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Reversing stress-induced impaired neuroplasticity by pharmaceutical means

afobazole proproten tenoten tianeptine stress depression anxiety plasticity

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#91 Virtual Reality

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Posted 16 December 2013 - 04:11 PM

Dont wanna hijack this thread or anything, but since we are talking about stimulant abuse right here, Id like to ask a question.
I abused stimulants like ritalin, cocaine , dexedrine.

Now I developed tachycardia , really high heart rate in every day situations. (Anxiety, panic attacks)
Ive noticed desorientation, and stumble on my feet every now and then. but this has gone away probably because ive stopped stimulants for a longer period right now
Also Ive became intolerant to GABA agonist like phenibut and alcohol , it makes me drowsey and tired. before i did all these drugs i enjoyed gaba agonists very much.
Anyone can relate? or explainable?


@flex thanks for your advice, ive read good reviews indeed about rhodolia rosea, im gonna order some tonight, maybe ill add some curcumin later.

@formergenius good luck with your protocol, NSI seems very promising! Please keep us updated,

Edited by alex921, 16 December 2013 - 04:36 PM.


#92 Virtual Reality

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Posted 17 December 2013 - 02:09 AM

Regarding to my previous post, ive found this article http://www.sciencema...6153/1521.short
Is it fair to say that cocaine inhibits gaba neurons? Can anyone send me on the right path with this article, it is quite hard for me to understand.

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#93 Flex

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Posted 18 December 2013 - 05:56 AM

Regarding Your panic attacks, I can only assume.

The only thing I know about anxiety is that the PFC sends an inhibitory signal to the Amygdala, which abolishes fear.
Maybe there are a lot of other causes (neurologicaly) but I dont know them.

I´ve noticed this summer the same effects as You regarding GABA.
If I drink Beer or something, it makes me immediately drowsy, unlike in the past where it causes in low doses disinhibition and in high doses drowsiness.

For me its hard too to understand this article(inhibitory NAC gaba which inhibits VAT gaba??), but You seem to be right.

I found this article which underpins the Article You´ve posted.
http://www.jneurosci...6/1385.abstract

Edited by Flex, 18 December 2013 - 06:50 AM.


#94 Virtual Reality

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Posted 19 December 2013 - 09:34 PM

Do you still have that issue what you noticed this summer regarding GABA? And how did you get over it?
Im also planning on taking 83% MDMA, with new years evening. The afterglow people report and the added social benefits which some of them still experience in their life , makes we want to try it.

Edited by alex921, 19 December 2013 - 09:36 PM.


#95 formergenius

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Posted 20 December 2013 - 06:41 PM

MDMA ruined my life in previously unimaginable ways. I suggest you avoid. I rephrase; don't touch with a 10 ft barge pole.

There's a TL;DR at the bottom
Anyway, I'm posting again because I desperately need a game plan. I'm listening to an album now which I heard every day during the time of my life for 6 months, and it's not affecting me in the slightest. No memories, nothing. Tom Waits - Heart of Saturday Night, if it's of interest. Can't even sing along to these songs I've previously thought engraved into my mind.

I really need help. After my cocaine escapade, things went downhill quickly, and now I'm basically retarded.

I've tried almost everything out there, yet so far nothing seems to help. I know nootropics are generally considered for that "extra" edge, but I need more than that.
I need something powerful. Something that can pull me back in to reality.

So far the only seemingly potent substances I've read about are NSI-189, JDTic, and NRX-1074.
Of these, I'll be able to try NSI-189 soon, with a bit of luck JDTic too, but that may take longer.

One of the things that have kept my hopes up thus far, has always been the thought that I haven't tried everything yet.
That perhaps somewhere, out there, there is something that can help me. Now more than ever I need something that actually works, yet simultaneously my options seem to diminish. I feel like I'm standing at the end of the line.

Now I have high hopes for NSI-189 to at least get me back to my previous baseline; not feeling like I'm on the edge of insanity, dementia, or suicide.
That said, I do have constant worries about what I'll do if it doesn't work. I don't see any options past that, and I've lost the cognitive ability to devise new ideas.

Thus ultimately, what I'm asking here for are ideas. What has the best chance of working? Is there anything left to explore beyond what I've tried already?
What's novel? As a previous thread mentioned; all conventional nootropics leave much to be desired for. What holds real potential?

Pardon the drama, but I've had some beers for the first time in months, and honestly this is a cry for help.

TL;DR: If NSI-189 doesn't help me, will anything possibly help me? I'm gasping for hope here..

Thanks to anyone who took the time to read that. Perhaps more appropriate in the Mental Health sub-forum.
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#96 Virtual Reality

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Posted 20 December 2013 - 11:37 PM

in regards with mdma, do you think ONE time could be catastrophic the way you describe? It was a desicion i had to think about for a day or 2. But I think it wouldnt hurt to try it one time. I would like your opinion on ithis.


In reply to your story, Looks where in the same boat, It seems that we have developed a drugs induced panic disorder. Which is quite common.. Its almost a year since I used cocaine and other drugs., and Ive made much more progress. All I can say it takes time, just hang in there. You will get over it,

The substances you mention indeed look very promising.

there is a peptide called FGL , also known as FG look. But I dont know how people respond on that peptide. There is a topic on this forum about it.
There is a substance called D-Cycloserine, but I dont know how effective it is.

Oyeah edit, and exercise helps alot, at least for me

Edited by alex921, 20 December 2013 - 11:54 PM.


#97 Ark

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Posted 21 December 2013 - 12:36 AM

Tenton source????

#98 Sciencyst

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Posted 21 December 2013 - 02:16 AM

@alex921, Chronic amphetamine administration causes disinhibition of the PFC, or basically poor/very reduced GABA signalling. Also you bring up D-cycloserine, which is a partial NMDA agonist. I am currently taking sarcosine, which increases the amount of NMDA co-agonists (NMDA and D-serine) by inhibiting the GlyT1 glycine transporter. Drugs of the same class are being developed for treatment of schizophrenia and OCD. Sarcosine has the same benefit but can't be patented.

I have had extreme success with sarcosine. I regain fine motor control and normal cognition when I take it. Apparently it ameliorates ataxia by intereacting with glutamate receptors and indirectly with dopamine receptors in the cerebellum. The ataxia has been unspeakably bad and this is the only thing that has helped it.

OP, sarcosine could potentially help you, as you did mention motor control issues. It also greatly helps with cognitive problems and will reduce or completely negate any residual psychosis or psychosis-like symptoms (irritability, confusion, weird body sensations, etc)

Also, I really think tetrahydropalmatine is worth looking into. It's a natural dopamine antagonist that works as a very effective anxiolytic and sleeping aid, and should encourage dopaminergic upregulation. I've currently been helped the most by sarcosine and bacopa, but I still feel a long way from normal. THP is next on my list to try.

Also, I want to note that the guanfacine is complete garbage and the somatic side effects far outway any psychiatric benefits. I also tried prozac and had a severely bad reaction a few days in with guanfacine and focalin which caused extreme tachycardia, ataxia, inability to control my muscles, weakness, etc. It was literally the scariest thing I've ever experienced. I have zero motivation each day, so I have tried to take the focalin a few times but it just makes me really really sweaty, anxious, fogbrained and irritable, and oddly makes me have to poop immediately after I take it. Vicodin has helped but I can't go down that path. I tried to pickup smoking again in hopes it would help but it just made things worse. I even tried cannabis a few times again but was extremely sensitive and it brought back the exact same sensations of MXE, however this didn't happen when I took sarcosine beforehand.

So maybe try looking into THP and/or sarcosine.

Edited by katuskoti, 21 December 2013 - 02:46 AM.

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#99 formergenius

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Posted 21 December 2013 - 08:50 AM

@alex92: Yes. One time did most of this to me. Then again; I hate to be scaremongering. Not everyone gets such long-lasting detriments from single MDMA use, though if you look around you'll see I'm not the only one. YMMV; I remember my first time on MDMA I walked out of it with no problems. Though if I had known at the time that this was even possible, I wouldn't have done it. I'd suggest at the very least that you get higher purity (confirmed, not just a say so) if you must try it, roll safe and use the lowest dose possible. Yes, I forgot to mention FGL, thanks. As for D-cyclo; been reading about it, but appears it may hold psychotomimetic effects which is not what I'm after. NMDA agonism however does remain an interesting avenue applicable to my symptoms; hence the interest in NRX-1074. Have you tried tDCS yet?

@Ark: Yes, I'll PM you in a bit soon as I find the receipt.

@katuskoti: Yes thanks! Totally forgot about Sarcosine. I have some which I don't trust, so I'll be ordering from SP in a minute and try that batch. Is this your source as well? I'll keep the THP in mind should that not help. Sorry to hear about your experience with Guanfacine; on paper it looked pretty nifty, but in practice indeed it seems disappointing. edit: Appears SP has Sarcosine out of stock, again. Ideas?

Thanks for the replies guys. No more beer for me though, haha.

Edited by formergenius, 21 December 2013 - 09:00 AM.


#100 3AlarmLampscooter

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Posted 21 December 2013 - 09:57 AM

Everyone talking about taking MDMA more than very occasionally at very low doses, stay away from it.

There are newer, non-neurotoxic drugs with the same effects that have been developed over the last couple decades by Nichols' at Purdue (see MDAI, MDAT, MDMAI, MMAI... etc)

I've personally tried MDAI, and can vouch for it being a good entactogen if you can obtain it in pure form.

MDMA is a revolutionary, but also old, outmoded and relatively dangerous drug. I'd compare it to Nichols' new entactogens the same way I'd compare Haldol to the latest atypical antipsychotics.
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#101 formergenius

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Posted 21 December 2013 - 04:29 PM

Very good points Scooter.

I have some Sarcosine 98% pure, but I bought it from a chemical reagent company, and it states "For laboratory use only".
Would it be a bad idea to go ahead and consume this? Smartpowders is out of stock, and ProFrontal.com doesn't ship this country.

#102 Sciencyst

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Posted 21 December 2013 - 07:06 PM

^ It would be fine to consume, probably more so than the sarcosine from SP. Lab use translates (for me at least) to much safer to consume than anything made for industrial use.

But yes, mine was from SP. When I ran out I got some on eBay but now I just have to wait for SP to restock, which I plan to email them about.

#103 Virtual Reality

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Posted 21 December 2013 - 08:12 PM

@alex921, Chronic amphetamine administration causes disinhibition of the PFC, or basically poor/very reduced GABA signalling. Also you bring up D-cycloserine, which is a partial NMDA agonist. I am currently taking sarcosine, which increases the amount of NMDA co-agonists (NMDA and D-serine) by inhibiting the GlyT1 glycine transporter. Drugs of the same class are being developed for treatment of schizophrenia and OCD. Sarcosine has the same benefit but can't be patented.

I have had extreme success with sarcosine. I regain fine motor control and normal cognition when I take it. Apparently it ameliorates ataxia by intereacting with glutamate receptors and indirectly with dopamine receptors in the cerebellum. The ataxia has been unspeakably bad and this is the only thing that has helped it.

OP, sarcosine could potentially help you, as you did mention motor control issues. It also greatly helps with cognitive problems and will reduce or completely negate any residual psychosis or psychosis-like symptoms (irritability, confusion, weird body sensations, etc)

Also, I really think tetrahydropalmatine is worth looking into. It's a natural dopamine antagonist that works as a very effective anxiolytic and sleeping aid, and should encourage dopaminergic upregulation. I've currently been helped the most by sarcosine and bacopa, but I still feel a long way from normal. THP is next on my list to try.

Also, I want to note that the guanfacine is complete garbage and the somatic side effects far outway any psychiatric benefits. I also tried prozac and had a severely bad reaction a few days in with guanfacine and focalin which caused extreme tachycardia, ataxia, inability to control my muscles, weakness, etc. It was literally the scariest thing I've ever experienced. I have zero motivation each day, so I have tried to take the focalin a few times but it just makes me really really sweaty, anxious, fogbrained and irritable, and oddly makes me have to poop immediately after I take it. Vicodin has helped but I can't go down that path. I tried to pickup smoking again in hopes it would help but it just made things worse. I even tried cannabis a few times again but was extremely sensitive and it brought back the exact same sensations of MXE, however this didn't happen when I took sarcosine beforehand.

So maybe try looking into THP and/or sarcosine.

Nice info about the substances ,they look very interesting, and im thinking of ordering sarcosine soon.



You stated that chronic amphetamine causes disinhibition of the PFC, or reduced GABA signalling, is this something that can be reversed? Or will it perhaps normalize over time?

#104 Flex

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Posted 21 December 2013 - 10:04 PM

@ alex921

I also wouldnt recommend MDMA ( if You ask me)

Even pure MDMA causes damage to neurons.
You can investiate it at ncbi.gov Pubmed, the animals in the Study get allways fed with pure MDMA

I´ve tried MDAI and I wasnt very excited about the effect. You dont get the Prosocial effects like from MDMA, the felling is more similair to that of Antidepressants instead of MDMA.
Furthermore the big problem regarding the Research Chemicals is, that nobody knows what they affect in Your body, (like changes of the epienetics or something else) beside the primary effect,
even today the researchers disover new mechanisms of 20 year old Medicines, who are either good or bad.

Mushrooms could be, in my view, a healthy alternative. They could cause good effects rearding anxiety and depression,
http://www.theguardi...reat-depression
but could cause also anxiety or panic attacs ( which would afaik last maximal 1 year after consumption, due 5-ht2a/c modulation)

#105 Flex

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Posted 21 December 2013 - 10:41 PM

I´ve bought in the past Testforce 2 as a Sarcosine source.
Scitec D-Test would be an alternative, but both are expensive in contrast to bulk powder.

The source where I get THP from, is Corydalis Yanhusuo extract from herbal remedies.

Its indeed a Neuroleptic but it also have accute effects on the presynaptic dopamine autoreceptors, like Amisulprid.
It affects all dopamine receptors and adrenergic alpha1, but not 5-ht receptors afaik, and is under investigation for Cocaine addiction because of the stroner D1receptor occupancy than D2 (regarding ncbi.gov). but it could also be benefical to amphetamine psychosis because of the D3 occupancy.

@ formergenius Im really sorry for Your situation.
If You find something new I will let You know.

As for Your desperate situation:
Look if we were born 30 or 50 Years ago, well then we wouldnt have great expetations of healing.
but we live now in a time where the Neuro science rises well. as an example, it is said that in about 15 Years the medicine could provide a stemcell therapy.
and this apart from the discovery of new substances and such.

Regarding NSI-189, if this induces the differentiation of Stemcells, this would take time. because there are 2 areas in the Brain that contains Stemcells( a part of the Hippocampus and a part of the olfactory bulb, and maybe some areas in the Pfc)
So immigration form these areas to the damgaged ones would take Time.

Furthermore the Brain is more capable of self renewal than we believe
http://www.newscient...ml#.UrYTbfv5_lc

Edited by Flex, 21 December 2013 - 11:04 PM.


#106 Flex

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Posted 21 December 2013 - 11:59 PM

Do you still have that issue what you noticed this summer regarding GABA? And how did you get over it?
Im also planning on taking 83% MDMA, with new years evening. The afterglow people report and the added social benefits which some of them still experience in their life , makes we want to try it.


It seems that this went (nearly) back to baseline.

I dont know what helped, if any.
Maybe the brain was it itself, or the different things that I´ve used.

This was Berberine, Gotu Kola, Quentiapine, Lithium Ororate, Amitryptiline, Mitrazepine and sometimes Fishoil.

Btw regarding Antidepressants caused neurotixicity, I´ve posted something about it in the Cerebrolysine thread.

#107 Flex

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Posted 22 December 2013 - 01:57 AM

@ Formergenius

this is a factor who improves/controls cell migration
stromal cell-derived factor-1
http://www.ncbi.nlm....pubmed/23392917

Just type at ncbi neurorestorative in, and You find:
http://www.ncbi.nlm....pubmed/23050817
http://www.ncbi.nlm....pubmed/20035795
http://www.ncbi.nlm....pubmed/23416149
http://www.ncbi.nlm....pubmed/23394537

So everthing what helps for traumatic Brain Injury or Stroke, could be benefical for You.

Btw Cerebrolysin is also Neurogenic regarding:

http://www.ncbi.nlm....pubmed/17131129

CEREBROLYSIN IN TBI: A PILOT STUDY OF A NEUROTROPIC AND NEUROGENIC AGENT IN THE TREATMENT OF ACUTE TRAUMATIC BRAIN INJURY
as PDF
http://www.google.de....58187178,d.Yms

#108 formergenius

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Posted 22 December 2013 - 12:52 PM

Good points on the advancements in neuroscience Flex; indeed if there's ever a time to be utterly neurologically screwed, now is the time.
As for NSI's MoA; I believe it remains unclear how exactly it induces neurogenesis, but indeed it may take a couple of weeks. 2 months, however, should be sufficient to gauge efficacy.
Perhaps if I'd continued with Cere, I would've started seeing results, but with NSI around the corner, daily oral dosing seems preferable if I must use it chronically.

From what I can collect, Cerebrolysin improves neurogenesis by inhibiting neuronal apoptosis, but does not actually spark neurogenesis. I could be wrong there though, but Cere doesn't seems particularly potent as a neurogenic agent.

I'll be starting Sarcosine tomorrow.

#109 jakord

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Posted 22 December 2013 - 02:09 PM

Also, I really think tetrahydropalmatine is worth looking into. It's a natural dopamine antagonist that works as a very effective anxiolytic and sleeping aid, and should encourage dopaminergic upregulation.




Dopamine antagonists cause downregulation, although it seems counterintuitive.

#110 turchin

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Posted 22 December 2013 - 05:58 PM

Formergenius, I have bad news for you. The problem with your brain is most likely with program not with the chemistry. Your messages are still messages of very clever man and «brain dead« just can't write them. But the main goal of your brain is to prove to you that you are brain dead. This is the main goal that you put for it. And in last years it was excellent in demonstrating symptoms. It was genius in performing command "I am brain dead". It even was able not to react to strong chemical when you were megadosing.
It still has ability to learn - all this new information about chemistry and supplements and doing so it deleted useless information about music and other memories. You still in 1 per cent cleverest people on the Earth.
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#111 formergenius

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Posted 22 December 2013 - 07:52 PM

Thanks turchin for trying to make me feel better, but in essence what you're saying that my problems are imaginary, when this is not the case. Plus my main goal is getting better, not confirming that I have a neurological problem. Regardless of whether or not there is a physical origin to my problems, psychological approaches have done little to mitigate them, despite continued efforts. As such I believe my pharmacological endeavours are the most logical approach, regardless of etiology.

Edited by formergenius, 22 December 2013 - 07:52 PM.


#112 turchin

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Posted 22 December 2013 - 08:58 PM

I suggest to take IQ test and put result here :) It would be objective measure of the damage to your brain.

#113 formergenius

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Posted 22 December 2013 - 09:36 PM

60% Mensa test. I once had ninety-something percent on that test.

Edited by formergenius, 22 December 2013 - 09:36 PM.


#114 turchin

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Posted 22 December 2013 - 10:52 PM

In fact, I think that it is better to have slow engine driving in right direction, than fast car going directly to the wall. Anyway you are in the top half of people in IQ. By the way I think that we need a measure of «general effectiveness« vs. general intelligence. While with aging IQ is normally declining, effectiveness sometimes is growing. I even know some tricks how to get more from less IQ. One of them is to do each task slowly and check the result many times.

By the way if you not reacting on most supplements your liver may be very effective in digesting them - you have trained it. But also liver problems could induce a liver coma or some cognitive decline because of constant toxication in mild cases. Did you check your liver enzymes level?

#115 Flex

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Posted 26 December 2013 - 05:45 PM

This one´s are for the Hope:
Japan Makes Advance on Stem-Cell Therapy
http://online.wsj.co...571363010820642

New method of convertion of Glial cells to working Brain cells !
http://news.psu.edu/...jury-alzheimers

for more info read:
Capacity to divide
http://en.wikipedia....acity_to_divide

Source of New Oligodendrocytes
http://en.wikipedia...._precursor_cell

#116 formergenius

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Posted 26 December 2013 - 06:03 PM

Thanks Flex. Yeah I read about the NeuroD1 retrovirus... Would be kind of hard to get a group buy for though if in vivo studies ever show promise.

Oh, and no turchin, I have not checked my liver enzymes. I doubt it has anything to do with my liver metabolism though. Besides 2 beers get me pretty intoxicated, that's not exactly indicative of heightened metabolism rate AFAIK.

Edited by formergenius, 26 December 2013 - 06:04 PM.


#117 Sciencyst

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Posted 27 December 2013 - 11:44 PM

Nice info about the substances ,they look very interesting, and im thinking of ordering sarcosine soon.



You stated that chronic amphetamine causes disinhibition of the PFC, or reduced GABA signalling, is this something that can be reversed? Or will it perhaps normalize over time?

Hmm well I haven't found anything that has been shown to specifically normalize GABA in the PFC, but I know bacopa seems to regulate the GABA system to an extent (at least in pilocarpine-induced-epilepsy), but ideally something more selective could be found. I'll start looking around for mechanisms of regulating the pfc, and I'll attempt to develop a more detailed understanding of chronic amphetamine's effects in inhibitory neurotransmission, etc. It's easy to point to things that acutely fix lack of GABA such as benzodiazepines, but so far I have found little about repairing such damage permanently, aside from bacopa

#118 Reformed-Redan

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Posted 28 December 2013 - 12:11 AM

Nice info about the substances ,they look very interesting, and im thinking of ordering sarcosine soon.



You stated that chronic amphetamine causes disinhibition of the PFC, or reduced GABA signalling, is this something that can be reversed? Or will it perhaps normalize over time?

Hmm well I haven't found anything that has been shown to specifically normalize GABA in the PFC, but I know bacopa seems to regulate the GABA system to an extent (at least in pilocarpine-induced-epilepsy), but ideally something more selective could be found. I'll start looking around for mechanisms of regulating the pfc, and I'll attempt to develop a more detailed understanding of chronic amphetamine's effects in inhibitory neurotransmission, etc. It's easy to point to things that acutely fix lack of GABA such as benzodiazepines, but so far I have found little about repairing such damage permanently, aside from bacopa

Check this thread:
http://www.longecity...ic-supplements/

#119 formergenius

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Posted 28 December 2013 - 12:24 AM

Of those; I'd go with Jiaogulan if I were to try any of them.

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#120 Reformed-Redan

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Posted 28 December 2013 - 12:27 AM

Of those; I'd go with Jiaogulan if I were to try any of them.

That's what I make my black tea with every morning.





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