8 replies to this topic

[OpenStrife]

Is there a certain reason behind it? Or does it operate off the principle of trying to balance the neurotransmitter(NT):NeurotransmitterReceptor(NTR) ratio?

For instance, I've read that supplements that boost your Dopamine can cause an upregulation of Dopamine Receptors, and quite possibly an upregulation of dopamine production.

Though, this idea comes into conflict with the basic idea of addiction. Where, if Neurotransmitter levels are too high, receptor density is decreased to balance back to the default psychological state.

Is there some sort of threshold to where upregulation will stop occuring and down regulation will occur based upon the levels of said Neurotransmitter?

For example, I take L-Theanine(GABA precursor - also raises dopamine) and L-Tyrosine(Dopamine Precursor).

L-Theanine is said to cause an upregulation of your GABA system over time, including upregulation of receptor density. L-Tyrosine is said to upregulate Dopamine Receptors and the Dopamine systems.

The only possible way I can see this being possible is... the brain does not increase receptor density(and that specific neurotransmitter system) as a direct result of a hightened level of neurotransmitters.... but rather, what if something in the conversation process of the precursor tells the brain more receptors are needed?

This idea would explain why upregulation of receptors does not happen with drugs that spike certain neurotransmitters(meth, sex, cocaine, heroin)... but would explain why upregulation of a NT System would occur when taking precursors.

What do you guys think? I feel if I better understood the actual causes of Upregulation and Downregulation, I could more easily gauge the long term effects of the precursoral supplements that I take.

[renfr]

L-Theanine is said to cause an upregulation of your GABA system over time, including upregulation of receptor density. L-Tyrosine is said to upregulate Dopamine Receptors and the Dopamine systems.

Where have you seen that L-theanine increases GABA receptor density?

[OpenStrife]

No clue... just one of those random facts I picked up in all the research I do. I could be wrong... but I do often use L-Theanine to restore my GABA functioning(over a few days-weeks) after periods of drug binges, and other generally unhealthy/lazy activities.

It could very well be by another mechanism other than GABA upregulation. As, L-Theanine can provide a number of long-term effects and changes to the brain that will continue for weeks after use, as far as I can tell from my experience with it.

It could have nothing to do with receptor density at all, and just in the idea that the extra GABA allows new behaviors to be learned and developed, and it is those behaviors that are kept.

One of the long-term side effects I get after excessive L-Theanine use, is very powerful inhibitory effects of the brain. I could be in a conversation, and if I happen to get distracted(by a thought/curiosity since outside things could not distract me), I will completely tune out what the other person is saying and not pick up on a single word of it. As if the GABA is inhibiting the stimuli that I am not paying attention to.... This effect continues, and gradually begins to lessen in the 1-2 month period after you stop taking L-Theanine. I would use this 'ability' and would be able to focus extremely powerfully in rooms that were as loud as could be.

Though, thing is, I only experienced the above super-inhibitory effects on the Source Naturals brand of L-Theanine(on amazon.com), which from what I have observed, is a TIME/extended released version. Their 200mg ER Tablets seemed to provide MUCH more significant effects than pure powder forms and even far greater effects than the official "suntheanine" brand. I do believe Source Naturals is the only maker of the ER L-Theanine TABLETS that I know of.

It seems the Time-Released effect(which I observed by trying to dissolve a tablet in water - which took a bit over 6 hours), allows the body to process the L-Theanine at a rate it can handle and not get rid of any excess like it normally would. Though this is only a theory.

I know I kind of went off-topic but here is the link to the ones I USED to take.
http://www.amazon.co...ils_o00_s00_i00

I only take the powder form now because it's much cheaper, and the extreme inhibitory effects of the Time-Released Tablets became a little too much for me. I believe it got to the point where nothing could distract me from anything which lead to potential car-accidents if I ever got lost in a thought. I once sat at a green light, staring at it, for a whole minute because I was lost in a thought. No doubt this could be used to an extreme academic advantage, as thoughts become very precise, but there are a few downsides, as mentioned above.


This effect could also be caused by upregulation, because I noticed, the longer I took these L-Theanine Tablets, (2,200mg tablets aday once morning, once before bed), the effects seemed to be accumulative. My focus would get stronger and stronger as did my ability to tune things out. Though I do not experience this accumulative focus effect with anything other than the ER versions.

This could be because, on the ER versions, there is always some in your system, being processed, so GABA is continuously increasing. Where as, if you were to take a Bulk Powder, twice aday, the excess would be out of your system within a few hours, and there would be periods where GABA decreases.

Edited by OpenStrife, 30 July 2012 - 09:14 PM.

[renfr]

That's really awesome! Compared to the powder is there truly a change? Do you still have those inhibitory effects with the powder?
I might try out that source naturals L-theanine, you said tablets right? because I can see two versions : tabs and tablets
My GABA system is screwed up to death and I need a radical repair of it.
So your dosage is 2 times 200mg or 2200mg? I found it on vitacost (shipping is lower for me there) : http://www.vitacost....rals-l-theanine
that's the same right?
I think I read somewhere it could upregulate GABA as well but I wasn't so sure.
All I know for sure is that L-theanine is responsible to generate alpha waves in your brain, GABA is somewhat related to alpha-waves, GABA surge increases alpha waves the contrary likely happens.
This is what people who do yoga do, they put their brain into a low wave state and research has proven that yoga increases GABA up to 30%.
I will look into source naturals L-theanine, looks very promising nevertheless I'll wait for my powdered L-theanine see if it does something.
If your time release theory is proven to be right then it that case, taking small doses of power several times a day should be as effective as taking a time release capsule, don't you think so?
Usually our body process substances in 45mins-1h, in that case if the tablet takes 6 hours to be totally dissolved, taking 35mg each hour 12 times in the day should be as effective.
Of course it's more annoying to do but since I will only get the powder for now I will try that out.
Anyway very interesting post you made.

[OpenStrife]

There is an astronomical difference between the bulk powder, or powder in gelatin compared to the ER Tablets.

Also, I tried what you were going to try. Small doses spaced throughout the day. Doesn't work.

The tablet versions seem to give me a completely different effect than the powders, even with the powders in the gelatin. Not sure why.

And the 6 hour guess was off the top of my head, I did the water dissolve test years ago. It's not hard to figure out yourself.

The only downside is that the tablets cost so much more, and I believe there is a good reason behind it. All I know is, the tablets are a million times more effective than any administration of the powder. It could be the form, or it could be the time release.

Even if it has nothing to do with the chemical form, it would be hard to match the ER timing by periodic dosing of the powder. Yes it may come down to 35mg an hour, but your body still absorbs all of it at once... compared to the ER tablet which may release 1mg every 2 minutes........

I believe too great of a surge of the powder at once could cause the brain to release enzymes that restrict the theanine conversion to gaba.... but having it released in 1mg every 2 minutes, would prevent that from happening.

Edited by OpenStrife, 30 July 2012 - 11:27 PM.

[adiosameobas]

it conflicts with the basic concept of tolerance. if you take an amphetamine which releases for the most part (as well as inhibits some reuptake of) more dopamine than normal, your neurons will downregulate the number of dopamine receptor sites over a given period of time, that is why you need to take more of the drug to get the desired effect. after cessation of the drug, the brain naturally is programmed to return to its "default psychological state" or moreover, natural physiological state, since your brain doesn't give a shit how you feel especially if you went on a week long speed binge....
but i digress....
in order to return to a homeostatic level, upregulation begins to occur, but this occurs on the cellular component, ie: you can take all the tyrosine you want, but it's not gonna do shit if you don't have any receptors, aka, more dopamine doesn't always equal more happy. also, conveniently, upregulation happens at a muuuuuuchhhhhh sloooooooooooweeeeerrrrrrr raaaaaaaaaatttttteeeeeeee.. than downregulation, which is somewhat intuitive if you think about it because it takes alot longer to dig a hole than to cave one in really quick. just a primitive example.... hope that helps, as far as theanine goes, i dont really know, all i have read about it is that it may boost dopamine, but im going to go ahead and guess that its not going to be on the level of any of your more classic mind bending drugs.

[gamesguru]

There are three main causes, and potentially more which are as yet undiscovered:

1) Certain receptor-ligand complexes undergo endocytosis (basically the cell is designed to eat them). This is the case with insulin and potentially cannabinoid receptors (don't quote me on that one). In this way, the cell must be constantly building new receptors since the old ones are eaten with every new dissociation (remember that dissociation, not binding, is what causes pharmacological activity). This may sound crazy, but it prevents too many receptors from being dissociated in a short time, therefore avoiding saturation, since the limiting factor is not how much drug you administer, but how quickly the receptors "repopulate", which is thought to vary logistically with time.

2) Gene expression regulates the receptor density via internal factors. Basically, the dissociation results in a buildup of certain proteins intracellularly which then reduce receptor repopulation. This is thought to be how cells adapt to drug abuse, for instance. Don't quote me on which receptors function this way. This is most appropriatedly called desensitization, since it is a result of tolerance, whereas receptor sequestration (#1) obeys linear equations.

3) Uncoupling or G-protein activation/deactivation cycle. Just read up about this one, I don't have any neat and succinct metaphors.

Edited by dasheenster, 31 July 2012 - 01:32 AM.

[OpenStrife]

Interesting post, dasheenster.

Though I still seem to be slightly confused.

Could you perhaps give an example of a certain scenario/drug which would cause upregulation of receptors. Like, explaining how exactly more of a specific neurotransmitter being produced, continuously, would lead to upregulation.

[tyler79]

How do you know Source Naturals L-Theanine tablets are extended release? I don't see it saying that on the supplement label?