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Modern antidepressants focus on the monoamine neurotransmitter system (serotonin, dopamine, noradrenaline, and even histamine and melatonin), but only two-thirds of the patients treated for major depression achieve clinically significant improvements. Available antidepressants have side effects that could negatively affect treatment. The largest potential for advances in treatment may require creating medications that use different mechanisms, which is what NSI-189 attempts to do. If you’re interested in cognitive enhancement that my clients and I have used for awesome results you should check out our book, SelfHacked Secrets. To receive the first chapter free click here.

Introduction to NSI-189

NSI-189 is an experimental antidepressant. Neuralstem, Inc is currently testing it for use in major depression, in addition to treating cognitive impairments, and brain degeneration. It may induce specific brain regeneration [R].

NSI-189 is most likely selective only to two nervous system controlling regions in the brain (hippocampus, subventricular zone) [R].

NSI-189, as of June 2017, failed phase II clinical trials for Major Depression Disorder [R].

According to the developer, NSI-189 is still currently in preclinical trials for [R]:

  • Cognitive Impairment and radiation-induced cognitive impairments
  • Diabetes-related weakness, and numbness and pain from nerve damage
  • Strokes associated with lack of blood flow or oxygen to the brain
  • Angelman Syndrome (a genetic disorder causing developmental disabilities and nerve-related symptoms)

NSI is experimental and no one knows the long-term side effects of the drug. The clinical trials being done were performed by the drug company selling it, so suspicion is always warranted until there are large-scale independent clinical trials.

Potential Uses of NS1-189

1) NSI-189 May Improve Depression

NSI-189 showed promise treating depression and cognitive impairment in a clinical trial (DB-RCT) consisting of 24 people split into these three groups [R]:

  1. 40 mg once a day or placebo
  2. 80 mg (40 mg twice a day) or placebo
  3. 120 mg (40 mg three times a day) or placebo

NSI-189 was relatively well-tolerated at all doses in this study shown in this table [R]:



The NSI group had significant improvements in depression symptoms compared to the control group starting from day 28 up to the follow-up (day 84). However, clinical significance was only shown in self-rating scales [R].

2) NSI-189 May Benefit Stroke Patients

Since it can increase nerve cell information, NSI-189 shows promise as a powerful stroke therapy [R].

Scientists gave rats NSI-189 6 hours after an induced stroke. NSI treatment that continued for 12 weeks post-stroke resulted in significant improvements in brain and motor deficits. This improvement lasted 24-weeks post-therapy [R].

NSI also helped remodel rat’s brains post-stroke and showed an overall improvement in the initial six months [R].

Mechanisms Observed:

In animals

  • There was new neuron development in the brain (observed by MAP2 immunoreactivity in the hippocampus, and partially the cortex) [R].
  • Reversed-oxygen glucose deprivation and reperfusion (OGD/R) cell death, indicated by MAP2 and Ki67 production [R].
  • Increased BDNF and SCF [R].

3) NSI May Improve Cognitive Function

In a study of 24 depression patients (DB-RCT), NSI-189 increased self-reported cognitive function [R].

More studies need to be done to determine if this was due to the reduction of depression symptoms, or specific effects of the neurogenesis effects [R].

4) NSI-189 May Help Increase Neuron Formation

The hypothesized mechanism for NSI-189 was neurogenesis (birth and growth of neurons that may repair parts of the brain) mainly in the hippocampus [R].

At day 28, NSI showed a non-significant growth in the hippocampus and Amygdala when compared to placebo [R].

Post-study, the left side of the hippocampus had medium (but not statistically significant) increases. There were similar effects on the right side of the amygdala [R].

The results failed to show selectivity at the hippocampus, which was previously hypothesized to be the mechanism of the drug [R].


There is a lack of human clinical trials, and the current trials only have a small sample size. Caution should be taken when using NSI-189 for its purported health benefits [R].

It’s important to note this is a new drug, with no long-term studies. Selfhacked does not condone the use of this or any drugs. This article is for informational purposes only.

User Experiences with NSI-189

NSI-189 while not being a well-studied, has been praised highly in the nootropics community.

Users report benefits such as:

  • Ability to control emotions that continues after quitting
  • Being fluent in speaking and writing
  • Improvement in memory
  • Slight energy boosts
  • Sharpness of vision
  • A connection between logical and emotional processing
  • Increased sexual enjoyment
  • Increased social ability
  • Motivation
  • Improving depersonalization
  • Making better life decisions
  • Disappearance of suicidal thoughts

However, users also report side effects including contradictions to other users such as:

  • Irrational anger
  • Fatigue
  • Drowsiness
  • Panic attacks and Anxiety
  • Social phobia
  • Caring less about important things like deadlines
  • Tingling, crawling, itching sensations
  • Nerve pain
  • Headaches
  • Memory issues
  • Cognitive impairment

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.


1 Star2 Stars3 Stars4 Stars5 Stars (46 votes, average: 4.65 out of 5)


  • Bob

    Alan, that was an amazing response. On a COMPLETELY UNRELATED note, where do you buy your meth?

  • Alan

    Thanks Joe
    I thought my body over reacted to eating a pizza, while I was away from my local area. I knew that I was going to hit peak hour traffic which has now become most of the day etc. I took the easy option once and I thought I had slipped back like we call snakes and ladders, I believe you call it shuts and ladders. As you know Australia has the deadliest snakes and spiders in the world so atleast I over reacted after being unwell all my life and the incarnations of previous diseases remind me of all the dramas I have suffered. I thought my parents were resilient for what they went through, which I believe was even worse than I have gone through. I apparently have hot that resilience as well. It comes out at being alarmist or over reacting and we hope like anything people are around to help. And I thank you Joe for hearing my call for help. I am living in hope,that there will be more people like you in the future. Australia hasn’t had a recession in 25 years and in this way I believe everyone in the world is similar. It’s the only thing that connects us to our neighbours. Suffering seems the link that binds us, wars poverty etc we look for a helping hand and hope it’s their. Compassion is humanitys greatest gift to others and to yourself. You just have to be willing to help.
    Thank you Joe, My body recovered overnight

  • JP

    I am curious since you say you personally consider it an amazing substance, how long have you been taking it and in which doses? What effects stated in the article would you say you experience with NSI-189 and which of the side effects?

  • eloc adra

    Sometimes things look good with small sample sizes and due to various other factors fail to measure up in bigger tests. I personally will say that NSI is an amazing substance

  • Alan Newman

    I think this drug is a synthetic form of Curcumin and they haven’t ironed out all the kinks in the drug yet and is biosimilar so they can charge the consumer 1000 times or more for a less effective product as other pharma have done for cheap pill based corticosteroids and Acthar gel. Another cash grab by pharma.
    p.s. thanks joe your notes have seriously helped me

  • gregg

    I don’t understand how NB-189 can show a significant reduction in depressive symptoms in self-reporting, yet be considered to have failed it’s phase 2 clinical trial? Definitely something that needs more study and warrants Selfhacked following it closely.

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