Compound · nsi-189
T3Nootropic

NSI-189 (Phosphate)

Small molecule neurogenic compound that stimulates hippocampal neurogenesis in adult human neural stem cells. Phase I/II data showed measurable hippocampal volume increases on MRI in depressed patients. Mechanism of neurogenesis stimulation is not fully characterized but appears to involve modulation of the PI3K/Akt signaling pathway and downstream CREB phosphorylation. Does not interact with known monoamine targets, making it mechanistically novel.

Half-life
6-10 hours (estimated from Phase I PK data)
Bioavailability
Not fully characterized (oral)
Route
oral
Evidence tier
T3 — Community / emerging
Optimization pillars
cellular-health
References
3 peer-reviewed
Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative
40 mg/day
Phase II clinical dose
moderate
40 mg 2x/day
Community-reported dose
aggressive
40 mg 3x/day
Not recommended without clinical oversight
Monitoring
  • alt
  • ast
  • creatinine
  • egfr
Contraindications
  • pregnancy
  • lactation
  • history-of-seizures
  • concurrent-maoi-use
  • bipolar-disorder
References
  • PMID:26907894NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural effects in depressed patientsNeuropsychopharmacology, 2016
  • PMID:30318083A Phase 2, double-blind, placebo-controlled study of NSI-189 phosphate in major depressive disorderJ Clin Psychiatry, 2019
  • PMID:25597878NSI-189 promotes neurogenesis in the hippocampusStem Cell Reports, 2015
Notes

NSI-189 sits at the frontier. Phase II data. Measurable hippocampal volume increases. A compound that appears to grow new neurons in adult humans. The Phase II depression trial missed its primary endpoint but hit multiple secondary endpoints. Neurogenics did not abandon the program because the compound failed. They abandoned it because depression trial design is brutally difficult. The self-experimenter community has accumulated years of anecdotal data. The pharmacological novelty is genuine. But this is a Tier 3 compound with incomplete safety profiling. The risk-reward calculus is personal.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

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