6220 replies to this topic

[formergenius]

Oh. Duh. Can't believe I missed that. Guess I could really use this stuff
Thanks!

[mait]

Also, I was wondering about the 20% growth in hippocampus size, when I read about Coluracetam once more:

Going simply by the names BCI-540 and BCI-632, the compounds can stimulate 20 percent more brain cells brain to grow than normal. Much of the new growth would be replacing cells that our brain is losing all the time.

(dodgy) source

How does 20% more neurogenesis compare to 20% growth in hippocampus? Would NSI be significantly more potent in this respect?
Coluracetam appears to me to be one of the most potent Nootropics available currently, however it's still lacking in my experience. I'm hoping NSI can offer more than that.

It depends what is the ratio of new neuron / glial cells generation in relation to the loss of after-mentioned cells is in time. For example if it is 1-1 then increasing the new cells formation by 20% will result 20% growth of hippocampus. Here I exclude the possibility of exponential growth of cells out of newly generated cells because there must be some homeostatic limits in brain that prohibit certain brain areas from reaching supra-anatomical sizes (lack of nutrients, level of neurotropic factors that keeps the built in aptotic cells pathways from activating etc.).

There may be an additional neural dynamic related to neurotropic factors in play here: in vitro tests have shown that in the case of external harmful shocks (for example oxidative stress or radiation) even somewhat damaged cells will not go into aptosis if there is enough neurotropic factors in cell culture. So maybe it is possible to have related situation in real brain, when NSI-189 increases the volume of some brain areas in nonsignificant amount that the concentration of neurotropic factors per brain area volumetric unit will drop, which in turn leads to the death of damaged neurons, which in turn are replaced by newly generated ones.

[formergenius]

edit: I just typed nonsense. I digress.

Edited by formergenius, 26 December 2013 - 08:56 PM.

[Puppeteer]

Given that the hippocampus has a significant role in spatial memory and navigation, presumably NSI-189 has the potential to improve functioning in that area. Has anyone here who's tried it experienced any such improvement?

Edited by Puppeteer, 28 December 2013 - 08:54 PM.

[Perek]

It's great to read your reviews guys. I'll postpone my final review until the end and oh boy it'll be interesting to see the MRI comparison
I'll post all my results here, but fellows! How about gathering the results in one place? I've prepared a form with a bunch of questions so we can have the results of our little trial in a bit better form. Go on and write down your observations:

https://docs.google....6ypUAM/viewform

Remarks very welcome

Did anything come out of this inititiative (great) of yours?

[tritium]

This guy in ebay seems legitimate, anyone here took the "risk" in trying NSI from him??

I believe he's legit. He's a really helpful, nice guy, and his tianeptine is great (a lot of Longecity users can attest to that). The NSI from the group buy is a little more pure and a fair bit less expensive per gram but if you can't wait I doubt there's anything wrong with nyles7's stuff.

I bought some the other day. Will investigate more about the impurities and potential implications before trying.

In any case I will start low and slow. 5-10 mg daily.

Any updates on the quality of his NSI-189?

[megatron]

Congratulations to everyone that invested in Neuralstem stock! It seems like the stock will go up about 10% on the last day of trading in 2013, and will have grown about 100% since most of the investors here at Longecity bought it. Hurrah!

[lourdaud]

Congratulations to everyone that invested in Neuralstem stock! It seems like the stock will go up about 10% on the last day of trading in 2013, and will have grown about 100% since most of the investors here at Longecity bought it. Hurrah!

Yeah, creds to Rior for the recommendation! I bought A LOT so I made a lot of money thanks to him!

Edited by lourdaud, 30 December 2013 - 11:58 PM.

[xks201]

As someone who takes cortisol to survive (adrenal insufficiency) I can tell you that cortisol is a calming hormone. It is labeled a stress hormone because it negates the stress response. It inhibits adrenaline release. Before you go on claiming you are having a cortisol spike get some lab work because what you describe in no way sounds like a cortisol spike. The only thing you would feel from a cortisol spike is more alert, not necessarily more agitated or anxious. If anything you would be calmer.

Edited by xks201, 31 December 2013 - 04:02 PM.

[aarfai]

Anyone have an update on the NSI-189 being sold on eBay?

[formergenius]

Anyone have an update on the NSI-189 being sold on eBay?

I bought a gram, and intend to use and report as soon as it arrives. Though bear in mind I have not used NSI-189 before, nor can I be considered a healthy individual.

[CortisolJunkie]

Anyone have an update on the NSI-189 being sold on eBay?

Posting here and for any of the nsi group by participants. i was able to get a smaller amount than one gram to test out (email nyles7, sure he can hook you up).

before you read the following keep this in mind: i really think my reaction was a personal one and not due to the quality of the substance.

i ended up asking for a refund for my group buy nsi due to my experience with the ebay nsi. I had bad anxiety on it that got out of control. this is not inconsistent with some other reports so i believe it is legit, if you're worried about that. it ended up triggering some night terror issues i was having and couldn't pin down..they went away naturally but this made it go up again.

to express the anxiety, it was more of the physical type, but i did get more stressed about something that happened with a buddy than i would have otherwise. i got really pissed off at him for something that wasn't a big deal and decided to take a breather and sleep on it - the next day i was still incredibly pissed off and just kind of blew up on him. i felt very edgy. the physical symptoms were, if not actual palpitations, more awareness of my heart beating and physical body in a way that made me uncomfortable and not able to sleep. during the day I was mostly fine but i dreaded night because i ended up feeling paranoid and unable to sleep.

i don't know if this would have died down, or it would have been worth it..but I took this for a week and had zero positive side effects. there was one morning when i was feeling pretty good but it was sunny and warmer, and the previous days it hadn't been, and later in the day when it got cloudy i crashed again :( I generally was taking 20mg 2x per day, but the first few (and last few) days I was down to 20-10mg. It didn't seem to help with the anxiety/sleep issues.

so don't be frightened about the ebay stuff, but I personally wasn't a responder. since I've read similar reports I feel better about it. If I ever have a long vacation maybe I can try again? Or when it comes on the market..but being around family is stressful enough during the holidays, and especially going back to work, so I just couldn't chance it to continue.

Hope this helps someone. again - don't be scared of the eBay stuff. but you may be a nonresponder, or alternatively respond but have anxiety.

[CortisolJunkie]

As someone who takes cortisol to survive (adrenal insufficiency) I can tell you that cortisol is a calming hormone. It is labeled a stress hormone because it negates the stress response. It inhibits adrenaline release. Before you go on claiming you are having a cortisol spike get some lab work because what you describe in no way sounds like a cortisol spike. The only thing you would feel from a cortisol spike is more alert, not necessarily more agitated or anxious. If anything you would be calmer.

i have had lab work. i have a history of hypercortisolemia that i am controlling now with nootropics. having too little or too much is going to be just as bad. since you are on the other side of things you may have had a different experience, idk.

[ranza]

It's great to read your reviews guys. I'll postpone my final review until the end and oh boy it'll be interesting to see the MRI comparison
I'll post all my results here, but fellows! How about gathering the results in one place? I've prepared a form with a bunch of questions so we can have the results of our little trial in a bit better form. Go on and write down your observations:

https://docs.google....6ypUAM/viewform

Remarks very welcome

Did anything come out of this inititiative (great) of yours?

Well, we've got a study of power n=2. Only two participants responded to my questions which gives us close to nothing.
I can post the results here already, but preferably I'd like to see more people report on their results...

[Kompota]

I am 28 months into protracted benzodiazepine withdrawal and it is clear that my symptoms nowadays are purely related to hypercortisolism. The GABA / NMDA dysregulation issue from the past is pretty much gone. How did benzos affect my neuroendocrine system, causing highly elevated cortisol levels ? It is highly likely that benzo intake and subsequent withdrawal has destroyed the so called autoregulatory negative feedback system. Cortisol produced by the adrenals travels back to the brain through the blood stream and binds to the glucocorticoid receptors in the hippocampal area of the brain. In response to actual cortisol levels, glucocorticoid receptors send a signal to the hypothalamus to reduce CRH (cortico-releasing hormone) release accordingly, thus complementing the whole HPA-axis loop. In my case, this negative feedback mechanism has been screwed somehow and cannot put proper brakes on the CRH->ACTH->Cortisol production. I wonder what exactly happened there. Either the existing glucocorticoid receptors have been desensitized or excitotoxicity during acute withdrawal has killed so many neurons altogether, so that I have ended up with too few receptors to provide a proper feedback.

It is a bit of a vicious circle: the hippocampus provides the necessary Cortisol feedback, however elevated Cortisol itself has a neurodegenerative impact on the hippocampus, which compromises it's ability to provide a feedback. Maybe this neurodegenerative effect of Cortisol is one possible explanation of the phenomenon of protracted benzodiazepine withdrawal - it is two steps forward, one step back. That is why NSI-189 may be my last hope - if it could ensure prolonged progenitor cell survival in the hippocampus by protecting them from the neurodegenerative impact of Cortisol. In other words: I am going to try making 4 or 5 steps forward at once, in the hope this may give an exponential kick to my recovery.

[telight]

Well, we've got a study of power n=2. Only two participants responded to my questions which gives us close to nothing.
I can post the results here already, but preferably I'd like to see more people report on their results...

Do your results include an MRI before or after NSI-189 treatment? I think everyone on this forum will want you to post those results. You post will be greatly appreciated.

[golden1]

I am 28 months into protracted benzodiazepine withdrawal and it is clear that my symptoms nowadays are purely related to hypercortisolism. The GABA / NMDA dysregulation issue from the past is pretty much gone. How did benzos affect my neuroendocrine system, causing highly elevated cortisol levels ? It is highly likely that benzo intake and subsequent withdrawal has destroyed the so called autoregulatory negative feedback system. Cortisol produced by the adrenals travels back to the brain through the blood stream and binds to the glucocorticoid receptors in the hippocampal area of the brain. In response to actual cortisol levels, glucocorticoid receptors send a signal to the hypothalamus to reduce CRH (cortico-releasing hormone) release accordingly, thus complementing the whole HPA-axis loop. In my case, this negative feedback mechanism has been screwed somehow and cannot put proper brakes on the CRH->ACTH->Cortisol production. I wonder what exactly happened there. Either the existing glucocorticoid receptors have been desensitized or excitotoxicity during acute withdrawal has killed so many neurons altogether, so that I have ended up with too few receptors to provide a proper feedback.

It is a bit of a vicious circle: the hippocampus provides the necessary Cortisol feedback, however elevated Cortisol itself has a neurodegenerative impact on the hippocampus, which compromises it's ability to provide a feedback. Maybe this neurodegenerative effect of Cortisol is one possible explanation of the phenomenon of protracted benzodiazepine withdrawal - it is two steps forward, one step back. That is why NSI-189 may be my last hope - if it could ensure prolonged progenitor cell survival in the hippocampus by protecting them from the neurodegenerative impact of Cortisol. In other words: I am going to try making 4 or 5 steps forward at once, in the hope this may give an exponential kick to my recovery.

what are your symptoms? I'm curious what to look for as I am almost done tapering off clonazepam(really long ~1yr taper). The only thing I have noticed is a minor problem focusing [subjectively] caused by a feeling of inner restlessness/noise. It seems to make my mind give up easier on difficult concepts, almost like its just short circuiting and going "NOPE sorry." I am assuming this will slowly go away though as it just seems like a much less extreme version of the focus issues benzo w/d causes(almost a complete inability to focus on a computer, etc)

thanks and best of luck

[ranza]

Well, we've got a study of power n=2. Only two participants responded to my questions which gives us close to nothing.
I can post the results here already, but preferably I'd like to see more people report on their results...

Do your results include an MRI before or after NSI-189 treatment? I think everyone on this forum will want you to post those results. You post will be greatly appreciated.

It will, but before I do an "after" MRI I want to make another NSI-189 trial for at least a month. So far I'm waiting for a response from our supplier.

[Kompota]

what are your symptoms? I'm curious what to look for as I am almost done tapering off clonazepam(really long ~1yr taper). The only thing I have noticed is a minor problem focusing [subjectively] caused by a feeling of inner restlessness/noise. It seems to make my mind give up easier on difficult concepts, almost like its just short circuiting and going "NOPE sorry." I am assuming this will slowly go away though as it just seems like a much less extreme version of the focus issues benzo w/d causes(almost a complete inability to focus on a computer, etc)

thanks and best of luck

Cognitive issues mainly - poor memory and inability to focus. It has been getting better, very slowly though. Nowadays, it prevents me from performing more complex mental work, while earlier, especially during acute withdrawal I couldn't literally perform simple 2+2 math. I even had problems finding my way home. The fog has lifted significantly so that reading, writing, basic comprehending are no longer a problem. The most obvious sign of excessive cortisol is that feeling in the muscles - not a pain, but rather a weakness, a tiredness. Also getting tired very quickly after physical effort. Those physical symptoms are not that uncomfortable or hard to endure, but just a typical sign of high cortisol.

[manic_racetam]

I bought the stuff from Nyles on ebay. I've got a question for the community and if anyone can help I'd certainly appreciate it.

I noticed people from the group buy mentioning their NSI-189 is white and fluffy and IIRC in phosphate form (like the study/trial).

The stuff sent from Nyles is crunchy and coarse, very different. So I contacted him and asked if it was in phosphate form and he replied that it wasn't.

Not exactly sure but am pretty sure that a different form of the NSI-189 will have a different molar mass, which would mean different dosages (by weight) for different forms.

He replied saying

It is : (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone

Unfortunately I have no idea what that means.

Can anyone with a more extensive background in chemistry explain what ratio this stuff is in comparison to the NSI-189 used in the trial?

For example 80mg of the phosphate form would equal how many mg of (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone?

Thanks!

Edited by manic_racetam, 06 January 2014 - 07:51 AM.

[telight]

He replied saying

It is : (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone

Unfortunately I have no idea what that means.

Can anyone with a more extensive background in chemistry explain what ratio this stuff is in comparison to the NSI-189 used in the trial?

For example 80mg of the phosphate form would equal how many mg of (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone?

Thanks!

That looks like its freebase, so according to wikipedia it has a molar mass of about 367g/mol and phophate has a molar mass of about 95g/mol. Therefore NSI-189 in phosphate form has a molar mass of 367+95=462g/mol. Comparing that to what you have, we can make a ration 367/462=.8. So you can multiply any NSI-189 phosphate dosage by .8 to acquire the dosage equivalent of the freebase form. Example dosage of 40mg of nsi-189 phosphate is equal to 40*0.8=32mg of freebase nsi-189.
I would be concerned somewhat stability of the freebase form, but i don't have enough knowledge to comment on that.

[Nattzor]

Isn't the results for phase II or III being released soon?

[telight]

Isn't the results for phase II or III being released soon?

Actually its just still phase 1b results that are coming.

[formergenius]

I read they announced on 26 Dec that they'll be releasing the results in the next few weeks. So that should be somewhere this month.
On the 4th of Nov it was announced that results would be released mid-Dec..

Edited by formergenius, 06 January 2014 - 09:34 PM.

[Puppeteer]

Coincides well with the completion of the group buy.

[formergenius]

FWIW: Received the "freebase" NSI yesterday, just took ~10mg sublingually about 20 mins ago. Makes my tongue numb...
Too early to comment on effects. I intend to take another 20mg 2 hours from now.

Edited by formergenius, 08 January 2014 - 02:50 PM.

[Kompota]

Why do you guys even bother about any immediate effects of NSI-189 ?
It is not supposed to be a stimulant. Neuroregeneration takes time, at least a few weeks to even start noticing anything. I even believe some short-term discomfort and unpleasant initial effects might bring benefits in the long term.

[formergenius]

I was just stating that I started, really. I intend to update only in a few weeks (~2-3), or if I think I'm seeing changes.

[arboles]

I was just stating that I started, really. I intend to update only in a few weeks (~2-3), or if I think I'm seeing changes.

can you do some cognitive tests pre and post supplementing in order to measure any improvements.

Edited by arboles, 09 January 2014 - 07:02 AM.

[formergenius]

Just did so with Cambridgebrainsciences, before today's dose. Made some new lows..