NSI-189
NSI-189 Phosphate — Neurogenic Antidepressant
What is NSI-189?
NSI-189 is a small molecule neurogenic compound discovered by Neuralstem Inc. that stimulates neurogenesis (new neuron growth) in the hippocampus — a region critical for memory, learning, and mood regulation. It completed Phase 2 clinical trials for major depressive disorder and shows promise as a cognitive enhancement compound beyond antidepressant applications.
NSI-189 stimulates hippocampal neurogenesis through mechanisms distinct from SSRIs, ketamine, or other known antidepressants. It increases the proliferation of neural progenitor cells in the dentate gyrus, increases hippocampal volume, and improves synaptic plasticity. The resulting hippocampal growth is associated with improved memory, cognitive flexibility, and mood stabilization.
Research Evidence
Phase 2 trial showed significant improvement in cognitive symptoms and some mood measures in MDD patients, with hippocampal volume increases on MRI. Primary endpoint for overall depression scores was not met, but the cognitive data was compelling.
Both in vitro and in vivo studies confirm NSI-189 stimulates neurogenesis in the dentate gyrus. Hippocampal volume increases have been documented in human Phase 2 participants.
Growing community use for memory, learning, and cognitive resilience. Subjective reports are consistent with the hippocampal neurogenesis mechanism. No Phase 2 data specifically for cognitive enhancement in healthy subjects.
Evidence grades: Gold = RCT human data · Silver = consistent animal/human data · Bronze = limited or preliminary
Dosing Protocols
Reconstitution Guide
This compound does not require reconstitution — it is available as a pre-mixed injectable or oral formulation.
Frequently Asked Questions
Is NSI-189 an antidepressant?
NSI-189 was developed as an antidepressant and completed Phase 2 trials for MDD. The primary depression endpoint was not statistically met, but cognitive symptom improvements were significant. It is more accurately described as a neurogenic compound with antidepressant-adjacent effects rather than a conventional antidepressant. Community use focuses heavily on the cognitive enhancement profile.
How long does NSI-189 take to work?
Hippocampal neurogenesis is a slow process — new neurons take weeks to integrate into existing circuits. Phase 2 participants showed measurable hippocampal volume increases at 12 weeks. Community reports suggest subjective cognitive improvements often become noticeable at 4-8 weeks of consistent use.
References
- [1]Fava M, Johe K, Ereshefsky L, et al. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2016;21(10):1372-1380.
- [2]Johe K, et al. NSI-189, a small molecule with neurogenic properties, promotes hippocampal neurogenesis and improves cognitive function in mouse models. Neuropsychopharmacology. 2015.
This profile was prepared using AI-assisted research synthesis. Citations are provided where applicable — verify with primary sources before clinical application.
Share this article