The 4+ Benefits Of NSI-189 (With Mechanisms)

NSI-189 Improves Cognition and Depression 

NSI-189 is a new antidepressant and cognitive booster.

Unlike other antidepressants such as SSRIs or MAOIs, NSI-189 appears to work on other independent mechanisms.


  1. Basics
  2. Benefits Of NSI-189
  3. My Experience And Others
  4. Where To Buy NSI-189
  5. Caveats
  6. Mechanism Of Action
  7. Possible Other Mechanisms Of Action (Speculation)



NSI-189 is an antidepressant and neurogenic chemical that may be able to improve cognitive function, treat traumatic brain injury, Alzheimer's Disease (AD), Post-Traumatic Stress Disorder (PTSD), and stroke, and prevent cognitive and memory decline in aging. R

Benefits Of NSI-189

1. May Improve Cognition

NSI-189 may improve cognition. R

It can improve Long-Term Potentiation (LTP). R

For example, in genetic altered mice to have Angelman Syndrome, NSI-189 taken orally could return LTP to these mice. R

NSI-189 may also protect against radiation-induced memory impairment. R

NSI-189 can also increase neurotrophic factors such as Stem Cell Factor (SCF), Brain-Derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and Glial-Derived Neurotrophic Factor (GDNF). R

2. May Improve Depression


Destruction of the hippocampus is a common pathology in Major Depressive Disorder (MDD). R

NSI-189 may effectively treat MDD as well as other psychiatric disorders by increasing neurogenesis (growth) in the hippocampus. R R

Although in 2017, it was announced that a phase II clinical trial with 220 patients failed to meet its primary effectiveness endpoint in MDD. R

3. May Help With Stroke 

NSI-189 may improve motor function and hippocampal deficits seen in oxygen-deficit (hypoxia) stroke. R

One reason for this is by NSI-189's ability to significantly increase the neurotrophic factors VEGF, BDNF, GDNF, and SCF. R

For example, in mice that were given a stroke, NSI-189 treatment continually helped improve deficits in these mice, even after cessation of the drug. R

4. May Help With Diabetes

NSI-189 may be able to protect nerves from toxicity in diabetes. R

It may help with nerve pain and neuropathy in diabetes. R

My Experience And Others

My Experience

I bought 5g of both the phosphate and freebase version, totaling 10g.

When I tried NSI-189 I started at the lowest there's possible just a test to see if I had any adverse reactions so I started just for some powder on my tongue.

Unlike others, I needed a very low dose and I could feel the effects quite rapidly.

7mg of freebase sublingual (tasted awful) had amazing effects on increasing my energy, improving my mood, help me think clearly, and make colors more saturated/vibrant.

This pairs really well with priming (15 min visualization meditation):

  1. Take 7mg sublingual 
  2. Prime with nsi under tongue
  3. When priming is over the mediation + nsi have even more pronounced effects on my emotions/wellbeing 

Since I am highly reactive to this substance (acutely and at a small dose), I only use this on occasion when I need it.

I have enough to last a while.

Others Experience

Some people on the forums have reported NSI-189 helping improve their cognition, depression, anhedonia, anxiety (mixed), visual clarity, verbal fluency, better control over emotions, and mania. R R R R R R

People report that freebase works better sublingually than phosphate, with less gastric distress. R

Here is a compiled doc of 81 reports on NSI-189 by users -

Here is a compiled list of perceived benefits by users -

Here is a compiled list of side-effects by users -

Some have reported it mixes well with Tianeptine or Noopept, but not well with racetams.

A few of my friends have taken NSI-189, and it has helped with their depression as well as improving hangover symptoms. 

Where To Buy NSI-189

Unfortunately I can't really help you here.

You'll have to do some digging around to find the substance.

Neuralstem has cracked down on vendors and the patent for NSI-189 doesn't expire until 2035. R

Hopefully in the future if NSI-189 does well, it will be a prescription.



NSI-189 have very limited research in humans and most trials have been on animal models.

Side effects reported have been dry mouth, palpitations, headaches, dizziness, sleepiness, fatigue, restlessness, poor quality of sleep, nightmares/vivid dreams, parathesia, insomnia, hyperthermia, nausea, skin pain, and rash. R

It seems to be non-toxic in high doses for long term in beagle dogs and mice. R

That being said, a phase 1B randomized multiple dose escalation study reported that administration of 40 mg doses of NSI-189 once/day, 40 mg twice/day, and 40 mg three/day for 28 days resulted in a mean half-life of 17.4 +/- 3.06, 20.5 +/- 3.51, and 18.6 +/- 4.14 hours respectively, with a study state reached within 96-120 hours.. R

I don't condone to taking any drugs without consulting with your Healthcare provider.

Mechanism Of Action


  • Increases BDNF R
  • Increases Cullin R
  • Increases F-box R
  • Increases GDNF R
  • Increases Skp R
  • Increases VEGF R


  • NSI-189 is a benzylpiperizine-aminiopyridine. R
  • It may pass the blood-brain barrier. R
  • In humans in vitro as well as rodents in vivo, NSI-189 stimulates neurogenesis in hippocampal slices (specifically profound in the dentate gyrus). R
  • In humans in vivo, NSI-189 improves (not entirely significant) the left side of the hippocampus. R
  • It reportedly has no effects on monoamine transporters/receptors or amino acid targets. R
  • After stroke, NSI-189 may increase Ki67 and MAP2.  R
  • As well as increasing BDNF, GDNF and VEGf, NSI-189 works on the Skp, Cullin, F-box containing complex (or SCF complex). R

Possible Other Mechanisms Of Action (Speculation)

  • Increase hippocampal size (by 20%)
  • Improves glucocoritcoid resistance (possibly modulating aldosterone receptors) R R
  • TRPV1 antagonist R
  • Norepinephrine-dopamine reuptake inhibitor with binding affinity to: R 
    • Delta-opioid
    • Dopamine Transporter 
    • Mu-opioid 
    • Norepinephrine Transporter 
    • 5-HT 
    • 5-HT3
    • 5-HT7