Read the full guides
NSI-189
Last reviewed: June 11, 2026 by The Peptide Catalog Team
A neurogenic small molecule that reached a Phase 2 depression trial which failed its primary endpoint; preclinical work reports hippocampal neurogenesis, now sold as a discontinued research chemical. NSI-189 is a small-molecule research compound studied for depression and neurogenesis; its Phase 2 depression trial missed its primary endpoint. Community-reported dosing is ~40-80 mg/day. Research use only.
Overview
Core Benefits
Key AdvantagesThese are educational summaries of commonly discussed effects in wellness/regenerative contexts, not guarantees.
NSI-189 Results Timeline
ProgressionTimeline is illustrative and non-guaranteed. Outcomes vary and are commonly discussed alongside training, nutrition, sleep, and cycling practices.
How It WorksNeurogenic Small Molecule — Mood / Cognition (Investigational; Phase 2 Failed Primary Endpoint, Development Discontinued)
Target → Signal → Effect → Outcomes
Hippocampal Neurogenesis — Proposed, Target Undefined
NSI-189 is a synthetic small molecule — a benzylpiperazine-aminopyridine, not a peptide — most commonly sold as the phosphate salt (CAS 1270138-41-4) and developed by Neuralstem. Its development rationale was stimulation of hippocampal neurogenesis, but the precise molecular target was never fully defined in the published record. The "neurogenic" label rests on preclinical models and a hippocampal-volume MRI signal, not a confirmed receptor.
LTP Enhancement via TrkB/Akt + BDNF — Preclinical
Preclinical work associates NSI-189 with increased neural stem cell proliferation, BDNF expression, and enhanced long-term potentiation (LTP) in hippocampal slices, with effects associated with TrkB and Akt pathway activation (Liu et al., 2019, PMID 30408487 — the cleanest mechanistic synaptic-plasticity evidence in the record). BDNF is reported downstream/associated, not a confirmed direct receptor mechanism. All of this is animal/in-vitro, not human.
Phase 2 Depression Trial Failed Its Primary Endpoint
NSI-189 reached human trials — and its pivotal Phase 2 study failed. The 220-patient, 12-week monotherapy trial in major depressive disorder (Papakostas et al., 2020, PMID 30626911) found no statistically significant MADRS improvement for either the 40 mg (p=0.224) or 80 mg (p=0.344) dose versus placebo. Some subject-rated secondary scales favored 40 mg and a hippocampal-volume increase was reported, but those are secondary and do not rescue a failed primary endpoint. A post-hoc analysis (PMID 32722729) is hypothesis-generating only.
Unvalidated for Enhancement in Healthy Users
Community users (anecdotal) describe improved mood, motivation, mental clarity, and a "neuroregenerative" or recovery-from-burnout sensation building over a multi-week course. Reports are inconsistent — some describe no effect, some describe a "blunting" or fatigue — and none is placebo-controlled. No trial has ever tested NSI-189 for cognitive enhancement in healthy people, so there is no validated enhancement effect to predict.
What Makes This Peptide Different
NSI-189 is unusual among nootropic research chemicals in that it reached human trials — and the headline is that its prospectively-defined Phase 2 primary endpoint for depression failed, after which clinical development was discontinued (Neuralstem's stock fell ~61% on the 2017 top-line miss). Its one genuine relative positive is short-term tolerability: the trials reported it was well tolerated at ≤12 weeks with no serious adverse events. It is not FDA-approved; material sold today is a research chemical, not for human consumption. Not a peptide — make that explicit so it is not mis-shelved.
NSI-189 Vendors
Dosing ProtocolMood / Neurogenesis (Investigational — Phase 2 Failed)
Educational reference only. Individual responses vary. Consult healthcare provider before use.
Why This Dosing Protocol
Form and route. The phosphate salt is the trial-used and more commonly stocked form; free-base powder is also sold. It is an oral small molecule (powder/capsule) — no reconstitution or bac-water step. Community sources describe time-limited courses mirroring the ≤12-week trial exposures, with no human safety data behind any specific cycle length.
Reconstitution Calculator
Dilution math and unit conversions. Prefilled using a common vial size for this peptide.
Open calculatorStorage & Handling
Storage at a glance
Proper storage temperatures, shelf life, reconstitution best practices, and travel tips for lyophilized and reconstituted peptides.
Handling specifics
Educational overview on storage, labeling, and traceability considerations for lab environments. Consult primary literature and vendor documentation for specifics.
- Freezer (-20°C): 1+ year
- Refrigerator (2-8°C): 1-3 months
- Room temperature: 2-3 weeks (emergency only)
- MUST refrigerate at 2-8°C
- 4-week maximum shelf life
- NEVER freeze after reconstitution
- Use bacteriostatic water for multi-dose
FAQ
Did NSI-189 work for depression in clinical trials?
No — its Phase 2 trial failed its primary endpoint. The 220-patient, 12-week Phase 2 study (Papakostas et al., 2020, PMID 30626911) reported no statistically significant MADRS improvement for either the 40 mg (p=0.224) or 80 mg (p=0.344) dose versus placebo. Some subject-rated secondary scales favored 40 mg, but the prospectively-defined primary endpoint was not met.
Is NSI-189 FDA-approved or still in development?
No. NSI-189 reached Phase 2 for major depressive disorder but is not FDA-approved, and the depression program did not advance to a successful Phase 3 after the 2017 top-line miss. It is a synthetic small molecule (a benzylpiperazine-aminopyridine), not a peptide. Material sold today is a research chemical labeled not for human consumption.
What dose do community sources report?
Community and vendor sources most commonly reference about 40-80 mg per day, taken orally once daily. That range is inherited directly from the doses used in the human depression trials — it is not a dose validated for cognitive enhancement in healthy users, and no such trial exists. There is no clinically-established enhancement dose.
What does the preclinical evidence show?
In rodents, NSI-189 has been reported to improve recovery in a stroke model (Tajiri et al., 2017, PMID 28181668) and to enhance synaptic plasticity and reverse cognitive/motor deficits in an Angelman-syndrome mouse model via TrkB/Akt activation (Liu et al., 2019, PMID 30408487). Its development rationale was stimulating hippocampal neurogenesis, but the precise molecular target was never fully defined. These are animal-model findings, not human-efficacy evidence.
Was NSI-189 well tolerated?
In its trials, yes — at ≤12 weeks. Phase 1B (PMID 26643541) and Phase 2 (PMID 30626911) reported it was well tolerated with no serious adverse events; the most common adverse events were headache, dizziness, and somnolence. There is no long-term human safety data. Community sources additionally describe irritability, fatigue or a "flat" feeling, and inconsistent mood effects — anecdotal and not placebo-controlled.
How long does reconstituted peptide last?
Once mixed with bacteriostatic water, peptides remain stable for up to 4 weeks when refrigerated at 2-8°C (36-46°F). Unopened powder can last 1+ year in the freezer. Get our complete Storage & Travel Guide.
Is this peptide legal to purchase?
Peptides sold "for research purposes only" are legal to purchase in the US, but are not FDA-approved for human use outside of specific medical applications. Always consult a healthcare provider before use.
New to peptides?
Take our Peptide Match tool to find the best peptide for your goals. You can also read our Complete Guide to Peptides to learn the basics.
NSI-189 Research Articles
NSI-189 Dosage: The 40-80 mg/day Trial Figure
NSI-189's 40-80 mg/day comes from a depression trial that failed its primary endpoint. See where the community dose really comes from.
side-effectsNSI-189 Side Effects: The Trial Safety Record
NSI-189 was well tolerated in trials at ≤12 weeks with no serious adverse events — but its Phase 2 failed and there is no long-term safety data. Graded by source.
resultsNSI-189 Timeline: What the Evidence Shows
Its Phase 2 depression trial failed the primary endpoint. So what does an NSI-189 timeline actually rest on? Trial data vs anecdote, labeled.
buying-guideBuy NSI-189: Price, COA & Cost Per Week
Only 1 vetted NSI-189 source right now: $22.99 a vial, $0.02/mg. Codes save up to 10%. COA status and real cost per week.
Disclosure: we may earn affiliate commission from qualifying purchases. Educational information only — not medical advice.