Magnesium glycinate and GABA downregulation

[MagickalKat777]

Okay so I've been researching supplements like crazy looking for some things to help me recover from GABA-A downregulation due to excessive abuse of alcohol over the years along with daily prescribed benzodiazepines. I came to the conclusion that magnesium, bacopa monnieri, l-theanine, and Relora (magnolia and phellodendron proprietary blend) would all be helpful and I chose magnesium glycinate as it is said to be much more bioavailable and I've had laxative and paradoxical anxiety from magnesium citrate before. The glycinate form was said to be one of the most bioavailable and lightly sedating due to the glycine so I chose that.

Reading, however, I am starting to think that taking the glycinate form would actually cause more damage through the NMDA-mediated excitatory effects that glysine has.

I'm fairly certain I have significant GABA-A downregulation - I have been tapering diazepam for almost a year now and I started at 20mg and I'm still on 7.5mg a day and I'm miserable more days than not even though I stopped smoking and drinking on the same day that I started my taper and I've remained totally sober throughout. I am at my breaking point with the withdrawal... either things turn around or I'm going to check out permanently hence my sudden interest in supplements.

I've read that bacopa actually upregulates GABA-A but it won't do me any good if I have glycine causing NMDA to go wonky.

I figured that you guys over here might be able to make more sense of it than I can. I have read that glycine can go either way but I don't really understand why.

I've got all of the other stuff but there was a mix up by the company I ordered the glycinate from that resulted in me sitting here with a kilo of citrate which is when I really started digging today... Now I'm thinking it may have saved me from a total train wreck. I can tell you all that I can't even eat ramen noodles anymore without having a panic reaction from the MSG so my system is crazy sensitive right now. I'm actually starting to think that it won't ever recover... I've been prescribed benzodiazepines since I was 20 and I'll be 30 in October so I've spent almost a third of my life on them and I've been drinking off and on since I was 17.

Any other information on the subject of GABA upregulation would be helpful too, including thoughts on the rest of my choices. I'm most concerned about the magnesium glycinate but I obviously am interesting in any information about the others or any other beneficial supplements. Thanks guys. I would have posted links but most of the links have source links as well.

I suppose I should note that I'm intending to take 3g of magnesium glycinate a day (working up from 250mg to start over the course of a month or two) which contains 20% elemental magnesium so I may just be worried for no reason but the fact is that I'm sensitive to everything right now and I don't want to feed NMDA so I'll find something else if that's the case.

I'm looking at 750mg of bacopa (20% ), 200mg of l-theanine, 300mg of Relora, and 3g of magnesium glycinate as my daily goals but I can play with the dosage of all of them since 3 are powder and I have a scale I can use to measure out the Relora from the capsules.

 

[SONN]

I'm not sure if this will be of much help, but after experimenting with multiple different types of magnesium supplements I found Magnesium Oil that you rub on your skin to have the most noticeable (and least laxative) effects. I use magnesium chloride oil from the great salt lakes.

http://www.ancient-minerals.com/transdermal-magnesium/how-topical/

^according to that website it's the best way to get magnesium in your body besides IV, but I'm not sure just how much I believe all that. the thing about oral magnesium supplements is that i'm pretty sure magnesium takes a really long time to absorb into your intestines/colon (I remember reading 7-8 hours somewhere) and the fact that it's also a laxative basically means that it's going straight through you. However, I still have noticed some laxative effects the morning after spraying a shitton of magnesium oil on my skin.

tbh, I'm pretty sure taking that much theanine per day is a little more than necessary as well, even though it has been shown to have no side effects in mice.

 

[MagickalKat777]

I won't be jumping to those doses overnight.

As for magnesium glycinate, it is carried straight into the cells thanks to the glycine which is why its got such great bioavailability. I'm just concerned because I can't find out exactly what it is that glycine does, at least not in terms that I understand. From what I've seen, it appears to act as an inhibitory neurotransmitter in its own right, alongside GABA, but also is a co-factor for NMDA receptor activation along with glutamate. That's concerning because it means it can go either way and I can't afford anymore excitotoxicity.

I wouldn't be messing with anything if I wasn't desperate. I'm not getting better with the slow taper process, I'm getting worse by the day and if I don't figure something out soon, I'll end up putting an end to it in a much more permanent way.

I have been told to get some epsom salts to bathe with to absorb the magnesium sulfate - but my nerves are so shot that water moving over me is actually painful. I can't even take a shower without feeling like I'm being stabbed by a million needles with every drop that hits me. To say my life is hell is an understatement.

 

[DL-ark]

I won't be jumping to those doses overnight.

As for magnesium glycinate, it is carried straight into the cells thanks to the glycine which is why its got such great bioavailability. I'm just concerned because I can't find out exactly what it is that glycine does, at least not in terms that I understand. From what I've seen, it appears to act as an inhibitory neurotransmitter in its own right, alongside GABA, but also is a co-factor for NMDA receptor activation along with glutamate. That's concerning because it means it can go either way and I can't afford anymore excitotoxicity.

I wouldn't be messing with anything if I wasn't desperate. I'm not getting better with the slow taper process, I'm getting worse by the day and if I don't figure something out soon, I'll end up putting an end to it in a much more permanent way.

I have been told to get some epsom salts to bathe with to absorb the magnesium sulfate - but my nerves are so shot that water moving over me is actually painful. I can't even take a shower without feeling like I'm being stabbed by a million needles with every drop that hits me. To say my life is hell is an understatement.

If you are really desperate, maybe eat the epsom salts, mix em in a smoothie or something. Hell, you could even try using them bucally or sublingually, which would probably have better BA than orally, and if magnesium sulfate can be administered transdermally, it can sure as hell be administered sublingually or buccally. Oral would also work for something like a magnesium salt, but it may have less BA.

 

[MagickalKat777]

Well I tried the Relora tonight and I have to say that I'm blown away. One 300mg capsule put to rest most of my anxiety like a benzodiazepine used to (they don't touch it anymore and haven't for a long time).

I found a study that says honokiol and magnolol are positive allosteric modulators but only in the presence of a BZD agonist - well I guess that tiny bit of Valium is enough for it to potentiate its effect quite a bit because I'm actually feeling kind of floaty right now.

Between this and the bacopa, I may not even need to fuss with magnesium, this is actually quite nice. There aren't really any reports on tolerance and its relatively cheap in bulk 95% extract form - I doubt the phellodendron in the Relora is really doing anything for the anxiety although berberine certainly has its own benefits.

I still am curious about magnesium glycinate specifically though. I believe I could benefit from magnesium supplementation and I already paid for a kilo of the stuff before finding out about glycine.

 

[sekio]

You forget about the great defender: the human blood brain barrier. People don't die of seizures when they drink beef broth from the huge amount of deadly neurotoxic glutamate, because it's not all delivered to the brain. Only what your brain needs is transported to it; all dietary nutrients aren't piped directly to your head first.

Panic attacks and other side effects from glutamate/MSG rich foods are entirely psychological by the way. It's been proven with double blind studies. Really, it's an old wives tale... MSG does not actually cause any sort of problems, well, aside from excessive sodium consumption if you use it to excess. Glutamate is a natural amino acid... you find MSG in places like tomato juice, where it acts as an umami enhancer - explains why people have tomato meat sauce, or tomato on sammiches. Glutamate, glycine and other amino acids are also a natural part of fermentation cultures and contribute to the flavor of stuff like cheese and miso.

Have you ever eaten gelatin? Jello? a gelcap? Or in fact any protein at all? You're getting glycine. Gelatine is a mixture of glycine, proline, and hydroxyproline. If you've ever eaten beets - they contain betaine, trimethylglycine. And to top it all off your body can make glycine too! So no worries about it being toxic. It's the simplest amino acid and it's good for you!

As for the magnesium: Glycinate, citrate, etc: they are all "chelated" magnesium. You just have to account for the fact that various counter ions contain different proportions of magnesium. All of them will give you the runs if you take too much because what isn't absorbed will hyper-saturate with water. (Mg citrate is used as a laxative in higher doses). All magnesium will act as a good mild sedative and tonic. Magnesium is actually absorbed transdermally; I find a nice way to relax in general is to have a warm bath with a cup or two of Epsom salts and maybe a drop of some lavender oil or something (not if your skin is sensitive). Or Dr. Bronner's soap...

BZD withdrawal has a tendency to make people panic over all sorts of things. That's the core issue here. You just need to relax and un-learn the panic associations you've made. And seriously, nobody has ever given themselves neurotoxicity by over-consuming glutamate or glycine. There's one context that those are going to be neurotoxic: if you inject them directly into your brain or into a cell culture. So don't do that. Like I said, people manage to drink soup or broth (brimming with excitotoxic amino acids) and - guess what - it usually tastes good because your body actually recognizes those amino acids as a sign of a protein source!

You're not going to hurt yourself taking supplements and eating healthy. Please convince yourself of that. I know benzodiazepine withdrawal can cause irrational fears, but ... a fear that eating healthy is damaging you is pretty... weird

 

[MagickalKat777]

Thanks for alleviating my fears, sekio.

I know that I'm pretty irrational... Its ridiculous what GABA agonists do to the mind compared to anything else and its so hard to sort between what is real and what isn't.

So you really think that citrate and glycinate are both going to be the same? Citrate is a salt, glycinate is chelated I thought?

I tried Relora last night... Its unsurprising that I found studies showing honokiol and magnolol to be positive allosteric modulators at the BZD site... I actually felt like I benzo'd out of my skull from one cap. I guess I'll use this... Even if it does have GABAergic effects, it would be better to taper off the Valium using Relora and then slowly come off the Relora. I think I'm at the point that being on Valium is actually hurting my taper and I might need to switch to something else. Relora worked so well that between it and my 7.5mg of mirtazapine last night, I slept until 1PM and barely woke up to shut my alarm off at 8:15AM, totally skipping my Valium. I ended up taking it at 1:47PM when I realized it was still sitting in the pill box. That's pretty remarkable for me.

I'm going to look into a 95% magnolia extract though, Relora is expensive and I doubt that phellodendron is really doing anything when it comes to anxiety.

 

[sekio]

So you really think that citrate and glycinate are both going to be the same? Citrate is a salt, glycinate is chelated I thought?

They're not exactly the same, but both are chelated magnesium salts.
A salt is an ionic compound formed from a positively charged cation (the magnesium) and a negatively charged anion (citrate or glycinate). All magnesium supplements are salts of magnesium, otherwise they would be magnesium metal!
A chelate is when one compound binds to another compound and forms a complex. Both glycine and citric acid will do this. So both are technically 'chelated magnesium'.

Anything you can use to taper off the benzos is good. Just take your time - getting off benzos/diazepam is not meant to be done in a few days. It's like a 2-3 month affair. But you'll get much better after the first week or so. Better to taper and feel OK rather than freak out.

 

[MagickalKat777]

2-3 months? I started at 20mg on 9/13/13 and I'm miserable at 7.5mg right now... This is absolute hell! I keep telling myself that it will get better but its just getting worse. I'm going to talk to the psychiatrist about moving from diazepam to clorazepate and tossing on oxcarbazepine I guess. When I've been "rapid detoxed" Tranxene actually is fully effective for my anxiety while Valium is not effective at all and that's why I used to drink so much - I think the problem I'm having is that Valium pooped out on me a long time ago so its not really doing anything to ameliorate my symptoms. I have had something similar happen with Klonopin where it stopped working almost entirely, leaving me in a constant state of withdrawal, so I switched to Valium but when I was out of Valium a few months later, I was able to go back on Klonopin and have it work again until I got my Valium prescription from the new doctor. Xanax pooped out on me too which is when I went to Klonopin so it seems to be a pattern with me that I have to go from benzo to benzo.

Interesting about the chelates... It seems that everything is a big marketing gimmick, including the "research" on them. Hmm... Well since I've reacted poorly to citrate before, I suppose the glycinate is still a better option to try. We don't have bath tubs so epsom salts are out.

Any thoughts on the Bacopa idea? It supposedly upregulates GABA which I believe would be very beneficial in this situation.

 

[SONN]

It really upsets me that big pharma is profiting off making your life a living hell. Best of luck to you

Sekio mentioned some anxiolytics that are 5ht1a agonists in my chamomile thread, like linalool and CBD (pretty sure ginkgo biloba is one too). According to wikipedia 5ht1a is really involved in neuromodulation

http://en.wikipedia.org/wiki/5-HT1A_receptor#Neuromodulation

maybe I'm just making associations for no reason but perhaps using 5ht1a agonist anxiolytics in combination with the Relora will help 'modulate' your brain into being less dependent on benzos?

 

[sekio]

I reiterate: Anything you can use to taper off the benzos is good. If you feel better after doing something or taking a particular herb, maybe that's something you should try again?

As long as it's not more benzos

 

[MagickalKat777]

Well being that honokiol is itself a positive allosteric modulator, I wonder if I'm not actually just going to end up trading benzos for herbs? lol.

Either way, I feel 100x better than I did and I'm just taking 300mg of Relora with my 2 doses of Valium so its doing something rather remarkable either way. I haven't been so low in anxiety without drinking in a very long time, even managed to pull off an hour of Bioshock Infinite without some serious anxiety and that game creeps the hell out of me.

It really upsets me that big pharma is profiting off making your life a living hell. Best of luck to you

Sekio mentioned some anxiolytics that are 5ht1a agonists in my chamomile thread, like linalool and CBD (pretty sure ginkgo biloba is one too). According to wikipedia 5ht1a is really involved in neuromodulation

http://en.wikipedia.org/wiki/5-HT1A_receptor#Neuromodulation

maybe I'm just making associations for no reason but perhaps using 5ht1a agonist anxiolytics in combination with the Relora will help 'modulate' your brain into being less dependent on benzos?

As for 5HT1A... traditionally anything that messes with serotonin my body tends to not like anymore... Probably from so much abuse of releasers and 5HT2A agonists over the years coupled with damage from pharmaceutical drugs.

With that said... I find it fascinating that so many things that had such a profound effect on me are on there like AMT, trazodone, and even MDMA itself. Honestly it wouldn't hurt me to add trazodone back in or even giving buspirone a try but from what I understand, 5HT1A agonists are virtually ineffective in the face of benzodiazepine withdrawal which is why buspirone is rarely prescribed to benzo addicts, present or past. Either way I have a crapload of trazodone lying around, I might just start taking 25mg of it with my 7.5mg of mirtazapine at night and see what happens, thanks for the tip.

 

[AlphaMethylPhenyl]

SSRIs should mitigate some of the withdrawal, at least combined with an AP.

 

[MagickalKat777]

SSRIs should mitigate some of the withdrawal, at least combined with an AP.

I don't get along with SSRIs or antipsychotics. The only atypical I haven't tried is Seroquel but based on my experiences with Zyprexa, Geodon, Abilify, and Risperdal, I don't think it would be of any benefit to me.

And nothing would ever sell me on the older antipsychotics, the risks are way too high.