42 replies to this topic

[VerdeGo]

I came across a post from an individual on another forum stating he used it for 8 months and it seemed to cure all his anxiety (see below). Does anyone or has anyone used L-theanine for prolonged periods? If so, do you still use it and what are the benefits? If you stopped, why did you stop? Its relaxing and mood uplifting effects are above par of anything else I've taken recently. I'm wondering if anyone's suffered rebound anxiety or major tolerance from long term use.

 

http://neurotalk.psy...read192621.html(post truncated)

 

I’ve been doing a lot of online research around something I’ve been taking for 8 months now. I would like to know others experiences with it.

The name of the supplement is L-theanine. I started taking it due to GABA not being strong enough to treat my anxiety on its own. It was after this point that about 6 months later I realized something. L-theanine has long-term positive effects from what I could tell.

Slowly but surely my mood has improved, my attention span increased, and my anxiety all but been forgotten. Now my weight has begun to drop from the lack of stress in my mind. What I’d like to know from all of you is what anybody who has been taking L theanine long term what its like for them? Has anyone had similar encounters? From what I can tell L theanine could potentially be a possible cure for a lot of my problems however I am not certain due to lack of scientific evidence.

My personal opinion on why a lot of my symptoms of what I’m dealing with are going away is due what is called neuroplasticity. Long term brain changes. I am doing a number of treatments that show signs of Neurogenesis as they call it. You can read about them farther down.

I have actually spoken to a friend that took this and from he said it did similar things to him. He ultimately stopped taking it because after it “cured” his anxiety it started doing the “reverse” and making him very sleepy instead of very awake. Ultimately he and I are both under the same impression. L theanine can long term cure certain illnesses.

 

http://www.reddit.co...with_ltheanine/

 

Hey all,

Background: I've suffered with anxiety since early childhood. Partway through college, I was diagnosed with anxiety with secondary depression; my particular kind of anxiety was very much the panic attack kind, versus the slow burn kind. I went on Lexapro and Ativan briefly, and did some Cognitive Behavioral Therapy, which got me in to a place where I could function fairly highly. I've been unmedicated for ~4 years since then, and have gotten by fairly successfully by white-knuckling. However, my work has gotten more difficult, and I've been looking for ways to reduce distraction from anxiety.

Theanine?: I was looking for ways to improve my sleep (insomnia issues, exacerbated but not entirely caused by anxiety) and stumbled across the existence of L-Theanine. What is L-Theanine? When people compare coffee and tea, tea is often described as a relaxing beverage (This should seem really odd, because tea, as a whole, is a stimulant.) This is because of the presence of L-Theanine, another psychoactive compound, in (especially green) tea. It has the effect of making you calm, without sedation; it's particularly good for taking the edge off stimulants like coffee, and is highly recommended in the nootropics community.

Effects on my anxiety: I've been fairly wowed by this substance. Now, there's no such thing as a miracle cure, so don't get your hopes up too much. BUT: for my particular kind of anxiety, which seems to be very visceral and fight-or-flighty, this stuff has a huge effect. I have issues with intrusive thoughts/rumination: I'll remember some faux pas from a decade ago, and be so shocked and horrified by it that I'll have a physical response. Theanine seems to blunt the physical response, which has had the effect of reducing how often I have these intrusive thoughts. Some kind of conditioning mechanism seems to be at play there. In general, I feel very "chill" while under the influence of this substance; it's much harder to get me physically worried about anything. My attention has benefited quite a bit, probably secondary to anxiety reduction.

I also had to quit caffeine because of its anxiety-/depression-inducing effects. Taken with theanine, however, those effects are largely absent. This is great, because decaf just doesn't taste the same.

Warning: Anecdotally, I've seen a few people mention they've had terrible rebound anxiety upon ceasing use of theanine. I don't think I have this issue, but more experimentation is warranted.

Some people do seem to develop tolerance, probably of the psychological variety, to theanine's effects. I think I'm one of them, so I've been cycling off on weekends. (Based off what research I've seen, you should not develop physical tolerance to theanine.)

Some people get/feel absolutely nothing from theanine. Beyond the basic "everyone responds differently to psychoactives", I think that different types of anxiety will respond to different types of intervention. Mine seems to be responding very well to this kind.

Conclusion: If you anxiety sounds anything like mine, I highly recommend you (at least) try this stuff. It's available OTC, as a supplement. I personally am currently using Suntheanine, which comes in 150mg capsules. I take 3-4 a day: 1 around breakfast, 1 around lunch, and 1 a little later. Sometimes the lunchtime one gets taken with breakfast as well. The fourth is for occasional help falling asleep.

 

From that post, it seems it may be useful for treatment of PTSD.

 

On the other side of the coin was this topic on Reddit (the original post is gone): Here to warn the community that I've experienced debilitating rebound anxiety when taking l-theanine. It was 100 percent this substance. Quit a week ago and back to baseline. Theanine is going in the trash.

 

So back to my earlier question. Does anyone here have experience with using theanine for more than a few months?

[VerdeGo]

Just for the record, I noticed mild anxiety roughly 24 hours after last using theanine. I normally don't encounter anxiety unless there's a reason, so this stuck out for me. Of course I was tempted to take more, but I'd probably be prolonging the effect. Luckily the half life is short, so the anxiety is probably short-lived. The only thing I took between my last two doses was a tea containing several GABAergic herbs. I noticed the effects of this tea were profound, and lasted for days. I guess the theanine could have made these herbs' effects more intense, but it's just a guess.

 

I'd like to continue using theanine and offset this anxiety with anxiolytic herbs like chamomile, skullcap, lemon balm, and so on. Is it safe to to alternate theanine (which raises GABA - by nearly 20% in one study - and dopamine) with herbs like lemon balm and chamomile (weak GABAergics)? I imagine these are working on GABA receptors in different ways. Would this create a "tug-of-war" on the GABA receptors and ultimately make the rebound anxiety worse? Is it dangerous in any way? For example, I know theanine is taken for benzo withdrawal, and benzos would probably be effective for theanine rebound anxiety, but what would the long term effects be of alternating these two types of chemicals on the GABA system? 

 

I also found another post on the subject: https://www.dmt-nexu...g=posts&t=63518

 

I wanted to start this thread to let others know about theanine's 'ugly' side... 

 

Background: I decided it was time to take a break from cannabis and reorder somethings in life. In times past cannabis withdrawal included things like low level anxiety, sleeplessness, night sweats, and general agitation that persisted for 7-14 day's. So this time I decided to give L-Theanine a shot.. and wow does it work. Like this is an amazing anxiolytic on par with I'd say Xanax... seriously. I would take them at night to help calm me and allow me to sleep..and yes theanine did work for this as I haven't had nearly the sleep disturbances from marijuana withdrawal that I have had in the past. 

 

However I started noticing that I was having moderate anxiety the next day... I am not an anxious person. Like I have never really felt anxioussness like this...that is anxious feelings without a 'cause'. This was clearly something over and above placebo since I didn't even think it could happen with theanine. So I have been doing this for a over a week... each time if I take theaning during the day while anxious...30 minutes later all traces of anxiety are gone. I am now in full taper mode on theanine..which is easy since it has a 3h half-life.. 

 

That was my first data point. Knowing theanine's safety for animals I decided to try and use it to help with my cats anxiety around food. Instead what has happened is that when the theanine wears off our cat is hiding from us and barely responding. I got up in the middle of the night last night and found him hiding in our basement. This is a social cat and this was very uncharacteristic behavior..he didn't even come when we shook his food canister. A dose of theanine and 15 minutes later he is a different cat. I'm pretty sure based on my personal observations that he is going through theanine rebound.. he is now also in taper mode.

 

So I made this thread here because of the responses HERE, which is the only other place I have seen this mentioned..

 

However, I was really troubled by the way this OP was treated. Are they a bunch of kids over there or what? So anyway I didn't see the need to share my experiences in that thread as they would just be lost in the noise. So I created a thread here were hopeful the information will be better received.

 

In any event I think theanine has amazing potential as a temporary anxiolytic.. However I recommend people use a taper approach to coming off if they notice any sort of rebound anxiety and I also find the so called standard 200mg dose to be WAY to much. If you try theanine start with 50mg and see if that helps. Tea actually has even less than that and I still get descent relief just from tea.

 

Edited by VerdeGo, 30 April 2015 - 04:45 AM.

[fntms]

I stopped taking it because it was too dulling. It felt great initially though. But after a while I had trouble ending my sentences etc... I took a regular dose, maybe 200mg max per day.

[Groundhog Day]

I've used it in the past for sleep and to cancel out caffeine jitters from morning dark chocolate, when I could tolerate a little caffeine -- I no longer can.

 

It never did much for my chronic insomnia, gave me a weird focused sedation sometimes, sometimes nothing, so I never really used it, but in the last week it's been big for me. I'm now taking much more at 450mg -- 300mg first thing in the morning and another 150mg in the afternoon and it's helped me fall asleep at night and sleep more so I'm going to ride with it for at least 2 months.

 

I also have a long history of anxiety.

Edited by Groundhog Day, 30 April 2015 - 07:09 PM.

[VerdeGo]

You mention caffeine jitters from dark chocolate. Do you think the theobromine in the chocolate could be causing this? I keep finding conflicting sources about the caffeine content in chocolate, and I am surprised to learn there's 12 mg of caffeine per 1 ounce of dark chocolate. Here I was thinking I had a caffeine-free diet. I eat a few Dove's dark chocolate pieces every night just before bed, though I sleep okay as it is. Chocolate appears to be one of the most addicting substances on earth. 

 

Have you tried l-glycine for insomnia? My fiancee takes it, and she barely wakes up through the night. I guess gelatin and bone broth have a high content of it, and it's an inhibitory neurotransmitter like GABA commonly found in the body. It seems like the safest, most non-addicting substance for solid sleep without waking up through the night. 

 

Getting back to the theanine, please keep us updated in this thread on how it goes. I usually take it around 5 pm, which lasts me through my shift. I'm also more sensitive to GABA-manipulating substances ever since withdrawing from GHB and other GABAergics many years ago, so I wasn't surprised to notice rebound anxiety. It was mild, but then again I've been using very low doses of it a few times a week. Again, I'm much more sensitive than others.

 

Theanine for me is a happy pill. It completely loosens me up without the sedation, and also affects the fluency of conversation and retrieval of vocabulary much better than my baseline. It's also a wonderful disinhibitor for me, but it's much more subtle than GHB. I have a feeling these magical effects will dissipate with tolerance. Luckily the rebound anxiety tends to only last 24-48 hours. I guess this is normal for substances with short half-lives, though the anxiety may be more severe for some because of its short duration. Not really sure. 

 

Fntms, how long were you taking theanine before these issues arose? 

 

I'm still finding conflicting information out there about how exactly theanine affects the GABA system. One study states L-theanine does not produce anxiolysis by modulation of the GABAA receptor. Another study states, "L-theanine's chemical structure is related to L-glutamate, suggesting it is able to act as a GABA agonist, capable of increasing brain GABA levels". Some people claim theanine is not a GABA agonist at all, but increases levels naturally. If indeed it is a GABA-B agonist, then it would fall in the category of picamilon, GHB, baclofen, phenibut, and others, but don't those have nasty withdrawals? However the Wikipedia article on GABA agonists makes no mention of theanine.

 

One last interesting tidbit I found from a Reddit discussion: http://www.reddit.co..._much_alcohol/ 

 

a: alcohol does NOT increase gaba, it agonizes the gaba receptor ... somewhere, think it's the gaba-b g-coupled receptor. It is not metabolized by gaba transaminase, but is believed to increase its production anyway (g-coupled receptors do that).

2: theanine increases gaba as it is a precursor. It is metabolically limited, so you can't "make" too much gaba, if you have too much above a certain threshold, the enzyme slows down, or gaba transaminase kicks in and breaks down the excess.

Why alcohol is bad:

1. goes around down-regulating gaba-b receptors and gaba-making proteins (it's been a while give me a break), so you have less gaba, and you need more for the same effect. This is how signalling pathways often work, too much of a signal makes you less sensitive.

2. causes you to make much MUCH more gaba transaminase, so any gaba you do have is destroyed quickly, so even your normal amount breaks down fast.

Theanine can cause 1, but usually only does so in very high doses, but is less likely to cause 2, because gaba levels wouldn't stay high enough to hyper-activate the transaminase production (cause the transaminase would break it down).

 

Oh sorry, yes you can have withdrawal from too much gaba, but it's a lot less likely than having it from a gaba analog (or benzodiazapine), because if you have too much gaba for a while gaba transaminase goes around destroying it, so you can't have too much for too long. MAO-B is similar, but much slower in terms of production ramp-up, hence l-dopa takes a decent bit longer to gain tolerance.

 

--

The idea of it being a precursor seems to make sense, considering higher doses don't necessarily intensify the effects. But how would taking GABA agonists before/after/during a GABA precursor affect the GABA system in the long run? What are the effects of GABAergics in relation to people with temporarily elevated GABA levels from theanine?

[VerdeGo]

Apparently l-glutamine, in which theanine is related to, is also a GABA precursor. Has anyone taken l-glutamine in supplement form and noticed similar effects to theanine in the way it increases GABA? In the past it definitely provided me relaxing effects, but sometimes it made me feel really out of it (not sedated, just completely detached and at peace). Does anyone use these for the same benefits of relaxation? I just picked up a new bottle of l-glutamine today, since my old one expired, and it appears to be another amino acid/chemical to keep on hand to combat low GABA levels.

[Junk Master]

I'd say L-theanine is very mildly effective.  I really only think it's worth bothering with as a byproduct of green tea drinking on a regular basis.

 

IMO it has no "drug like" effects and any profound reactions are surely the byproduct of the placebo effect, and short lived.  That said, it can't really hurt...

 

 

[OneScrewLoose]

For those interesting in directly increasing GABA, a supplement called Picamilon crosses the BBB and delivers GABA directly to the brain, by being ingeniously attached to a niacin molecule. I don't like it much, for me, when it wears off, I feel like shit, but it might help some.

[Junk Master]

Thanks for the tip!   I'll try that.

[OneScrewLoose]

Please report back with your experiences!

[VerdeGo]

There seems to be three approaches at increasing GABA. GABAergics/agonists (temporary elevation, then downregulation, by tricking the receptors. Eventually, with enough use, they stop making their own GABA, which leads to withdrawal), GABA precursors (theanine and glutamine, which through various biochemical reactions naturally create more GABA in the brain, which is less likely to cause withdrawal, though there may be rebound effects once the GABA returns to normal or possibly dips below normal before correcting itself back to baseline), and GABA itself (GABA, picamilion) which directly puts GABA into the brain. 

 

OneScrewLoose: How exactly do you feel like shit when it wears off? Is it anxiety-related, physical, or both? 

 

Speaking of glutamine, I found this interesting thread: http://www.mindandmu...-increased-gaba

 

Here's some studies and highlights of the thread:

 

(re l-theanine) My n=1 anecdotal experience is that it is certainly capable of bombing me out, but for a relatively short period of time. I haven't researched its MOA, but from the chemical structure I would guess that it might have some commonalities with n-acetyl-l-glutamine (a more bioavailable form of l-glutamine).

 

As for the various mild herbal anxiolytics, many of them contain poorly bioavailable flavonoids which either don't make it past the liver too well, or don't cross the BBB. There is research indicating that chemical transformations of these flavonoids can dramatically increase their bioavailability, but it could very well be that you then wind up with a benzo-like substance with all the attendant tolerance issues. Kava certainly works acutely, but it has multiple MOAs and can actually function as an upper initially.

-

I'm interested in this enzymatic manipulation. Doing something like increasing glutamate decarboxylase or stimulating it's synthesis could well provide means to increase natural (endogenous) GABA. I'm not sure how Gabapentin plays into this; as far as I know, it's just a GABA analogue, like Phenibut. I could be wrong. Pregabalin I'm not familiar with, but apparently it increases GAD in a does-dependent manner. It also functions as an NE antagonist, a class which I'm also not familiar with. If anyone has any more on these, or Pregabalin, feel free to chime in. Pregabalin is something I may be interested in.

 

On the subject of increasing GAD by other means, I found this:

 

 

Glutamate and gamma-aminobutyric acid (GABA), act as excitatory and inhibitory neurotransmitters in

CNS respectively. An increase in glutamate and a decrease in GABA concentration were observed in

aged brain. However, the mechanism of these changes has not been very well elucidated. Glutamate

decarboxylase (GAD) catalyzes the conversion of glutamate to GABA. Since the vitamin B6 is essential

for the activities of GAD, this study was undertaken to investigate the effects of vitamin B6

administration on age related changes in rat brain. The animals were injected intraperitoneally with 1,

10 and 100 mg vitamin B6 /kg body weight /day for 30 days, and specific activity of GAD was assayed in

the brain supernatant. The activity of the enzyme in aged rats was significantly lower as compared to

that of young animals. Vitamin B6 induced activation of the brain enzyme in both ages, but the rate of

the activation was markedly pronounced in aged animals. Significant activation rate of GAD by vitamin

B6 in aged rat brain may be resulted from either lower availability of vitamin B6 in aged animals, or

lower affinity of the enzyme for pyridoxal -5-phosphate, which is likely to be related to conformational

changes of the enzyme during aging. It is suggested that vitamin B6 may restore the activity of the

brain glutamate decarboxylase in aged rat.

 

 

I'd also like to know more about GABA reuptake inhibitors. I did a quick search, and hyperforin and adhyperforin seem interesting, as these are consitiuents of SJW, which Ex Dubio mentioned as having anxiolytic effects. This is a product standardized to hyperforin. And this. Here is the pure chemical, which is probably preferred to the extract. One cause of concern is that, correct me if I'm wrong, I think read SSRI's produce more serotonin in synapses due to less reuptake, but ultimately result in less serotonin in the whole brain. Perhaps a GABA reuptake inhibitor would do the same with GABA, in whick case it may even more useful to increase production of GAD.

-

Gotu Kola(Centella asiatica) has been shown to be anti-anxiety. It does this by raising GABA levels. It also has been shown to grow dendrites.

 

I recall a study on valerian saying it grew GABA neurons, but I can't find the study so I'm not sure if that is accurate.

BTW, Gotu Kola is one of my favorite herbs and it works well for anxiety. It should, in theory, work better over the long run.

 

 

Centella asiatica (CeA) is a creeping plant growing in damp places in India and other Asian countries. The leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternative system of medicine in India. In this study, we have investigated the effect during the rat growth spurt period of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions of the brain concerned with learning and memory. Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the rats were killed, their brains were removed and the hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using a camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with data for age-matched control rats. The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that the constituents/active principles present in CeA fresh leaf extract have a neuronal dendritic growth stimulating property; hence, the extract can be used for enhancing neuronal dendrites in stress and neurodegenerative and memory disorders.

 

PMID: 16951719 [PubMed] 

Centella asiatica (CeA) is a creeper, growing in moist places in India and other Asian countries. Leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternate system of medicine in India. In the present study, we investigated the role of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions concerned with learning and memory, in adult rats.

 

METHODS:

In the present study, adult rats (2.5 months old) were fed with 2, 4 and 6 mL/kg body weight of fresh leaf extract of CeA for 2, 4 and 6 weeks, respectively. After the treatment period, the rats were killed, brains were removed and hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with those of age-matched control rats.

 

RESULTS:

The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 6 mL/kg body weight/day of CeA for 6 weeks. However, the rats treated with 2 and 4 mL/kg body weight/day for 2 and 4 weeks did not show any significant change in hippocampal CA3 neuronal dendritic arborization.

 

CONCLUSION:

We conclude that constituents present in Centella asiatica fresh leaf extract has neuronal dendritic growth-stimulating properties.

 

PMID: 18218554 [PubMed - indexed for MEDLINE]

Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.

 

PMID: 16105244 [PubMed - indexed for MEDLINE]

 

 

I'll have to look further into Gotu Kola. Has anyone used it? I did find these highlights from this study. http://www.ncbi.nlm....les/PMC3116297/

 

Indian J Pharm Sci. 2010 Sep-Oct; 72(5): 546–556.

doi:  10.4103/0250-474X.78519

PMCID: PMC3116297

Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all

Asian CA increases the cerebral levels of GABA, which explains its traditional use as anxiolytic and anticonvulsant. 

CA is known to re-vitalize the brain and nervous system, increase attention span and concentration and combat aging[8]. A study demonstrated cognitive-enhancing and anti-oxidant properties of CA in normal rats. 

A laboratory study was reported in which aqueous extract of CA was found to be effective in inhibiting gastric lesions induced by ethanol administration[39]. 

 

From the University of Maryland Medical Center: 

1. Side effects are rare but may include skin allergy and burningsensations with external use, headache, stomach upset, nausea,dizziness, and extreme drowsiness. These tend to happen with high doses of gotu kola.May 7, 2013

I still can't figure out if this is a GABAergic and prone to withdrawal or downregulation, or if gotu kola actually increases cerebral GABA in the long run. Can anyone shed any light? I also welcome more theanine and/or glutamine experiences to the thread.

[OneScrewLoose]

I just feel the opposite effects I felt when it was working.

Baclofen can be an interesting option for some people. It's a GABAB agonist the can help with some people's anxiety, build far less of a tolerance than benzos, and is not habit forming.

The gotu kola study is from a journal with an Impact Factor off .6. That's tabloid level. The Vitamin B6 study also comes from a journal with an IF of .8, and only references aged mice. Anything under 1 is almost completely disregardable. 1-2 is grain-of-salt territory. 2-3 is great, and anything above that is fantastic.

[VerdeGo]

Thanks for the insight. I did notice the study was from India, and a lot of foreign studies don't meet the expectations of rigorous protocol followed in the West. I just wish there were other glutamine analogs like theanine that provided better, longer-lasting effects and increased GABA levels naturally through upregulation (SSRIs do, but I'm not going that route because I don't suffer from depression, just situational anxiety at times). For me agonists are a great short-term solution to the problem, but they carry their risks. GABA precursors seem to be a safer long-term solution, but I only know of two at this time (theanine and glutamine), and they both work quite well for me. 

[OneScrewLoose]

Thanks for the insight. I did notice the study was from India, and a lot of foreign studies don't meet the expectations of rigorous protocol followed in the West. I just wish there were other glutamine analogs like theanine that provided better, longer-lasting effects and increased GABA levels naturally through upregulation (SSRIs do, but I'm not going that route because I don't suffer from depression, just situational anxiety at times). For me agonists are a great short-term solution to the problem, but they carry their risks. GABA precursors seem to be a safer long-term solution, but I only know of two at this time (theanine and glutamine), and they both work quite well for me. 

 

Check this out:

http://www.ncbi.nlm....les/PMC3648625/

 

400mg of Pregnenolone can greatly increase allopregnanolone, a potent GABAa positive allosteric modulator that works on the neurosteroid site instead of the benzo or barbiturate sites. Allopregnanolone in high enough doses actually causes anesthesia, and it's synthetic analog, Ganaxolone, is a common anesthetic.

 

Another possibility is Memantine. GABA increases inhibition and sensory gating. Memantine is fascinating as it is an 'uncompetitive antagonist' at the NMDA receptor. This is wholly different from a noncompetitive antagonist. It means that the antagonism doesn't begin until the receptor fires. That means it acts like an audio compressor, reducing the strength of the signal without blocking any signals, thereby reducing the need for GABA and inhibition. I take 35mg/day for this purpose.

I know I know other GABA related things, just give me a moment to jog my memory. 

Edited by OneScrewLoose, 04 May 2015 - 04:46 AM.

[VerdeGo]

I'll certainly look into those two substances and do some further research. Thanks!

 

BTW I was in another thread just a moment ago and learned about gastrodin from Strelok. He referenced this article: http://www.lifeexten...n-Aging/Page-01

 

Gastrodin helps restore the vital balance of neurotransmitters. Studies show that gastrodin increases levels of the inhibitory neurotransmitter GABA by as much as 34%, which exerts a calming effect on the brain and counteracts the overactive brain activity.11,29,30

 

The studies cited appear to be Asian in origin, so I'm not sure how accurate they may be. Perhaps you could tell me if they are from reputable journals or not. The neuroregeneration and nootropic effects sound interesting. I really don't know if this stuff is a GABA precursor or elevates GABA in some other way? Any ideas?

 

I did look up Amazon reviews of LIfe Extension's gastrodin product, and the reviews sound similar to that of l-theanine. So I'm wondering if this could be the next best thing, or better, than l-theanine for raising GABA levels. I'm just wondering if it's upregulation of GABA as opposed to temporary elevation caused by theanine? Someone mentioned in an older thread that it was quite a "mind brightener", but I don't know if he/she was referring to a "mood brightener" or not. Either way, this sounds promising on many levels. I'm not sure why it hasn't been mentioned much in this forum.

 

 

[OneScrewLoose]

I'm a bit tired right now, so I'll give you a starting point and let you take it from there, The main ingredient appears to be 'Gastrodia Elata', so here's a good Google scholar search:

 

http://bit.ly/1GM1iRs

You can put the same term into pubmed for more results.

If you want to know whether the journal is reputable, search for the journal name (not the name(s) of the authors of the study) plus the words 'impact factor' into Google. An impact factor of less than 1 is usually trash. 1-2 is a bit sketch and their methods section needs to be thoroughly reviewed. Above 2 and your usually on solid ground, though not always.

 

Well, get science-ing and tell us what you find!

[VerdeGo]

The first cited journal had an impact factor of 0.0. I'm not sure if this is possible, but it doesn't look too good. The other two cited references to journals had impact factors averaging 2.9, so I guess there is some validity to the statements about gastrodin being able to increase GABA levels substantially. Thanks for showing me this trick.

 

I am limited on time right now as well, so I'll update you with what I find as to whether or not gastrodin might be a good substitute for theanine, or a better supplement to increase GABA levels than theanine. 

 

I am confused about one thing regarding the LEF Gastrodin on Amazon. Part of the item description reads:

 

Gastrodin acts as a "brain shield," calming brain cells and helping to protect against oxidant, inflammatory, and excitatory damage

Alpha-glyceryl phosphoryl choline boosts levels of acetylcholine; a neurotransmitter that enables brain cells to communicate

 

However, the only two ingredients are calcium (as dicalcium phosphate) 20 mg, and gastrodin 300 mg. And Alpha-glyceryl phosphoryl choline is Alpha-GPC, not gastrodin from my understanding. Also, wouldn't boosting acetylcholine levels also drop GABA levels automatically? 

 

Could this be a mistake in their product description, or am I missing something here?

 

[VerdeGo]

My last question was resolved, as it was an error that cannot be removed on the Amazon description. I went ahead and bought a bottle of LEF's Brain Shield, with gastrodin as its main ingredient. I will report back probably next week to share my experience with it and how it relates to theanine. I'm also going to experiment with glutamine again to determine its effects on silencing the mind and producing a calm state. 

 

I took theanine today after not taking it for the last 9 days. I was singing and dancing at work (I'm usually quite reserved) and I was feeling pretty darn good. Now I'm going to wait to see what happens 24-48 hours from now with my anxiety levels. 

[VerdeGo]

Well, 24 hours after my last theanine dose I noticed my mind was racing, negative, and stressed. Every little thing turned into a big deal, and I appeared to be unnaturally agitated and restless. I know it's not placebo, because if my GABA levels were still high I would not be experiencing these effects. So now I'm on a mission to find out possible causes or a substance I can take following theanine to negate these effects. I must admit I seem to be in the minority when it comes to experiencing rebound anxiety, but it does exist for some, and I do know my GABA receptors are quite finicky and sensitive thanks to other GABA agonists I've taken in the past.

 

Today I tried l-glutamine, which is another GABA precursor (theanine is n-ethyl-glutamine I believe). I last tried it in 2013, and I'm still not sure why I stopped taking it. At the onset I became more excited and energized, though in a happy, talkative way. At the same time I noticed my mind was free from any distraction, and quite settled. About 30 minutes later, after eating lunch, all excitement and adrenaline subsided and I was cool as a cucumber. Even dealing with very high levels of stress at work didn't affect me. My mind was completely relaxed, and my body relaxed as well. The only downside was the complete lack of excitement, though I encountered no agitation. Glutamine is very similar to theanine, with the exception of its effects on dopamine, which appear nonexistent for me. Glutamine is also fuel for the muscles, and it's used quite widely by bodybuilders. For me it seemed to convert to glutamate first, causing the excitation, and then increasingly converted to GABA, causing an eventual all-around relaxation of body and mind. This stuff would probably be good for stress and possibly anxiety. 

 

I'm wondering if theanine perhaps drains the body of its reserve glutamine/glutamic acid, and that's why GABA seems to drop (along with serotonin, though I'm not sure the cause of that unless it's from the high amounts of dopamine in several areas of the brain during a theanine dose) after 24 hours of use for me, and for many others. Or perhaps it's down regulation, but I've noticed my mind continues to be racy days after use, with the peak of it being after 24 hours of use, which is why I took the glutamine today. I also noticed a tendon in my arm started hurting 48 hours after last working out, and the pain increased over the last few days until I took glutamine today, in which it is now nearly absent. That's what gave me the notion that theanine might be draining glutamine itself from the body by converting it to GABA, but I I really don't know. Any ideas?

 

I plan to use theanine tomorrow, followed by glutamine the following day. I'll report back if anything substantial occurs. I'm taking a week off work for a vacation, and I'll have some time to experiment. 

 

I also plan to test out gastrodin (boosts GABA supposedly by 34%), California poppy (GABA agonist and possible serotonin antagonist), lavender oil (GABA agonist), lysine (works on serotonin and can boost mood), DLPA (limits the breakdown of endorphins, and also plays a role in dopamine), lemon balm tea (GABA agonist), and magnesium glycinate (calming and can also boost GABA levels). Any suggestions on trying these?

 

Theanine's effects are too wonderful to simply stop taking it. But there has to be a way around its rebound anxiety or the sudden drop in GABA the day after using it. 

[VerdeGo]

One thing I've been noticing following theanine use is increased apathy, restless mind, lack of excitement, the blahs, etc. I feel like my enjoyment for life has gone way down, except for the first 24 hours following the dose. The next 24 hour period seems to give me a substantial dip in at least dopamine and maybe GABA, though levels seem to gradually return to baseline following this period. 

 

Since having last taken theanine on Monday (and of course it was a great experience), I felt less motivated yesterday with little excitement in life, and I felt this even worse today. I decided to try l-lysine since I heard it can elevate mood and affect serotonin. The first thing I noticed was a pressure around my ears and head. I noticed a slight increase in general anxiety/edginess (I had none beforehand), and a major lack of motivation or enthusiasm. Midway through today, not being able to stand it anymore, I took vitamin B9 because it's boosted my dopamine in the past quite effectively. This seemed to do the trick, and I was feeling like myself again. My head became tingly, everything looked more interesting and bright, and I became motivated almost instantly.

 

Based on these observations, I believe theanine may cause a temporary dip or downregulation in dopamine receptors/levels in the 24-48 hour period following use, or possibly longer. I'm not sure which of the four or five areas of the brain that theanine increases dopamine in is responsible for these noticeable downstream effects. I'm guessing it's an area not normally targeted by other dopaminergics. I have no proof beyond my own assertions that it does indeed do this. But the fact I needed to take a dopamine-booster today just to feel like myself again, along with the consistency of apathy and restless mind following use, leads me to believe (at least for me and some others) that this is the case.  

 

I plan to take a dopamine-booster 24 hours after my theanine dose tomorrow, and we'll see how it goes. Gonna stick to folic acid (b9) for now, but I may try DLPA or tyrosine in the future. As far as the restless mind/agitation, I'm thinking a GABA agonist like lemon balm, or pure lavender essential oil. Lavender is known for anti-aggressive thoughts and behavior in agitated animals, and it's been used to tame lions. I guess it only binds to the GABAa receptor when it's combined with lemon balm (the combination of the two in a 50:50 ratio can bind to the benzo receptor simply by inhaling the aroma), but the two supposedly synergize very well, and are viable options to address overactive mind either in combination or on their own.

 

L-Glutamine is also an option. But since it's related to theanine (n-ethyl-glutamine) and doesn't raise dopamine levels, it should only be used for racing thoughts and not to increase motivation. It helped with exactly that the last time I used it, but didn't address the lack of motivation and excitement. The fact that l-glutamine doesn't appear to have rebound anxiety following its use again points to theanine's effects on dopamine being to blame.

 

Any thoughts/suggestions/ideas?

[tintinet]

I think theanine and green tea exacerbate my anxiety.

Edited by tintinet, 13 May 2015 - 10:27 PM.

[stan08]

One thing I've been noticing following theanine use is increased apathy, restless mind, lack of excitement, the blahs, etc. I feel like my enjoyment for life has gone way down, except for the first 24 hours following the dose. The next 24 hour period seems to give me a substantial dip in at least dopamine and maybe GABA, though levels seem to gradually return to baseline following this period.

Since having last taken theanine on Monday (and of course it was a great experience), I felt less motivated yesterday with little excitement in life, and I felt this even worse today. I decided to try l-lysine since I heard it can elevate mood and affect serotonin. The first thing I noticed was a pressure around my ears and head. I noticed a slight increase in general anxiety/edginess (I had none beforehand), and a major lack of motivation or enthusiasm. Midway through today, not being able to stand it anymore, I took vitamin B9 because it's boosted my dopamine in the past quite effectively. This seemed to do the trick, and I was feeling like myself again. My head became tingly, everything looked more interesting and bright, and I became motivated almost instantly.

Based on these observations, I believe theanine may cause a temporary dip or downregulation in dopamine receptors/levels in the 24-48 hour period following use, or possibly longer. I'm not sure which of the four or five areas of the brain that theanine increases dopamine in is responsible for these noticeable downstream effects. I'm guessing it's an area not normally targeted by other dopaminergics. I have no proof beyond my own assertions that it does indeed do this. But the fact I needed to take a dopamine-booster today just to feel like myself again, along with the consistency of apathy and restless mind following use, leads me to believe (at least for me and some others) that this is the case.

I plan to take a dopamine-booster 24 hours after my theanine dose tomorrow, and we'll see how it goes. Gonna stick to folic acid (b9) for now, but I may try DLPA or tyrosine in the future. As far as the restless mind/agitation, I'm thinking a GABA agonist like lemon balm, or pure lavender essential oil. Lavender is known for anti-aggressive thoughts and behavior in agitated animals, and it's been used to tame lions. I guess it only binds to the GABAa receptor when it's combined with lemon balm (the combination of the two in a 50:50 ratio can bind to the benzo receptor simply by inhaling the aroma), but the two supposedly synergize very well, and are viable options to address overactive mind either in combination or on their own.

L-Glutamine is also an option. But since it's related to theanine (n-ethyl-glutamine) and doesn't raise dopamine levels, it should only be used for racing thoughts and not to increase motivation. It helped with exactly that the last time I used it, but didn't address the lack of motivation and excitement. The fact that l-glutamine doesn't appear to have rebound anxiety following its use again points to theanine's effects on dopamine being to blame.

Any thoughts/suggestions/ideas?

Lavender and lemon balm aren't gaba agonists.

Lavender is a 5-ht1a agonist -http://m.ijnp.oxford...pyu063.full.pdf

Lemon balm is a GABA transaminase inhibitor - http://www.ncbi.nlm....pubmed/19165747

[VerdeGo]

Thanks for pointing that out, as I'm still on the road to learning about these individual substances. It's interesting to note that lysine, which I took earlier today, is a 5ht4 partial antagonist, which did not have the desired effects of mood elevation during my theanine deficit. In fact it made it seem as if I was experiencing life with only part of my brain. I still can't sum up the mental and physical state I was in during this time, which is why I had to take folic acid/b9 to partially escape it. Because of this, I've decided not to try California poppy at this time, because its actions on serotonin are in question. Statements like "Highly potent interactions at the level of the receptor with the ethanolic extract, but it is not known whether this is an agonist (activator) or antagonist (inactivator), or whether it is biologically relevant" from Examine.com (I have an ethanol extract of California poppy, fyi), and "California poppy may bind with the same receptors as monoamine oxidase (MAO) inhibitors and selective serotonin reuptake inhibitors (SSRIs). Caution should be used in patients taking these agents" from livingnaturally.com doesn't exactly put to rest my concerns about serotonin antagonists. I am not on either SSRIs or MAOIs, but I don't want to take anything that may erase some of the progress I've made lately with diet and mood.

 

As for lavender: Several hours after taking b9, I felt highly agitated when company arrived. I was agitated for no apparent reason, just as I normally am a day after taking theanine, but this was day 2. I blame the lysine for "aggravating" my serotonin levels, and the B9 for possibly lowering serotonin even more, but that's just a guess since things went downhill for me after ingesting the lysine. 2-3 hours after taking lysine I also ate a lunch high in proteins containing tryptophan, and I had a somewhat complete lunch (wild/brown rice, black beans, spinach drizzled with olive oil, a red potato loaded with organic omega-3 butter substitute, nuts, whole grain crackers, orange slices). By 7 pm, I was so depressed, agitated and frustrated that I went into my bedroom and sat on the floor, resting my head on my shoulders, and finding it hard to motivate myself enough to do anything. This was not me, not even on a bad day. What the hell? I forced myself to try lavender as a last resort, and I put a drop of it on my wrist. Within minutes I had absolutely no agitation, and I was quite calm without the typical "drug-like/GABA agonist" effect. The thought of picking up a book enraged me moments before (I'm not normally an angry, moody, agitated person. This happens maybe twice a month, though it's occurring far more since I introduced theanine into my life), but now I was finding comfort in sitting on the patio, reading the book, and admiring the setting sun. A total turn of events. I will probably be bringing lavender oil with me wherever I go for situational anxiety and agitation. It truly works wonders. 

 

How would a GABA transaminase inhibitor like lemon balm affect GABA in the brain? This quote from Examine is confusing me: "(Lavender) Shows affinity for GABAA receptors with no per se affinity for the benzodiazepine binding site, but is profoundly synergistic with Lemon Balm essential oil for affinity to the benzodiazepein binding site." And regarding lemon balm: "Appears to have GABAergic activity, although by a mechanism not common to other nutraceuticals (possible additive or synergistic possibilities that are not yet explored)." Should the two be combined then? Unfortunately Melissa/lemon balm essential oil is 30 dollars a bottle, though I do have lemon balm-only tea here. And is it safe to cycle with GABA agonists and GABA precursors? I tried to find a simple answer online, but couldn't. Can you please take the time to enlighten me in laymen's terms? Thanks 

[VerdeGo]

I took theanine again today in a very minimal dosage like I usually do. It's only been three days since I last used it, and tolerance is already starting to build. It was lacking the effects I was used to, and despite the raise in dopamine levels I found my excitement at a bare minimum. I should've been excited, since it was an anniversary, a fancy dinner, and a murder mystery play. However it seemed pointless, and now I'm wide awake 7.5 hours after taking it. 

 

I will be abandoning this amino acid for now, and will only use it during rare social engagements that make me anxious.

 

I'm far more interested in lavender. Not only does it bind to the 5HT1a receptor, but it appears to block the binding of glutamate. I don't know if this would increase GABA, or simply make its presence more profound since glutamate is blocked. I'm seeing no reports of rebound anxiety, tolerance, or withdrawal online regarding lavender, so it's looking far more promising for situational anxiety and stress than theanine.

 

I'm also wondering what a L-Glutamine+lavender combination would be like. Since glutamine increases both GABA and glutamate in the brain by providing the raw material, and lavender blocks glutamate, what would be the effect? Extreme relaxation without sedation? 

[stan08]

I took theanine again today in a very minimal dosage like I usually do. It's only been three days since I last used it, and tolerance is already starting to build. It was lacking the effects I was used to, and despite the raise in dopamine levels I found my excitement at a bare minimum. I should've been excited, since it was an anniversary, a fancy dinner, and a murder mystery play. However it seemed pointless, and now I'm wide awake 7.5 hours after taking it. 

 

I will be abandoning this amino acid for now, and will only use it during rare social engagements that make me anxious.

 

I'm far more interested in lavender. Not only does it bind to the 5HT1a receptor, but it appears to block the binding of glutamate. I don't know if this would increase GABA, or simply make its presence more profound since glutamate is blocked. I'm seeing no reports of rebound anxiety, tolerance, or withdrawal online regarding lavender, so it's looking far more promising for situational anxiety and stress than theanine.

 

I'm also wondering what a L-Glutamine+lavender combination would be like. Since glutamine increases both GABA and glutamate in the brain by providing the raw material, and lavender blocks glutamate, what would be the effect? Extreme relaxation without sedation? 

 

I'm not sure about l-glutamine as the only time I've tried it was in a BCAA product (scivation xtend go) which included it, BCAAs, caffeine, l-theanine and kanna.  I didn't really like the effects.

 

A stack that Area-1255 recommended to me, and that I recently started, is lavender (I use the product called CalmAid which contains the Silexan extract) and lemon balm.  His description of them is as follows: 

 

Lemon balm is a GABA-reuptake inhibitor..therefore it PROLONGS the effects of GABA, it's basically like an SSRI but FOR GABA instead..it locks GABA in the synapse preventing it from being used up to quickly and preventing it from being biologically and neurally degraded.

 

Lavender is a selective agonist for 5-HT1A and thus will help excess serotonin be inhibited , it will also raise oxytocin due to that property and lavender can also increase dopamine receptor expression.

 

So far, this combination has been working very well.  In particular, it really decreases my anxiety and irritability a lot.  I'm much calmer in social situations.  

[VerdeGo]

What an awesome stack! After spending money and time on several useless supplements, everything points to those two ingredients which I've had but set aside to try more experimental remedies. I was quite amazed when I tried lavender oil on my wrist, and so was my fiancee. She put it on her wrist for the first time last night, remained calm all night, and woke up in a really good mood. The anxiolytic effect of lavender for me lasts nearly 24 hours after the initial effects. I love it. 

 

So we have two unique GABA herbs that on their own don't bind to the benzo receptor sites. One blocks the breakdown of GABA, and the other (lavender) blocks the buildup of glutamate:

 

In rats, an inhibitory effect of linalool on glutamate binding in the cerebral cortex has been reported suggesting that this neurochemical effect might be underlying the mode of action of lavender oil (Elisabetsky et al., 1995).

 

Plus we have the positive effects on serotonin, dopamine, and oxytocin. Would be interesting to see if these two herbs could cancel out theanine's negative effects, of if theanine would make their effects more potent.

 

According to Examine.com, when lemon balm and lavender are combined, there is some binding to the benzodiazepine receptor site:

 

(Lavender) Shows affinity for GABAA receptors with no per se affinity for the benzodiazepine binding site, but is profoundly synergistic with Lemon Balm essential oil for affinity to the benzodiazepein binding site

 

Not sure if only the essential oils create this binding, or if teas, extracts, and other combinations of the two have the same effect.

 

Do you think there is any possibility of tolerance or rebound anxiety after stopping this combo, and should it be safe to use on a daily basis? Chamomile affects the benzodiazepine site, so I know there'd be downregulation and after effects if I took it daily for weeks and then stopped abruptly. I'm hoping there is no downside to regular use of lemon balm and lavender on the GABA or 5ht1a receptors (I'm not worried about each one individually, but the combined effects on benzo receptors causing possible tolerance or mild withdrawal).

 

How long have you been on this stack, and do you use it daily?

 

As for theanine, I now agree with fntms earlier in the thread in which he stated that theanine has a "dulling effect." I came to that conclusion last night when it dulled my emotions and I later reread his statement. I did wake up in a good mood today, but I know by the end of the day my mind will be overactive and stressed, so I'll take lavender and possibly some lemon balm tea. I will not be using theanine as often, in fact rarely, because of these dulling effects and the rebound issues.

[stan08]

I hadn't seen that quote from Examine.com (somehow missed it when reviewing both supplements).  

 

I don't know if there's a chance of tolerance or rebound.  Honestly, a lot of this is past my understanding.  I'm just glad we have someone as nice and helpful as Area-1255 on here to give such great advice on supplements/stacks.  So, he'd probably be the best one to ask about that.

 

I've only been on the stack for about a week and I use it daily (both with breakfast and dinner).  So far, it's been awesome.  There is some sedation.  However, it seems to get better with time and I think the lemon balm I got is maybe a little too strong.  I'm using the New Chapter Lemon Balm Force (300 mg).  However, it's expensive and I'll likely switch to the Cyracos extract (sold on vitacost and swanson) next since it's a standardized extract and significantly cheaper (it's also the extract used in many of the studies).  

 

I've never been a fan of theanine.  It also seemed to increase my brain fog and just make me feel out of it in general (even at only 100 mg).  

Edited by stan08, 15 May 2015 - 06:32 PM.

[VerdeGo]

Summoning Area-1255.

 

I'm guessing the sedation could be from the lemon balm, since lavender isn't generally known for sedation (except at higher doses). However, since the synergy of the two can bind to benzodiazepine receptors, it's probably due to that. Have you tried either by themselves?

 

I personally like essential oils, because I can get an idea of their effects simply by inhaling their aroma, but lemon balm oil is the only essential oil not sold at my local Vitamin Shoppe (no idea why, but it costs $30/bottle on Amazon, so it may not be cost efficient for them). They do sell the capsules, but I have an unopened box of lemon balm tea I'll probably try tomorrow evening, without the lavender. There's also a popular chamomile/lavender/lemon balm tea that is supposed to be very potent. 

 

Beyond tolerance/withdrawal issues (which seems doubtful, but then again GABA receptors are a little tricky), the only other thing I'm concerned about is the estrogen-like effects of herbs like lavender and lemon balm. Have you noticed lower libido while on this stack? What symptoms or reasons do you have for starting this stack?

 

Because of the estrogen issue, I plan to only use it for situational anxiety and agitation, and I'm hoping Area-1255 can chime in and put my mind at ease. Also, how hard is it for the liver to break down linalool and the other chemicals in these two herbs? I enjoy two beers every evening (also increases estrogen), and I'd hate to put an extra load on my liver.

 

And for theanine, it definitely increased brain fog, though today I felt amazing following its use. I also didn't experience any rebound anxiety after the 24-hour mark, and my mood was elevated all day. So just when I swore it off, it's teasing me. After dinner, I took a drop of lavender oil, which further relaxed my mind, but without any sedation. 

[OneScrewLoose]

These things might effect the GABA receptors? But what is there Ki? How much do they effect those receptors? For instance, a lot of SSRIs effect the dopamine transporter, but it's so small of an effect, that it's negligible.

I like CBD because it causes you to release more GABA. As far as effecting GABA receptors, Baclofen is great at agonizing GABAb with minimal tolerance. Ashwagandha also seems to effect GABA-B. I haven't find a good evidence for an OTC supplement that potently interacts with GABAa. But, IMO, this is unnecessary with things like CBD.

[VerdeGo]

GABA agonists have their own risks and are more likely to cause dependence, tolerance and withdrawal. GABA precursors like glutamine can raise GABA without withdrawal or dependence, causing a calm state of mind. N-ethyl-glutamate is the exception, but I believe the rebound anxiety from theanine is probably due to a general, temporary lowering of several neurotransmitters following use (for some, myself included). Beyond that, you have substances that block glutamate, thus increasing relaxation from GABA (lavender), and substances that help block the breakdown of GABA (lemon balm). Then there's gastrodin, which seems to be in a class of its own (derived from the root of a Chinese orchid and shows promise of neuroregeneration).

 

I think you can overdo it with science. If you have situational anxiety or other forms of anxiety, it probably can't hurt to try each one of these in a low dose to see what helps you. If something works, and you do your research to rule out interactions, then use it as needed, in moderation, to help with the anxiety. Amino acids and time honored herbs like lavender are probably the safest bet before jumping into gastrodin and especially any GABA agonist that binds to benzodiazepine receptors and causes withdrawal like phenibut. The question is how do these different substances and different modes of action intermingle, and are they safe to use as a whole? Or should one only stick to precursors, not mixing them with agonists, and so on. 

 

That's the answer that eludes me.