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NSI-189

nsi-189

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#2101 5ht2a

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Posted 20 June 2014 - 05:43 PM

If somebody has a legitimate source for NSI-189, please pm me. Seems to have gotten scare since their lawyers gave ceretropic a warning!

 

 

That actually happend? Seriously, that was only a matter of time. I really wondered what all those individuals who try to make a buck with a patented molecule have in their minds. They can be lucky they got a warning, something like that could have ruined their enterprise completely.

 

I hope neuralstem will pubilish the dose-response curve of nsi, I'd love to know what is the most effective dosage is.


Edited by 5ht2a, 20 June 2014 - 06:07 PM.


#2102 SearchingForAnswers

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Posted 20 June 2014 - 06:48 PM

Yes, Ceretropic reposted the letter they received from Neuralstem's lawyers in the NSI-189 group buy thread, I believe.

 

Personally, I don't blame them for protecting their property. They developed it, their sweat, blood and tears. My only thing is, I don't want to wait 5 years for our snail-like FDA approval.


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#2103 DaneV

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Posted 20 June 2014 - 08:38 PM

I Received my NSI yesterday. After trying a very small dose yesterday (2mg), today was my first "real" dose of 30mg this morning, which i`m planning to raise to 40mg starting tomorrow. I Can confirm to the unique, bitter, "numbing" taste. As expected, nothing to report as of yet, apart from a mild headache. 

 

My situation: 27yo Male with GAD, SAD, Chronic depression/dysthymia and ADHD-PI. I Tried SSRI`s, Methylphenidate, Bupripion and numerous supplements before without any success. Only thing that worked really well for a couple of months was Tianeptine, but it completely stopped working after a while. Silently, I`m hoping the positive effects of Tianeptine were due to neurogenisis, and that I will experience something similair on NSI. 

 

I Will keep this thread updated on my findings. Any new updates from current users ?


Edited by DaneV, 20 June 2014 - 08:59 PM.


#2104 Flex

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Posted 20 June 2014 - 11:14 PM

No, I´ve tried just one time 40mg.

Will post the results when starting it.



#2105 nat

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Posted 21 June 2014 - 12:34 AM

I've had approximately 3/4g so far, dosage fluctuations at the beginning, now settled into 2x40mg daily. Will continue this cycle until my 3g stash runs out. These are my subjective effects (and, vaguely, their perceived intensity) so far. YMMV.

  • Improved sense of smell (medium)
  • Increased hunger (medium)
  • Improved depth perception (mild)
  • Cranial parasthesia (mild)
  • Dorsocranial pressure/ache (medium)
  • Increased average flow duration (medium)
  • Dry mouth (medium : high :: oral : subl)
  • Hollow tooth feel (low : medium :: oral : subl)
  • Increased propensity for canker sores (none : medium ::  oral : subl)
  • Increased musical focus (high)
  • Increased musical memory (high)
  • Improved visual memory (medium)
  • Improved linguistic memory (medium)
  • Decreased tip-of-tongue phenomenon (medium)
  • Increased morning energy (medium)
  • Sleep cycle advancement (high)
  • Increased semax side effects (medium)
  • Increased tianeptine side effects (medium)
  • Increased efficacy of tianeptine (low)
  • Increased efficacy of selank (medium)
  • Alleviation of MDD symptoms (high)
  • Alleviation of stimulant-induced mania (medium)
  • Decreased desire for classic stimulants (medium)
  • Decreased desire for classic depressants (medium)
  • Increased social confidence (low)
  • Increased sleep quality (medium)
  • Improved dream recall (low)
  • Increased correlation between dream content and recent events (medium)
  • Increased enjoyment of environmental temperature fluctuations (low)
  • Increased enjoyment of happy music (high)
  • Increased recognition of facial expressions (low)
  • Increased willingness to engage in salesmanship (low)
  • Increased libido (medium)
  • Increased control over libidinous impulses (medium)
  • Decreased immediate interest in diving down philosophical/ethical rabbitholes (medium)
  • Decreased internal monologue (medium)
  • Decreased need for perfection (medium)
  • Increased control over obsessive compulsions (low)
  • Increased self esteem (medium)
  • Decreased acceptance of current bodily appearance (low)
  • Immediate stimulant effect (none : low :: oral : subl)
  • Improved recognition of familiar somatosensory stimuli (medium)
  • Decreased general social anxiety (high)
  • Decreased situational anxiety (medium)
  • Increased willingness to eschew current social identity/tendencies (high)
  • Increased willingness to alter plans in-the-moment for longterm gain (low)
  • Increased willingness to stick to plans despite in-the-moment detriment (low)
  • Improved general mood (high)
  • Increased willingness to meditate (high)
  • Decreased verbosity in writing (low)
  • Decreased noticeable response to noopept (medium)

Other notes:

  • I've been stacking NSI-189 with ostarine. This combination has led to a dramatic improvement in piano skills for such a short time, by dint of increased fine motor endurance and ability to remember compositional/technical progress from sessions on previous days. Though interestingly my internal "musilogue" -- which has always been fairly disruptive of sleep and focus -- is fading.
  • For anyone that cares, I've now stacked semax, tianeptine, noopept and NSI-189, all of which are hippocampal growth agents, with no noticeable issues. That doesn't mean there aren't any. I won't be making a habit of doing that and don't suggest that others do. Though my regular use of these other substances over the past few months could be related to my quick response to NSI-189.
  • The most impressive effect besides the complete destruction of my depression is the sleep alteration. I'm waking up at 5:30am daily with no trouble at all and meditating in front of the sunrise for an average of 1 hour. This was not something I liked to do before starting NSI-189.
  • Other supplementary intake: multivitamin (with mostly 100% RDAs), 3g fish oil, 7000 IU vit D3, C60oo (just started today), 600mg NAC, 250mg anthocyanins, 200mg mag chelate, 500mg lemon balm, LEF vit K complex, 500mg bacopa, 250mg UMP, 50-100mg caffeine, 150-300mg theanine, 1000mg taurine
  • Stopped racetam use in general. Tried 20mg coluracetam today and the response was better than usual.
  • Diet includes a lot of eggs right now.

Edited by abc, 21 June 2014 - 12:47 AM.

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#2106 world33

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Posted 21 June 2014 - 02:51 AM

Wow great detailed report. Did you notice any increased visual acuity?

#2107 nat

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Posted 21 June 2014 - 03:11 AM

Wow great detailed report. Did you notice any increased visual acuity?

 

Don't want to speculate. Vision is improved in the sense that I'm observing certain types of things more effectively, but I haven't noticed any raw improvement in visual clarity. It would be hard to measure anyway, since my vision has been 20/12 in both eyes since getting PRK a year ago.

 

And with respect to visual memory, I've always been very good at manipulating 4D representations of objects/scenes in my head. It's hard to tell if an improvement of visual memory is due to improved internal manipulation, improved visual acuity or improved observational behaviors.

 

One thing I'm sure of is that there's no improvement in dim-light visual acuity.



#2108 jefferson

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Posted 21 June 2014 - 05:48 AM

 

Wow great detailed report. Did you notice any increased visual acuity?

 

Don't want to speculate. Vision is improved in the sense that I'm observing certain types of things more effectively, but I haven't noticed any raw improvement in visual clarity. It would be hard to measure anyway, since my vision has been 20/12 in both eyes since getting PRK a year ago.

 

And with respect to visual memory, I've always been very good at manipulating 4D representations of objects/scenes in my head. It's hard to tell if an improvement of visual memory is due to improved internal manipulation, improved visual acuity or improved observational behaviors.

 

One thing I'm sure of is that there's no improvement in dim-light visual acuity.

 

 

IMHO, people who are taking it for depression should take the Hamilton Depression Rating Scale before taking it, and then again a month after to see the effects rather than subjectively reporting how they feel.

 

People who are taking it for cognitive enhancement... I'd expect to see the most effects on spatial intelligence of different sorts. The posterior hippocampus is quicker to atrophy with age, and among other things, it is heavily involved in navigation and spatial representations. Is it easier to find your way around a new city?



#2109 DaneV

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Posted 21 June 2014 - 10:10 AM

I Took 40mg this morning on empty stomach, which gave me some temporary nausea. Will take it with food next time.

My Current (self assessed) HRSD score is 33.


Edited by DaneV, 21 June 2014 - 10:15 AM.


#2110 KieranA001

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Posted 21 June 2014 - 10:55 AM

What would your opinion be on taking NSI-189 with some Pramiracetam? Apparently, Pramiracetam seems to have a high affinity in influencing choline uptake into the hippocampus. Other areas of the cerebral cortex do not seem to be affected by the chemical. Pramiracetam is believed to strictly influence acetylcholine uptake and channel specific nerve impulses in the hippocampus. Maybe both of these could have a synergy of some sort?

 

Common Benefits of Pramiracetam:

  • Overall Improved Cognition
  • Higher Sensory Perception
  • Improved Working/Long-Term Memory
  • Increased Learning
  • Enhanced Focus
  • Advanced Logical/Technical Thinking
  • Unlocked Areas of Thought

 

I have heard that it increases the firing of the neurons in the hippo-campus, but it's recommended to take it with some choline to prevent headaches due to ACh burnout.



#2111 ByAnyMeansNecessary

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Posted 21 June 2014 - 12:13 PM

Greetings everyone,

 

I recently received my 2.5 gram sample of NSI-189 and proceeded with a full daily dose of NSI-189 (projected 80mg) just to see how I felt. I had take it immediately after work, and this had also been after I had taken my usual stack (though a little bulked up due to sleep issues).

 

I didnt notice much other than a slight pressure in my head. Its to new and brief for me to place it, but it wasnt uncomfortable. The only thing I can really say that was out of the ordinary was that yesterday night when I went to bed, I woke up at about 1am with this drive to "go do something". SO. I decided to go play a strategy game to try and think a little bit more outside the box. It is now currently 7:06am and I plan on taking a brief nap before dosing 40mg, going about my chores and getting stuff done. 

I plan on making a bunch of changes while on NSI-189-- like improving eating, and generally improving overall lifestyle choices and if this weird "experience" is anything that is indicative of its effects, then, making good changes may be really helpful. In particular, I plan on trying to stop smoking nicotine (I use a vaporizer).

 

I will continue to post my experiences here later. . : :-D 

 

 



#2112 idontknow

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Posted 21 June 2014 - 01:28 PM

I'm getting similar results as most here, although my dosing is just ~5mg of vlk's NSI roughly 3 times a week. I've gotten a lot better in regards to depression, social anxiety, cognitive functioning and I also did regularly test my reaction time, which has dramatically improved from ~260ms to ~220ms over like 3 months. I wouldn't solely attribute these changes to the NSI, as I was already gradually improving upon those issues before I started dosing. Though I feel like the NSI played a part in getting myself back together much more quickly.

 

The thing about depression, at least for me, always was that I believed my condition to be normal and that most others are dealing with the same grim reality. Only after I did improve, I realized how messed up my psyche actually was. 

 

Btw. I also donated to reimburse vlk for his losses. Hope he gets some of his money back. What happened to him is really unfortunate.


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#2113 VP.

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Posted 21 June 2014 - 07:27 PM

 

If somebody has a legitimate source for NSI-189, please pm me. Seems to have gotten scare since their lawyers gave ceretropic a warning!

 

 

That actually happend? Seriously, that was only a matter of time. I really wondered what all those individuals who try to make a buck with a patented molecule have in their minds. They can be lucky they got a warning, something like that could have ruined their enterprise completely.

 

I hope neuralstem will pubilish the dose-response curve of nsi, I'd love to know what is the most effective dosage is.

 

 

This is part of the slide presentation. The most interesting finding is that NSI-189, in a albeit small study, has better MARDS scores then any other antidepressant on the market. (http://www.nejm.org/...=articleResults) See summary appendix and figure 3.

 

Analysis of Efficacy:
 
1) SDQ data looks pretty darn good! Results were statistically significant at Day 28 (p=0.02) and Day 84 (p=0.03). No real dose response, suggesting that 40 mg QD may offer target saturation. Effect size (Cohen's d) was 0.9 at Day 28 and 1.1 at Day 84 (suggestive of large effect).
 
3.JPG Source: ASCP - M. Freeman, 2014
 
2) MADRS data looked just ok. Not quite as strong as SDQ, but separation from the placebo (albeit not statistically significant). Higher doses of NSI-189 looked to produce a more sustained effect, but p-values for individual cohorts was not provided.
 
4.JPG Source: ASCP - M. Freeman, 2014
 
3) CGI-I data was inconsistent, although did show a trend toward improvement by Day 84, especially with the highest dose of 40 mg TID (yellow line). We suspect that the 40 mg TID dose did offer statistically significant separation from the placebo, although this was not reported and the trial was not large enough to report individual cohort statistics.  
 
5.JPG Source: ASCP - M. Freeman, 2014
 
4) CPFQ data was the most impressive. This is Massachusetts General Hospitals own scale to assess depression and physical function (note the study took place at MGH). Results look excellent, with clear separation from the placebo at both Day 28 and Day 84 (both p<0.01) and strong effect size. Higher doses of NSI-189 looked slightly better.
 
6.JPG Source: ASCP - M. Freeman, 2014
 
More Data Next Week
 
Next week, at the 29th CINP World Congress of Neuropsychopharmacology meeting, additional data will be presented on the effects of the drug. Data should include quantitative electroencephalography (qEEG) discussion. We reached out to management to ask about MRI data. We were told that MRI data probably would not be presented at CINP, but that his analysis was still ongoing. So perhaps we will see MRI data when the Phase 1b results are published in a peer-review journal - which we fully expect to take place.

An abstract of the data can be found on the CINP website. We present that abstract below:
 
7.JPG Source: CINP Website, 2014
 
Summary Thoughts
 
We caution investors that these are very early-stage data in only 18 patients on active drug. The study was designed to assess safety and tolerability and not powered for efficacy endpoints. As such, reading too much into the results (bullish or bearish) is imprudent. However, in terms of a Phase 1b study, this looks very good. Safety was confirmed and there are clear trends toward efficacy. Next step is a multicenter Phase 2 study more statistically powered to show separation on the efficacy endpoints over a longer duration of time. We will have additional analysis after the presentation at CINP.
 
 

http://bionapcfa.blo...-ascp-oral.html


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#2114 DaneV

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Posted 21 June 2014 - 11:14 PM

Today has been a extraordinary smooth day for me. Allthough some stressful events happened, I did not dwell on them like I normaly do. Another thing that I noticed, is that my short term memory, which is normally a disaster, worked pretty well today. Someone even said I was less absent as I normally am.

I'm still counting on these effects to be either placebo or coincidence, but if this is really the NSI, I cant wait to feel the effects when it really kicks in.

#2115 world33

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Posted 22 June 2014 - 12:02 AM

Has anyone ever tried nasal administration (snorting) of NSI-189?
Apex at http://www.longecity...-11#entry670281 mentioned he tried with 7,8 DHF and had better results than sublingual administration. I guess I would try with the NSI-189 freebase version but I would be hesitant to try with the phosphate version considering the unpleasant effects in my mouth.
Also has anybody tried to inject the substances? I have no idea whether it is safe and I most likely would not try it.

Edited by world33, 22 June 2014 - 12:05 AM.


#2116 Lobotomy

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Posted 22 June 2014 - 01:18 AM

I have come into what I'm pretty sure is NSI-189. Let me describe it.

 

Taste is hardly noticeable until it hits the back of my tongue. Kind of plastic-y bitter taste, not as bad as most racetams.

 

Powder packs like Coluracetam.

 

Taking 40mg sublingual/oral 2x a day, notice some of a noopept-like sensation of an alteration of pressure in my head, maybe 40m-1hr after dosing, not unpleasant, but instead of just one part of my head, it covers all of it.

 

I feel insanely, almost unnaturally productive. Usually I'm extremely down in the dumps, defeatist, slow, fatigued. I still am, but not NEARLY as much, and I'm only my third day in. I feel like I have massive gains in headspace. Visualizing things is marginally easier, it almost feels like I have eyes in the back of my head, when I imagine a rough estimate of what is behind me, I'm pretty close.

 

Does this sound about right? Sounds like it could be placebo, so I'm not discounting the possibility. We'll see what happens in the coming months.

 

ONE LAST THING.  I want to send a sample to a lab for independent testing. How would I do that, how much does it cost, is it worth it, and how much would I send?


Edited by Lobotomy, 22 June 2014 - 01:21 AM.


#2117 themadscientist

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Posted 22 June 2014 - 02:00 AM

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.



#2118 nat

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Posted 22 June 2014 - 02:05 AM

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.

 

This is both correct and incorrect. Obviously neurogenesis takes much longer than a day. But almost everyone, including myself, has reported head pressure that is more prominent at the beginning and fades throughout the cycle. These reports are more or less the same for multiple sources of NSI-189.


Edited by abc, 22 June 2014 - 02:06 AM.


#2119 swolo

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Posted 22 June 2014 - 02:09 AM

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.

Neurogenesis does take weeks, but I don't think immediate effects and long term effects are mutually exclusive. Tianeptine produces a mild stimulant effect plus spurring neurogenesis. It could be that NSI-189 boosts a neurogenic precursor state immediately that fosters neurogenesis in the long term. FWIW, I also get the mild head pressure (not unpleasant) that others report.

#2120 themadscientist

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Posted 22 June 2014 - 02:11 AM

http://www.ncbi.nlm....les/PMC1413959/



#2121 themadscientist

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Posted 22 June 2014 - 02:16 AM

I have also experienced the mild head pressure, which I'm hoping is neurogenesis. But as for this individual, it's a 85% chance its just a placebo effect he is experiencing.



#2122 scarredforlife

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Posted 22 June 2014 - 02:44 AM

Can anyone explain to me how these charts fit the claimed U-shaped dose-response curve? From what I can see, 120mg showed better effects than 40 or 80mg in the long run.



#2123 VP.

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Posted 22 June 2014 - 02:56 AM

Can anyone explain to me how these charts fit the claimed U-shaped dose-response curve? From what I can see, 120mg showed better effects than 40 or 80mg in the long run.

 

A number of investors have asked that question with no answer so far. Maybe we will find out Tuesday when a more complete report comes out from Neurlstem.



#2124 VP.

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Posted 22 June 2014 - 03:01 AM

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.

If you look at the slides Neuralstem presented there were rather dramatic MARDS score reductions over a placebo. Ten days seems very short but the data is there, I don't know how to explain how it appears to work so fast.

4.JPG

 

http://bionapcfa.blo...-ascp-oral.html



#2125 DaneV

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Posted 22 June 2014 - 09:12 AM

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.


Wow, so you already know the exact pharmacodynamics of this drug... I think neuralstem will be happy to hire you.
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#2126 5ht2a

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Posted 22 June 2014 - 09:26 AM

 

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.


Wow, so you already know the exact pharmacodynamics of this drug... I think neuralstem will be happy to hire you.

 

 

Almost everyone starts to notice the effects after 1 Week. Strangely, although it does still get better after this until week 3-4, the fact that new neurons are ready to do neuron-stuff after 4-5 weeks doesn't provide (at least for me) any noticeable additional improvement of any kind.


Edited by 5ht2a, 22 June 2014 - 09:27 AM.


#2127 themadscientist

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Posted 22 June 2014 - 12:42 PM

Dane v their is no need to criticize me.

Based on the description of that post, it's seems he has only taken it for one day. I didn't start experiencing the head pressure in till my forth day in. So when I hear someone is feeling positive benefits on only the first day it becomes questionable to me.

#2128 VERITAS INCORRUPTUS

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Posted 22 June 2014 - 02:46 PM

I have a theory that simply the promotion of marked neurogenic signalling in and of itself creates signalling pathways of some nature that promote neurochemical signalling that results in antidpressant and mood-elevating effects.  This I theorize is generally universal to most all pathways of 'neurogenic' signalling (such as GDNF/BDNF/NGF neutrophic signalling, synaptogenic signalling, etc.) and likely also correlates in degree of rapidity of onset and how pronounced the degree of effects are relative to the strength of the signalling.  Promotion of cascades comprising multiple neurogenic pathways may be extremely potent as such and as well be synergistic.


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#2129 world33

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Posted 22 June 2014 - 11:11 PM

I felt positive effects the first day I took it as I wrote in a previous post. More focus and concentration, better visual acuity and slightly better energy. I was wondering why I would feel these effects even if neurogenesis take a long time to occur. I guess everyone is different and probably depends on the individual "starting threshold". Some people do not feel anything even after continuous intake probably because they do not need NSI-189 in the first place and there is no underlying problem that NSI-189 could address in the short term (?) or long term (adult neurogenesis). That is my 2 cents theory.
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#2130 Lobotomy

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Posted 23 June 2014 - 12:14 AM

It's really not possible to feel the effects of NSI-189 immediately. Neurogenesis takes time, and even after it does occur, it takes new neurons 4-5 weeks to become functional. So what you have is ether not NSI or you're just experiencing a placebo effect.

-----------------------------------------------------------------------------------------------------------------------------------------------------

 

Based on the description of that post, it's seems he has only taken it for one day. I didn't start experiencing the head pressure in till my forth day in. So when I hear someone is feeling positive benefits on only the first day it becomes questionable to me.

 

I don't think neurogenesis is the one-and-only effect of NSI. Also by the time of my posting, I was on day 3.

 

 


Edited by Lobotomy, 23 June 2014 - 12:16 AM.

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