Reverse Tolerance - I call thee out

[Buddhacide]

I posted this as a response to another post but nobody answered it. Ive always been skeptical about the concept of "reverse tolerance" with regards to kava. I readily admit I do not fully understand it, and may be wrong. However, I'd like to explore the idea and treat it with a bit of skepticism. I would appreciate any non-anecdotal information people could provide to help enable me to understand exactly what is going on when people refer to this. I have googled to no avail. I believe what may be going on is people actually taking greater quantities until an effect is reached, or people learning the subtleties of the experience to the point they actually know whats going on. Also, I appreciate the users experience may differ and some of you swear this exists, but thats not how I'm looking to be convinced. Majorities of people believe in all sorts of things I know to be false because there is better information out there. So no offense to anyone's personal belief or experience but I'd really like to understand the physiology and logic of whats happening.  Below are my comments

"I honestly believe its a matter of amount and quality of the kava. I
personally am skeptical of reverse tolerance. I think most people just
dont take enough. I have given strong doses of nambawan and paradise awa
to several people that had never taken kava before and nobody ever
complained it didnt work. I never experienced it either, I just didnt
know what I was looking for until I did an isa that really kicked my
ass. at the time I just found the others crappy by comparison. Now I
have a more refined taste for it, and can appreciate a less intense
experience in its own right. But I dont think my neurochemistry had to
adapt in the way people assume with RT. Kava just didnt seem like it was
worth the effort until I found one that really bludgeoned me.

I
also dont know exactly how a "reverse tolerance" would work
physiologically. Tolerance is when your body stops producing, say a
neurotransmitter, as a ratelimiting factor based on the presence of
exogenous substances. Ie, your body sees there is a lot of extra
serotonin floating around and therefore stops creating its own.
Eventually the brain changes physiologically to accommodate the presence
of the drug (receptors re-regulate etc....) This has the effect of both
making you require the drug to be otherwise normal, and reducing the
amount of efficacy the drug has to attain added effects (the high). Its
been a while since I studied neuroscience, but I dont recall learning
anything that would describe "reverse tolerance". 

Edit:
Even in this wiki article it refers to a process much different
(seemingly) than how users here refer to "RT" - the cessation of
unwanted side effects not the outright effects of the drug itself.

http://en.wikipedia.org/wiki/Reverse_tolerance"

 

[Vekta]

hmm...That's interesting. I don't really have an answer you're looking for but I can say there is no way I can use the same amount of root I did when I started. I've been fairly consistent with my 2tbsp: 10 oz. water ratio and I get far more out of it now than I did in the past. I can't have it 2-3 days in a row like I used to. *do not want*



I've seen all different level of RT with people I've introduced to kava. Some never felt anything, some where hit like a truck and some started to get more out of it the 2nd or 3rd time they sat down with me. So umm...Buddhacide...how are you with research method and APA format? *poke poke nudge nudge* cuz you know...some research by a fellow Kavalounge member would be kinda cool ya know... *poke poke nudge nudge* (smiley: happy)

 

[August West]

I started out with a nine dollar bottle of extract capsules, and felt scary strong effects upon my first dose. I gave two pills to each member on my bowling team, and we were rolling gutter balls all night. We all felt it. And yeah. I've commented on this several times now. I wanna hear what people have to say.

 

[kl.Flank]

hmm...That's interesting. I don't really have an answer you're looking for but I can say there is no way I can use the same amount of root I did when I started. I've been fairly consistent with my 2tbsp: 10 oz. water ratio and I get far more out of it now than I did in the past. I can't have it 2-3 days in a row like I used to. *do not want*



I've seen all different level of RT with people I've introduced to kava. Some never felt anything, some where hit like a truck and some started to get more out of it the 2nd or 3rd time they sat down with me. So umm...Buddhacide...how are you with research method and APA format? *poke poke nudge nudge* cuz you know...some research by a fellow Kavalounge member would be kinda cool ya know... *poke poke nudge nudge* 

Well I just started and 2 tbsp in 10oz of water wouldn't do shit for me.... I need about 1 cup of kava in 2 cups of water to have any noticable effects.

 

[Buddhacide]

.Buddhacide...how are you with research method and APA format? *poke poke nudge nudge*

Lol, may need to poke and nudge a bit harder. Do you mean do I have any experience with it? I have a decade old Hon.Bsc in psychology if that answers anything. Dont plan on writing any papers but I love stirring up shit whenever I get the chance, lol.

 

[Vekta]

Mmmm...I think there is something to what you're saying though.

 

[Buddhacide]

I just reviewed the notion of "downregulation" with regards to SSRI's, which rang a bell.



"Another adaptive process provoked by SSRIs is the downregulation of postsynaptic serotonin 5-HT2A receptors. After the use of an SSRI, since there is more serotonin available, the response is to decrease the number of postsynaptic receptors over time and in the long run, this modifies the serotonin/receptor ratio. This downregulation of 5-HT2A occurs when the antidepressant effects of SSRIs become apparent. Also, deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These considerations suggest that 5-HT2A overactivity is involved in the pathogenesis of depression.[100]"



Thus antidepressants work because they cause tolerance in the form of reducing the number of receptors available to receive serotonin (by first flooding it with the drug, which mimics serotonin). The brain is doing this to compensate for the presence of the drug. This creates the antidepressant effect, which is pretty counter intuitive and does produce a period of time before the desired effects of the drug are achieved. But that being said, this is not how a "high" works. A "high" is typically caused by a "flooding" of the neurons with an abnormally high amount of a substance - creating an immediate inhibitory or excitatory effect.



So, what would make sense then is if "reverse tolerance" was actually the result of some sort of gradual "upregulation" of receptors - creating a heightened sensitivity with continued use. A google search shows this is apparently quite possible and not that uncommon. And a further google search using that term digs up this thread



http://www.longecity.org/forum/topic/58386-kava-kava-for-anxiolysis-and-gaba-a-receptor-upregulation/



So I may have just put my foot in my mouth, which by god for science I do with earnest! lol

But to go down fighting, we still must reevaluate the notion of reverse tolerance as some sort of "breakthrough". It must be a gradual effect if it is actually happening.

Another interesting thing to consider is whether experience with other drugs mediates this in any way. Or are some people more disposed to success with kava than others are due to genetic variation in the number of receptors. One would assume a "spectrum" of sensitivity - which does appear to be the case.

 

[sɥɐʞɐs]

I don't have any official science to add. but, from my own experience every time i get back into kava over the last few years i basically have the same results.

The 1st couple days don't effect me much....but then a couple days in i start feelin' it with possibly drinking a bit more of it than i should. The longer i do it though, the more reliable the effects become from a standard dose without any need to increase my dosage. So for me it's more like it settles into a non-tolerance that develops...the same amount works the same 'most' of the time. where as most other psychoactive substances would require higher and higher dosages the more frequently you use them.



i always heard about the reverse tolerance thing and thought someday id break into some magic zone that people seemed to be describing where drinking 1 or 2 shells would just make ya feel blissful...but i never noticed anything drastically different.



i've also been to samoa and i knew someone who had a house in fiji...i heard the same thing of both places 'these guys (the locals) will drink it all night long....shell after shell after shell...etc...'

if reverse tolerance was anything major...the islanders would surely have it. yet they slam shells all night...

 

[Buddhacide]

i've also been to samoa and i knew someone who had a house in fiji...i heard the same thing of both places 'these guys (the locals) will drink it all night long....shell after shell after shell...etc...'

if reverse tolerance was anything major...the islanders would surely have it. yet they slam shells all night...

This is a good point. Another in the same vein is that if effects are primarily the result of upgreulation of receptors that would mean that varying the amounts of initial dosages shouldnt do anything (as technically the brain doesnt have the receptors to respond past a certain point). I dont know about you but the more kava I do the stronger I find the effects. And as I said before, I have yet to meet the person that can toss and wash 2 tablespoons of nambawan and not feel anything. I propose a "soft" theory that reverse tolerance is possible through upregulation of receptors (although not really established), but mediated effects for most people most of the time are in fact better predicted by the amount of kava and quality of kava taken rather than the amount of re-regulation that has occurred.

 

[kl.Redfox]

( I try it with my "outlandish" English ... (smiley: wink) )

About 15 years ago - when Kava (pharmaceutical) was not yet banned in Germany - my doctor suggested to me to take Kava capsules (75mg extracted kavalactones each) against my nervosity, stress and burn-out symptomes (burn-out was at this time not yet "created", they call it light depression symptomes or so).

I took 2 capsules a day for about 10 days before I noticed a "remarkable" effect. I became really unstressed and I was in the mood to sing a song all day long ... (smiley: wink)

After some days more taking the capsules I stopped to consume it because the effect did not increase any more - but the effect lasted for about another week without taking the stuff.

Than the effect obviously weakened from day to day ... so I took my daily dose (2 caps) for another two days ... and whoop, the full effect occured after only taking the 4 caps in two days.
I then again stopped taking the caps ... and the full effect lasted for some days.
I reapeted this procedure several times. In the end I only had to take 2 caps and the (full) effect holds on for at least 3-4 days.

Unfortunately the "authorities" banned Kava in any kind here in Germany (in 2001 I think). So I was deprived of the only "successful" pharmaceutical (a one with no side-effects to me or the risk of addiction!!!) for my symptomes which was until then to get in any pharmacy without a prescription and at a decent price.

None

 

[mos3z]

This is my completely non-scientific theory, i'm a designer not a scientist

But I feel that specific kavalactones need to build up in a persons system for you to achieve full effect.

I think after drinking kava that kavalactones hang out in your body somehow and you build up a reserve of them.

Once that reserve gets full enough you start to feel the strong effects.

The kavalactones will eventually leave your system after a while, thats why if you stop drinking for several months or a year people have to drink more again at first to refill the reserves.

Personally I believe this is also true for specific kavalactones.

When I started I had great success with certain kavas, but when i tried an ISA it didnt do anything. Not that I've tried drinking ISAs for several months the effect has gotten stronger. The same thing happened with pk extract, the effects got stronger after a week of daily use.



I think some people are immune to this entire process though and can feel it without having to buildup the reserve.

Buddha, maybe you are just one of the people immune to this effect that's why you cant relate to it.



Feel free to call me out on bullshit, as I said i'm only an artist.

That's just the only theory that has fit what has happened to me since i started drinking.

 

[The Kap'n]

But I feel that specific kavalactones need to build up in a persons system for you to achieve full effect.I think after drinking kava that kavalactones hang out in your body somehow and you build up a reserve of them.

Being that kavalactones are lipid, or fat, soluble (think how people add coconut milk and soy lecithin as emulsifiers) it would seem they do build up in the fat of the body. Since there seems to be no large tolerance effect to kava it would make sense that as your body stores lactones it would cause more to become available the more you consume.
On the topic of the negative effects lessening the more you drink, I can say that isn't necessarily the case. I've been consuming kava continually for 7 or so years, and sometimes the negative effects can follow the reverse tolerance profile. Double-bonded lactones stick around just as long if not longer than kavain so you may actually experience more negatives the longer you drink. This is of course based on your selection of type of kava. 
On the topic of some people not experiencing the reverse tolerance. I have no explanation other than we may metabolize things at different rates from person to person.

 

[kl.Jerome]

Never experienced reverse tolerence.  First time I tried kava twelve years ago,  I felt and loved it. I can clearly remember the warm sense of peace and euphoria that creeped over my body and brain.   And everyone I've given the juice to noticed the effect.

 

[jkw]

I can only provide unfortunately some anecdotal evidence, but it's very recent, so it is very accurate.  I started drinking kava 2 weeks and 4 days ago.  I logged the majority of my use up until today.  Overall the kava effects were subtle but pleasant until 2 days ago when the experience was markedly more profound.  I will paste the log below:





Sat Feb 9: BKH Boroguru arrived in the mail. Strained and squeezed 5 rounded tbsp for 10-15 min in 2 cups tepid water.  Ended up with about 1.5 cups.  Maybe didn't squeeze enough.  Consumed it around 9pm.  Significant numbing of mouth and throat.  Relaxation of body felt, very subtle, but slightly more than baseline.  Effects more noticeable when getting up and moving around.  Had a cold, so illness was a factor as well.  Cold symptoms felt reduced.  Not much trouble falling asleep, but not quick either. 





Sun Feb 10: Strained and squeezed 2 rounded tbsp for 10 min in one cups tepid water.  Consumed in the afternoon.  Less numbing of mouth and throat.  Felt slight relaxation.  Mixed 2 tbsp in one cup of milk and left to soak for an hour.  Strained and squeezed for 10 min but did not feel satisfied by the amount extracted, so did a second wash in another cup of water and combined with the first.  Had a huge meal at 6, and consumed kava at 10.  Very little numbing of mouth, very little effects felt.  Milk did not change the taste for the better.  Still not done with cold, but possibly symptom improvement.  Fell asleep quickly.





Mon Feb 11: Strained and squeezed 4 topped tbsp for 15 min in 1 3/4 cups tepid water and 1/4 cup coconut milk.  Did a second wash in 1 cup cold water and combined with first.  Consumed over the course of about 30 min.  Taste improved by coconut milk.  Slight numbing of mouth.  Felt nice and relaxed and a great mood.  Went to sleep easily.





Tue Feb 12: Mixed 2 rounded tbsp into 3/4 cup water and 1/4 cup coconut milk.  Shook it thoroughly and let it sit for 2 hours.  Shook it up and consumed at 9:30 pm.  Slight numbing of mouth.  After about 15 min had a sudden body rush which lasted a minute or so.  Body felt relaxed, movement felt slightly clumsy, mood elevated.  Felt a slight persistent nausea so ate some crackers which helped.  Had a difficult time falling asleep though was relaxed and not upset about it.  Awoke at 3 am for no reason.  Nausea persisted through the next day.





Wed Feb 13: Soaked 4 rounded tbsp in 2 cups water and 1/4 cup coconut milk for about an hour.  Strained and squeezed for about 15 minutes.  Consumed half at 10 pm and the rest at 10:30.  Dinner was around 6:30 pm.  Didn't feel much effects other than a pleasant mood elevation and a mental relaxation.  Fell asleep quickly.





Thu Feb 14: Took 1 tsp of K@ leaf powder at around 2:30pm after eating around 12:30.  Modest effects felt from about 3:00 - 4:30.  Consumed the other half of last nights prepared kava around 10:00.  Dinner was around 6 pm.  Felt some relaxation, but little effects.





Fri Feb 15 - Wed Feb 20: Did not log usage.  Had extracts a few times at 1/4tsp dose, and boroguru several times at 4tbs/2 cups water dose.  K@ at 1 tsp dose used on a few days.  Kava generally made me feel chatty and a little relaxed.





Thu Feb 21: Blended 8 tbsp boroguru in 4 cups water plus some coconut milk and pineapple juice.  Poured into strainer but could barely strain it through the bag.  Took about 15 min to actually just strain it through one time.  This method will not work with this muslin bag.  Will order fijian bag.  Consumed half around 10:30pm.  Felt subtle effects.





Fri Feb 22: Consumed 1 1/4 tsp K@ around 3 pm.  Strong stimulation effects felt.  Consumed other half of prior night's prepared kava around 9:30pm.  Same subtle effects as the night before.  Consumed maybe 1/8 tsp of extract around 10:30.  Didn't notice much difference in effect.





Sat Feb 23: 1/4 tsp of extract consumed around 10pm.  Felt a warmth and relaxation, but nothing too significant.  Fell asleep quickly.





Sun Feb 24: 4 rounded tbsp boroguru in 2 cups water plus 1 tsp soy lecithin.  Squeezed and strained for about 20 min.  Consumed from 10-10:30.  Effects were subtle, fell asleep with no issues.





Mon Feb 25: Had 1 tsp of K@ around 2 pm.  Effects were more subtle than usual this time.  Had 1/4 tsp kava extract at 9:30pm.  By 10 could barely focus my mind on the TV show I was watching and could barely stay awake.  Body felt overly sensitized, i.e. I was more acutely aware of all physical sensations and heart beat and so forth.  Vision had an atypical sharpness to it. Very similar to low threshold experiences of psychadelics, or after effects of prolonged marijuana use.  Tried to go to bed at 11 but kept getting strange alternating feelings of cold in my extremities, and rushes of warmth in my trunk.  Watched a show in bed for about 20 min to take my mind off it and fell asleep promptly.  Wild dreams all night.





Tue Feb 26: Woke up still feeling the effects in a significant way.  The effects lessened as the day progressed.  Felt close to baseline by the evening, and did not indulge in any kava.  Had a very difficult time falling asleep, as I kept coming in and out of very vivid dreams.





Wed Feb 27: Finally felt pretty much baseline when I woke up.

 

[Buddhacide]

I don't believe there is any evidence (but who knows) that levels of kava build up in the body, in fat cells or otherwise. Its not unreasonable to presume that, as kapmkrunk notes lactones are fat soluble, but I don't think  that's whats going on.  I believe if reverse tolerance exists at all its at the receptor level in the form of up-regulation.  I'm no biologist, but generally speaking the body does not "store" excess levels of things (despite what people in the health food store tell you when). It can certainly metabolize some toxins into the fat cells (certain heavy metals and a few drugs come to mind), but generally speaking it expels what it doesn't need. If anyone has any evidence to the contrary please post it because I would love to know if that is actually going on.

Also, since we are anecdotalizing I find that kava continues to hit me in random and unpredictable ways. Sometimes the dose that knocks me on my ass on Friday does nothing to me on Sunds, and vice verse. Its a really curious substance that way.

 

[krunkedout]

Kava is pretty much always constant for me. I know the right amount that gets me to where I wanna be

 

[mos3z]

If kava is stored in the fat, could being overweight or skinny affect RT?

I'm overweight and experienced RT. any overweight people not experience RT?



Kava is pretty predictable for me as long as my stomach is completely empty. The strange thing for me which I've posted before is that kava doesn't work for me if I drink small amounts repeatedly, I need to drink a large amount at first to get the desired effect. If I start with a small amount and don't have a strong enough effect then even if I drink a gallon of it an hour later I usually don't get any stronger effect, very strange. But if I get a strong effect at the start I can usually reactivate it several hours later

 

[Ed!]

I'm skinny and definitely experienced reverse tolerance (my first post here was a sad-sack "It's not working!"). I drank kava for a month before I felt anything, and the feeling I get now is beyond what I initially felt as well.



I'm also no scientist, but I do think there are a lot of substances that build up in your system. There is no evidence that deodorant causes cancer, but I do find it interesting that breast cancer tends to develop near the armpits, where we're rubbing artificial substances into our skin. Allergies as well... do a cleanse and allergies tend to improve. I believe that's because you're washing substances from your body, even substances that we don't really consider to be persistant.



I am made of what I consume, so if I consume anything regularly it's going to affect what I'm made of.