Pharmacology - A little bit basic of pharmacology for those who are interested in trying Kava Kava

[Swimster]

In theory: Kava~Kava should have a mix of-mild elation properties-coupled with an antaginization of elation, aswell as Benzodiazepine-like(but not same) effects compared to large doses of Diazepam(valium).

Kava Kava contains kavalactones, which are the responsible chemicals for the kava experience.

Kavalactones are shown to potentiate GABAa activity, the same area benzodiazepines effect but not by the same mechanism whatsoever.

All responsible kavalactones:
Kawain
Methysticin
Demethoxy-y
Dihydrokawain
Dihydromethysicin
Yagonin

Kava extract is composed of D,L-Kawain, dihydrokawain, methystian, dihydromethystian, yangonin, and desmethoxyyangonin

In rats, kava proves to change extra cellular dopamine levels for 8 hrs. Yangonin has dopamine antogonism effects, whereas the rest of the indivudual kavapyrones increased dopamine(dosnt mean they are DRIs, but somehow they are shown to increase EC dopamine as doseage increases). Yangonin can reduce the activity of the rest of the kavapyrones elation effects at times, although it is not present in high amounts which makes it more negligable then other kava pyrones in producing effects.

Dihydrokavain is much weaker then (+)kavain, (+)methysticin, (+)-dihydromethysticin, reqiuring a 100-fold concenteration to become eqivelantly active to the later kavalactones. Yangonin is also weaker then these aswell.

So,

Kavain: NRI which enhances focus, Enhances GABAa activity
(+)Methysticin: Enhances GABAa activity
(+)dihydromethysticin: Enhances GABAa activity
Dihydrokavain: Enhances GABAa activity the weakest of all prominant psychoactive kavalactones(dosn't mean it isn't important)
Yangonin: Enhances GABAa weaker like dihydrokavain; Is a dopamine antagonist
Desmethoxy-yangonin: MAO-B Inhibitor, resposible for increasing levels of dopamine in the nucleus accumbens providing slight euphoria.

New very interesting info to add to this topic
All of the Kavalactones except yangonin, individually increase extracellular dopamine levels with dosage. Although:

The lowest dosage of kava induced sedation, and as the dosages increased so did dopamine levels. Each of the individual kavapyrones initiated an increase in dopamine levels with the exception of yangonin, a dopamine antagonist. Kava is believed to be effective because of this ingredient. The effects of yangonin supersede the effects of the other kavapyrones at times and do not allow dopamine neurons to become active, preventing elation. However, yangonin is present in small amounts in kava and therefore does not always prove effective.

See Nizzles chart/post, 3 posts down, for good information...

refs: http://cat.inist.fr/?aModele=afficheN&cpsidt=14429932 ,
http://cat.inist.fr/?aModele=afficheN&cpsidt=2411755 , &
http://healthpsych.psy.vanderbilt.edu/kava.htm

So, if you are like me and like to compare drug pharmacology before you try something, i think this gives you a good idea of expectation...alchohol, benzos, concentration, euphoria, etc.

Reputation Comments on this post:

	Excellent information. Please expand if possible. Swim finds all this very useful.
	Very interesting
	awsome info! Rare to find pharmacology on a newer drug

[Alfa]

It would be nice if you would list the main actions of each these kavalactones, if known: what the dose range of each of these kavalactones is and what % is normally present in kava-kava.

Here's an example table:

Kavalactone	pharmacological action	dose range	% in kava-kava
Kawain	"SNRI" which can increase focus
Methysticin
Demethoxy-yangonin	mild MAO-B inhibitor which can increase dopamine
Dihydrokawain
Dihydromethysicin
Yagonin

[Swimster]

EDIT: Moved this post to the first one for convenience...

Reputation Comments on this post:

Excellently detailed information

[nnizzle]

Kavalactone	pharmacological action	dose range	% in kava-kava
Kawain (kavain, gonosan)	NRI which enhances focus, Enhances GABAa activity	1.05mg-3mg	1-2%, .5-2%*
Methysticin	Enhances GABAa activity	1.12mg-3.2mg	1.2-2%, 0.1-2%*
Demethoxy-yangonin	MAO-B Inhibitor, resposible for extra levels of dopamine in the nucleus accumbens providing slight euphoria	.35mg-1mg	negligible-1%*
Dihydrokawain	Enhances GABAa activity the weakest of all prominant psychoactive kavalactones	.56mg-1.6mg	0.6-1%, up to 2%*
Dihydromethysicin	Enhances GABAa activity	.455mg-1.3mg	0.5-0.8%
Yagonin	Dopamine antagonist, Enhances GABAa weaker like dihydrokavain	.35mg-1mg	negligible-1%*

All alkaloids excluding yagonin increase extracellular levels of DA (yagonin is a DA antagonist [inhibits the release of DA] rather than agonist [ultimately increases the release of DA]).
*= personal approximation according to levels discovered in ONE study
SWIM WOULD LIKE TO THANK SWIMSTER:http://www.drugs-forum.com/forum/member.php?u=17206 for his contribution to this table--explaining mechanisms of action for various alkaloids, suggesting revisions, explaining physio/neurological effects of various alkaloids, etc. His contributions are not to be neglected.

http://www.herbs2000.com/herbs/herbs_kava.htm
some important kavapyrones like methysticin (1.2 to 2 percent), dihydomethysticin (0.5 to 0.8 percent), kawain (1 to 2 percent) and dihydrokawain (0.6 to 1 percent) have been isolated and characterized.

However the attached article states

Quantities of desmethoxyyagonin, kavain, 7,8-dihydrokavain, yagonin, methysticin, and dihydro-
methysticin detected were 4.3, 6.9, 18.6, 5.7, 1.4, and 5.4 mg/g of dry weight, respectively.

Which would give percentages of
demothoxyyagonin- .43 percent
kavain- .69 percent
yagonin- .57 percent
methysticin- .14 percent
dihydromethysticin- .54 percent
dihydrokavain- 1.86 percent

Assuming dosage of kavalactones (NOT dose of dried/prepared kava kava plant) between 70-200mg (various sources.... none gave a straight answer and attached article shows POSSIBLE hepatoxicity at not much higher levels), that would give dose range (ROUGH estimate, dose range was calculated by median percent [taken from estimate when necessary, otherwise values written in http://www.herbs2000.com/herbs/herbs_kava.htm] x mg total kavalactones(70 and 200)

demothoxyyagonin- .5% x 70 and 200= .35mg-1mg
kavain- 1.5% x 70 and 200= 1.05mg-3mg
yagonin- .5% x 70 and 200= .35mg-1mg
methysticin- 1.6% x 70 and 200= 1.12mg-3.2mg
dihydromethysticin-.65% x 70 and 200= .455mg-1.3mg
dihydrokavain- .8% x 70 and 200= .56mg-1.6mg

I think I did all those calculations right (even though they are all quite rough)... let me know if that is not the case.
Kawain: NRI which enhances focus, Enhances GABAa activity
(+)Methysticin: Enhances GABAa activity
(+)-dihydromethysticin: Enhances GABAa activity
Dihydrokavain: Enhances GABAa activity the weakest of all prominant psychoactive kavalactones(dosn't mean it isn't important)
Yangonin: Enhances GABAa weaker like dihydrokavain
Desmethoxy-yangonin: MAO-B Inhibitor, resposible for extra levels of dopamine in the nucleus accumbens providing slight euphoria

Reputation Comments on this post:

	good addition
	Brilliant information. Good table too
	Awesome info

[Alfa]

Please consider if it is possible that there is a difference between kawain and kavain.

[Bajeda]

I've read that levels of particular kavalactones very considerably from strain to strain, and even from different crops of the same strain. Plus different varieties have different kavalactone makeups. Its hard to paint an accurate picture of how the overall end effects are produced due to this variability, though we can get a general idea of how specific kavalactones act on the neurological system. I like the topic of this thread, but am not sure if "% in Kava" is an accurate or useful measure to include at this point in time, since it may only be the case for the specific strain used in the study.

[Alfa]

It will possibly give an indication if a kavalactone may be of major influence.

[nnizzle]

http://www.lycaeum.org/leda/docs/12668.shtml?ID=12668

[top]Kawain

5,6-dihydro-4-methoxy-6-(2-phenylethenyl)-2H-pyran-2-one, C14H14O3 (mol. wt. 230.26)
Also known as kavain or gonosan

I don't know much about O Chem nomenclature but other sources have used them interchangeably also.

[Swimster]

EDIT: Iv'e seen the word Kevain used at studies. Sry for being weird about it nizzle, lol.
I'm not sure the correct one...
Kawain and Kevain is the same, im sure.

[nnizzle]

Originally Posted by Swimster

Kawain maybe...

Sorry I have been trying to understand what this means for like an hour haha? I'm not trying to sound like a dick at all man just don't know what you're referring to.

[zornthro]

So yagonin is a dopamine antagonist, demethoxy-yangonin is an MAO-B inhibitor, while the rest (??) somehow increase dopmaine levels in the brain?

I've seen a couple studies cited in other articles claiming that kava [might] be able to treat schizophrenia. Being that it has complicated effects on dopamine receptors maybe it might actually be useful. kavain also inhibits the reuptake of noradrenalin which is another chemical / receptor sometimes targeted by atypical antipsychotics.

[Swimster]

Thanks, thats good info man. Post what you want

[Bajeda]

Originally Posted by zornthro

So yagonin is a dopamine antagonist, demethoxy-yangonin is an MAO-B inhibitor, while the rest (??) somehow increase dopmaine levels in the brain?

I've seen a couple studies cited in other articles claiming that kava [might] be able to treat schizophrenia. Being that it has complicated effects on dopamine receptors maybe it might actually be useful. kavain also inhibits the reuptake of noradrenalin which is another chemical / receptor sometimes targeted by atypical antipsychotics.

If you could post these in the archive or request them in the Medline Access thread (look in Improving Drugs-Forum section), it would be appreciated.