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.

Disclaimer: 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 clinical and scientific literature.

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]:

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

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:

• 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