49 replies to this topic

[medievil]

I feel like this may be something that may be best left to the scientific community. In my mind it seems like once said blocker wears off you would feel the rebound which would be sleepiness and fuzzy memory. But that contradicts the fact that downregulation causes memory impairment, so one would think that up regulation would have the opposite effect. This leads me to believe that perhaps GABA just needs to be balanced for optimal memory functioning. That being said I know little about the GABA system, so if someone could shed some light on the subject and explain this to me it would be much appreciated.

Your forgetting that those herbs usually act on specific subunits and have a multitude of effects, as an example lemon balm increases gaba and improves anxiety while simultaniously improving cognition to the increase in acetylcholine levels.

[Healthy Tony]

Your forgetting that those herbs usually act on specific subunits and have a multitude of effects, as an example lemon balm increases gaba and improves anxiety while simultaniously improving cognition to the increase in acetylcholine levels.

That's a fair point, but I was referring simply to a GABA-A antagonist. Also, how do we know that this won't have unwanted longterm effects such as benzos. We have no idea really...

[thedevinroy]

Your forgetting that those herbs usually act on specific subunits and have a multitude of effects, as an example lemon balm increases gaba and improves anxiety while simultaniously improving cognition to the increase in acetylcholine levels.

That's a fair point, but I was referring simply to a GABA-A antagonist. Also, how do we know that this won't have unwanted longterm effects such as benzos. We have no idea really...

Like I said before, we have an IDEA, based on other neurotransmitter systems. Whether or not it is true is up for time to tell. GABA-A Blockade is not a common treatment. It's a fairly new idea to the nootropic world. It will, in my opinion, cause some tolerance, but not cause an issue with continual use or fair adjustments to taper off. Again, this is an idea. We do have some idea.

What is your main concern, if so, at what level?

[QuantumTubule]

devinthayer
Im sorry but using GABA-A blockers is fu*king crazy. I dont know where to start except to say that do you realise that there is a strong hypothesis the adhd/autismU is caused by inactivity of the GABA system. Also the temporal dynamics of concentration of these substances cause intense neurodegeneration. Zn and Ginko Bibola have other strong effects that outweigh GABA inhibtion.

[thedevinroy]

devinthayer
Im sorry but using GABA-A blockers is fu*king crazy. I dont know where to start except to say that do you realise that there is a strong hypothesis the adhd/autismU is caused by inactivity of the GABA system. Also the temporal dynamics of concentration of these substances cause intense neurodegeneration. Zn and Ginko Bibola have other strong effects that outweigh GABA inhibtion.

I realize some GABA blockers are potentially harmful. That is obvious. However, some improve cognition by limiting or regulating the amount of inhibition. Please also note that the D4 receptor, heavily studied for ADHD, down regulate GABA-A receptors (as do stimulants). It is not crazy. It is innovative, and this is a fairly new and interesting theory that many doctors shy away from because they are also trying to treat hyperactivity, which BZD's tend to treat. Adult ADHD (especially inattentive type) is entirely different. BZD's make things worse.

"GABA_ARs are down-regulated by D₄ signaling independent of neuronal activity."
http://www.ncbi.nlm....les/PMC3009820/

More studies on the link between D4 and GABA-A:
http://www.ncbi.nlm....pubmed/12417643
http://www.ncbi.nlm..../pubmed/8622768

In addition, I also want to point out that stimulants tend to down regulate the GABA-A receptor.
http://www.ncbi.nlm....pubmed/20581658

Non-anxiogenic / Non-convulsant GABA Blockers increase cognition, LTP, etc.
http://www.ncbi.nlm....les/PMC1907590/
http://www.ncbi.nlm....pubmed/15084116
http://www.ncbi.nlm....pubmed/12747794
http://www.ncbi.nlm....pubmed/16633803
http://jpet.aspetjou...316/3/1335.long

Benzos counter Atomoxetine (Strattera) toxicity:
http://www.ncbi.nlm....pubmed/16982359

"Lithium, benzodiazepines, antihistaminic sedatives, and buspirone are potentially detrimental [for Adult ADHD treatment]."
http://www.ncbi.nlm....pubmed/10944659

Edited by devinthayer, 01 December 2011 - 03:58 PM.

[Healthy Tony]

Wow that's a lot of data to sift through... Later when I get to a computer and can properly analyze this information I will reply with a GABA A blocker that you might find interesting. But if what you summized from the data is correct wouldn't a d4 antagonist be ultimately what we would want for ADHD-PI?

Edit: The last link did nothing to explain why lithium is detrimental, which is unfortunate because I take a lithium supplement every night before bed. I wonder if this could be doing more harm than good in the long run.

Edited by TheRockst4r, 01 December 2011 - 04:38 PM.

[thedevinroy]

Wow that's a lot of data to sift through... Later when I get to a computer and can properly analyze this information I will reply with a GABA A blocker that you might find interesting. But if what you summized from the data is correct wouldn't a d4 antagonist be ultimately what we would want for ADHD-PI?

Edit: The last link did nothing to explain why lithium is detrimental, which is unfortunate because I take a lithium supplement every night before bed. I wonder if this could be doing more harm than good in the long run.

D4 Agonist (not antagonist) would work and has worked, but the body tends to build tolerance quickly to dopamine agonists. In addition, they tend to activate other dopamine receptors and may increase or start manic symptoms such as gambling and lavish spending. Thus, attacking the circuitry from different angles tends to be a better approach.

Typically, lithium dosages for psychiatric purposes are damn near toxic doses (upwards of 150mg elemental lithium). Nootropic doses of lithium are far below that which is prescribed (5mg to 10mg of elemental lithium). Chronic lithium is bad, but small doses are good, if not down right nutritional. The study was referring to an administration routine similar to that of bipolar (or a form), most likely over 100mg of elemental lithium, since rarely is lithium prescribed for anything else but for mood disorders.

[QuantumTubule]

" Please also note that the D4 receptor, heavily studied for ADHD, down regulate GABA-A receptors"


This argument has no real argumentative value.
1. There is no evidence that GABA-A down regulation is in any shape or form responisble for the effects of D4 agonist on ADHD. Pls prove me wrong, the testing wouldnt be to hard
2. Conceptually D4 agonist have an effect X, this effect X has been shown to improve function in ADHD(or we assume unless hormosis this the cause in which case switch X,Y). The Body always responds with effects Y's involve restoration of equilibrium towards original. Now Tell me weather D4 agonist down reg GABA-a receptors via effect X or Y, there are opposite by the way. If it is via Y then your fact is contraindicating your hypothesis.

I respect what you have wrote in other threads but it is common knowledge that negative modulation of GABA-a receptors is neurotoxic in a strong profound way. Furthermore ADHD is caused by insufficient inhibtion, increasing inhibition increase metabolism and quite a few other things.
I just fail to understand why you started looking at a class of substance that are all potent toxins.

That Being said you are correct in a very objective sence. GABA-a antagonist can eliminate ADHD in all People in one dose, 100% of the time. Its called being Dead mate

[thedevinroy]

" Please also note that the D4 receptor, heavily studied for ADHD, down regulate GABA-A receptors"


This argument has no real argumentative value.
1. There is no evidence that GABA-A down regulation is in any shape or form responisble for the effects of D4 agonist on ADHD. Pls prove me wrong, the testing wouldnt be to hard
2. Conceptually D4 agonist have an effect X, this effect X has been shown to improve function in ADHD(or we assume unless hormosis this the cause in which case switch X,Y). The Body always responds with effects Y's involve restoration of equilibrium towards original. Now Tell me weather D4 agonist down reg GABA-a receptors via effect X or Y, there are opposite by the way. If it is via Y then your fact is contraindicating your hypothesis.

I respect what you have wrote in other threads but it is common knowledge that negative modulation of GABA-a receptors is neurotoxic in a strong profound way. Furthermore ADHD is caused by insufficient inhibtion, increasing inhibition increase metabolism and quite a few other things.
I just fail to understand why you started looking at a class of substance that are all potent toxins.

That Being said you are correct in a very objective sence. GABA-a antagonist can eliminate ADHD in all People in one dose, 100% of the time. Its called being Dead mate

I feel like numbering my responses, too.

• It's not purely increased inhibition vs. decreased inhibition. Adult ADHD, especially inattentive type, is a different animal than ADHD with hyperactivity. Stimulant treatments overlap, sedative treatments do not.
• You've made no mention of cognitive enhancements from GABA-A down regulation. I have provided you studies in which two separate GABA blockers increased cognition without convulsive or anxiogenic effects. Lowering above-normal GABA-A transmission results in cognitive benefits! If ADHD sufferers lack D4 stimulation, then they have higher than normal GABA-A function. You do the logic, Mr. X-Y-man.
• I feel like you are extremely closed-minded on this matter, not attributing enough information to support your cause. Yes, GABA is good for you, in fact, it increases NGF. Dopamine is also good for you, it increases BDNF. You need both, or you will not function. There must exist a balance, and you seem entirely one sided about this. You've made no mention of a BALANCE.
• Of course blocking all GABA transmission is stupid and will kill you. I wasn't proposing that. I was proposing that we find a way to throttle it during the day, for those that would benefit.

[Delafuente]

There is a specific GABA-A receptor known as the GABA-A-rho receptor. It used to be called GABA-C but was recently reclassified as a GABA-A subtype. Antagonists of the GABA-A-rho receptor have a significant nootropic effect and significantly inhibit the development of myopia in test animals: http://www.ncbi.nlm....les/PMC2630368/

The paper is very interesting, glad I stumbled upon it. A nootropic that inhibits myopia seems like an awesome combo. It would be great to get a hold of one of these GABA-A-rho antagonists.

[thedevinroy]

A new member (Delafuente) messaged me this: http://www.ncbi.nlm....les/PMC2630368/ . It's a study done on a GABA-A-Rho Blocker (also known as GABA-C) that improves cognition (including memory) and has anti-myopia effects (helps nearsightedness) at 10x full GABA-A-Rho inhibition. The article goes over a brief explanation of the different receptor type groups.

One thing I want to put out there: GABA-B inhibition probably has no effect or ill effect on ADHD related issues. In fact, activation of this receptor type may be beneficial. In a way, it is similar to some AMPA receptors as well as some dopamine receptors. It is both a Potassium channel and a G-I/O protein coupled receptor. Activation of GABA-B (by phenibut, at least0 may increase dopamine release. When I talk about GABA Blockers, I am referring to GABA-A subtypes, specifically A-Alpha5 and A-Rho... not B.

Edited by devinthayer, 17 December 2011 - 03:10 AM.

[Delafuente]

" Please also note that the D4 receptor, heavily studied for ADHD, down regulate GABA-A receptors"


This argument has no real argumentative value.
1. There is no evidence that GABA-A down regulation is in any shape or form responisble for the effects of D4 agonist on ADHD. Pls prove me wrong, the testing wouldnt be to hard
2. Conceptually D4 agonist have an effect X, this effect X has been shown to improve function in ADHD(or we assume unless hormosis this the cause in which case switch X,Y). The Body always responds with effects Y's involve restoration of equilibrium towards original. Now Tell me weather D4 agonist down reg GABA-a receptors via effect X or Y, there are opposite by the way. If it is via Y then your fact is contraindicating your hypothesis.

I respect what you have wrote in other threads but it is common knowledge that negative modulation of GABA-a receptors is neurotoxic in a strong profound way. Furthermore ADHD is caused by insufficient inhibtion, increasing inhibition increase metabolism and quite a few other things.
I just fail to understand why you started looking at a class of substance that are all potent toxins.

That Being said you are correct in a very objective sence. GABA-a antagonist can eliminate ADHD in all People in one dose, 100% of the time. Its called being Dead mate

Could you provide studies demonstrating that negative modulation of GABA-A is neurotoxic? Perhaps the drugs you looked at had neurotoxic effects by a different mechanism than GABA-A antagonism/negative modulation. Cyclothiazide acts as a negative allosteric modulator of GABA-A, yet does not result in neuronal cell death, even at doses that induce strong convulsions*

*Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo.

Edited by Delafuente, 17 December 2011 - 07:19 AM.

[Ark]

What about high dosages of Lemon Balm instead of Thujon?

[thedevinroy]

What about high dosages of Lemon Balm instead of Thujon?

Lemon Balm is high in rosmarinic acid, which although is a substrate of COMT, actually inhibits GABA-T like Valproic acid, inhibiting conversion from GABA to glutamate, which both raises GABA and lowers glutamate. It would counteract Thujone to some degree. It's more or less the opposite of thujone in terms of psychological effects. It is in no way a replacement.

[Ampa-omega]

how does gaba relate to myopia,?
that is a really nice find!
thanks for sharing about that antimyopia drug,
could be a wonder for people who are always reading for hours!
we need a thread on all eyesight enhancing substances nootropics etc

Edited by Ampa-omega, 18 December 2011 - 04:13 AM.

[Delafuente]

Good idea! Vision is something that interests me very much. I've gathered lots of information on pharmacological agents that modulate vision in some way. Does such a thread exist? If not, I could start one up.

how does gaba relate to myopia,?
that is a really nice find!
thanks for sharing about that antimyopia drug,
could be a wonder for people who are always reading for hours!
we need a thread on all eyesight enhancing substances nootropics etc

[Delafuente]

As devinthayer mentioned, bilobalide is a component of Ginkgo Biloba that has been shown to inhibit the GABA-A-rho receptor.
Found bilobalide extract, 100 mg for $941, probably the most expensive nootropic I've ever seen. Found it on nacalaiusa . com

Gingko Biloba supplements are the way to go then. According to a smartpublications article on gingko biloba, most USA supplements of the plant offered contain very low levels of bilobalide (usually around 2%) and potentially high levels of toxic ginkgcolic acid. It also states that in other countries, manufacture of gingko supplements are regulated to contain at least 5% of bilobalide as well as a maximum set limit of allowable gingkolic acid concentration. The countries are unfortunately unspecified.

[Ampa-omega]

Good idea! Vision is something that interests me very much. I've gathered lots of information on pharmacological agents that modulate vision in some way. Does such a thread exist? If not, I could start one up.

how does gaba relate to myopia,?
that is a really nice find!
thanks for sharing about that antimyopia drug,
could be a wonder for people who are always reading for hours!
we need a thread on all eyesight enhancing substances nootropics etc

yes, lets get one started asap, haha i think i need some visual help for books and online articals

what are some that you know of? we need a list of stuff.

[Delafuente]

Good idea! Vision is something that interests me very much. I've gathered lots of information on pharmacological agents that modulate vision in some way. Does such a thread exist? If not, I could start one up.

how does gaba relate to myopia,?
that is a really nice find!
thanks for sharing about that antimyopia drug,
could be a wonder for people who are always reading for hours!
we need a thread on all eyesight enhancing substances nootropics etc

yes, lets get one started asap, haha i think i need some visual help for books and online articals

what are some that you know of? we need a list of stuff.

I started a thread on myopia control/treatment:
/forum/topic/53244-myopia-pharmacological-intervention/

Edited by Delafuente, 18 December 2011 - 08:07 PM.

[Area-1255]

Very interesting stuff, wrote an article about it now.

http://area1255.blog...s-blockers.html

Never knew about the muira puama one..though this would explain the pro cognitive effects....

Thing is , it's also an AcHe inhibitor...so too much muira with something like thujone or ginkgo would probably result in anxiety attacks or even seizures for some.

Although...I've combined them with no issue...who knows what the actual affinity translates to in humans...and there are just a ridiculous number of other factors in GABA production and activity.