![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 23 of 23. This is the beginning of the thread.
Posted by Questionmark on June 16, 2004, at 8:45:22
i have read a number of reports/anecdotes from people on here who have said that they notice an effect from taking GABA supplements-- usually an anti-anxiety effect. But i was under the impression that GABA does not cross the blood-brain barrier, so how is this possible? Do you think it Is possible for GABA supplementation to work? ..Maybe a certain proportion of the GABA is able to cross the BBB? What do you think?
Posted by Larry Hoover on June 16, 2004, at 9:09:05
In reply to GABA, posted by Questionmark on June 16, 2004, at 8:45:22
> i have read a number of reports/anecdotes from people on here who have said that they notice an effect from taking GABA supplements-- usually an anti-anxiety effect. But i was under the impression that GABA does not cross the blood-brain barrier, so how is this possible? Do you think it Is possible for GABA supplementation to work? ..Maybe a certain proportion of the GABA is able to cross the BBB? What do you think?
First off, the blood-brain barrier is not a wall. It's more like a filter, but not even a perfect filter. GABA is a pretty small molecule, relatively speaking, so, perhaps if the blood concentration gets high enough, there's enough of a trickle-in effect to be noticeable.
Someone recently raised an interesting conjecture....if GABA is converted to GHB by a certain enzyme (succinic aldehyde reductase or something like that), and that happened outside the blood-brain barrier, then most certainly the GHB can enter freely. If I recall correctly, GHB is soluble in the BBB, so it doesn't need to be transported across. It just drifts on over by diffusion.
More generally, I think the argument itself is somewhat moot. Arguing mechanisms to explain (or refute) actual experience is not going to tell us much. Empiricism (what people actually observe) is reality. If people feel less anxiety with oral GABA, then that sounds like a good thing to me. Geeks have been wrong before.
Lar
Posted by Questionmark on June 17, 2004, at 14:47:05
In reply to Re: GABA » Questionmark, posted by Larry Hoover on June 16, 2004, at 9:09:05
> > i have read a number of reports/anecdotes from people on here who have said that they notice an effect from taking GABA supplements-- usually an anti-anxiety effect. But i was under the impression that GABA does not cross the blood-brain barrier, so how is this possible? Do you think it Is possible for GABA supplementation to work? ..Maybe a certain proportion of the GABA is able to cross the BBB? What do you think?
>
> First off, the blood-brain barrier is not a wall. It's more like a filter, but not even a perfect filter. GABA is a pretty small molecule, relatively speaking, so, perhaps if the blood concentration gets high enough, there's enough of a trickle-in effect to be noticeable.
>
> Someone recently raised an interesting conjecture....if GABA is converted to GHB by a certain enzyme (succinic aldehyde reductase or something like that), and that happened outside the blood-brain barrier, then most certainly the GHB can enter freely. If I recall correctly, GHB is soluble in the BBB, so it doesn't need to be transported across. It just drifts on over by diffusion.
>
> More generally, I think the argument itself is somewhat moot. Arguing mechanisms to explain (or refute) actual experience is not going to tell us much. Empiricism (what people actually observe) is reality. If people feel less anxiety with oral GABA, then that sounds like a good thing to me. Geeks have been wrong before.
>
> Lar
i compLETEly agree (w/ your last paragraph). That's the trap that so many psychiatrists fall into and it ticks me off beyond words. i just wasn't sure how many people did feel something with GABA and how noticeable/potent any effects were.
i didn't know that GABA was a relatively small molecule. You're probably right then (about the "trickle-in effect").
i think i also remember reading that GHB crosses the BBB via passive diffusion. But do you think that GABA is really converted into GHB by an endogenous enzyme (okay i think all enzymes are endogenous but i mean without taking anything with the GABA or anything)? That's great if that's true, considering all the positive things i've heard about GHB and anxiety & depression. How likely do you think it is that some [peripheral/ supplemental] GABA is converted to GHB in the body? And if you have any idea, what proportion of GABA (in supplement form, ingested) do you think IS converted to GHB?
Finally, do you or anyone else have any good idea about how much GABA to take to notice significant (i.e., definitely noticeable) anxiolytic (anti-anxiety) effects?
Thanks so much for your help Larry, & anyone else who might reply.
Posted by Larry Hoover on June 18, 2004, at 16:21:20
In reply to Re: GABA » Larry Hoover, posted by Questionmark on June 17, 2004, at 14:47:05
> > Someone recently raised an interesting conjecture....if GABA is converted to GHB by a certain enzyme (succinic aldehyde reductase or something like that...
Okay, here's the post that I'm recalling....
http://www.dr-bob.org/babble/alter/20040418/msgs/351881.html
> > More generally, I think the argument itself is somewhat moot. Arguing mechanisms to explain (or refute) actual experience is not going to tell us much. Empiricism (what people actually observe) is reality. If people feel less anxiety with oral GABA, then that sounds like a good thing to me. Geeks have been wrong before.
> >
> > Lar
>
>
> i compLETEly agree (w/ your last paragraph). That's the trap that so many psychiatrists fall into and it ticks me off beyond words. i just wasn't sure how many people did feel something with GABA and how noticeable/potent any effects were.Apparently, people do feel the effect of oral GABA.
> i didn't know that GABA was a relatively small molecule. You're probably right then (about the "trickle-in effect").
> i think i also remember reading that GHB crosses the BBB via passive diffusion. But do you think that GABA is really converted into GHB by an endogenous enzyme (okay i think all enzymes are endogenous but i mean without taking anything with the GABA or anything)? That's great if that's true, considering all the positive things i've heard about GHB and anxiety & depression. How likely do you think it is that some [peripheral/ supplemental] GABA is converted to GHB in the body? And if you have any idea, what proportion of GABA (in supplement form, ingested) do you think IS converted to GHB?
Here's a representation of the different chemical pathways involved:
http://www.ceri.com/ghbalt.htmUnfortunately, the poster who raised the question of conversion of GABA to GHB had some factual errors. The oxidation product of GHB is succinic semialdehyde. The enzyme succinic semialdehyde reductase reduces succinic semialdehyde back to GHB. The interconversion of GABA and GHB involves quite a different enzyme altogether (one of the transaminases).
Enzymes are not "smart".....they don't only cause reactions to go in one direction. Although we think of GHB being aminated to form GABA, if the concentration of GABA is high enough, the enzyme will tend to deaminate GABA to GHB. Looking at the cycles, though, I doubt that is a common occurrence, even with oral GABA. But, I'm guessing.
> Finally, do you or anyone else have any good idea about how much GABA to take to notice significant (i.e., definitely noticeable) anxiolytic (anti-anxiety) effects?I do not know. I suspect there is individual variation on that, but I never did a good experiment to know my own threshold.
> Thanks so much for your help Larry, & anyone else who might reply.
You're welcome.
Lar
Posted by Questionmark on June 18, 2004, at 16:38:58
In reply to Re: GABA » Questionmark, posted by Larry Hoover on June 18, 2004, at 16:21:20
Posted by chemist on June 19, 2004, at 3:27:39
In reply to GABA, posted by Questionmark on June 16, 2004, at 8:45:22
hello there, chemist here... lar is spot-on. the entire question is quite moot, really: gamma butyric acid is water-soluble and lipid soluble, so crossing the BBB is not an issue. what is an issue is activating the GABA_{A} receptor and inducing chloride flux. if you take GABA and it works - as lar has said - then great. otherwise, there really is no need to go for it, as your GABA_A} (mostly) receptor needs to be inhibited by reuptake, so any additional flooding is not going to help unless you have a drug in the binding site that will inhibit...all the best, chemist
Posted by Larry Hoover on June 19, 2004, at 7:57:20
In reply to Re: GABA » Questionmark, posted by chemist on June 19, 2004, at 3:27:39
> hello there, chemist here... lar is spot-on. the entire question is quite moot, really: gamma butyric acid is water-soluble and lipid soluble, so crossing the BBB is not an issue. what is an issue is activating the GABA_{A} receptor and inducing chloride flux. if you take GABA and it works - as lar has said - then great. otherwise, there really is no need to go for it, as your GABA_A} (mostly) receptor needs to be inhibited by reuptake, so any additional flooding is not going to help unless you have a drug in the binding site that will inhibit...all the best, chemist
Dude, you raised more questions.
Both niacinamide and magnesium ions have been shown to increase GABA-ergic activity (my perhaps not totally correct/concise description). Do either/both of these qualify as "drug in the binding site"? I know both bind to the receptor, but not at the benzo site.
And that other point, about flooding. You're really saying that chronic dosing with oral GABA will not be as effective as taking it in pulses?
Thanks.
Lar
Posted by chemist on June 19, 2004, at 15:00:17
In reply to Re: GABA » chemist, posted by Larry Hoover on June 19, 2004, at 7:57:20
> > hello there, chemist here... lar is spot-on. the entire question is quite moot, really: gamma butyric acid is water-soluble and lipid soluble, so crossing the BBB is not an issue. what is an issue is activating the GABA_{A} receptor and inducing chloride flux. if you take GABA and it works - as lar has said - then great. otherwise, there really is no need to go for it, as your GABA_A} (mostly) receptor needs to be inhibited by reuptake, so any additional flooding is not going to help unless you have a drug in the binding site that will inhibit...all the best, chemist
>
> Dude, you raised more questions.
>
> Both niacinamide and magnesium ions have been shown to increase GABA-ergic activity (my perhaps not totally correct/concise description). Do either/both of these qualify as "drug in the binding site"? I know both bind to the receptor, but not at the benzo site.
>
> And that other point, about flooding. You're really saying that chronic dosing with oral GABA will not be as effective as taking it in pulses?
>
> Thanks.
>
> Lar
>
>
the deal with niacinamide and magnesium is that they are important for conformational changes of the C-loop, which is at the ``bottom'' of the ligand-gated ion channel. niacinamide will bind between the alpha and beta sububits, but not at the BZ site, as you state. the other player is calcium, which was co-crystallized with AChBP homopentameric alpha_{7} (Brejc et al, Nature, 2001). the cations are not near the binding site(s); niacinamide qualifies as a ``drug bound in a ligand binding domain,'' but again, it's not the BZ site. as for taking GABA orally to increase concentration - i use the term flooding, as it''s the best way i think about it - i think there are too many variables that come into play before the rubber hits the road. first off, the pKa of the acidic proton is going to be above that of the GI juices, but not significantly so, so i suspect you have the neutral and deprotonated GABA before it hits your liver, at which point is there deamination or decarboxylation? i don't know, but assumming actual neutral GABA makes it into the noggin, you now have increased [GABA] (assume activity coefficient = 1). so, if now more GABA needs to be ``turned around,'' and this is going to keep [GABA] in the synape high, as only so much can be brought back into the fold/degraded. so what i am getting at is that chronic extra GABA introduced not by agonism of GABA_{A} (by a BZ) leads to desensatization. i would think acute dosing would be more effective and not lead to ``poop-out,'' same deal with ssris, except dopamine is implicated, and serotonin receptors (some) are structurally homologous with the LGICs like GABA and AChBP.....any of this jibe with your take? chemist
Posted by arrie on June 19, 2004, at 21:24:33
In reply to GABA, posted by Questionmark on June 16, 2004, at 8:45:22
Question for Lar and Chemist please:
1. can you safely take 5htp and Gaba at the same time?
2. are these stressful to the liver like medicine?
3. is there any speculation/evidence that these are helpful to opiate addicts who are tapering off meds, in terms of helping the old neuro transmittors get back on path.
You both sound like you are highly qualified to answer my questions. I just get sick of blowing money on supplements if they dont really do anything to help.
Posted by Questionmark on June 20, 2004, at 9:55:37
In reply to Re: GABA » Larry Hoover, posted by chemist on June 19, 2004, at 15:00:17
> > > hello there, chemist here... lar is spot-on. the entire question is quite moot, really: gamma butyric acid is water-soluble and lipid soluble, so crossing the BBB is not an issue. what is an issue is activating the GABA_{A} receptor and inducing chloride flux. if you take GABA and it works - as lar has said - then great. otherwise, there really is no need to go for it, as your GABA_A} (mostly) receptor needs to be inhibited by reuptake, so any additional flooding is not going to help unless you have a drug in the binding site that will inhibit...all the best, chemist
> >
> > Dude, you raised more questions.
> >
> > Both niacinamide and magnesium ions have been shown to increase GABA-ergic activity (my perhaps not totally correct/concise description). Do either/both of these qualify as "drug in the binding site"? I know both bind to the receptor, but not at the benzo site.
> >
> > And that other point, about flooding. You're really saying that chronic dosing with oral GABA will not be as effective as taking it in pulses?
> >
> > Thanks.
> >
> > Lar
> >
> >
> the deal with niacinamide and magnesium is that they are important for conformational changes of the C-loop, which is at the ``bottom'' of the ligand-gated ion channel. niacinamide will bind between the alpha and beta sububits, but not at the BZ site, as you state. the other player is calcium, which was co-crystallized with AChBP homopentameric alpha_{7} (Brejc et al, Nature, 2001). the cations are not near the binding site(s); niacinamide qualifies as a ``drug bound in a ligand binding domain,'' but again, it's not the BZ site. as for taking GABA orally to increase concentration - i use the term flooding, as it''s the best way i think about it - i think there are too many variables that come into play before the rubber hits the road. first off, the pKa of the acidic proton is going to be above that of the GI juices, but not significantly so, so i suspect you have the neutral and deprotonated GABA before it hits your liver, at which point is there deamination or decarboxylation? i don't know, but assumming actual neutral GABA makes it into the noggin, you now have increased [GABA] (assume activity coefficient = 1). so, if now more GABA needs to be ``turned around,'' and this is going to keep [GABA] in the synape high, as only so much can be brought back into the fold/degraded. so what i am getting at is that chronic extra GABA introduced not by agonism of GABA_{A} (by a BZ) leads to desensatization. i would think acute dosing would be more effective and not lead to ``poop-out,'' same deal with ssris, except dopamine is implicated, and serotonin receptors (some) are structurally homologous with the LGICs like GABA and AChBP.....any of this jibe with your > take? chemist
>That sounds extremely interesting, especially the "same deal with SSRIs" statement. Can you/someone please translate that post into layman's?
Your statement regarding SSRIs was particularly interesting since, after i got off Paxil and before i got on anything else (Nardil), i would occasionally take a small dose of Paxil (5-15mg, believe it or not) and would feel tremendous benefits for that day. However, it seemed that a couple days or so after taking it, if i didn't take any again, i would start to feel really bad-- even worse than normal. But i'm not sure if that's true since i was already feeling horrendous from the overall Paxil withdrawal and intense depression it with which it left me.
Posted by chemist on June 20, 2004, at 16:42:10
In reply to Re: GABA, posted by arrie on June 19, 2004, at 21:24:33
> Question for Lar and Chemist please:
> 1. can you safely take 5htp and Gaba at the same time?****yes*****
> 2. are these stressful to the liver like medicine?
*****no*****
> 3. is there any speculation/evidence that these are helpful to opiate addicts who are tapering off meds, in terms of helping the old neuro transmittors get back on path.
****not that i am aware of. the opioid receptors (kappa, mu, delta) are not, to the best of my knowledge, affected by GABA or 5-HTP (lar, please confirm)*****
> You both sound like you are highly qualified to answer my questions. I just get sick of blowing money on supplements if they dont really do anything to help.
****well, thank you for the compliment. larry is extremely qualified in my opinion and i do hope that he can confirm the validity of my answers. i wish you all the best, chemist*******
Posted by Larry Hoover on June 21, 2004, at 10:32:30
In reply to Re: GABA » Larry Hoover, posted by chemist on June 19, 2004, at 15:00:17
Thanks, chemist. Your specific knowledge of the GABA receptor is considerably beyond my own. I have a more functional knowledge of trans-membrane structures. Conformational changes induced by ligands, ion flux, second-messengers, and such. I couldn't have answered my own questions in the detail you provided, had I tried to tackle the literature myself.
Lar
Posted by Larry Hoover on June 21, 2004, at 10:39:14
In reply to Re: GABA, posted by arrie on June 19, 2004, at 21:24:33
> Question for Lar and Chemist please:
> 1. can you safely take 5htp and Gaba at the same time?
Absolutely. I have no concerns whatsoever.> 2. are these stressful to the liver like medicine?
No. Absolutely not. Unless you take whole bottles-full at a time.> 3. is there any speculation/evidence that these are helpful to opiate addicts who are tapering off meds, in terms of helping the old neuro transmittors get back on path.
GABA or niacinamide might give some symptomatic relief, as might magnesium. Phosphatidyl-serine could also be mellowing.> You both sound like you are highly qualified to answer my questions. I just get sick of blowing money on supplements if they dont really do anything to help.
I wish that my advice might always be applicable, but, for the record, I have many 100's of dollars worth of supplements which have proven useless or even adverse, in my own supplement trials. You have to "do the experiment" to know. No amount of thinking can replace actual experience.
Lar
Posted by Larry Hoover on June 21, 2004, at 10:42:46
In reply to Re: GABA (and for Lar, too!!!) » arrie, posted by chemist on June 20, 2004, at 16:42:10
> > Question for Lar and Chemist please:
> > 1. can you safely take 5htp and Gaba at the same time?
>
> ****yes*****
ditto> > 2. are these stressful to the liver like medicine?
> *****no*****
ditto> > 3. is there any speculation/evidence that these are helpful to opiate addicts who are tapering off meds, in terms of helping the old neuro transmittors get back on path.
> ****not that i am aware of. the opioid receptors (kappa, mu, delta) are not, to the best of my knowledge, affected by GABA or 5-HTP (lar, please confirm)*****
As far as I know, that is correct. However, I perceive withdrawal symptoms in a more systemic light. You may be able to address some of the symptoms by influencing interacting neurotransmitters. (As suggested by my direct reply to arrie.)> > You both sound like you are highly qualified to answer my questions. I just get sick of blowing money on supplements if they dont really do anything to help.
> ****well, thank you for the compliment. larry is extremely qualified in my opinion and i do hope that he can confirm the validity of my answers. i wish you all the best, chemist*******Thank you. That is high praise indeed. I might have said the same thing about you. I've certainly thought it many times.
Lar
Posted by chemist on June 21, 2004, at 11:17:16
In reply to Re: GABA » chemist, posted by Larry Hoover on June 21, 2004, at 10:32:30
Posted by chemist on June 21, 2004, at 11:20:27
In reply to Re: GABA (and for Lar, too!!!) » chemist, posted by Larry Hoover on June 21, 2004, at 10:42:46
> > > Question for Lar and Chemist please:
> > > 1. can you safely take 5htp and Gaba at the same time?
> >
> > ****yes*****
> ditto
>
> > > 2. are these stressful to the liver like medicine?
> > *****no*****
> ditto
>
> > > 3. is there any speculation/evidence that these are helpful to opiate addicts who are tapering off meds, in terms of helping the old neuro transmittors get back on path.
> > ****not that i am aware of. the opioid receptors (kappa, mu, delta) are not, to the best of my knowledge, affected by GABA or 5-HTP (lar, please confirm)*****
> As far as I know, that is correct. However, I perceive withdrawal symptoms in a more systemic light. You may be able to address some of the symptoms by influencing interacting neurotransmitters. (As suggested by my direct reply to arrie.)
>
> > > You both sound like you are highly qualified to answer my questions. I just get sick of blowing money on supplements if they dont really do anything to help.
> > ****well, thank you for the compliment. larry is extremely qualified in my opinion and i do hope that he can confirm the validity of my answers. i wish you all the best, chemist*******
>
> Thank you. That is high praise indeed. I might have said the same thing about you. I've certainly thought it many times.
>
> Lar
>
>
the feeling is mutual, lar....btw, i'm up against the wall with the phosphadityl serine: what gives? all i'm finding is muscle-building supplements.....appreciate the info when you get a chance, many thanks, chemist
Posted by arrie on June 21, 2004, at 16:57:15
In reply to Re: GABA (and for Lar, too!!!) » Larry Hoover, posted by chemist on June 21, 2004, at 11:20:27
Well thank you both so much, I do indeed appreciate it. I am taking both right now, but cant tell a thing because I am tapering off opiates, so the spacial thing is an issue, oh yeah its Mon and I still feel like ........it is getting a bit better.
After having this experience with opiates I do have a new found respect for the brain. I had NO idea that these drugs could change someones constituition so much. Against hope I look for something as effective at the health food store. I am going in about 2 weeks to see specialist for Buprenephrine regime and hoping since this is a longer acting narcotic I dont do further damage. We shall see I guess. Thank you both and if I had half the brains you guys do I WOULD NOT BE DEPRESSED! Grass always greener.
Posted by johnj on June 21, 2004, at 17:21:20
In reply to Re: GABA (and for Lar, too!!!) » chemist, posted by Larry Hoover on June 21, 2004, at 10:42:46
Larry,
It is good to see you back. I have not come here in quite some time. Honestly, after you left I had a bad taste in my mouth and felt bad for you. Kudos for coming back because we all missed you. You and chemist are a great compliment to each other. How have you been??
johnj
Posted by traveler on July 1, 2004, at 15:52:08
In reply to Re: GABA (and for Lar, too!!!) » Larry Hoover, posted by chemist on June 21, 2004, at 11:20:27
I am kind of new to this stuff - so would someone mind explaining exactly what GABA is, and who it would benefit?
thank you
Posted by Larry Hoover on July 3, 2004, at 11:52:49
In reply to HELLO LARRY, posted by johnj on June 21, 2004, at 17:21:20
> Larry,
>
> It is good to see you back. I have not come here in quite some time. Honestly, after you left I had a bad taste in my mouth and felt bad for you. Kudos for coming back because we all missed you. You and chemist are a great compliment to each other. How have you been??
>
> johnjJohn, I'm so sorry I missed this message. I haven't been too thorough on this board, lately.
I never even replied to your email a couple months ago....I was too depressed to know what to say. Losing Babble really hit me hard. And losing it the way I did hit me harder still. I really felt unfairly treated.
Good to see you still take a peak now and again.
Lar
Posted by Larry Hoover on July 3, 2004, at 11:54:45
In reply to What does GABA do for you?, posted by traveler on July 1, 2004, at 15:52:08
> I am kind of new to this stuff - so would someone mind explaining exactly what GABA is, and who it would benefit?
> thank youGABA is gamma-amino butyric acid, a neurotransmitter. Tranquilizers like benzodiazepines (Valium et al) increase the signal at GABA receptors. Anxious people benefit from increased GABA signals, very generally stated.
Lar
Posted by johnj on July 13, 2004, at 17:46:03
In reply to Re: HELLO LARRY » johnj, posted by Larry Hoover on July 3, 2004, at 11:52:49
Hey Lar,
Don't worry about responding when you don't feel very well. I have had a bit of a row recently and don't feel the best right now. I have some conversation/questions when I am able to write with a clearer head. Insomnia has been bad this last week and it really drags me down. Take care Lar.
johnj
Posted by Larry Hoover on July 14, 2004, at 7:54:58
In reply to Re: HELLO LARRY, posted by johnj on July 13, 2004, at 17:46:03
> Hey Lar,
>
> Don't worry about responding when you don't feel very well. I have had a bit of a row recently and don't feel the best right now. I have some conversation/questions when I am able to write with a clearer head. Insomnia has been bad this last week and it really drags me down. Take care Lar.
>
> johnjHey John, no need to hold back. I've always had problems to deal with (or so it seems). What's going on now is same old same old, ya know?
Whenever you're ready, buddy.
Lar
This is the end of the thread.
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