

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.
Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
What is 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 depressive disorder (MDD) [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
- Ischemic (lack of blood flow or oxygen to the brain) stroke associated
- 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) May Improve Depression
NSI-189 showed promise treating depression and cognitive impairment in a study (double-blind randomized controlled trial) consisting of 24 people split into these three groups [R]:
- 40 mg once a day or placebo
- 80 mg (40 mg twice a day) or placebo
- 120 mg (40 mg three times a day) or placebo
The NSI-189 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].
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2) May Benefit Stroke Patients
Since it can increase nerve cell formation (neurogenesis), NSI-189 shows promise as a potential therapy for those that experienced a stroke to improve brain structure and function [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 increased neurogenesis 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 (a marker for cellular proliferation) production [R].
- Increased BDNF and SCF [R].
3) May Improve Cognitive Function
In a study of 24 depression patients (double-blind randomized controlled trial), 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 a result of overall neurogenesis [R].
4) May Help Increase Neuron Formation
The hypothesized mechanism for NSI-189 was neurogenesis mainly in the hippocampus [R].
At day 28, NSI-189 showed a non-significant growth in the hippocampus and amygdala when compared to placebo [R].
Post-study, the left side of the hippocampus showed a moderate increase (but not statistically significant). 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 involved in the mechanism of the drug [R].
Limitations and Caveats
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
- The disappearance of suicidal thoughts
However, users also report side effects including contradictions to other users such as:
Alan, that was an amazing response. On a COMPLETELY UNRELATED note, where do you buy your meth?
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
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?
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
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
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.