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Reversing stress-induced impaired neuroplasticity by pharmaceutical means

afobazole proproten tenoten tianeptine stress depression anxiety plasticity

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#61 Flex

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Posted 22 November 2013 - 01:47 PM

Didnt saw your post.

Thanks for the advice.

I guess I understand Your point of view.
Some people, as example, who are neurotic and are too insistent to them self and/or in they toughts, do sometimes need a vacation from "they selves".
because their behaviors are seeming to be a kind of obsessive ones, and they dont know that.
this could cause stress and etc.

So, yeah to be honest this describes me sometimes. And this is why the trick in my previous post helped me.

But nevertheless something has changed since the time of EP usage.
I have tried 3,4 dcmp as well to find out if the pain was limited to EP but It caused to me the same pain again and made it for weeks worser.

further when I took Lavender tea, which was unproblematic before the EP, it made it worser.

So I (guess) I understand your point of view, but it unfortunaetly dont seems to be the caues ( I wish it would)

Edited by Flex, 22 November 2013 - 02:01 PM.

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#62 formergenius

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Posted 22 November 2013 - 01:55 PM

So I got my LongVida in today.. Took one capsule about an hour ago with 1.2g NAC. Still feeling extremely dissociated, but of course I can't expect changes to occur so swiftly, though oh how I would love it to be so.

I also received my Afobazole today, which I am eager to try, however I wonder if there are any interactions with Curcumin?
Both having slight MAO-A inhibitory properties, I wonder whether there would be any tyramine interactions with the two combined?
Any input on this would be appreciated.

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#63 Flex

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Posted 22 November 2013 - 02:17 PM

You shouldnt have to worry about reversible mao´s.

this is olnly the case for the irreversible ones.
or maybe high inhibition of mao
(correct me if Im wrong)

but if you want to be certain:

tyramine rich foods
http://www.erowid.or...ois_info2.shtml

but instead bringing the prophet to the mountain you could bring the mountain to the prophet:

eat your usual food and increase day by day the ammount of Afobazole, and look out for side effects.

What are the symptoms? Excessive levels of tyramine can cause headache, palpitations, nausea, vomiting, and hypertensive crisis (dangerously high blood pressure)
http://www.truestarh...iet-Indications

again, at least for me there is nothing to worry

Edited by Flex, 22 November 2013 - 02:17 PM.


#64 formergenius

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Posted 22 November 2013 - 10:03 PM

Thanks for reminding me of the reversibility Flex.
I proceeded to take Afobazole 10mg today as well.. Nothing special to report. Meanwhile I've ordered an Aniracetam sample because I've become an impatient bastard. Removed Resveratrol as it was giving me headaches; something very rare for me.

Now, I wonder about adding Aniracetam.. Interactions? Maybe best to cycle Afobazole and Aniracetam?
I'd like to try as many things as possible without interactions, and then remove accordingly.. Seems it would be faster that way.
Isolating the benefactor only becomes important when there is in fact a benefit, for now it seems.

#65 Virtual Reality

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Posted 22 November 2013 - 10:48 PM

I took aniracetam yesterday and I noticed a subtle improvement and felt calmer, but it could have been placebo.
@formergenius , have you tried lithium Orotate? i might order it...

#66 formergenius

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Posted 22 November 2013 - 10:58 PM

Interesting Alex.. what dose was that?
No I have not.. I don't see how that would be beneficial.

#67 Virtual Reality

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Posted 22 November 2013 - 11:12 PM

I purchased my order from denkbeter , i measured my dose with a spoon (which was included in the package, make the spoon with aniracetam smooth) In total it was about + - 600 mg.
Im not enterilly sure , but I thought lithum has some beneficial effects on dopamine(d2 ??)

#68 GetOutOfBox

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Posted 23 November 2013 - 04:33 AM

You mentioned you gave Noopept a try and didn't notice much. Which vendor did you get it from? There are a few vendors who have recently been found to be very shady (Cerebral Health,a longecity sponsor was found to be shipping several fake products, and some sort of likely neurotoxic recreational research chemical as pyrinitol, likely accidentally. The theory is that the owner was running Cerebral Health as a front for illicit drug importation, and that he accidentally mislabeled one of the recreational drugs as pyrinitol and shipped it out. Another possibility is that his source was doing that accidentally sent him the drugs. Still his fault that he seems to have not been quality controlling any of his products). Also, the otherwise amazing New Star Nootropics accidentally sent out a "dud" batch of Noopept a few months back (a reddit thread correlated several non-responding redditors and a particular batch of NNN's noopept). It seemed to be inert, producing no discernible effects, negative or possitive. You can tell if you have the dud thanks to NNN's diligent labeling, batch NS183 was affected.

My point is that for brain damage, Noopept is one of the best there is. Increasing BDNF and NGF will directly assist regrowing synaptic pathways and rescuing damaged neurons. The main benefits are not acute however, to really see if there's an improvement, especially when you're talking about brain damage, you need at least a month of regular use, perhaps two. I would seriously advise trying it again. My personal source recommendation is New Star Nootropics, they're one of the most trustworthy vendors, but that's just me. There are several good vendors, just make sure you research your choice before buying, to see if a lot of longecity/reddit users have had a positive experience.

I would also try Uridine (the UMP form is ideal, can be purchased from Superior Nutraceuticals) and fish oil together, as this combo would be ideal for restoring damaged cells in the brain (increasing cell membrane fluidity and synaptic branching). Uridine also serves to modulate dopamine, which might help to stabilize the dopaminergic pathways if they have indeed become dysregulated as a result of amphetamine abuse.

Bacopa would be ideal for restoring serotonergic dysfunction, just be careful you get a reliable source. Herbal supplements are very hit and miss, as there is little if any regulation of the quality of plant matter in the supplement. AOR are expensive, but generally a good brand.

#69 formergenius

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Posted 23 November 2013 - 10:50 AM

@Alex:
Thanks! I figure I'll try a 750mg dose when it gets here. As for lithium; I'm not sure. Maybe someone else can comment on that.

@GetOutOfTheBox:
Thanks for that elaborate reply! I purchased my Noopept from Intellimeds.co.uk around last year. At that time, I was attempting to attend school (failed miserably), hence I did not give it a proper trial for I wanted immediate results. I still do, who doesn't, but if it's something I can take w/o interactions I'll be happy to add it to my stack. Speaking of NGF and BDNF, I forgot that I also have LMM, which I'll add into the mix for long-term benefits.

As for UMP; how is this product? As for Bacopa.. I'll think about it, but I don't think I will add it.
In the meantime I've been considering adding Cerebrolysin, something I had previously avoided due to its RoA.
Maybe it would serve me well to give it a month's cycle, by that time NSI-189 should (almost) be in my hands.

So far my stack looks like this:

Morning:
2 x B-50 complex
1gram Ascorbic Acid
100mg CoQ10
10.000 IU D3
1 cap CurcuViva LongVida (80mg Curcumin)
1.2g NAC
10mg Afobazole

Afternoon:
10mg Afobazole

Night:
100mg Niacin
2.5g LMM
1 cap CurcuViva LongVida
1.2g NAC
Full-skull LED 30sec/spot every other night

Suntheanine as needed, and soon to add Aniracetam 750mg (if no interactions :/).

Possibly adding Noopept, Fish Oil, UMP. I think now I should seriously start looking in to interactions.. Any thoughts on this would be very appreciated.

Edited by formergenius, 23 November 2013 - 11:33 AM.


#70 BioFreak

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Posted 23 November 2013 - 11:27 AM

I would increase it to two longvida caps / day, in the morning and evening, together with nac. Amyloid reduction was reported with 400mg/day in healthy subjects, I've had the best result so far with 500mg 2x/day. (morning and evening)

I'm sorry to hear you had no immediate effects from the combo as I did, so that'll reduce the chance of inflammation as a cause, it'll still help regenerate your brain, but this of course will take longer. Adding a choline source and o3's might be a good idea now. If your brain is indeed healing, it'll need the proper building blocks to do so. And since this is part of the uridine stack, this would be a great time to add uridine, too.

#71 formergenius

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Posted 23 November 2013 - 11:35 AM

Yes indeed a pity, but who knows what might happen in due time. Have updated the regimen to include 1 more Nacurcumin dose at night.
Thanks again!

#72 Flex

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Posted 23 November 2013 - 05:36 PM

Back in 2008 after Risperidone I´ve tried this:

Pantocrine
..Russian scientist, Dr. Taneyeva,..claiming that the mental capacity of a group of young men was improved significantly following pantocrin administration prior to a mathematical test
http://www.bonniebra...lvet_antler.php

The results were similair (moderate) like Humanobol

but with a more effect in Adrenaline( and agression, at least for me)

#73 Sciencyst

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Posted 24 November 2013 - 05:41 AM

@3AlarmLampScooter: Thank you; I was considering this for a long time as well (particularly Propranolol), however I already have low BP, hence I doubt it would be a good idea. This is why somewhere in the above posts I think I've mentioned Guanfacine, as it has less potent BP effects. However, this doesn't seem a realistic option for me.

EDIT: No, I don't drink alcohol.
EDIT 2: This is pretty convincing in regards to curcumin, however I don't know whether conflict of interest is playing a role.


I have a prescription waiting to be filled for Guanfacine. I'll try to fill it and let you know if it's helpful. As far as adrenergic (beta) blockers go, they were slightly helpful.

I have been feeling dramatically better the past few days due mainly to bacopa monnieri, ubuquinol, 5-HTP, UMP, & sarcosine .

Remember that sometimes the cause can be more obvious and more immediate than one would like to admit (due to emtional scarring/trauma like mentioned above).

I've recently found that much of my symptoms are psychogenic and can be rapidly resolved through breathing and calming my hyper-emotional thoughts.

An example: yesterday a new co-worker bummed me a cigarette, and I felt different than I normally would after smoking. It somehow induced a panic attack and I thought I had been poisoned or something; I felt warm and close to fainting, and anxious.. I caught my self and turned around my thought process. The feelings vanished after about 10 minutes, and I just laughed at myself for believing my fear response. In retrospect, the thought came first, and the panic came second.

EDIT: I also just recalled THP, or tetrahydropalmatine, from the corydalis plant. It's a dopamine antagonist, and could be used as an herbal anti-psychotic-like medicine. It has a wide range of potentially useful actions in this case. Also of interest recently is rosemarinic acid, which is a GABA transaminase inhibitor, the equivalent of acetylcholinesterase inhibitor (AChEI) but which leads to increases in GABA.

Edited by katuskoti, 24 November 2013 - 06:26 AM.


#74 formergenius

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Posted 24 November 2013 - 09:29 AM

@Flex: Interesting.. but that's not for me.

@katuskoti: Thank you. Yes I won't deny that there's also a psychological factor, however I do believe there's a neurological factor that's limiting my ability to properly process such things. I'll look in to rosemarinic acid; sounds like an interesting anxiolytic.

Meanwhile I've ordered 200ml Cerebrolysin and will use that for 4 weeks.

#75 Sciencyst

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Posted 02 December 2013 - 09:22 PM

Have you gotten then cerebrolysin yet? If so, how is it?

I just filled my script for guanfacine but also gave in and went back on prozac, which may interfere in judgment of its effects. I'll tell you how the guanfacine seems on its own though.

#76 formergenius

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Posted 02 December 2013 - 09:53 PM

Yep. Day 3 today (doing 2 x 5ml in the morning, 5 days on, 2 off). Too early to comment.. not sure of effects, though I've noticed some things. Nothing to go on a profound rant about yet though, seeing as I'm very spaced out at the moment again. Hoping it'll become apparent over the next few days.
Ordered some UMP, and some night-vision (anti-glare) glasses in an attempt to mitigate visual distortions (which get worse at night it seems). Other ideas I have are few and currently unavailable.

Good luck with the guan!

#77 Babychris

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Posted 03 December 2013 - 07:54 AM

Flex and Outthebox gave you some good advice.

Furthermore as I've told you, stick with the minimum of supplements. Since I'm pretty sure and without offensing anyone that most of us are equally suffering from potential physical condition than some mental issues. To be honest I think with some clue in my bag that many here have more of an addict problem than mercury poisoning haha.

So you seem to respond pretty bad to a lot of supplements (like me) it's kind of a psychological response or just that your body is very tightly build and can't bear that some pretty hasardous chemicals try to take place in that smooth body.
Nevertheless you might need some extra help AND I'M PRETTY SURE that a consistent use of Noopept coupled with some Lion's mane and a combo of Fish Oil and maybe a bit of choline/Uridine would be very beneficial for some obvious reason. But you need to put a goal and get this with consistent desire to advance straight in the experience.

Nota Bene ; Noopept sounds the best on paper and when it works it's not far from truth. It could restore some emotion and cognitive function dramatically. It could be really strong and give you negative side-effect though. But i'm pretty sure that after 2 weeks (which is long I have to admit) you would see some benefits. Personnally I've added some piracetam which become funnier day after day.

#78 Sciencyst

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Posted 05 December 2013 - 02:40 AM

to take place in that smooth body.


This made me lol

I added some piracetam which become funnier day after day.

What do you mean by funnier?

#79 Virtual Reality

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Posted 06 December 2013 - 01:08 AM

Regarding of VMAT2 I found this:

http://www.ncbi.nlm....pubmed/12921866
Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration.
...Specifically, pramipexole rapidly increases vesicular dopamine uptake in synaptic vesicles prepared from striata of treated rats.
This effect is: (1) associated with a redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity within nerve terminals
The implications of this finding relevant to the treatment of neurodegenerative disorders are discussed.

http://www.ncbi.nlm....pubmed/12007678
Chronic clozapine, but not haloperidol, treatment affects rat brain vesicular monoamine transporter 2

http://www.ncbi.nlm....pubmed/17693585
Methylphenidate administration alters vesicular monoamine transporter-2 function in cytoplasmic and membrane-associated vesicles
...and they may have implications regarding treatment of disorders involving abnormal DA disposition, including Parkinson's disease and substance abuse.

http://www.ncbi.nlm....pubmed/12604695
Methylphenidate alters vesicular monoamine transport and prevents methamphetamine-induced dopaminergic deficits.

Btw:Pramipexole can cause addiction, psychosis etc
and Clozapine needs to be monitored weekly (blood test)

And this ive found to be my case:
Collectively, these findings suggest that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

and this maybe the cause:
demonstrates that a single, low-dose injection of methylphenidate (2 mg/kg, s.c.) reduced VMAT-2 immunoreactivity in the synaptosomal membrane (P3) fraction while increasing it in a non-membrane-associated (referred to as cytoplasmic, S3) fraction. In contrast, a single low-dose administration of amphetamine (2 mg/kg, s.c.) decreased VMAT-2 immunoreactivity in the cytoplasmic (S3) fraction
http://www.ncbi.nlm....les/PMC2581712/

I dont know how much is damage and how much is disregulation.
I hope i can reverse it as much as possible

PM me if you want to know a Pramipexole source

Lithium(orotate) also upregulates vmat2

Edited by alex921, 06 December 2013 - 01:34 AM.


#80 Flex

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Posted 06 December 2013 - 04:22 AM

Thanks a lot alex,
I know that Lithium does it but only in the pfc, amygdala and substancia nigra pars compacta.
But not in the striatum (especially in the caudate!) as far as i know.

Its difficult for me to find anything in ncbi.gov that affects the vmat in the striatum

#81 hani

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Posted 07 December 2013 - 09:14 AM

I think your problem OP that you're not giving each medication enough time to repair your brain and induce enough neurogenesis that gets you back to normal. Tianeptine for example is proven to reduce reverse the stress-induced decreases in hippocampal volume.

From the literature it seems that, amongst the antidepressants, tianeptine has been the most extensively investigated for its prominent and consistent protective effect against stress induced neuronal remodeling.


http://www.ncbi.nlm....les/PMC2902200/

Changes in the brain structure take time, you might have to consistently take a medication for a year or more to get results. I also think NSI-189 seem to perfectly fit your case, as it might induce neuroplasticity significantly quicker than tianeptine.



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#82 formergenius

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Posted 07 December 2013 - 11:28 AM

Thanks hani, indeed I don't tend to stick with one thing at a time it seems.
However, now I am giving Cerebrolysin a month long trial, surely this should be sufficient to notice at least some benefits?
My plan was that if Cere doesn't prove to be effective, that I'm going to trial NSI-189 for as long as 5 grams last me, which is at least a month, more like 2. Certainly 3 months of such potent substances should do the trick? Or so I hope.

BTW: 1 week in to Cere, no benefits to report yet, but I'll keep at it. Week 2 starts today, so I'm off to inject myself.

Edited by formergenius, 07 December 2013 - 11:28 AM.


#83 hani

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Posted 07 December 2013 - 12:12 PM

Honestly, so far, the only two substances that are proven to reverse stress induced impaired neuroplasticity as you put it are tianeptine and NSI-189. I haven't read much about Cerebrolysin. Here's a very extensive study on tianeptine:
http://www.ncbi.nlm....les/PMC2902200/

It seems like a perfect wonder drug. I myself suffer from anxiety and in my family there's a history of mood disorders (bipolar i & ii). I am going to try and get a prescription for it next week. It seems like it will help with anxiety as well as sort of protect me from developing a mood disorder:
http://www.jaoa.org/.../111/4/298.full

I wish you gave it more time, as it could have been certainly worth while. You said yourself before:
http://www.longecity...ptine-duration/

That you would try to take it for a year. It just doesn't make sense to take it for a couple of months and stopping it, considering it took many years of stress and abuse for your brain to reach its current state. Good luck with your condition and I will keep you updated if I get a prescription for it.

Edited by hani, 07 December 2013 - 12:13 PM.


#84 magniloquentc0unt

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Posted 07 December 2013 - 01:41 PM

I have taken tianeptine for 6 months. while on it at first i didnt feel much, then i noticed good effects on anxiety and motivation, then it plateaud and i tought it pooped out. After 6months i stopped cold turkey. I felt it had a slight anticholinergic effect, and it made me slightly dumber and less accurate in how i expressed myself, also a lot of "tip of the tongue" moments etc. After ive been off of it, i must say i feel much better than i used to feel before going on it. I think it is a good antidepressant but not as good as people on these forums think it might be, aka no silverbullet
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#85 Flex

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Posted 15 December 2013 - 06:25 AM

I´ve recently read about potential causes of Dopamine delpetion for me and found out that Amphetamine increases the ammount of alpha-synuclein.
http://www.ncbi.nlm....pubmed/23743292
Its something like beta amyloid plaque, who agreggates(but could be degradated/reduced by the body it self) in or at Neurons and causes distruption of neurotransmitters.
http://www.jneurosci...8/3090.abstract
http://www.ncbi.nlm....pubmed/22941029

I found out that those herbs reduce or reverse the alpha-synuclein content
http://www.iospress....eimers-disease/
http://www.ncbi.nlm....pubmed/22113202

http://www.ncbi.nlm....les/PMC3690243/

I´ve allready ordered them for me from a UK shop (originated from Taiwan), but I´m worried about the possible Pesticide/Heavy Metal content
http://www.foxnews.c...bs-safe-to-use/
although mine are form Taiwan, but who knows. I´m trying to get an offer for a cheap labor analysis(HLPC etc)

Btw M30 could be interresting :
Promises of novel multi-target neuroprotective and neurorestorative drugs for Parkinson's disease.
http://www.ncbi.nlm....pubmed/24262165
I´ve posted allready the (alleged) structure in a topic

#86 Virtual Reality

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Posted 15 December 2013 - 01:56 PM

I found a interesting thread http://www.bluelight...on-amphetamines
So far ive tried lithium orotate, in the link above they were talking about that lithium could upregulate vmat2, and d receptors.
The studies were related to lithium, at the moment I am taking lithium orotate, and im not quite sure if it will work the same.

So far ive been taking lithium orotate for 4/5 days, I cant recall any positive changes, It makes me very sleep , tired.

I´ve recently read about potential causes of Dopamine delpetion for me and found out that Amphetamine increases the ammount of alpha-synuclein.
http://www.ncbi.nlm....pubmed/23743292
Its something like beta amyloid plaque, who agreggates(but could be degradated/reduced by the body it self) in or at Neurons and causes distruption of neurotransmitters.
http://www.jneurosci...8/3090.abstract
http://www.ncbi.nlm....pubmed/22941029

I found out that those herbs reduce or reverse the alpha-synuclein content
http://www.iospress....eimers-disease/
http://www.ncbi.nlm....pubmed/22113202

http://www.ncbi.nlm....les/PMC3690243/

I´ve allready ordered them for me from a UK shop (originated from Taiwan), but I´m worried about the possible Pesticide/Heavy Metal content
http://www.foxnews.c...bs-safe-to-use/
although mine are form Taiwan, but who knows. I´m trying to get an offer for a cheap labor analysis(HLPC etc)

Btw M30 could be interresting :
Promises of novel multi-target neuroprotective and neurorestorative drugs for Parkinson's disease.
http://www.ncbi.nlm....pubmed/24262165
I´ve posted allready the (alleged) structure in a topic


great findings!

So you have ordered isorhynchophylline and polyphenols, right?

I would like to know how this went for you.






#87 Flex

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Posted 15 December 2013 - 06:35 PM

Thanks :)

I tr to help if I can. I do some research anyway for my self, so therefore it isnt a big thing either to investigate for others.

No, I´ve ordered Plant extracts from: Uncaria Rhynchophylla aka Gou Teng - Uncaria Stem With Hooks,
Polygonum Multiforum( Fo Ti) and Scutellaria Baicalensis Georgi.

I´ve allready get a CoA from the distributor but it was only tested for Heavy Metals and Bacteria but not for Pesticides.
So therefore I trying first to get a cheap offer for pesticide analysis before i try it.

Btw: I noticed a lasting improvement after ingestion of Rhodiola Rosea extract.
its a Mao-A + Mao-B (up to ca.90 % inhibition for both) inhibitor and to a lesser extend a Compt(up to 60%) inhibitor.

I wanted to suggest it in this topic, but I couldnt find any connection of Amphetamine and Mptp, and therefore I dont know if this would help.
But you could give it a try, it isnt expensive and healthly in any case.

If you are interrested, Curcumin would also be an option.
http://www.ncbi.nlm....umin mao b mptp

Edited by Flex, 15 December 2013 - 06:36 PM.


#88 Sciencyst

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Posted 16 December 2013 - 08:30 AM

^ MPTP is a very,very, very good model for amphetamine induced damage.

Amphetamine causes reactive oxygen species which destroy dopaminergic neurons much in the same way as MPTP. Also there is an astounding correlation between amphetamine use and Parkinson's

"According to the study, those people who reported using Benzedrine or Dexedrine were nearly 60 percent more likely to develop Parkinson's than those people who didn't take the drugs."

http://www.sciencedaily.com/releases/2011/02/110220193013.htm

Formergenius: have you tried diphenhydramine? I took a single pill last night and all of my symptoms disappeared. It doesn't exactly make your smart (quite the opposite) but it helps an amazing amount with the irritability and extrapyramidal symptoms if you have them. The positive result from DPH made me realize I had been seriously wasting my time with all of the cholinergics I had been supplementing with. No more Uridine or AlphaGPC for me.

Also, I'm curious.. do you have any motor symptoms? Like loss of balance or coordination, or stiffness of muscles?

#89 formergenius

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Posted 16 December 2013 - 01:16 PM

Thanks, but I wouldn't take DPH for a million bucks, moreover I think it's Rx here.
Yes I have motoric dysfunction it would seem.. all those you've mentioned, plus walking into walls and doors on a much too frequent basis.
Anyhow; in the meantime I've suspended my Cerebrolysin trial (after 2 weeks / 100ml). This because I discovered that it's primarily synaptogenic, whereas NSI-189 is neurogenic, so it would make more sense to do NSI-189 first. No benefits noted so far, and to be honest I'm just waiting for NSI. Trying a Mr. Happy stack in the meantime, along with most of the things I've been taking.
Been looking for other things to try in the meantime, but it seems there's nothing worth trying if I'm already going to try NSI (thinking of things like Noopept which would be inferior).
So it seems like I just gotta bunker down for 2-3 weeks and hope for the best. Thanks for all the suggestions though.

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#90 Ark

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Posted 16 December 2013 - 01:44 PM

Consider adding Skullcap to your regime.





Also tagged with one or more of these keywords: afobazole, proproten, tenoten, tianeptine, stress, depression, anxiety, plasticity

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