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View Full Version : Oral GABA to increase GHB levels?



Broshious
03-11-2007, 01:21
I know people have taken lots of GABA orally and had little to no effect, but I was wondering if GABA could be metabolized into GHB outside the brain.

Broshious
03-11-2007, 06:52
If only we could be so lucky. Unfortunately, the conversion of GABA -> GHB occurs only in brain tissue, as the enzyme which catalyzes the reaction (Succinic semialdehyde reductase) has been found only in the brain (http://www.biochemj.org/bj/334/0043/bj3340043.htm).

Even if you could get GABA to cross the BBB, it's normal catabolism actually does NOT favour the production of GHB.

For anyone out there who is interested, the normal metabolism of GABA in the brain is:

GABA --(1)--> Succinic semialdehyde (SSA) --(2)--> Succinic Acid (SA)

Step 1 is catalyzed by GABA transaminase, and is an irreversible reaction
Step 2 is catalyzed by Succinic semialdehyde dehydrogenase, and is an irreversible reaction.

GHB is produced in brain tissue by the following:

SSA <---(3)---> GHB

Step 3 is catalyzed by Succinic semialdehyde reductase, and is a reversible reaction

Step 2 is irreversible and fast, therefore SSA is formed only transiently. As a result, there is very little SSA that actually gets converted into GHB. So even if you put more GABA into your brain, it would still all just get pushed into SSA, and then SA.

The exception to this would be if you had a defect in Succinic semialdehyde dehydrogenase, which would result in an accumulation of SSA, which would get pushed into GHB. There actually is a genetic disease (http://en.wikipedia.org/wiki/Succinic_semialdehyde_dehydrogenase_deficiency) that results in this happening, leading to high levels of GHB in the brain blood.

Although this 'disease' does sound fun, children born with it suffer brain damage as a result of chronic GHB intoxication while their brains are forming, leading to mental retardation, seizures, and a bunch of other nasty things.

Could one take a Succinic Semialdehyde Dehydrogenase inhibitor to then make GABA metabolize into GHB?

Also, this would probably not work, but seeing as you actually seem to know shit about brain chemistry while I do not...here it is. The reaction to form GHB uses NAD(P)H while the reaction back from GHB uses NADP+. Now, these two cofactors seem to be involved in a lot of shit, but could one possible lessen the amount of NADP+ or increase the amount of NAD(P)H to help the reversible reaction favor GHB production?

narutokun
06-11-2007, 01:29
^you're joking about the NAD and GHB thing right?

narutokun
06-11-2007, 01:32
I've taken tons of gaba as a benzo potentiator even though everyone says it doesn't cross the bbb, i don't think it is placebo effect it really does help my benzos! am i missing something here? can anyone provide further info?

Broshious
06-11-2007, 01:56
I've taken tons of gaba as a benzo potentiator even though everyone says it doesn't cross the bbb, i don't think it is placebo effect it really does help my benzos! am i missing something here? can anyone provide further info?

I could swear that I've read that it just has a real hard time crossing the BBB. Don't quote me on that though.

kidamnesiac
06-11-2007, 02:01
Could one take a Succinic Semialdehyde Dehydrogenase inhibitor to then make GABA metabolize into GHB?




I love it, that was my first thought too: "There must be an easily clearable competitive inhibitor somewhere..."
In theory this wouldn't help you with GABA (BBB), but should work natively as this rxn is always taking place...

narutokun
06-11-2007, 02:02
so it doesn't cross the bbb at all? =/

indelibleface
06-11-2007, 03:10
Of course, you could always synthesize GBL from GABA (and hence, GHB from GBL)...

...but it's kind of a messy reaction. Gotta love them nitrogen dioxide fumes!