86 replies to this topic

[PAM2]

Hi everyone, as promised in the first ISRIB group buy I opened up a new one by the name "ISRIB-Group buy New".

I will copy the latest post there for all to know what it is here about:

" I answered all the questions came in yesterday in pm-s, it looks like some of you have the intention to help in organizing the transfer of ISRIB.
I woul like to highlight, tha ISRIB is aliqouted by the lab in 2.5 grams portions, so I only have the chance to provide amounts divided by 2.5 (2.6-5-7.5 grams etc...), as I don't have analytical scale, and I think it is safer/precise, that the lab measured it by themself.
So the ISRIB is ready to get shipped, we only have to organize it clean.

Thx all for the help in advance. "

So it is practically not a group buy, as I let the synthesis began already in last december, ISRIB is already made by the lab, and as seen I will sell 80 grams from 100 grams I let made. I'm only able to sell 2.5 gram portions, or portions multiple 2.5 grams, as it is already measured like that in vials.

The process is very simple, if someone is seriously interested, please pm me, I'll get back as soon as possible (I think so far noone can have any complaint to my communication, by the way, thanks for the ones, who offered their help, and showed clear evidence in helping me..After that I will send the hplc analyses (HPLC-MS and NMR-1H) to the person, and I will attach photos as well. The transfer has to go through pay-pal, after receiving the amount, I will send it by post (I prefer EMS, not regular post, as it is secured!!!), or if someone prefers private carrier companies (DHL, DPD etc...), please sign before making the payment, and I will calculate a shipping cost.

Please all get back to me after receiving the package.

Please-please ask (!!!), before placing an order, even, if it sounds dumb!!

For the future I'm completely next to the initiative of the Group buy poll topic to work out regulations, and standardize group buys, as it will easy, and secure all of our lives..

Thanks

[PAM2]

Hi Guys,

I sent out the COA of the newly synthesized ISRIB, for about one third is taken, I have about 50 grams left, if requested I will send the COA out to the ones, who are interested!

[JPC16]

So PAM2, you are not yet in possession of ISRIB? What is the ETA going to be? I am thrilled to hear about the results if ISRIB. Keep us posted.

[PAM2]

Hi JPC,
ETA is 0, as I already have it (the synthesis began last december, and unlike other substances, it was easier, or at least faster to get the raw materials, and to get synthesized).
I'm continously sending out the details of ordering for the ones, who already saw the coa, and placed an order.
Currently I'm on a stack of cerebrolysin, NSI, and PRL, I already got FGL, and now ISRIB, so this is going to be the next turn, but before using FG-Loop, I have to make sure the dephosphorilation, and HDAC-inhibitory effect of ISRIB, not to get some long-term relations interference.
How is C16-test going?
Please pm me, if you have some details, maybe we can discuss about it!

[Nattzor]

Hi JPC,
ETA is 0, as I already have it (the synthesis began last december, and unlike other substances, it was easier, or at least faster to get the raw materials, and to get synthesized).
I'm continously sending out the details of ordering for the ones, who already saw the coa, and placed an order.
Currently I'm on a stack of cerebrolysin, NSI, and PRL, I already got FGL, and now ISRIB, so this is going to be the next turn, but before using FG-Loop, I have to make sure the dephosphorilation, and HDAC-inhibitory effect of ISRIB, not to get some long-term relations interference.

>not to get some long-term relations interference.

Mind expanding on that?

And that's the nicest stack I've seen in a long time, atleast if you add one the two you're not taking.

[JPC16]

Hi PAM2

First of all I would recommend you not to combine ISRIB with anything else (initially). Most importantly because of the fact that an interaction might occur (“molecule-wise” but also through intracellular pathways). And even if an interaction might not seem plausible, I would still be cautious because you really never know what is going to happen.
The second reason why I don't recommend combo's is simply because of the fact that you won't fully be able to assess the effect of ISRIB itself. This of course also applies to other nootropics such as FG-loop. But I don't “condemn” combo's completely since synergistic effects can occur, but I think you should always first try to evaluate one compound before combining.

I myself am still in the predicament of preparing a dose of C16. But in less than a month I hopefully will finally be able to weigh one (at least) so I can finally trial it. I myself can hardly believe there is someone who finally obtained ISRIB. I would almost immediately try it. When can we espect the first results from ISRIB from you?

[Metagene]

Where did you get FG-Loop?

[PAM2]

Now I can now just add, what is the basic principle of using ISRIB/PKR-C16-inhib., and as first why should be considered administrating simultaneously with a Growth factor-derived (or GF/citokin like) molecule. If ISRIB has a potent eif2-alpha phosforilation-inhibitory effect, it means it helps releasing inhibiton of numerous protein synthesis pathways (the exact names, and numbers are not specified yet), and if you add an indirect FGF-receptor agonist, these effects can easily exert a synergistic effect on mRNA (the ribonucleic acid, that codes proteins) synthesis, resulting in excessive anabolic effect, plus the stress response inhibition, originating from ISRIB is diminished, sot the brake is off. If this synergism happens (now we are talking in theoretical actions), maybe you can overshoot the desired effects from the chemicals.

So my recommendation is not to use them simultaneously, but to test them one-by-one, and after experiencing the sole effect of the drug, you can test it with others if neccessary.

Yes, so far NSI works far better, than expected, cerebro gives a cool inner drive, and PRL helped in focusing on a task already in 5mg doses (actually over 10 mgs I didn't notice any benefits from it).

Hi JPC,
ETA is 0, as I already have it (the synthesis began last december, and unlike other substances, it was easier, or at least faster to get the raw materials, and to get synthesized).
I'm continously sending out the details of ordering for the ones, who already saw the coa, and placed an order.
Currently I'm on a stack of cerebrolysin, NSI, and PRL, I already got FGL, and now ISRIB, so this is going to be the next turn, but before using FG-Loop, I have to make sure the dephosphorilation, and HDAC-inhibitory effect of ISRIB, not to get some long-term relations interference.

>not to get some long-term relations interference.

Mind expanding on that?

And that's the nicest stack I've seen in a long time, atleast if you add one the two you're not taking.

[PAM2]

JPC, I agree on, each and every substance have to be tested solely first, and taken in combo later, if it is needed for proper functioning for the subject.
Now I will finish my cycling with cerebro, and waiting for the bacteriostatic water for FGL (and epithalon), after I will pause my current stack, and start with ISRIB. Actually ISRIB is simplier to let synthesized, than s32212, or DiHexa. So to let some agents custom synthesized is not impossible, but I completely understand the labs, who are approaching custom synthesis with caution.

[Nattzor]

Now I can now just add, what is the basic principle of using ISRIB/PKR-C16-inhib., and as first why should be considered administrating simultaneously with a Growth factor-derived (or GF/citokin like) molecule. If ISRIB has a potent eif2-alpha phosforilation-inhibitory effect, it means it helps releasing inhibiton of numerous protein synthesis pathways (the exact names, and numbers are not specified yet), and if you add an indirect FGF-receptor agonist, these effects can easily exert a synergistic effect on mRNA (the ribonucleic acid, that codes proteins) synthesis, resulting in excessive anabolic effect, plus the stress response inhibition, originating from ISRIB is diminished, sot the brake is off. If this synergism happens (now we are talking in theoretical actions), maybe you can overshoot the desired effects from the chemicals.

So my recommendation is not to use them simultaneously, but to test them one-by-one, and after experiencing the sole effect of the drug, you can test it with others if neccessary.

Yes, so far NSI works far better, than expected, cerebro gives a cool inner drive, and PRL helped in focusing on a task already in 5mg doses (actually over 10 mgs I didn't notice any benefits from it).

Then I understand fully, a safety thing.

[PAM2]

Yes, exactly.

[Izan]

JPC, I agree on, each and every substance have to be tested solely first, and taken in combo later, if it is needed for proper functioning for the subject.
Now I will finish my cycling with cerebro, and waiting for the bacteriostatic water for FGL (and epithalon), after I will pause my current stack, and start with ISRIB. Actually ISRIB is simplier to let synthesized, than s32212, or DiHexa. So to let some agents custom synthesized is not impossible, but I completely understand the labs, who are approaching custom synthesis with caution.

could you also organise a nsi-189 groupbuy for us?

[PAM2]

Actually I will have to refill my NSI-store, so I will have to let is synthesized, meaning, it is not impossible, I will be able to obtain more (as I got NSI a lot earlier - around last November- from the same lab, as the other group buy, and they're still struggling with...), but it is no promise!!

[Porkman]

I would be interested in nsi-189.
Possibly isrib too, what are expected costs?
Made an account just to ask, but might have to become active on these forums as I read them far to much!

[PAM2]

Please send me a pm, and I will mail you the details (shipping, coa ect..), and some information about ISRIB:

http://elife.elifesc...ontent/2/e00498

About NSI you can see the main infos on the site of Neuralstem, and there are already some reports of personal experiences on longecity as well.

[PAM2]

Hi, guys, my ISRIB trial has begun today (I stopped cerebrolysin 3 days ago, prl today), and will only continue NSI with it, I'll report how it goes...

[Nattzor]

Hi, guys, my ISRIB trial has begun today (I stopped cerebrolysin 3 days ago, prl today), and will only continue NSI with it, I'll report how it goes...

Really nice, keep us updated daily (preferably many times a day ).

[Porkman]

Looking forward to hearing how this goes!

Are you taking any other stack, other than nsi/isrib?

[PAM2]

Today I had the second "shot", so far one experience, dmso tastes like hell, literally, it is really awful, still it is needed according to the poor solubility of ISRIB. Yesterday started with half dose (7mg), today did 10 mg dissolved in dmso.
The first experience is something similar to, when I took PRL, but way stronger (a slight pressure around my forehead), and looks like everything got a lot sharper (counter to PRL, when my vision became sharper as well, but not as significant, as my perception grew here), but all of these experiences came from feelings, not through datas. I'm considering to make some cognitive testing to evaluate the effects in numbers. So this report is only for making my first SUBJECTIVE report, I have to have a lot more experiences to make a real, more OBJECTIVE summary...

[PAM2]

Currently I only take ISRIB mornings+NSI late afternoon (20 mg-s).

[p3x888]

So ISRIB can't be consumed without dmso?

[JPC16]

Wow , I can't believe someone finally tried ISRIB. Absolutely looking forward about hearing more results!
You should definitely test your cognitive abilities on Cambridge brain sciences! It's a good start. The memory tests in paticular! I personally think that ISRIB will only have an effect on LTP and therefore long term memory, which will present itself (at least) in a subtle way. I think testing your long term memory should be your primary goal. Keep us posted.

[PAM2]

I'm planning to make a proper cognitive testing, but actually never done so far, so I'll have to find a good strategy.
Why do you think, ISRIB will only/mainly affect long term memory, and won't concern other mental functions?

[JPC16]

Why would it affect other cognitive functions? ISRIB (and C16) only have a nootropic strategy that targets eif2a dephosphorylation (which I think leads to gamma interferon release which in turn suppresses GABAergic neurons in the hippocampus). I have written more about this on the C16 thread: http://www.longecity...210#entry640319

Molecules like ISRIB should make it a lot easier to encode long lasting memories. It reduces the threshold to form LTP. Simply put: you will need less repetitions to form a long term memory. As a matter of fact, if you “learn” too much it will actually worsen your memory: http://jeb.biologist...209/3/vii.short

So I think that compounds like ISRIB and C16 are ideal for root-learning (for example: vocabulary learning), which of course is a major advantage in the society we live in nowadays. Maybe a vocabulary long term memory test (comparable to that of the original PLR study) wouldn't be a bad idea. A vocabulary test in addition to the previous one with 'made up' words (by combining vowels and consonants to make artificial syllables and eventually 6 or 7 letter words for instance) would also be preferable since it excludes associative memory because the words don't mean anything to you. I think the same kind of test was used in one of the ampakine trials, wherein Cortex Pharmaceuticals tested one of the CX-compounds on old people.

But I don't think it will enhance other cognitive areas unfortunately. Don't get me wrong, I am not trying to be a negative nancy but rather realistic, but if the compounds even work half a good as the animal tests initially show then they could make a 'dramatic' impact. The should definitely work better than a CILTEP stack (if they work of course).

[megatron]

Would you care to try and see how quickly you can memorize a sheet completely filled with words while on the drug vs. not on the drug? If this drug is anything that we'd hoped for, this should take no longer than 5-10 minutes or else I'm really disappointed.

[PAM2]

As first, I will use ISRIB for a couple of days (at least 5 consec. days), meanwhile I'll try to figure out how to test it, but I wouldn't wait "miracle" in two day usage, even, if it is a potent memory consolidating agent (sorry to mention, but guys, NZT doesn't exist, or the structure is not known yet IMHO..). Actually I'm studying most of my week, so it will be quite obvious, if my memory consolidation efficacy changes, but I would like to evaluate it more precisely, as I don't expect, that ISRIB alone will accelerate my memorisation process 10 fold, or so..from feelings so far, it resembles on PRL, but really a lot stronger (my impression is, that this agent will be far the most potent from the NSI-Cerebro-PRL-ISRIB quartet, however they have different target points, and mechanisms of action). Another issue is, that it has to be dissolved well, and to be honest, today I used 10 mg-s dissolved in dmso, and it was really a bad experience, as dmso has a strange, warm effect on while swallowing (this is my first experience with it..). Now we are up to figure out, how to dissolve it in dmso, but by diluting it (to diminish the garlic like characteristics of dmso), so if anyone has professional chemical background, please don't hide your ideas...I think we won't be disappointed in ISRIB itself, but it is important as well, to be able to ingest it in an acceptable way for everyday use.

[megatron]

It would be great if you could take the Cambridge tests, track your progress and present it somewhat like this:

Edited by Megatrone, 22 February 2014 - 06:34 PM.

[MasterHerb]

As first, I will use ISRIB for a couple of days (at least 5 consec. days), meanwhile I'll try to figure out how to test it, but I wouldn't wait "miracle" in two day usage, even, if it is a potent memory consolidating agent (sorry to mention, but guys, NZT doesn't exist, or the structure is not known yet IMHO..). Actually I'm studying most of my week, so it will be quite obvious, if my memory consolidation efficacy changes, but I would like to evaluate it more precisely, as I don't expect, that ISRIB alone will accelerate my memorisation process 10 fold, or so..from feelings so far, it resembles on PRL, but really a lot stronger (my impression is, that this agent will be far the most potent from the NSI-Cerebro-PRL-ISRIB quartet, however they have different target points, and mechanisms of action). Another issue is, that it has to be dissolved well, and to be honest, today I used 10 mg-s dissolved in dmso, and it was really a bad experience, as dmso has a strange, warm effect on while swallowing (this is my first experience with it..). Now we are up to figure out, how to dissolve it in dmso, but by diluting it (to diminish the garlic like characteristics of dmso), so if anyone has professional chemical background, please don't hide your ideas...I think we won't be disappointed in ISRIB itself, but it is important as well, to be able to ingest it in an acceptable way for everyday use.

Any updates?

[PAM2]

So far I'm very much surprised about the effect on the overall cognition. My personal experiences are, that ISRIB definitely has it's effects on memory consolidation, but in my experience it doesn't only influence the long term memory formation (as JPC suggested), but the short term memory as well. It mens practicaly, that while reading a text, it is way much easier to remember the words, expression, and contexts as well (after 1-2 days). For instance currently I'm studying medicine basics again (I will enter a residency program soon), the subjects floaded with unique expressions related to molecular biology, basics of anatomy etc.. meaning, they are not very easy to link while memorizing even for a medical professional (they are meant to be boring..), and so far, after two days (meaning the text I read on friday) I can still remember a lot sharper on the names of for example cellular proteins, special basic physiological mechanisms than before, it is very obvious to me. I have to add, that I would value my memory above the average (as far as I can asses), but lately I somehow got slower by memorisation (I think it is an aging effect, and that was one of the reasons, why I started to search for some chemical hacking of my brain..).
In the past, while I was studying, I had to consider, that the time (during the day) of memorysation can influence the number of pages, read in a time period, and the efficacy as well, but the last two days, even at the end of the day I could memorize the text really a lot easier than before.
I will try the Cambridge test soon, and send you an update, but without that I can say, ISRIB is a lot more potent, than anything, I used so far. I'm not sure why, but I also feel a squeezing sensation in my forehead, followed by a potent perceptional increasement effect, similar to PRL, but a lot stronger (I already wrote before), and as PRL helped me a lot to focus, it seems to help also in focus (and this is a reason as well, why it is so much easier to memorize), but solely focus increasement wouldn't do a strong effect I experience with it. I think, if the effect will last for couple of days (or even gets stronger), we can say, we found a bomber gentleman!
And just a small observation to dmso: during the first 2 days it was a disaster to ingest it, but by now I accomodated to it, and I don't know why (maybe because of the strong antioxidant effect of it), my common sense increased a lot, so now I'm completely not against using it with dmso.

[MasterHerb]

So far I'm very much surprised about the effect on the overall cognition. My personal experiences are, that ISRIB definitely has it's effects on memory consolidation, but in my experience it doesn't only influence the long term memory formation (as JPC suggested), but the short term memory as well. It mens practicaly, that while reading a text, it is way much easier to remember the words, expression, and contexts as well (after 1-2 days). For instance currently I'm studying medicine basics again (I will enter a residency program soon), the subjects floaded with unique expressions related to molecular biology, basics of anatomy etc.. meaning, they are not very easy to link while memorizing even for a medical professional (they are meant to be boring..), and so far, after two days (meaning the text I read on friday) I can still remember a lot sharper on the names of for example cellular proteins, special basic physiological mechanisms than before, it is very obvious to me. I have to add, that I would value my memory above the average (as far as I can asses), but lately I somehow got slower by memorisation (I think it is an aging effect, and that was one of the reasons, why I started to search for some chemical hacking of my brain..).
In the past, while I was studying, I had to consider, that the time (during the day) of memorysation can influence the number of pages, read in a time period, and the efficacy as well, but the last two days, even at the end of the day I could memorize the text really a lot easier than before.
I will try the Cambridge test soon, and send you an update, but without that I can say, ISRIB is a lot more potent, than anything, I used so far. I'm not sure why, but I also feel a squeezing sensation in my forehead, followed by a potent perceptional increasement effect, similar to PRL, but a lot stronger (I already wrote before), and as PRL helped me a lot to focus, it seems to help also in focus (and this is a reason as well, why it is so much easier to memorize), but solely focus increasement wouldn't do a strong effect I experience with it. I think, if the effect will last for couple of days (or even gets stronger), we can say, we found a bomber gentleman!
And just a small observation to dmso: during the first 2 days it was a disaster to ingest it, but by now I accomodated to it, and I don't know why (maybe because of the strong antioxidant effect of it), my common sense increased a lot, so now I'm completely not against using it with dmso.

Thanks for update I hope this is safe longterm