809 replies to this topic

[SearchingForAnswers]

ScienceGuy,

Pardon if the answer is already in this thread, I'm going through it. However, as Magnesium Malate is difficult to find in bulk (at least in the U.S.), is there a second and third form of oral magnesium that would be good runner-ups?

[world33]

^{Magnesium Glycinate at purebulk.com http://purebulk.com/...ml#.U47-PhCIqmQ}

[Duchykins]

http://www.bulksuppl...um-citrate.html

Citrate is my preferred form. You can also find it dirt cheap in liquid form in whereever they keep all the laxatives, it would be only the citrate and with either sodium bicarbonate or potassium bicarbonate, only catch it that you have to keep it referigerated.

Edited by Duchykins, 04 June 2014 - 08:01 PM.

[Duchykins]

Forgot to add that you shouldn't take the citrate if you plan to take large doses, I take smaller doses with theanine and potassium (sometimes lysine) and find that I can less of all of them if I let them work together

[Duchykins]

Just ordered some magnesium malate from Swanson's. 1000mg caps, cheap. We'll see how it goes. If I do better with the malate, then I think getting it in caps makes it worth the extra money. And I think if more people buy it, eventually they'll be encouraged to sell it in bulk powder.

[world33]

Understanding Different Types of Magnesium http://www.drnibber....s-of-magnesium/

Magnesium Citrate is laxative where Magnesium Glycinate and Magnesium Taurate are not and have better bioavailability apparently.

Magnesium by itself is not going to make such a big difference in anxiety levels, at least in my personal experience.

Edited by world33, 04 June 2014 - 11:09 PM.

[Duchykins]

I know about the different kinds of mangesium, thank you. Thanks for telling me citrate could be used as a laxative, I didn't know that either. The form of magnesium doesn't really matter too much, it's the actual magnesium that can be used to relieve constipation and the dosage for that varies depending on what's going on in an individual's body. Oxide, citrate, sulfate (epsom salt), hydroxide (milk of magnesia), glycinate, malate, taurate, all of these can have laxative effects. It's partly because magnesium itself is an electrolyte. All of this is easily verifiable. The citrate form is not that scary and if it messed up people's GIs with any consistency then it wouldn't be so popular a supplement. Your own link listed it as one of the preferred forms of magnesium.

The citrate has never messed with my bowels which is why I kept taking it for more than three months. I also take less than 300mg a day, in divided doses. Often it was only 200mg at night. I had adverse reactions to oxide and glycinate, I've observed a pattern of not doing well with glycinates and gluconates in general, and malate was a pain to get in bulk powder so I got citrate. There was also a period of three weeks where I ran out, all I noticed was that my migraine threshold decreased a bit ( why I started taking mag in the first place) and some of the old irritability came back, but that's normal with migraines. People who take higher doses of mag cit will get more problems, and they cannot take higher doses for a long time because their bowels will become somewhat dependent on it. It's not something to mess around with partly because magnesium is an electrolyte and people can imbalance their electrolyte levels (causing bowel problems, anxiety, among other things), and because of citrate's role in the Kreb cycle, which can also be thrown out of whack.

Edited by Duchykins, 05 June 2014 - 04:28 AM.

[world33]

No problem. I think Magnesium Glycinate and Magnesium Taurate are still superior for anxiety no matter your particular reaction to them and my reply was meant to be a suggestion for SearchingForAnswers who started asking the question not an attack to your knowledge ... :-) I would suggest l-Theanine as a much better supplement for anxiety anyway.

Edited by world33, 05 June 2014 - 07:44 AM.

[Duchykins]

No matter your particular reaction to them? That works well for the person who does worse with glycinates. There isn't anything particularly universal about the application of these supplements.


Well, at least we agree theanine is superior, that's one I don't ever want to give up and works consistently. Though I have wondered why some people say they feel worse on it. Just 100mg is enough for me. Even gave it to my cat when she was stressed out from our recent move, got a whole new cat (yes you can do this). Theanine is sorcery.

Edited by Duchykins, 05 June 2014 - 02:07 PM.

[Duchykins]

Magnesium malate arrived yesterday. I threw out the rest of the cal/mag citrate powder after taking just half a capsule of the malate, it was that immediately good. I think perhaps something is off in my citric acid cycle and ATP production or transport, causing a lot of problems including the irritability especially at sound, tinnitus, slow shallow upper-lung breathing, pausing on exhalation & periodic arrhythmia, lethargy, weakness, confusion and brain fog, things everyone including doctors are telling me are probably anxiety induced and want me to take a benzo for, which I refuse. Got some ribose too. I might go back on 1gram of micronized creatine because my kidney tests came back okay with low creatinine, the creatine did me good while using it. Probably back on alpha lipoic acid as well. Never stopped 120mg coQ10.

I'm being put on a heart monitor for two weeks starting this Monday, I wonder if I should hold off on the malate and other stuff while on the monitor so that they don't potentially mask any symptoms of something more serious?

[Plasticperson]

After reading this thread I have to congratulate Science Guy and his dedication. However, I'd like to point out that sometimes logic doesn't coincide with predictions. Supplements can have down stream effects that are not documented in science journals. But more importantly the human psyche is a unique interaction of biochemical reactions that yields a mood. Individual receptor subtypes may alter mood but the whole picture is more important than a single color.  If one can use a gaba agonist supplement to set in motion a perpetual change in these biochemical reactions the alteration affects parts of the brain that aren't directly related to GABA. The GABA agonist has down stream effects resulting in a mood that results from ubiquitous changes within the brain. Keep in mind after someone experiences this new mood they have a higher probability of replicating it again after the GABA agonist wears off.

 

 

Good moods are perpetual.. they can last after drugs where off. One of the best examples of this was when Abram Hoffer used LSD as a treatment for alcoholism. 

[chris7900]

hey guys, what about pregnenolone ?

 

some sources claim that it is a gaba A inhibitor.

 

[...]pregnenolone inhibits GABA receptors. Thus, too little NMDA activity combined with excessive GABA activity would tend to promote mental sluggishness and depression. Since pregnenolone raises NMDA activity and lowers excessive GABA activity, pregnenolone seems to be a natural antidepressant. Indeed a recent study of 27 depressed patients found that their cerebrospinal fluid (which circulates through the brain and spinal cord) was significantly lower in pregnenolone than in 10 non-depressed volunteers. Cerebrospinal fluid levels are generally believed to accurately reflect levels of various biochemicals in the brain.

http://intelegen.com...al_function.htm

 

 

also pregnelolone sulfate is an gaba A antagonist.

 

Our previous study showed antagonism of GABA_A receptor-mediated whole-cell currents by pregnenolone sulfate (PS). Here, the effects of PS, picrotoxin (PTX) and pentobarbital (PB) were tested on GABA-activated single Cl⁻ channels recorded from membrane patches of rat cortical neurons in primary cultures. PS and PTX selectively decreased the opening frequency of the channels, while PB increased mean open time and burst duration without affecting opening frequency. It is suggested that PS and PTX may antagonize GABA_A receptor function through the same mechanism and/or the same binding site.

http://www.sciencedi...006899389900243

 

in the book "edge effect" by dr. eric braveman, pregnenolone is recommendet as a hormone for people with gaba-deficiency

 

"Other natural hormonal supplements that might be useful for a GABA deficiency include pregnenolone, which is a calming precursor of DHEA, and growth-hormone-releasing hormone (GHRH), which may shrink tumors and may enhance fertility."

"Pregnenolone: increases total GABA levels"

 

maybe its an cheaper/safer alternative to naltrexone ?

and also it has other positive effects on mood and memory.

 

what do you say ?

 

 

 

 

 

Edited by chris7900, 15 June 2014 - 03:14 PM.

[world33]

maybe its an cheaper/safer alternative to naltrexone ?

You can buy 10 x 50mg tablets of naltrexone for 19USD at http://www.alldayche...om/naltima.html
Daily dosage is 4.5 mg before bed. That means (50mg x 10 tablets = 500mg; 500mg / 4.5mg = 111 days) a daily cost of 0.17 cents.
You can use a precision scale to measure 4.5mg or dissolve a 50mg tablets in the proper amount of distilled water and take the proper amount of drops (equivalent to 4.5mg) each night before bed. I did not made the calculations for this method but I am sure you can find them on the internet or ask someone in this forum.
You can pay by e-check (US) or epayworx (outside US). As usual I would not recommend using visa in any online pharmacy unless it is a pre-paid one with the exact amount of money you need to finalise each transaction at the time.

Edited by world33, 15 June 2014 - 11:51 PM.

[Duchykins]

I'm having powerfully positive responses to relora. Better than theanine, perhaps. Infinitely better than bacopa or ashwagandha. It's important that I'm not sedated by anything, but also not irritable as I get under stress, and relora seems to be fitting the bill. I almost gave up on herbs after my experience with bacopa, and was afraid of the relora at first, but I'm glad I didn't throw it away. I'm going to make my mom take this one.

Edited by Duchykins, 16 June 2014 - 05:51 AM.

[world33]

blood,
I have just found out that rupharm.com sells the same Russian anxiolytic drugs (including selank) but much cheaper than awakebrain.com. I have never used rupharm.com before but when you check out they seem to use shopify.com as their e-commerce platform which, if I am not wrong and judging from their website, include paypal as a form of payment. By searching rupharm.com in google there are positive reviews even from people in this forum so it must be legit.

 
Looks to me like they only take bitcoin.

rupharma.com should accept PayPal now if I am not wrong

[Ethrem]

Hi everyone, I'm new here but I have been reading off and on for years.

 

I struggle with anxiety badly. To the point that I am completely and totally disabled, only leave the house for doctor's appointments, etc.

 

I have been prescribed benzodiazepines since 2004 (started with Xanax then to Klonopin and now to Valium) and I've had many subsequent mental health issues that have come along with this wonderful benzo dependency. 

 

I'm currently in the midst of a taper from Valium. Down from 20mg a day on 9/17/13 when I started to 7.5mg a day now.

 

Talking with my buddy the other day he referred me to this thread and so I'm wondering about this stack. I am fairly certain I have cortisol issues (one of the big markers I've been told is the feeling like your blood sugar is crashing but when you go to check your sugars, they're actually perfect which is something that I experience often (and actually am experiencing as I type this) so I ordered some Relora. 

 

Since I've been on benzodiazepines for so long, GABA-A down-regulation is definitely an issue (compounded by the fact that up until 9/17 when I stopped drinking cold turkey, I was quite the alcoholic) so I believe that bacopa may help here.

 

I am extremely low in my Vitamin D levels (both my psychiatrist and my general medicine doctors have expressed concerns about how low it actually is) so I most likely am low in magnesium as well but I don't tolerate magnesium citrate at all so I opted for magnesium glycinate.

 

The last thing is l-theanine. I have heard of a lot of success with theanine so I might as well try it.

 

Is there anything that I should be considering with this stack? Any potential pitfalls? I should point out that I have had full workups and amazingly, I have a fully functional liver and kidneys. I only take 7.5mg of diazepam a day, 7.5mg of mirtazapine every other day or less (for sleep at night, I try not to take it daily), 2g of fish oil a day, and now 5000 IU of D3 a day. I don't have any other health issues to speak of although I do have other mental health issues that are intermittent (some sort of mood disorder, adjustment disorder - its nothing major though, my biggest impact issue would definitely be my anxiety disorders).

 

I'm overall a healthy 29 year old male who is desperately trying to regain control of his life.

 

Things that I have tried in the past:

 

NMDA antagonists: memantine and dextromethorphan polisterex - limited benefit with tapering benzos although dextromethorphan was instrumental in my successful cessation of smoking,

SSRIs: citalopram and escitalopram - citalopram was actually extremely effective in combination with clonazepam but had to be discontinued at 60 days due to hypomania that required an inpatient intervention,

bupropion: huge disaster, some of the worst panic attacks I've ever had, dangerous weight loss, insomnia, tachycardia, hypertension

tiagabine: very expensive with no real perceived benefits, stopped taking it

pregabalin: effective at 400mg+ with rapid tolerance development, stopped working after 2 weeks

gabapentin: highly sensitive to it, was not aware of dextromethorphan's interaction with it at the time and just ended up very intoxicated for days - tried it a second time and just 100mg was enough to precipitate a panic reaction weeks after stopping dextromethorphan

lithium: paradoxical psychotic reaction that required intervention in an inpatient setting

divalproex sodium: intolerable side effects

hydroxyzine: zero effect

diphenhydramine: paradoxical stimulation, hallucination, panic reaction

mirtazapine and trazodone: only effective for sleep, nothing else.

lamotrigine: increased anxiety

ziprasidone: increased anxiety, rapid heartbeat

olanzapine: panic, rapid heartbeat, dramatically increased general anxiety

oxcarbazepine: improved mood but did nothing for anxiety

alpha-methyltryptamine when it was legal was a go-to antidepressant and probably the only truly effective one I've ever come across.

 

There are others that I'm forgetting right now I'm sure but that is a somewhat decent chunk of history.

 

Supplements I'm not going to go into as much detail but I've tried:

 

Valerian

GABA

Piracetam

Phenibut (proprietary formula by Metabolic Response Modifiers called "Relax-All" that had a blend but included phenibut): Unsurprisingly, this worked very well but being familiar with phenibut's nasty GABA-B properties and already being addicted to a GABA-A agonists, I made the intelligent decision to use this one no more than twice a week and only for sleep.

Picamilon (found out the hard way that this is not one to take when you have a GABA agonist dependency, it was like going cold turkey and hitting withdrawal in just a few hours)

Valerian

Kava

Inositol

5-HTP

Rhodiola

B complex (can't tolerate it, crazy anxiety trigger for me when I take one)

Phosphatidyl Serine (no effect noted and was too expensive so I stopped using it)

Chamomile

Fish oil (this actually does seem to help - when I'm having an anxious day, I will take one and get some amount of relief within an hour or so which has prompted me to take it twice a day)

 

As you can see, I've tried a lot... And I know there are obscure things that I'm not remembering.

 

Any thoughts? I don't really think that any of the supplements can actually hurt things any since none of them act directly on GABA so anything that happens should go away when I stop them and I bought them in bulk powder so I can measure them out (I bought a cheap Gemini-20 since these aren't milligram sensitive - a Gemini can probably be trusted to be within +/- 10mg at the absolute worst - if I go into other supplements, I'll pick up a Gempro 250 or find an analytical balance on eBay again) so I am going to start slow and build up rather than dive in head first. The only thing that I got that isn't bulk is the Relora, which I got in 300mg caps.

 

One final thing: I'm open to tianeptine. I've been interested in that chemical for a long time and I do see that its available, however, I have heard conflicting reports on discontinuation syndromes with it and since I had such a nasty discontinuation syndrome from 60 days of 20mg of citalopram, I'm leery of serotonergic drugs and their associated withdrawal almost as much as I am with GABAergic drugs.

Edited by Ethrem, 07 July 2014 - 05:43 AM.

[Duchykins]

I've adjusted my 'meds' once again, with further improvement. I stopped taking my nightly doses of theanine (100mg) and just stick to a small dose of lysine with my ambien. I have also decided to taper off ambien and will be seeing my doc about that next week, perhaps I could use small doses of gabapentin during the transition. I went cold turkey off ambien before through a communication mistake between the doc office and pharmacy, so I went 6 days without, the first 3 days were fine and then it was like I hit a brick wall of horror, so I cannot do that again. My sleep quality has improved a bit, so it seems my suspicions were correct in that theanine was interefering with recovery during sleep somehow, perhaps through shortening of REM cycle which I believe is already quite short.

Of course theanine is still a fantastic drug and I continue using it in the daytime. I also stopped taurine and beta alanine, I plan to cycle these 3 weeks off.

Since my acute anxiety attacks, and palpitations, are brand new and uncharacteristic of the generalized tension and vigilance I usually have, I began going through everything I've been doing in the past 7 months, one of the only potential causes I've yet to eliminate is methylation. After trying various B complexes with various adverse effects, I began taking Bs separately and managed to isolate cyanocobalamin and synthetic folic acid as the likeliest candidates causing trouble with those complexes. I gradually switched things over to active Bs, 2500mcg of methylcobalamin, the exception being folate which I decided to get through foods such as spinach, liver, beet, etc. My potassium crash happened within a month of beginning methylcobalamin and eating lots of folate foods daily, the attacks continuing randomly afterward with decreasing severity. The docs believed it was caffeine alone that brought it on, but that just seems too fantastical since I've had larger Red Bulls without incident, I think the caffeine and sugar were just the 'last straw' things. The attacks kept happening when avoiding caffeine and taking taurine, magnesium, potassium citrate and bitartrate, and often coincided with sugary or high carb foods, even potatoes and chocolate. There seems to be plenty of anecdotes of similar events at Pheonix Rising.

In any case I never stopped methylcobalamin and I have no intention of doing so since I'm getting better. I have less need of extra potassium now, and can scoot by with just one cap of potassium citrate and a couple 1/8 tsp potassium bitartrate during the day. I'll be able to stop all that soon and no longer need to watch salty and sugary foods and avoid even caffinated tea. Last 4 metabolic panels came through with all electrolytes back within norms, potassium staying at 4.5.

Last three days were pretty awesome. I decided to give aniracetam another try since I still had about 30 grams hanging around, and sure enough, my experience was veryy different this time (not using choline or anything that moderately increases ACh like bacopa, ashwagandha). Started with a microdose of 1/16 tsp, then another 1/16 about 6 hours later, did this three days in a row since it's going so well. Less really is more, lol.

Morning

bupropion 75mg
relora 250mg
magnesium malate 1000mg
methylcobalamin 2500mcg
P5P 50mg
thiamine, riboflavin, pantothenic acid, 100mg each
lysine 250mg
glycine 1/8 tsp
mucuna 15% 1/8 tsp
ribose 1/8 tsp
micronized creatine m1/8tsp
potassium citrate 99mg
potassium bitartrate 1/8tsp
methionine 1/16 tsp
inositol 100mg
theanine 100mg
chromium picolinate 200mcg (cycle chromium)
Emerald Balance, 1/4 dose

with breakfast

coQ10 120mg
D3 1000IU
zinc gluconate 15mg
Albion chelated multimineral w/o iron, half dose
aniracetam


bedtime

glycine (sometimes)
lysine
potassium bitartrate
ambien

[Duchykins]

Hi everyone, I'm new here but I have been reading off and on for years.
 
I struggle with anxiety badly. To the point that I am completely and totally disabled, only leave the house for doctor's appointments, etc.
 
I have been prescribed benzodiazepines since 2004 (started with Xanax then to Klonopin and now to Valium) and I've had many subsequent mental health issues that have come along with this wonderful benzo dependency. 
 
I'm currently in the midst of a taper from Valium. Down from 20mg a day on 9/17/13 when I started to 7.5mg a day now.
 
Talking with my buddy the other day he referred me to this thread and so I'm wondering about this stack. I am fairly certain I have cortisol issues (one of the big markers I've been told is the feeling like your blood sugar is crashing but when you go to check your sugars, they're actually perfect which is something that I experience often (and actually am experiencing as I type this) so I ordered some Relora. 
 
Since I've been on benzodiazepines for so long, GABA-A down-regulation is definitely an issue (compounded by the fact that up until 9/17 when I stopped drinking cold turkey, I was quite the alcoholic) so I believe that bacopa may help here.
 
I am extremely low in my Vitamin D levels (both my psychiatrist and my general medicine doctors have expressed concerns about how low it actually is) so I most likely am low in magnesium as well but I don't tolerate magnesium citrate at all so I opted for magnesium glycinate.
 
The last thing is l-theanine. I have heard of a lot of success with theanine so I might as well try it.
 
Is there anything that I should be considering with this stack? Any potential pitfalls? I should point out that I have had full workups and amazingly, I have a fully functional liver and kidneys. I only take 7.5mg of diazepam a day, 7.5mg of mirtazapine every other day or less (for sleep at night, I try not to take it daily), 2g of fish oil a day, and now 5000 IU of D3 a day. I don't have any other health issues to speak of although I do have other mental health issues that are intermittent (some sort of mood disorder, adjustment disorder - its nothing major though, my biggest impact issue would definitely be my anxiety disorders).
 
I'm overall a healthy 29 year old male who is desperately trying to regain control of his life.
 
Things that I have tried in the past:
 
NMDA antagonists: memantine and dextromethorphan polisterex - limited benefit with tapering benzos although dextromethorphan was instrumental in my successful cessation of smoking,
SSRIs: citalopram and escitalopram - citalopram was actually extremely effective in combination with clonazepam but had to be discontinued at 60 days due to hypomania that required an inpatient intervention,
bupropion: huge disaster, some of the worst panic attacks I've ever had, dangerous weight loss, insomnia, tachycardia, hypertension
tiagabine: very expensive with no real perceived benefits, stopped taking it
pregabalin: effective at 400mg+ with rapid tolerance development, stopped working after 2 weeks
gabapentin: highly sensitive to it, was not aware of dextromethorphan's interaction with it at the time and just ended up very intoxicated for days - tried it a second time and just 100mg was enough to precipitate a panic reaction weeks after stopping dextromethorphan
lithium: paradoxical psychotic reaction that required intervention in an inpatient setting
divalproex sodium: intolerable side effects
hydroxyzine: zero effect
diphenhydramine: paradoxical stimulation, hallucination, panic reaction
mirtazapine and trazodone: only effective for sleep, nothing else.
lamotrigine: increased anxiety
ziprasidone: increased anxiety, rapid heartbeat
olanzapine: panic, rapid heartbeat, dramatically increased general anxiety
oxcarbazepine: improved mood but did nothing for anxiety
alpha-methyltryptamine when it was legal was a go-to antidepressant and probably the only truly effective one I've ever come across.
 
There are others that I'm forgetting right now I'm sure but that is a somewhat decent chunk of history.
 
Supplements I'm not going to go into as much detail but I've tried:
 
Valerian
GABA
Piracetam
Phenibut (proprietary formula by Metabolic Response Modifiers called "Relax-All" that had a blend but included phenibut): Unsurprisingly, this worked very well but being familiar with phenibut's nasty GABA-B properties and already being addicted to a GABA-A agonists, I made the intelligent decision to use this one no more than twice a week and only for sleep.
Picamilon (found out the hard way that this is not one to take when you have a GABA agonist dependency, it was like going cold turkey and hitting withdrawal in just a few hours)
Valerian
Kava
Inositol
5-HTP
Rhodiola
B complex (can't tolerate it, crazy anxiety trigger for me when I take one)
Phosphatidyl Serine (no effect noted and was too expensive so I stopped using it)
Chamomile
Fish oil (this actually does seem to help - when I'm having an anxious day, I will take one and get some amount of relief within an hour or so which has prompted me to take it twice a day)
 
As you can see, I've tried a lot... And I know there are obscure things that I'm not remembering.
 
Any thoughts? I don't really think that any of the supplements can actually hurt things any since none of them act directly on GABA so anything that happens should go away when I stop them and I bought them in bulk powder so I can measure them out (I bought a cheap Gemini-20 since these aren't milligram sensitive - a Gemini can probably be trusted to be within +/- 10mg at the absolute worst - if I go into other supplements, I'll pick up a Gempro 250 or find an analytical balance on eBay again) so I am going to start slow and build up rather than dive in head first. The only thing that I got that isn't bulk is the Relora, which I got in 300mg caps.
 
One final thing: I'm open to tianeptine. I've been interested in that chemical for a long time and I do see that its available, however, I have heard conflicting reports on discontinuation syndromes with it and since I had such a nasty discontinuation syndrome from 60 days of 20mg of citalopram, I'm leery of serotonergic drugs and their associated withdrawal almost as much as I am with GABAergic drugs.

I was very surprised at lysine. I first began taking it last year to prevent migraine, and it's an effective part of my stack for that purpose. But I read more about it, trying to understand why it was migraine prophylactic (helps with serotonin and gaba), and that's when I came across studies of lysine being used successfully for anxiety, depression and sleep, with results even more pronounced in people who have diets low in lysine. We've already been using it with animals for a very long time for stress-anxiety; household pets, horses, livestock. It's even the primary ingredient in a calming urinary health paw paste I give my cat when she is stressed and consequently vulnerable to urinary tract problems, but after I read about lysine I stopped wasting my money on the cat supplement and just started mixing my own lysine powder into her food when needed. The second ingredient was methionine so I gave her some of mine too, lol. I don't understand why lysine is so frequently overlooked for therapeutic use in humans when it so clearly has psychoactive properties.

Your reaction to fish oil in contrast to all the other stuff is curious, I wonder if your anxiety has something to do with dopamine rather than serotonin or gaba since fish oil can increase dopamine in a relatively short amount of time, which is one reason I stopped using it (the other being various symptoms of inflammation). Have you tried full spectrum mucuna, 15% l-dopa? But perhaps you should wait until you give relora a trial, since magnolia has both dopamine reuptake inhibition and dopamine antagonist properties.

[protoject]

pregabalin: effective at 400mg+ with rapid tolerance development, stopped working after 2 weeks

Any thoughts?

 

Hi Ethrem,

some people wouldn't recommend pregabalin, but I've been using it on and off for over a year so I can see its potential.

I believe it's possible it could work for you again, but at a different dosage.

In my experience, once I've been off the drug for a while, the tolerance level goes back down. I'm assuming you've been off of it long enough for tolerance to have gone down.

 

I find this drug works consistently but only if you take a low enough dose, and take breaks.

 

Maybe try something like 150 mg and see if you feel anti anxiety effects again. If it's working, maybe try continuing it and see if it continues to work, wait until it poops out, then quit for a couple days, and go back on it again.

 

If that seems like far too low of a dose to affect you, try perhaps taking pregabalin less often, but at the dosage that still works for you. For example, if 400 mg is your most effective dose, try taking it every 2nd day; and if you still notice tolerance doing it that frequently, maybe every 3rd day or 4th day. Have you tried that? Or maybe try doing that with a slightly lower dose, like 300, not too far off, but perhaps less tolerance inducing?

 

Really, taking breaks puts the tolerance way down again, in my experience.. heard others saying the same too.

 

I've almost stopped taking it entirely at this point, but when I was taking it, sometimes when things were better or if the drug seemed not to be working as well, I'd knock my dose down a few notches. Then when I really hardcore needed it I would knock the dose back upwards and the effects would return.

 

Just a thought.

 

I used it mainly for sleep but it did help my racing heart and anxiety to a degree.

Edited by protoject, 08 July 2014 - 05:45 PM.

[Ethrem]

 

Hi everyone, I'm new here but I have been reading off and on for years.
 
I struggle with anxiety badly. To the point that I am completely and totally disabled, only leave the house for doctor's appointments, etc.
 
I have been prescribed benzodiazepines since 2004 (started with Xanax then to Klonopin and now to Valium) and I've had many subsequent mental health issues that have come along with this wonderful benzo dependency. 
 
I'm currently in the midst of a taper from Valium. Down from 20mg a day on 9/17/13 when I started to 7.5mg a day now.
 
Talking with my buddy the other day he referred me to this thread and so I'm wondering about this stack. I am fairly certain I have cortisol issues (one of the big markers I've been told is the feeling like your blood sugar is crashing but when you go to check your sugars, they're actually perfect which is something that I experience often (and actually am experiencing as I type this) so I ordered some Relora. 
 
Since I've been on benzodiazepines for so long, GABA-A down-regulation is definitely an issue (compounded by the fact that up until 9/17 when I stopped drinking cold turkey, I was quite the alcoholic) so I believe that bacopa may help here.
 
I am extremely low in my Vitamin D levels (both my psychiatrist and my general medicine doctors have expressed concerns about how low it actually is) so I most likely am low in magnesium as well but I don't tolerate magnesium citrate at all so I opted for magnesium glycinate.
 
The last thing is l-theanine. I have heard of a lot of success with theanine so I might as well try it.
 
Is there anything that I should be considering with this stack? Any potential pitfalls? I should point out that I have had full workups and amazingly, I have a fully functional liver and kidneys. I only take 7.5mg of diazepam a day, 7.5mg of mirtazapine every other day or less (for sleep at night, I try not to take it daily), 2g of fish oil a day, and now 5000 IU of D3 a day. I don't have any other health issues to speak of although I do have other mental health issues that are intermittent (some sort of mood disorder, adjustment disorder - its nothing major though, my biggest impact issue would definitely be my anxiety disorders).
 
I'm overall a healthy 29 year old male who is desperately trying to regain control of his life.
 
Things that I have tried in the past:
 
NMDA antagonists: memantine and dextromethorphan polisterex - limited benefit with tapering benzos although dextromethorphan was instrumental in my successful cessation of smoking,
SSRIs: citalopram and escitalopram - citalopram was actually extremely effective in combination with clonazepam but had to be discontinued at 60 days due to hypomania that required an inpatient intervention,
bupropion: huge disaster, some of the worst panic attacks I've ever had, dangerous weight loss, insomnia, tachycardia, hypertension
tiagabine: very expensive with no real perceived benefits, stopped taking it
pregabalin: effective at 400mg+ with rapid tolerance development, stopped working after 2 weeks
gabapentin: highly sensitive to it, was not aware of dextromethorphan's interaction with it at the time and just ended up very intoxicated for days - tried it a second time and just 100mg was enough to precipitate a panic reaction weeks after stopping dextromethorphan
lithium: paradoxical psychotic reaction that required intervention in an inpatient setting
divalproex sodium: intolerable side effects
hydroxyzine: zero effect
diphenhydramine: paradoxical stimulation, hallucination, panic reaction
mirtazapine and trazodone: only effective for sleep, nothing else.
lamotrigine: increased anxiety
ziprasidone: increased anxiety, rapid heartbeat
olanzapine: panic, rapid heartbeat, dramatically increased general anxiety
oxcarbazepine: improved mood but did nothing for anxiety
alpha-methyltryptamine when it was legal was a go-to antidepressant and probably the only truly effective one I've ever come across.
 
There are others that I'm forgetting right now I'm sure but that is a somewhat decent chunk of history.
 
Supplements I'm not going to go into as much detail but I've tried:
 
Valerian
GABA
Piracetam
Phenibut (proprietary formula by Metabolic Response Modifiers called "Relax-All" that had a blend but included phenibut): Unsurprisingly, this worked very well but being familiar with phenibut's nasty GABA-B properties and already being addicted to a GABA-A agonists, I made the intelligent decision to use this one no more than twice a week and only for sleep.
Picamilon (found out the hard way that this is not one to take when you have a GABA agonist dependency, it was like going cold turkey and hitting withdrawal in just a few hours)
Valerian
Kava
Inositol
5-HTP
Rhodiola
B complex (can't tolerate it, crazy anxiety trigger for me when I take one)
Phosphatidyl Serine (no effect noted and was too expensive so I stopped using it)
Chamomile
Fish oil (this actually does seem to help - when I'm having an anxious day, I will take one and get some amount of relief within an hour or so which has prompted me to take it twice a day)
 
As you can see, I've tried a lot... And I know there are obscure things that I'm not remembering.
 
Any thoughts? I don't really think that any of the supplements can actually hurt things any since none of them act directly on GABA so anything that happens should go away when I stop them and I bought them in bulk powder so I can measure them out (I bought a cheap Gemini-20 since these aren't milligram sensitive - a Gemini can probably be trusted to be within +/- 10mg at the absolute worst - if I go into other supplements, I'll pick up a Gempro 250 or find an analytical balance on eBay again) so I am going to start slow and build up rather than dive in head first. The only thing that I got that isn't bulk is the Relora, which I got in 300mg caps.
 
One final thing: I'm open to tianeptine. I've been interested in that chemical for a long time and I do see that its available, however, I have heard conflicting reports on discontinuation syndromes with it and since I had such a nasty discontinuation syndrome from 60 days of 20mg of citalopram, I'm leery of serotonergic drugs and their associated withdrawal almost as much as I am with GABAergic drugs.

I was very surprised at lysine. I first began taking it last year to prevent migraine, and it's an effective part of my stack for that purpose. But I read more about it, trying to understand why it was migraine prophylactic (helps with serotonin and gaba), and that's when I came across studies of lysine being used successfully for anxiety, depression and sleep, with results even more pronounced in people who have diets low in lysine. We've already been using it with animals for a very long time for stress-anxiety; household pets, horses, livestock. It's even the primary ingredient in a calming urinary health paw paste I give my cat when she is stressed and consequently vulnerable to urinary tract problems, but after I read about lysine I stopped wasting my money on the cat supplement and just started mixing my own lysine powder into her food when needed. The second ingredient was methionine so I gave her some of mine too, lol. I don't understand why lysine is so frequently overlooked for therapeutic use in humans when it so clearly has psychoactive properties.

Your reaction to fish oil in contrast to all the other stuff is curious, I wonder if your anxiety has something to do with dopamine rather than serotonin or gaba since fish oil can increase dopamine in a relatively short amount of time, which is one reason I stopped using it (the other being various symptoms of inflammation). Have you tried full spectrum mucuna, 15% l-dopa? But perhaps you should wait until you give relora a trial, since magnolia has both dopamine reuptake inhibition and dopamine antagonist properties.

 

 

I may have to look into lysine. I've heard about it before but nothing too serious.

 

It wouldn't surprise me if I have problems with dopamine in addition to serotonin and GABA because of the things that I used to do. I was a significant abuser of certain dopamine and serotonin releasing agents in the past. Fish oil used to make me anxious, its only recently that it appears to help. That could, of course, be a placebo effect however. I will see how I do with the Relora. If its a DRI, it may not be good for me if we can draw anything from my reaction to bupropion. I have been cautioned against l-dopa because of my bipolar and other disorders that they believe I have.

 

 

pregabalin: effective at 400mg+ with rapid tolerance development, stopped working after 2 weeks

Any thoughts?

 

Hi Ethrem,

some people wouldn't recommend pregabalin, but I've been using it on and off for over a year so I can see its potential.

I believe it's possible it could work for you again, but at a different dosage.

In my experience, once I've been off the drug for a while, the tolerance level goes back down. I'm assuming you've been off of it long enough for tolerance to have gone down.

 

I find this drug works consistently but only if you take a low enough dose, and take breaks.

 

Maybe try something like 150 mg and see if you feel anti anxiety effects again. If it's working, maybe try continuing it and see if it continues to work, wait until it poops out, then quit for a couple days, and go back on it again.

 

If that seems like far too low of a dose to affect you, try perhaps taking pregabalin less often, but at the dosage that still works for you. For example, if 400 mg is your most effective dose, try taking it every 2nd day; and if you still notice tolerance doing it that frequently, maybe every 3rd day or 4th day. Have you tried that? Or maybe try doing that with a slightly lower dose, like 300, not too far off, but perhaps less tolerance inducing?

 

Really, taking breaks puts the tolerance way down again, in my experience.. heard others saying the same too.

 

I've almost stopped taking it entirely at this point, but when I was taking it, sometimes when things were better or if the drug seemed not to be working as well, I'd knock my dose down a few notches. Then when I really hardcore needed it I would knock the dose back upwards and the effects would return.

 

Just a thought.

 

I used it mainly for sleep but it did help my racing heart and anxiety to a degree.

 

 

I have tried pregabalin twice. I noticed a rapid tolerance building both times and a bit of a weaker effect from GABAergic agents in its absence which to me suggests some sort of a cross tolerance between them. Its also prohibitively expensive so its not a viable option for me at all. I happened to have great insurance at the time. Now not so much - thanks to my anxiety and panic attacks, I am unemployable and I'm on disability so I have Medicare...

[Ethrem]

Add Relora to the no no list.

 

Honokiol is a GABA-A modulator

 

 

 

Honokiol and magnolol have been identified as modulators of the GABAA receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABAA receptor subtypes. This possibility was examined in the current study by 3H-muscimol and 3H-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA(A) receptor subunit combinations expressed by the Sf-9/baculovirus system. Generally, honokiol and magnolol have a similar enhancing effect on (3)H-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased (3)H-muscimol binding to hippocampus compared to cortex and cerebellum (with a maximum enhancement of 400% of control). As for subunit combinations, honokiol and magnolol have a more potent enhancing effect on alpha2 subunit containing combinations (with a maximum enhancement of 400-450% of control). This action was independent of the gamma subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on alpha2 containing combinations) or the binding affinity (on alpha1 containing combinations) of (3)H-muscimol binding to various GABAA receptor subunit combinations. In contrast, honokiol increased only binding sites on alpha2beta3gamma2s and alpha2beta3 combinations, but both the number of binding sites and the binding affinity on alpha1beta2gamma2S and alpha(1)beta2 combinations. These results indicate that honokiol and magnolol have some selectivity on different GABAA receptor subtypes. The property of interacting with GABAA receptors and their selectivity could be responsible for the reported in vivo effects of these two compounds.

 

http://www.ncbi.nlm....pubmed/11408830

 

It seems like everything is doomed to be a ligand for GABA in some way if it relaxes you... Maybe I'm getting to the point that I don't care. I think I was almost relieved when I read that honokiol is a GABA-A agonist. In fact, I'm pretty sure a sigh of relief moment happened. Relora combined with Bacopa could still reverse the downregulation and lower my dependence on Valium. Every time something is discovered that is said NOT to be GABAergic, it is found later to act through GABA in some way. -_-

 

I'm going to talk the the psychiatrist about oxcarbazepine though. I didn't seem to have any problems with it when I was using it when they thought I was bipolar, it just was quite expensive at 175 a month. Now that I'm on Medicare, it won't be near that much, I just have to get it approved as an exception since I already know I won't tolerate carbamazepine. 

Edited by Ethrem, 13 July 2014 - 06:13 AM.

[Duchykins]

FFFFFFFFFFFFUUUUU!! >.<

A modulator is not necessarily an agonist or antagonist, right?

Magnolia bark is also uniquely dopaminergic, I remember considering it when I wanted to get off bupropion (DNRI), do we kmow anything else about that?

That plus the cortisol action may outweigh risk of reversible GABA downregulation for me... depends on how bad the withdrawals are.

I'm off to google 'relora withdrawal' and see what I get...

[Ethrem]

Benzodiazepines are positive allosteric modulators of GABA-A technically.

 

I'm not sure the extent that honokiol and magnolol modulate GABA. It would appear on paper though that honokiol is significantly more potent than diazepam as an anxiolytic but I'm not versed enough in pharmacology to make a real guess as to what any of this means. I was just pointing out that it does appear that Relora exhibits its anxiolysis via the honokiol in the magnolia extract.

[Duchykins]

I'm fucked no matter what I try, it seems. Relora seemed too good to be true, and now it looks like it's not.

[Ethrem]

I know how you feel. I found out today that magnesium glycinate may actually be harmful to my recovery as well since glycine is a co-factor (both it and glutamate are required) in the activation of NMDA.

 

I think its pretty much a damned if you do, damned if you don't thing. 

 

I am doubtful that things such as valerenic acid in Valerian or honokiol in Relora are actually as harmful as benzodiazepines. After all, they do not bind to the BZD receptor site. People have successfully used Relora to kick benzodiazepines - a friend of mine actually used it in combination with Bacopa, magnesium, and theanine to kick Klonopin. The success stories would seem to show that it is beneficial, not harmful.

[Ethrem]

Well I did some more research... It would appear that honokiol functions as a positive allosteric modulator just like benzodiazepines.

 

 

 

GABAA receptors have a benzodiazepine binding site, and both honokiol and magnolol appear to be positive allosteric modulators (reducing the amount of a ligand required to activate the receptor).[25] Honokiol (5uM) is able to reduce the EC50 of GABA in binding to these receptors from 200-450nM down to 39-79nM and the same concentration of magnolol reduces the EC50 down to 78-89nM.[25] In a set amount of 200nM GABA, honokiol and magnolol have EC50 values at 0.25-0.61uM and 1.1-1.6uM reaching 22-33% and 34-47% respectively[25] and they have failed to inherently influence neuronal activity when not in the presence of an agonist.[26]  

 

http://examine.com/s...ia officinalis/

 

There is actually a lot of collected information on that site and its explained quite well. Magnolia itself just became a rather fascinating study... I wonder if there is added benefit to using Relora over just using a standardized honokiol and magnolol extract, removing the phellodendron entirely?

 

Based on what is said above, it would appear that honokiol and magnolol only exert their properties in the presence of another agonist... Which sounds to me like they wouldn't cause downregulation. I wish I knew more about pharmacology so I could really dive into this.

Edited by Ethrem, 13 July 2014 - 08:03 AM.

[Duchykins]

Relora has antihistamine properties, I did not know this and this makes me like it more, and perhaps I could take it closer to bedtime (I've been taking the second dose no later than 7pm) to help my sleep quality. I look forward to experimenting.


I googled for relora withdrawal and got nothing but relora being used for benzo withdrawal. When I tried using quotes nothing came up, relora addiction, addicted to relora, withdrawal from relora, relora withdrawal, sick after stopping relora, stopping relora... nothing came up indicating gaba downregulation. If people have experienced withdrawal symptoms after ending a relora regimen, not enough are reporting it on the internet.

I'll keep using it in the meantime, I don't think I have a viable choice right now anyway, it's the only thing significantly reducing my anger-anxiety and auditory hypersensitivity, other than lysine and potassium, which a benzo has never done before. I think my problem is more than GABA.

I'm sorry to hear about your glycine issue. Try mag malate? I loved it since day one.

I just changed up my stack again a couple of days ago when the activated B complex from Swanson's came. I think if it was going to bother me like all the other complexes it would have done it the first day. This is the first time trying a B complex that doesn't have synthetic folic acid and has pantethine. I'm relieved to not have to take Bs separately.

[Ampamet]

Just found an anxiolytic that does not act at any GABA receptors called fenobam. It's a mGluR5 antagonist that was discoverd in the 1970s. It's actually made from creatine too. Lately it has been researched for fragile X syndrome and as an analgesic. 

http://en.wikipedia.org/wiki/Fenobam

http://www.ncbi.nlm....pubmed/16040814

http://www.dddmag.co...gile-x-syndrome

http://journals.lww....sm_with.19.aspx (good info in this one, speculation on use for depression, weight loss, chronic pain)

[Ethrem]

I took the Relora last night... What a punch it packed! I ended up sleeping so hard between 1 300mg capsule of Relora and 7.5mg of mirtazapine that I woke up just enough to shut my alarm off this morning and didn't even take my Valium that was due at 8:15AM until 1:47PM just now when I realized it was still in the pill box!

 

This stuff is gold! I'm going to have to start taking it with each dose of Valium I take (I take two 3.75mg doses a day).

 

Fenobam had some interesting discussion on it before but it never really went anywhere so I don't know anyone who has taken it.

[Ampamet]

Yeah fenobam doesn't seem to have gone anywhere for its anxiolytic properties that I can tell. Still might be worth pursuing due to its novel MOA.