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Non-Standard Anti-Anxiety Treatment

Hip

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Raising GABA doesn't seem to do anything for me. I've taken GABA, Taurine, Theanine, Valerian, Neurontin/Gabapentin, and Taurine without any effect. Well, my skin gets itchy if I take too much GABA, but the other ones didn't do anything. What does this mean?
These anti-anxiety drugs and supplements you have tried work on the GABA receptor mostly (as do benzodiazepine drugs). However, for reasons that I will explain, I think it is best to treat anxiety symptoms primarily using drugs/supplements that work on the NMDA receptor, not the GABA receptor.

Remember, the actual state of the neuron — that is, whether it is excited or relaxed — depends on both the GABA and NMDA receptors. NMDA excites, GABA relaxes. There is a seesaw relationship, with NMDA and GABA sitting on either side of the excited–relaxed seesaw.

Activating the NMDA receptors on a neuron will make the neuron more excited, where as activating the GABA receptors on a neuron will make the neuron more relaxed. Anxiety symptoms most likely derive from over-excited neurons (in the amygdala), so to reduce anxiety, you have to relax the neurons.

Thus for anti-anxiety purposes and to relax the neurons, you have a choice: you can either block NMDA receptor activation, or stimulate GABA receptor activation (or, for the strongest anti-anxiety effect, do both). Both will serve to relax the neurons.

However, if your anxiety symptoms are driven by NMDA receptor over-stimulation in the first place, then it would make sense to try to tackle this by blocking this NMDA receptor over-stimulation, rather than trying to compensate for it by increasing GABA receptor stimulation in order to try to keep the NMDA–GABA seesaw balanced.

To use a metaphor to help understand this: if someone is punching you hard on the chest such that you are in danger of losing your balance and falling backwards, it is best to try to block these chest punches, or eliminate the puncher entirely, rather than to get someone else to simultaneously punch you on your back with equal force, in order to achieve a balance of force and not fall over.

Thus if your anxiety symptoms arise from NMDA receptor over-stimulation, it may be best to try to block or prevent this from happening, rather than trying to over stimulate the GABA receptors in compensation.

As explained earlier in this thread, NMDA blocking is achieved using NMDA receptor antagonists such as dextromethorphan or transdermal magnesium; and preventing NMDA over-stimulation in the first place is achieved by lowering brain inflammation, which is the source of excessive amounts of compounds like glutamate and quinolinic acid that stimulate the NMDA receptor.

So by using both NMDA receptor antagonists and by reducing the brain inflammation that causes NMDA over-stimulation in the first place, you have an effective way to tackle anxiety disorder.

(The brain inflammation itself most likely derives from an infection in the brain, and/or infections in very nearby structures such as the sinus mucous membranes, and/or infections in more distant areas such as in the intestines or kidneys — toxins and cytokines from such distant infections are now known to be able to precipitate inflammation in the central nervous system. This is why supplements or drugs that reduce inflammation or infection in the gut, kidneys or sinuses, and thereby reduce brain inflammation, can be effective in reducing anxiety symptoms.)




Regarding the supplements and drugs you used:

As is well known, GABA (gamma aminobutyric acid) itself does not cross the blood-brain barrier, so supplementation with GABA will not activate the relaxing GABA receptors on the neurons, and thus as a supplement, GABA has no anti-anxiety effects.

Try the supplement picamilon instead. Picamilon is in fact a GABA molecule and a niacin molecule bonded together, and this combination does pass through the blood-brain barrier. I found picamilon to be reasonably effective, though you need to take it 3 times a day, as its effect wears of quite fast.

But the problem with compounds that have GABA receptor stimulating effects is the tolerance build-up, and possible withdrawal symptoms. There always seems to be tolerance problems with GABA receptor agonist drugs and supplements. By contrast, there do not seem to be any tolerance problems with NMDA receptor blocking drugs. So in this respect as well, NMDA receptor blocking drugs and supplements are better.

Theanine and valerian have quite weak GABA effects, so don't expect too much from them.

Taurine has both NMDA receptor blocking and GABA receptor stimulating effects. I found that you need a high dose of taurine (around 3 grams) to get a noticeable anti-anxiety effect. Thus you really need to buy taurine as a bulk powder for these sort of high doses, as bulk powder suppliers are much cheaper sources of supplements.
 
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Lotus97

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Since I posted that (a year ago?) I've learned that niacinamide is considered a 'methyl sponge' -- in other words, it can use up methyl groups quickly, so that if one is doing the methylation protocol, those supplements may need to be adjusted/increased in order to find the right balance -- all depending of course on one's genetics.

I tried the niacinamide last year for a bit, but it just made things worse, but at the time, I hadn't figured out what methylation supps I needed. I'm doing better now with folinic, TMG, a little methylfolate, a little methylb12, and some ad-b12 -- so am trying to find a low, low dose b-complex that is balanced, and has a little niacinamide and some of the other b's as well.
I remember in some of your older posts you were talking about trying chelation. Did you go through with chelation treatment? If so, do you think doing that before starting methylation was helpful?
 

dannybex

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I did about a month or so of chelation using ALA (the Cutler protocol) and was doing a lot better back then (Sept 2009) -- I totally took my situation for granted. I was able to get up 2 - 3 times during the night to take the ALA without much trouble.

Perhaps if I had continued, I'd have improved even more, who knows? The problem with his protocol is that he has his own rules for the various mineral values on the hair test results, so one could, for example have very low copper in the hair, but he might say that it could be high, due to mercury or aluminum, but has no research to back that up.
 

PhoenixDown

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These anti-anxiety drugs and supplements you have tried work on the GABA receptor mostly (as do benzodiazepine drugs). However, for reasons that I will explain, I think it is best to treat anxiety symptoms primarily using drugs/supplements that work on the NMDA receptor, not the GABA receptor.

Remember, the actual state of the neuron — that is, whether it is excited or relaxed — depends on both the GABA and NMDA receptors. NMDA excites, GABA relaxes. There is a seesaw relationship, with NMDA and GABA sitting on either side of the excited–relaxed seesaw.
...
Here, skip to about 30 minutes, I think he's on the same wavelength as you.
Guy on the video said:
The more calcium that flows in, and remember this is just, a lot of pain signals could do this - turn on on NMDA and then you get too much calcium... OR an opiate (too much calcium) and you start getting breaks in the DNA, in the genetics of the cell, which through a couple more steps leads to DAMAGE, to inhibitory neurons, you can see this actually in the spinal chord, If you are on opiates a long time, OR if you have lots of these pain signals coming in all the time, you start literally seeing, the inhibitory neurons start to shrink.
 

triffid113

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Since I posted that (a year ago?) I've learned that niacinamide is considered a 'methyl sponge' -- in other words, it can use up methyl groups quickly, so that if one is doing the methylation protocol, those supplements may need to be adjusted/increased in order to find the right balance -- all depending of course on one's genetics.

I tried the niacinamide last year for a bit, but it just made things worse, but at the time, I hadn't figured out what methylation supps I needed. I'm doing better now with folinic, TMG, a little methylfolate, a little methylb12, and some ad-b12 -- so am trying to find a low, low dose b-complex that is balanced, and has a little niacinamide and some of the other b's as well.
Darn! Well, thanks.
 

Lotus97

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The more calcium that flows in, and remember this is just, a lot of pain signals could do this - turn on on NMDA and then you get too much calcium... OR an opiate (too much calcium) and you start getting breaks in the DNA, in the genetics of the cell, which through a couple more steps leads to DAMAGE, to inhibitory neurons, you can see this actually in the spinal chord, If you are on opiates a long time, OR if you have lots of these pain signals coming in all the time, you start literally seeing, the inhibitory neurons start to shrink.
When he mentions Calcium, Magnesium, Potassium, and Sodium does that have anything to do with how much we consume or is that entirely different?
 

Hip

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I have found any supplement that contains arginine seems to reduce my anxiety. This includes L-arginine powder (at a dose of a few heaped teaspoons) and arginine pyroglutamate powder (which crosses the blood-brain barrier very well, so you will find only one heaped teaspoon is required). I have also tried arginine alpha ketoglutarate, and ornithine alpha ketoglutarate, and these work too.

It takes an hour or two for the anti-anxiety effects of oral arginine to kick in, I find. But long term arginine use tends to cause a herpes cold sore flare ups in me, so I am always concerned about taking arginine regularly, in case it generally boosts herpes infections in the body.

Certainly arginine removes ammonia, so if ammonia-driven NMDA receptor stimulation was the cause of your anxiety symptoms, then this could explain why arginine has anti-anxiety effects.

Arginine also potentiates GABA neurotransmission (ref: here), so this might explain its anti-anxiety effects.


Intranasal Arginine — A New and Fairly Potent Anti-Anxiety Technique I Happened Upon

One particularly useful trick that I recently figured out is taking small doses of L-arginine powder intranasally: that is to say, snorting around 50 mg of L-arginine powder into each nostril with a drinking straw.

Not only does intranasal arginine have very powerful effects against anxiety symptoms, but moreover, its anti-anxiety effects kick in fast: we are talking about 20 minutes. You can be feeling quite high levels of anxiety, yet just 20 minutes later, after snorting a small amount of arginine, you are calm again. I don't know any other supplement that is this fast acting. So intranasal arginine is very good for those anxiety emergencies, when your anxiety levels have hit a high, and you want to regain a calm state quickly.

Also, since your overall intranasal arginine dose is much smaller than the oral heaped teaspoon dose required to achieve the same anti-anxiety effects, snorting is probably less likely to cause herpes flare ups.

Of course, proceed at your own risk. Intranasal arginine is an experimental treatment, and I am not sure if some adverse effects might arise from taking arginine intranasally. Though I have not had any problems in all the times I have snorted L-arginine powder.

I found arginine pyroglutamate to be the best form of arginine in terms of anti-anxiety effects. This is probably because arginine pyroglutamate crosses the blood-brain barrier more effectively than other arginine supplements.


Note: do not snort any supplement into your nose that is acidic (ie, tastes tart), as it will sting like hell.
 
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triffid113

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arginine causes production of NO if your blood pressure is not a problem. I always worried it would make ONOO in my case. However I did find that arginine would lower my bp in the past. Which struck me as weird since high bp a piori means I am making ONOO instead of NO, right? It does not matter anymore since I used DHEA to help me make NO. I think there was some problem with how long NO would stay in the system...I can't recall. I used to carry a bottle of arginine in my purse for blood pressure emergencies before discovering DHEA.

Lot's of life threatening things can cause panic/anxiety. Low blood sugar will cause it. Perhaps high blood pressure will cause it too. At any rate arginine produces NO, a vasodialtor, which is relaxing. I can feel when my blood vessels are dilated...such as from 1 g Olive Leaf extract...ahhhhh!!!!! blood vessel peace.
 

triffid113

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If you have significant anxiety symptoms driven by NMDA receptor over-stimulation, you need a very high dose of magnesium in order to effectively block your NMDA receptors. Orally, you cannot take more than around 500 mg of magnesium daily, otherwise it gives you diarrhea, and the magnesium is flushed out.

By contrast, if you apply magnesium to the skin of your whole body, from head to toe, you are going to absorb a much higher dose of magnesium that you can orally. Of course, you can take both oral and transdermal magnesium if you really want to maximize your dosage.



You are mixing up glutamate and ammonia here. Both these substances can over-stimulate NMDA receptors, sure, but in ME/CFS I think glutamate that is likely causing the problem. Glutamate is produced by activated microglia (ref: here). Ammonia might be the problem in Lyme, as Borrelia bacteria produce ammonia, I understand.

Quinolinic acid is another very potent activator of NMDA receptors, and might also be involved in ME/CFS. Quinolinic acid is also produced by activated microglia in the brain (ref: here and here). Microglia become activated during brain inflammation.

Taking high daily doses of transdermal magnesium will help block NMDA receptor activation, but you need to keep taking the magnesium every day to maintain the protective shield against NMDA receptor over-stimulation.

When I had very severe, hellish constant anxiety symptoms, which I believe were likely caused by NMDA receptor over-stimulation, I applied magnesium to my skin twice daily, from head to toe, and this helped reduce anxiety symptoms.

Remember, in this context, you are not taking magnesium just to fulfill your body's daily magnesium mineral requirements; rather you are taking magnesium more like a therapeutic drug, for its ability to block NMDA receptor over-stimulation.

Of course, it would be much better to prevent the excess glutamate and quinolinic acid from being produced in the first place. That way, you would not have any NMDA receptor over-stimulation. However, a belts and braces approach (using both anti-inflammatory supplements and NMDA receptor blockers like high dose transdermal magnesium) is a good idea if you have high levels of brain inflammation and anxiety symptoms.

I found that the anti-inflammatory supplements I listed at the beginning of this thread were very helpful in reducing my anxiety symptoms, and it is my assumption that some of these anti-inflammatory supplements helped because they reduced brain inflammation, thereby reducing microglia activation, thereby reducing glutamate and quinolinic acid production, thereby reducing NMDA receptor over-stimulation and thereby reducing the anxiety symptoms.

Please also see the very effective anti-anxiety drugs and supplements listed in this thread:
Completely eliminated my severe anxiety symptoms with three supplements!


Quinolinic acid, by the way, is a very interesting and very potent neurotoxin that is involved in lots of neurodegenerative diseases. Quinolinic acid severely impairs energy metabolism (ref: here).

I find it fascinating that in poliovirus infections, if you block the activity of quinolinic acid, all the damage resulting from poliomyelitis can be prevented (ref: here).
Thanks for pointing out I could take a higher dose magnesium via the oilk - I did not know that!

However I am not mixing up glutamate toxicity and ammonia. They both act on ethe NMDA receptors to strip off the magnesium. (This I read). Experientally, when I had glutamate toxicity from high dose MSG I could not relax my muscles and felt like I would die. High ammonia (which I never verified I had but only construe since I was on a high protein diet and I have issues excreting ammonia (BH4 issues) caused me constant low blood sugar issues. Now an inbetween strug-out-forever, which I guess you guys call 'wired' happened to me every PMS and at menopause. It was an I-cannot-relax, but it was not every-muscle-is-clenched. That is glutamate/ammonia toxicity too but I now believe it was due to that I could not hang on to magnesium (experientially - dunno the actual reason). One of the guys here used to publish long lists of foods that cause glutamate toxicity if you have a problem with this and since I ate food I am sure many of the things I ate caused this. I used to try to starve myself during PMS because it was the only thing that made me feel better.
 

Stretched

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Summary

To try this anti-anxiety protocol, start with say grape seed extract 500 mg. Add to this 1000 mg of propolis, 3 times a day (best not to take propolis before bed - it may keep you awake). Finally, you can add vitamin E (alpha tocopherol) 400 mg twice a day. These three supplements will act to reduce brain inflammation, and thus reduce anxiety (hopefully).[/quote]

Great post! You seem current on BioChem... . I wonder if you could comment on what the effects on an SSRI
(e.g. Zoloft) add or detract from your alternative protocol, which sounds right on. Also, as strange as it may sound how about the same when adding Adderall XR with or w/o the SSRI?

I would image a lot of us use an SSRI (for various applications; probably Adderall as well). I realize Adderall is a stimulant and that at first blush might seem ridiculous to take with Anxiety. However, personally it is calming and focuses the mind. I have even taken it on 7 am early awake and it has enabled back to sleep and then getting up
four hours later feeling better!
 

jeffrez

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Surprised you didn't try kava. Originally that was used for relaxation and easing social anxiety at tribal gatherings, etc. Was there some particular reason (liver toxicity, etc.) that you avoided it?
 

Hip

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I wonder if you could comment on what the effects on an SSRI (e.g. Zoloft) add or detract from your alternative protocol, which sounds right on. Also, as strange as it may sound how about the same when adding Adderall XR with or w/o the SSRI?
@ Stretched.
First of all, there is a more recent and more up-to-date thread on some potent anti-anxiety supplements that were very effective in treating my severe generalized anxiety disorder; see this thread here:

Completely eliminated my severe anxiety symptoms with three supplements!


I should imagine that the supplements in these threads will complement SSRIs, though I have not taken SSRI's myself (I get a very bad reaction from SSRIs: they make me much more depressed).

I sometimes take the TCA antidepressant/anti-anxiety drug imipramine with these supplements, and it works fine. I also take very low dose amisulpride for anxiety and depression, and this I find works well in combination with these supplements.
 

Stretched

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I went back through this thread and outlined some appealing anti anxiety regimens and synthesized a hybrid to try.

I have been on Zoloft (Sertraline) since it was first on the market! It's one Rx I would like to to now see the affect without it. However, in prior attempts to titrate off the withdrawal symptoms were hellish - especially the last 25mg or so.

Any thoughts re supplementing off of it?
 
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well if one has POTS that causes anxiety

when you stand up your blood supply to heart and brain decrease

so you release more adrenaline to attempt to vasoconstrict in order to stay upright comfortably
so if you get treatment for the POTS OR MANAGE IT WITH salt electrolytes Iv fluids etc you may not need the anxiety meds

Ally
 
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I went back through this thread and outlined some appealing anti anxiety regimens and synthesized a hybrid to try.

I have been on Zoloft (Sertraline) since it was first on the market! It's one Rx I would like to to now see the affect without it. However, in prior attempts to titrate off the withdrawal symptoms were hellish - especially the last 25mg or so.

Any thoughts re supplementing off of it?
you could also see if there is any correlation between being uprght and the anxiety

that differentiates anxiety from POTs/EDS where it usually only occurs when you are sitting or standing up


ALly
 

Little Bluestem

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You can make your own cheap transdermal magnesium cream, simply using Epsom Salts mixed with some hand cream. Oral magnesium may also help, but most people reach bowel tolerance (they get diarrhea) after about 500 mg or so of oral magnesium supplements. The magnesium content of Epsom Salts (magnesium sulfate MgSO4) is 20%, so 5 grams of Epsom Salts provides 1 gram of elemental magnesium. One heaped teaspoon of Epsom Salts weights about 7 grams, just for reference. You need to use at least 1 heaped teaspoon of Epsom Salts (dissolved in little bit of water, and mixed into a hand cream) on each transdermal application.
@Hip, is there any harm in the 80% sulfate in MgSO4? Could other powdered forms of Mg be used, such as citrate?
 

Hip

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@Hip, is there any harm in the 80% sulfate in MgSO4? Could other powdered forms of Mg be used, such as citrate?
Not as far as I am aware. Dr Myhill uses magnesium sulfate injections (containing 1 gram of MgSO4) for ME/CFS.

You can use other magnesium salts for transdermal absorption, such as magnesium chloride (this molecule contains 26% Mg), magnesium citrate (contains 11% Mg) or magnesium glycinate (contains 14% Mg).

So ME/CFS doctors recommend magnesium suppositories.
 
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@Hip, Hi can you tell me if you mean 1000mg or 3000mg per day of propolis? Today I ordered some of the supplements you recommend and will try it out. I also ordered some DHEA to take 50mg per day in case I have adrenal exhaustion, hopefully it will work!
 

Hip

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@jordan2tagg
I often take up 4000 mg of propolis, for its COX-2 anti-inflammatory effects, which I find helps reduce the anxiety levels of my generalized anxiety disorder. Are you looking for good anti-anxiety treatments? If so, you might want to look at an updated thread I started on anti-anxiety supplements: Completely eliminated my severe anxiety symptoms with three supplements!

Be careful with the DHEA dosing. I find that anything above around 15 to 20 mg daily starts to create an aggressive and argumentative stance in my mind. DHEA is an "Incredible Hulk" sort of hormone!