Genetic Influences on Kava Effects...maybe?

[The Kap'n]

Hi Kava lovers. I've been reading a paper titled "Contemporary Pacific and Western perspectives on 'awa toxicology" (https://pubmed.ncbi.nlm.nih.gov/25464054/).

In this paper it points out something I think may be linked to some people's difficulty in feeling anything from kava.

Kava is metabolized by the CYP group of enzymes. Specially CYP2C9, CYP2C19, and CYP2D6. The main being CYP2D6

Different people have different rates of metabolization for the CYP2D6 enzyme. There is poor, extensive, and ultrarapid metabolizers.

If you are a poor metabolizer this means that kavalactones in their original form stay in your system longer, hence a more apparent effect profile from kava. On the other end of the spectrum are ultrarapid metabolizers. In that situation the kavalactones are broken down extremely quickly giving kava a short duration, reduced effects or both.

This one is simply a theory from me, so please poke whatever holes in this you need to. There's just got to be a reason that some people don't feel kava.

 

[Halibut_Acid]

Is this the same enzyme that breaks down caffeine? Because I know there are people who metabolize caffeine faster or slower. It's based on wether you have two copies of the fast metabolism gene, one of each, or two slow. Ultrarapid would be two copies of fast, etc...

Anyways that would make sense. I believe I metabolize caffeine extremely slowly, it lasts quite some time for me. I also never had to get through any kind of reverse tolerance with kava.

 

[The Kap'n]

Is this the same enzyme that breaks down caffeine? Because I know there are people who metabolize caffeine faster or slower. It's based on wether you have two copies of the fast metabolism gene, one of each, or two slow. Ultrarapid would be two copies of fast, etc...

Anyways that would make sense. I believe I metabolize caffeine extremely slowly, it lasts quite some time for me. I also never had to get through any kind of reverse tolerance with kava.

It's quite similar to caffeine, and I would think those with slow or ultrafast metabolism of that enzyme would see the same effects with caffeine as you would with CYP2D6 deficiency and kava.

 

[Halibut_Acid]

It's quite similar to caffeine, and I would think those with slow or ultrafast metabolism of that enzyme would see the same effects with caffeine as you would with CYP2D6 deficiency and kava.

Would make sense. Maybe I'll dig into the literature a bit as well. Wonder how this relates to alcohol dependence, as there are quite a few of us here who've had our struggles with alcohol.

 

[Alia]

Hi Kava lovers. I've been reading a paper titled "Contemporary Pacific and Western perspectives on 'awa toxicology" (https://pubmed.ncbi.nlm.nih.gov/25464054/).

In this paper it points out something I think may be linked to some people's difficulty in feeling anything from kava.

Kava is metabolized by the CYP group of enzymes. Specially CYP2C9, CYP2C19, and CYP2D6. The main being CYP2D6

Different people have different rates of metabolization for the CYP2D6 enzyme. There is poor, extensive, and ultrarapid metabolizers.

If you are a poor metabolizer this means that kavalactones in their original form stay in your system longer, hence a more apparent effect profile from kava. On the other end of the spectrum are ultrarapid metabolizers. In that situation the kavalactones are broken down extremely quickly giving kava a short duration, reduced effects or both.

This one is simply a theory from me, so please poke whatever holes in this you need to. There's just got to be a reason that some people don't feel kava.

That paper you are referring to is complex and a bit scary. It supplies a great deal of data and it's easy to get confused when reading the "toxicology";
there are a few critical sentences that bring it all together and demonstrate aqueous kava safety.
I told them, can't we get a smart 10 year old to summarize these issues for me and other Maka'ainana?