoples names and listen to what they were saying properly. Usually this is a problem for me at such events. I can't say yet if the effect has got any stronger though. It certainly hasn't got weaker, and I'm tempted to say it's got stronger, but I'm not sure. It can take several weeks for reverse tolerance to build so it's early days yet.

It gives you very vivid and memorable dreams if taken before bedtime, which I have been enjoying. I had a terrifying nightmare a few nights ago, but on the whole I don't mind these occasionally, like a good horror movie :)

I tried the theanine again a couple of times whilst not on kava and got minimal effects. I guess if a reverse tolerance does emerge and theanine suddenly starts having a larger effect then that will be pretty interesting.


Do you know approximately what dose you would take for anxiolytic effects like that? I bought the NOW brand of capsules despite negative reviews because I could buy it locally. Following the label's recommended dosage I get nothing but perhaps a placebo effect that produces subtle calm.


Yes - I take 250mg of 40% kavalactone extract. So 100 mg of kavalactones. The problem is that kavalactones are not one chemical, they are a group of at least 15 with varying properties. The amount of each in any given kava product can vary wildly, and I do not know which is having the anxiolytic effect. It may be that whatever product you have is deficient in whatever is working for me. Try a higher dose, see if you get anything (but not too high obviously, don't go over 300 mg kavalactones and don't start habitually taking large doses of the stuff, probably not good for you). It's also possible that you need to try taking them for a week before you notice anything at low doses. One thing is for sure, this stuff is certainly not placebo and I don't think you are a non-responder, any more than you can be a non-responder to vodka. It's a drug, take enough and you will certainly get inebriated. The idea is to find a dose which is calming but doesn't go this far :)

As for the tarry extract - I don't reckon it would be tarry. I think it would be a powder. The root itself isn't tarry and acetone is a simple ketone, when it evaporates it all goes. Leave a little puddle of pure acetone and by the end of the day it will all be gone without a trace, in just the same way as distilled water would. As it evaporates the whole molecule becomes a gas, it's the same stuff just more spread out and floating around. If it's leaving a tarry residue then it must be cheap 80% pure stuff for thinning paint or something, and yes definitely don't ingest this...

#48 neuropill

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Posted 30 October 2012 - 10:22 AM

I've found an effective dosage for producing an anxiolytic effect around 500-1,000 mg of kavalactones. I currently use an 84% extracted organic pure root paste form here:

https://www.konakava...avalactone.html

Numbs like hell but a great way to indirectly measure kavalactone levels.

Edited by neuropill, 30 October 2012 - 10:27 AM.


#49 Dark Vision

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Posted 30 October 2012 - 12:12 PM

An update - I stopped taking kava sublingually because whilst it makes me salivate whilst it's in my mouth, afterwards it gives me a very dry mouth for several hours. This is not good for teeth, especially at night when salivation is already suppressed somewhat. I now take 750mg (300mg kavalactones) orally, two or three times a day. I find it works fine with food in your stomach, it just takes a while longer. This is probably why people say kava doesn't work on an full stomach, you don't get a rush of euphoria because it takes a good hour or so to work instead of 20 minutes.

As for reverse tolerance, well the 750mg oral dose gives me a very noticeable effect now whilst it didn't when I first got the kava and took two 500mg doses separated by an hour or so iirc. So I guess you could call this reverse tolerance. I also find that whilst for a while kava's effects were calming but could be somewhat anhedonic, for the last week this has not been the case. I will need more time to see if this effect persists though. I should mention that I am now, as of yesterday, taking 2.25mg of hydergine in the morning so further results will be skewed by that. So far I find the hydergine very nice, gives a mood boost and helps me focus. However the change in kava's effects happened before I started the hydergine.

I just did 500mg sublingual theanine and have noticed no effects (and I've don't no kava so far today). I also find that I don't really feel any difference to my usual anxiety level when I am not on kava. If it were up-regulating gaba-a to any great extent then I would expect to feel more calm even when I haven't had any kava.

Another possible theory for the reverse tolerance is kava's suppression of the CYP450 enzymes.

Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity.

Potential for interaction of kava and St. John's wort with drugs.

Could it be that kava supresses these enzymes more and more over time causing the body to process it less effectively?
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#50 Raza

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Posted 30 October 2012 - 03:45 PM

From what I read the last time I looked into Kava and P450 enzymes, it did the opposite, inhibiting a couple on the short term but causing their upregulation and increased activity with chronic use. This is the normal pattern for drug tolerance and homeostasis; an new substance starts out with powerful effects, but with continued use the body tries to restore homeostasis and resistance is built. I don't think it explains the reverse tolerance of the anxiolytic effect.

My guess is that theanine just isn't a very sound indicator of GABA-A sensitivity. It has several mechanisms of action as an anxiolytic, only a small portion of which utilizes the GABA-A receptor... plus, my personal experience lately has been that its effects are difficult to predict, often remaining inexplicable absent after significant dosing. It was worth a shot though; thanks for keeping up the experiment and keeping us in the loop. =)

I've found an effective dosage for producing an anxiolytic effect around 500-1,000 mg of kavalactones. I currently use an 84% extracted organic pure root paste form here:

https://www.konakava...avalactone.html

Numbs like hell but a great way to indirectly measure kavalactone levels.

Looks like a sound source. Pricey, but sound.

How long have you been using this dosage?

Edited by Raza, 30 October 2012 - 03:48 PM.

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#51 Dark Vision

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Posted 31 October 2012 - 12:45 PM

Ok, that's good to know Raza. I wasn't particularly keen on that idea. I like my enzymes ;)

#52 SuperjackDid_

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Posted 25 December 2012 - 06:03 PM

How to take this to avoid gaba receptor down regulation from normal aging or substance abuse like alcohol use.?

http://www.iherb.com...0-Capsules/6919 (yellow power color)

http://www.iherb.com...eggie-Caps/2872 (grey powder color)

Should separate thread ?.

Today i have tried Natrol Kava ,effect slight relax without sedation i felt less anxiety when i go outside and less worried .
Should i continue Natrol or switch to Eclectic Institute ?

I usually take Ashwagandha daily and felt of gaba receptor down (irritability ,increased in anxiety ) so with 2 day Kava a week is it potent enough to bring back gaba receptor up that cause down by Ashwagandha daily use?

Edited by Nootropix, 25 December 2012 - 06:08 PM.


#53 Dark Vision

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Posted 25 December 2012 - 08:15 PM

The upregulation thing is somewhat unclear Nootropix. I still take Kava but only at night, for sleep. It doesn't really make me sleepy, but helps with anxiety issues which are the main cause of insomnia for me. This together with 0.5mg of melatonin has all but fixed my insomnia. I would say I often feel in a good mood the morning after but it does not seem to have helped my anxiety, or made it worse. It does help if I take it during the day, obviously, but I find it inhibits motivation so I don't. I am trying picamilon but so far it is doing nothing much (after 3 days).

Kava definitely does not work well on a full stomach, so I still take it sublingually. This works well but causes dry mouth all night, which ain't good for teeth. So I try to do it only once every two or three days. Perhaps this is not enough for up-regulation to happen. I take a fairly large dose, about 600mg of kavalactones, which really kills any anxiety. I am not too worried about this as I'm not doing it every day.

Kava is certainly an interesting and complex substance and I think you don't get too much down-regulation of gaba receptors from it, like you would from booze or benzos. But I never noticed any up-regulation from it even when I was using it every day (based on my anxiety level. A feeling of persistent calm did not magically appear after two weeks for instance. It did make me feel cheerful in the mornings). Perhaps LazarusMan is right and the kavalactones pull in different directions. I wouldn't rely on it as a method of countering problems from alcohol consumption, I don't think it would work, and using the two together, or even separately, could stress your liver more than either substance alone would.

One thing I never did do is get "krunk" (drunk on kava). Perhaps getting krunk is necessary for long lasting up-regulation. I should give it a try and report back on how I feel the next day.

#54 nupi

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Posted 26 December 2012 - 09:05 PM

This seemed to work pretty well against AD induced dry mouth (I thankfully only ever got that from Cymbalta, other AD's are fine for me): http://www.iherb.com...ing-domes/17160

#55 protoject

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Posted 18 January 2013 - 12:49 PM

sorry for flooding the board with a possibly useless question but Im wondering how these 40% extract doses might convert into regular root powder doses. Approximately. Thanks! I have a bunch of root powder, that's why I'm asking. Also I am at work so just dropping this question in quickly, i know kinda sillyl maybe i should look it up later...

#56 Dark Vision

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Posted 18 January 2013 - 01:10 PM

Well the percentage of kavalactones in raw kava varies so it is impossible to say for sure how much is in your powder. An average amount is 10-15%, but some kava powder might be 5% and some might be 20%.

#57 machete234

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Posted 18 January 2013 - 09:10 PM

I have an extract that has supposedly 70% of kavalactones and I will share my experiments after a while.

Yesterday I took only around 100mg in case that this is very potent but it wasnt I just had mild sedation/relaxation.

#58 moleface

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Posted 18 January 2013 - 09:26 PM

For whatever it's worth, my own experience with kava seems to suggest that it causes some sort of GABA receptor downregulation.

A few months ago I got ahold of some ultra-potent kava from Nakamal At Home (which is fantastic- you're missing out if you've only tried the crappy kava extracts sold in caps) and I drank one serving every evening for five days. When I stopped, I got anxiety and irritability reminiscent of the GABA-related rebound anxiety I get after drinking alcohol. It was more minor than the anxiety I get from drinking, and I didn't feel mentally impaired like I would after an alcohol binge, but I had cold sweats and moderate hand tremors/irritability for several days before the side effects leveled off.

#59 protoject

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Posted 18 January 2013 - 10:22 PM

Booh, that's sad to hear. Do you think it was dose related? I took it this morning. It's kind of a mixed bag. There's a slight dysphoria but i think overall throughout the day it did have a mild and nice anxiolytic effect, and a kind of body numbing effect. I only took 1 tablespoon of raw powder

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#60 xsiv1

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Posted 19 January 2013 - 01:38 AM

Interesting. I found the Now brand capsules to be junk....at least at the recommended dose. I haven't really tried anything beyond that capsule-wise. I small herbal shop here in the city sells Kava Kava and I bought it in it's powdered form. The bag they took it out of looked dusty and well, not really touched for a while so I wasn't sure how old it was but was referred to them from a girl at work. I took a few tablespoons of that and just got minor anxiolysis...threw the rest out. I am interested in trying some actual good quality Kava though. If the literature isn't clear as of yet as to whether there is any upreg of Gaba A receptors, I'd only consider using it sparingly. I've had my share of experiences with Gaba agonist withdrawal symptoms and it isn't fun but have learned to taper off properly and utilize the proper supplements to minimize any sides.





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