NSI-189

NSI-189 is an experimental nootropic and neurogenic compound developed by Neuralstem, primarily studied for its potential in treating major depressive disorder (MDD) and cognitive impairment. Its chemical name is (benzylpiperizine)nicotinamide, and it is classified as a small-molecule hippocampal neurogenic agent. Unlike traditional antidepressants, which usually target monoamine neurotransmitters like serotonin or dopamine, NSI-189 is thought to work by promoting neurogenesis, the growth and proliferation of new neurons in the hippocampus—a brain region crucial for memory, mood regulation, and learning.

​

Mechanism of Action:
NSI-189 appears to stimulate the proliferation of neural stem cells in the hippocampus. By increasing hippocampal volume and enhancing neural connectivity, it may improve cognitive function and alleviate depressive symptoms. Preclinical studies in rodents demonstrated enhanced neurogenesis and improved performance on learning and memory tasks, suggesting potential cognitive enhancement effects.

​

Clinical Research:
NSI-189 has been evaluated in early-phase clinical trials for depression and cognitive impairment associated with MDD. Phase 1 and Phase 2 trials reported that the compound was generally well-tolerated, with mild side effects such as headache, nausea, and fatigue. Some patients showed modest improvement in depressive symptoms and cognition, though results were variable and larger trials are needed to confirm efficacy.

Potential Benefits:

• Antidepressant effects without directly targeting monoamines

• Cognitive enhancement, particularly in memory and learning

• Potential neuroprotective effects due to hippocampal regeneration

• May support mood stabilization and resilience against stress

Limitations and Considerations:

• Still experimental, not approved by the FDA for clinical use

• Long-term safety and efficacy data are lacking

• Effects may vary significantly between individuals

• Mechanism of neurogenesis in humans is not fully understood

​

Forms and Dosage:
In research studies, NSI-189 has been administered orally, often in capsule form, with doses ranging between 40 mg to 80 mg per day for up to 28 days. Because it is experimental, there is no standardized therapeutic dosing or guideline for general use.

​

In summary, NSI-189 is an experimental neurogenic compound with promising but preliminary evidence for mood improvement and cognitive enhancement. Its primary appeal lies in stimulating hippocampal growth rather than altering neurotransmitter levels directly, positioning it as a novel approach to depression and cognitive dysfunction.

​

NSI-189 is still an experimental compound, so there is no officially approved dosing protocol. The dosing information we have comes from early clinical trials, mostly Phase 1 and Phase 2 studies for depression. Here’s a detailed breakdown based on those studies:

​

1. Typical Clinical Trial Dosing:

• Oral administration: Usually in capsule form

• Doses tested: 40 mg, 40 mg twice daily (80 mg/day), and 40 mg three times daily (120 mg/day)

• Duration: Typically 28 days in most studies, though some trials went slightly longer

2. Observations from Trials:

• The compound was generally well-tolerated at all doses.

• Most reported side effects were mild, including headache, nausea, fatigue, or mild gastrointestinal upset.

• There was no clear dose-response relationship in terms of efficacy, though higher doses were generally safe.

3. Key Points to Consider:

• There is no established therapeutic dose, so using it outside of a clinical trial is experimental and carries unknown long-term risks.

• NSI-189’s effects may take weeks to appear, as neurogenesis is a gradual process.

• Because it targets hippocampal growth, abrupt changes in dosing are not likely to produce immediate effects.