6219 replies to this topic

[daouda]

I don't know much but I can tell you this :
1,2,3> We don't know squat about any of this, but the more knowledgeable ppl here can probably extrapolate some hypothetical answers based on what little we know about this compound and its mode of action. So I'll humbly step back and llet them chime in

[OpaqueMind]

I am by no means an expert, but I can hazard a reasonable guess as to the answers to your questions. The mechanism of action is purported to be increased proliferation of stem cells, which will result in neurogenesis and synaptogenesis to a degree. This happens in various places in the CNS, but the clinical effects (at least those seen in patients with Major Depressive Disorder) seem to be manifested through this process occuring in the Hippocampus.

1) This drug is being trialled on people with MDD, with the intended effect of alleviating depression via the reversal of hippocampal atrophy that is typical in MDD and is implicated in the latest models of the disorder. If it reverses depression in unhealthy subjects, it is safe to assume that it won't induce depression in healthy ones, and it may even lead to an increase in general mood.

2) Given its mechanism of action, I see no reason why it would be physically addictive. Mentally though, of course, anything that gives pleasure directly or abstractly can be behaviourally reinforcing. Who doesn't want a better brain!

3) There probably won't be a withdrawal in the typical sense (think SSRIs or Opiates) because it does not seem to affect neurotransmitter levels directly and this is where adaptation and withdrawals primarily occur. However there may be unknown mechanisms which come into play in a more subtle way once the drug is discontinued... perhaps a reduction in neural stem cell populations for a while afterwards? If my experience with Cerebrolysin, which also increases neurogenesis, has any relevance to this then there may be a very slight lowering of mood which returns to normal after finishing the cycle. Note that this may be purely due to moving closer to the baseline mental state (ie subjective experience) than any actual withdrawal or homeostatic mechanism which tipped me in the other direction.

As daouda wisely mentioned, this is of course merely (amateur) speculation based on very limited information and should not be taken to be conclusive.

Here's a quote from the official neural stem website which basically describes the MoA:

NSI-189 has been shown to stimulate neurogenesis of human hippocampus-derived neural stem cells in-vitro and in vivo. In healthy normal adult mice, NSI-189 stimulated neurogenesis in the hippocampus and significantly increased its volume, apparently by increasing its synaptic network after 28 days of daily oral administration. In mouse models of depression, NSI-189 significantly improved behavioral responses associated with depression. In humans, NSI-189 may reverse the human hippocampal atrophy seen in MDD and other disorders and reverse their symptoms

Edited by OpaqueMind, 30 April 2013 - 04:58 PM.

[sunshinefrost]

What other supplements will you ba taking with 189 ?

I won't be trying anything heavy like piracetam (ok not that heavy) or cerebrolysin wih it. But what about the light supplements like lecithin, omega 3, green tea, phosphatidylserine ? any thoughts if those could still be use while testing with this new noot ?

Edited by sunshinefrost, 30 April 2013 - 07:17 PM.

[Artificiality]

I plan to keep taking Omega 3 when I start trying the 189. Since it's something that we naturally get from our diet I'm going to assume, unless someone says otherwise, that it should be fine to take.

[sunshinefrost]

I plan to keep taking Omega 3 when I start trying the 189. Since it's something that we naturally get from our diet I'm going to assume, unless someone says otherwise, that it should be fine to take.

I will too, plus something to support cellular structure during neurogenesis at the least.... Phosphatidylcholine and serine.

[moomoo]

Perhaps too late, but if not I'm in.

[Xenix]

I'd really like to see the data that confirms hippocampal size actually increase by 20% - what dosages were necessary, and how long it took to grow, etc - even if they were only based on animal models.

[crusader]

Sparkk, the anwser is explicitly given just a few pages back in this thread... But since some other ppl might also be extremely lazy :
http://clinicaltrial...how/NCT01520649
Clinical trial : 3 cohorts given 40mg once to thrice per day for 28 days. Total 1120mg, 2240mg or 3360mg per cohort. We're getting 2500mg per person. Voilà.

I am not well versed when it comes to nootropics, let alone the technicalities when it comes to clinical trials, but why is it only limited to 28 days? is this some type of drug/nootropic that only requires a short term dose?

or due to the restrictions of clinical trials, they were forced to do such a short term dosage? im confused.

[hadora]

it's not limited to 28 days but in the clinical trial they treat them for 28 days because it's a safety trial (phase IB) in the Phase II they probably gonna treat them for longer

I'd really like to see the data that confirms hippocampal size actually increase by 20% - what dosages were necessary, and how long it took to grow, etc - even if they were only based on animal models.

you need to read the patent

[Reformed-Redan]

So, 40 mg every day or 40 mg twice or trice a day to be taken?

[megatron]

I'm probably going with 30mg t.i.d.

[Reformed-Redan]

What does t.i.d mean? Till I die, lol?

[DamnedOwl]

Till I Dominate

[Xenix]

Till I Dominate

Hahahahahahaha

[hadora]

What does t.i.d mean? Till I die, lol?

It's mean 3 time a day

[Izan]

Till I Dominate

LOL!!

[therein]

Haha this thread just keeps getting better.

First time I heard T.I.D and B.I.D was when I got a prescription for Ritalin/Adderall. I looked it up - it is in latin:

TID: Ter in die (Three times a day)
BID: Bis in die (Twice a day)

[OpaqueMind]

From reading the NeuralStem briefing on NSI-189 it seems that the neuro/synaptogenesis is not confined to the hippocampus, only that the intended clinical effects of that trial were most likely mediated by that mechanism. From my reading the effect is not localised, so there will most likely be increases in other areas. If these are volumetric increases, as is indicated in the hippocampal growth ('20% size increase') could that not be potentially problematic?

It doesn't help that they're so vague with that quote. Is it a 20% increase in volume or density, or a quantitative increase in neuronal population? Who knows...

[ScienceGuy]

UPDATE:

Hi Everyone,

To confirm, the order has now been placed with the respective custom synthesis lab.

This is what they emailed me:

1-3 may in our country is a national holiday, so we will start 6th may - Monday. We have already ordered almost all necessary chemicals at appropriate scale.

I will be sure to keep everyone updated, but please kindly note that the LEAD TIME is anticipated to be circa 5 WEEKS

[therein]

Thanks for the update ScienceGuy. They must be celebrating the Labour Day and the Constitution Day.

[Reformed-Redan]

nvm

Edited by yadayada, 03 May 2013 - 05:39 AM.

[peakplasma]

Damn, those Poles and their holidays.

Edited by peakplasma, 03 May 2013 - 05:21 AM.

[Reformed-Redan]

nvm

Edited by yadayada, 03 May 2013 - 05:39 AM.

[MizTen]

UPDATE:

Hi Everyone,

To confirm, the order has now been placed with the respective custom synthesis lab.

This is what they emailed me:

1-3 may in our country is a national holiday, so we will start 6th may - Monday. We have already ordered almost all necessary chemicals at appropriate scale.

I will be sure to keep everyone updated, but please kindly note that the LEAD TIME is anticipated to be circa 5 WEEKS

Thanks for this update ScienceGuy!

[Steve Zissou]

A big thanks to everyone involved in this. Looking forward to being a human guinea pig.

[megatron]

From reading the NeuralStem briefing on NSI-189 it seems that the neuro/synaptogenesis is not confined to the hippocampus, only that the intended clinical effects of that trial were most likely mediated by that mechanism. From my reading the effect is not localised, so there will most likely be increases in other areas. If these are volumetric increases, as is indicated in the hippocampal growth ('20% size increase') could that not be potentially problematic?

It doesn't help that they're so vague with that quote. Is it a 20% increase in volume or density, or a quantitative increase in neuronal population? Who knows...

It would be awesome if the growth is not only limited to the hippocampus, though if it is, it is very good anyways. It would be great if it promoted growth in the prefrontal cortex as well.

[sunshinefrost]

For all those that emailed me concerning available places left, i'm sorting out how many places i have left. I have to consolidate paypal and payitsquare... I should be able to tell you during the weekend.

[Xenix]

So do I buy shares in Neuralstem Inc before or after our little longecity human experiment?

[focus83]

So do I buy shares in Neuralstem Inc before or after our little longecity human experiment?

I was wondering the same. Seems like some people already bought shares. Maybe it's wise to wait for the results of this group buy so we have a better idea of the compound's potential. But even if the NSI-189 doesn't satisfy our expectations, Neuralstem has other things in its pipeline which could boost the stock price enormously should they ever make it to the market.

[Xenix]

So do I buy shares in Neuralstem Inc before or after our little longecity human experiment?

I was wondering the same. Seems like some people already bought shares. Maybe it's wise to wait for the results of this group buy so we have a better idea of the compound's potential. But even if the NSI-189 doesn't satisfy our expectations, Neuralstem has other things in its pipeline which could boost the stock price enormously should they ever make it to the market.

Mmm... it will be years before NSI-189 - let alone its other compounds - will even make it to the market, so it will take a while to see returns; that is assuming they will pass the FDA and all other regulatory bodies.

I'm curious about the competition Neuralstem Inc will face if (best case scenario here) their compound really can possibly cure clinical depression as they claim. I mean, the other companies providing antidepressants (Lilly, Pfizer, Wyeth, etc) that make billions of revenue from their products annually sure aren't going to like the idea of a drug that renders theirs' completely useless... I'm positive that they will 'persuade' Neuralstem to stay out of the market.

For pharmaceutical companies, never-ending treatment is FAR better than a cure. I'm sure they'd like to keep it that way.