3 replies to this topic

[Believer]

Theanine-stupid is where you take theanine and suddenly you can't concentrate or think right. Your reaction time is slowed and you feel mentally retarded and vulnerable to insults.

Theanine is good for anxiety and other issues but this side-effect is horrendous. Never mind the day after where glutamate levels are elevated which causes a whole host of other issues to deal with.

 

I believe it's caused by an anti-noradrenaline effect. Why? Because noradrenaline is important for reaction time and anger and theanine makes me even more unable to express anger whereas fasting has the opposite effect because it increases noradrenaline.

We can say with a certain amount of faith that it is not the nmda receptor that is responsible for this side-effect because other nmda agonists do not cause this effect.

 

What we know is that theanine is an AMPA and kainate ionitropic glutamate receptor antagonist and a weak nmda receptor agonist. We also know it increases glutamate levels by at least two mechanisms, the first being its ability to convert to glutamate via metabolism and the second mechanism is via blocking reuptake transporters.

It seems to me it has no effect on mGluR5 receptors, neither activating nor blocking those receptors as those receptors can cause certain effects (rage and ocd) that theanine neither exacerbates nor reduces. It is supposed to affect the mGluR1 receptor and this is supposedly the mechanism whereby it should be neuroprotective by reducing glutamate levels but my experience is that it does nothing to reduce glutamate at all, actually it increases glutamate mildly and after its effects wear off it seems to increase glutamate activity (especially in the morning) strongly, but probably in specific brain parts as opposed to the entire brain.

[Kinesis]

What leads to to conclude that it is (isn’t) having the receptor activities you cite? Aren’t pretty invasive procedures required to establish activity at the molecular level in synapses?

[Believer]

What leads to to conclude that it is (isn’t) having the receptor activities you cite? Aren’t pretty invasive procedures required to establish activity at the molecular level in synapses?

What are you referring to? The NMDA receptor, the mGluR5 receptor, the mGluR1 receptor?

It is supposed to reduce glutamate levels and be neuroprotective in that way but my experience is that it does not do so. I have the quite normal mutation that causes the enzyme which converts glutamate to gaba to be only 30% functional or something like that. This means I can experience "autistic" rage, ocd, muscle coordination difficulty and other symptoms from drinking caffeine (causes a release of glutamate in the brain), consuming protein powder (it contains glutamine, glutamine gets converted to glutamate) and many other things.

Creatine reduces glutamate by competing with one of the glutamate transporters and abolishes these "autistic" symptoms but theanine does not help these symptoms. In fact theanine causes side-effects that appear to be glutamatergic but this could be exclusively activation of the NMDA receptor. For example theanine gives me tinnitus which is even worse when theanine is out of the body (a day later). Interestingly, tinnitus can both be caused by a lack of glutamatergic signaling and also be caused by glutamatergic signaling itself. An example of this is glutamate agonists like fasoracetam causing tinnitus (some claim it reduces glutamate but I doubt it) but also things like creatine causing it. So it seems to me that theanine slightly increases glutamate when ingested and once it has left the body then it either does the opposite of decreasing glutamate or increasing it even further than baseline.

As always it's possible that in the one brain area it increases glutamate and in another it decreases glutamate.

 

As for studies on pharmacology, it's complex and sometimes it's found out that a drug is an antagonist rather than agonist, or a drug does the opposite of what it has been assumed to be doing for a long time.

 

 

[Kinesis]

 

What leads to to conclude that it is (isn’t) having the receptor activities you cite? Aren’t pretty invasive procedures required to establish activity at the molecular level in synapses?

What are you referring to? The NMDA receptor, the mGluR5 receptor, the mGluR1 receptor?
It is supposed to reduce glutamate levels and be neuroprotective in that way but my experience is that it does not do so. I have the quite normal mutation that causes the enzyme which converts glutamate to gaba to be only 30% functional or something like that. This means I can experience "autistic" rage, ocd, muscle coordination difficulty and other symptoms from drinking caffeine (causes a release of glutamate in the brain), consuming protein powder (it contains glutamine, glutamine gets converted to glutamate) and many other things.
Creatine reduces glutamate by competing with one of the glutamate transporters and abolishes these "autistic" symptoms but theanine does not help these symptoms. In fact theanine causes side-effects that appear to be glutamatergic but this could be exclusively activation of the NMDA receptor. For example theanine gives me tinnitus which is even worse when theanine is out of the body (a day later). Interestingly, tinnitus can both be caused by a lack of glutamatergic signaling and also be caused by glutamatergic signaling itself. An example of this is glutamate agonists like fasoracetam causing tinnitus (some claim it reduces glutamate but I doubt it) but also things like creatine causing it. So it seems to me that theanine slightly increases glutamate when ingested and once it has left the body then it either does the opposite of decreasing glutamate or increasing it even further than baseline.
As always it's possible that in the one brain area it increases glutamate and in another it decreases glutamate.
 
As for studies on pharmacology, it's complex and sometimes it's found out that a drug is an antagonist rather than agonist, or a drug does the opposite of what it has been assumed to be doing for a long time.

 

All of them. As you correctly point out, neuropharmacology is complex and that assumptions regarding synaptic processes often turn out to be wrong.  It's notoriously difficult to establish exactly what's going at the molecular level in the brain ... usually what we're going on is conjecture extrapolated from in vitro or animal studies.  Any degree of certainty generally takes invasive procedures like inserting sensitive probes into the brain or sophisticated imaging studies, the main reason why in vitro and animal studies are used in the first place. Facts like Substance X made me feel this way, or didn't make me feel that way, are a long way from facts about transmitters and receptors.  Since you're making claims regarding molecular processes, especially ones that challenge existing theory, it would be helpful to know how you obtained your data.  In other words, what factual evidence you have for your conclusions about how specific molecules are interacting with specific receptors.

 

...

 

 

Edited by Kinesis, 01 December 2017 - 09:06 PM.