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Synthetic nootropics & research compounds

NSI-189

NSI-189 (ALTO-100)

NSI-189, also developed as ALTO-100, is an investigational synthetic compound. Controlled patient trials have missed primary endpoints; they do not establish healthy-user memory or focus benefits. Clinical dose context is for oral phosphate. Compare free-base and phosphate labels separately, then check labeled content, batch testing and local rules.

Memory SupportMood SupportNeurotrophic PathwaysSyntheticClinical ResearchLimited Human EvidenceMixed Evidence
Updated October 2026/5 min read/10 citations
Reviewed by the NootropicsIndex editorial team.Method: prioritize cited human research and official safety or regulatory sources; compare retailer-listed prices without endorsing products.Affiliate disclosure
01

What is it?

What NSI-189 is

10

NSI-189 is an investigational small molecule originally developed by Neuralstem. The former owner's SEC filing identifies its later development code as ALTO-100. Published phosphate trials and retail free-base products should not be assumed clinically equivalent.

What changed in the later trial?5
Alto's six-week, 301-person study missed its primary endpoint and pre-specified key secondary analyses. Earlier exploratory findings have not established a reliable healthy-user nootropic benefit.
02

Names, aliases and forms

Research CodesNSI-189; ALTO-100
Spelling VariantNSI189
Salt FormNSI-189 phosphate
Freebase FormNSI-189 free base
03

Mechanisms of action

Neuroplasticity is a hypothesis

2

Cell and animal work motivated a hippocampal neuroplasticity hypothesis. Human trials do not demonstrate that retail NSI-189 products grow neurons or reliably improve cognition.

04

Potential effects and evidence map

Evidence is limited and population-specific. The 220-person phosphate trial missed its primary clinician-rated depression endpoint; some self-rated outcomes and CogScreen tests favored the lower dose, while Cogstate did not. In 2024, Alto reported that a separate 301-person ALTO-100 trial also missed its primary and key secondary endpoints. Neither establishes enhancement in healthy adults.

Effect domainMagnitudeGrade
Mood / wellbeing5
CumulativeConfidence: Medium

Earlier secondary self-report signals in patients remain exploratory; the later ALTO-100 trial missed its primary and key secondary endpoints.

Note Mixed patient findings do not establish a mood benefit in healthy adults.

1/5
C
Memory / learning2
CumulativeConfidence: Low

Selected CogScreen measures differed in the earlier patient trial; Cogstate did not. Healthy-user learning benefits remain unestablished.

Note Exploratory cognition analyses used no multiplicity correction and require replication.

1/5
C
Focus / attention2
UnknownConfidence: Medium

The cited patient trials do not establish acute attention or productivity enhancement in healthy adults.

Note Patient cognition outcomes cannot establish healthy-adult enhancement.

0/5
E
05

Typical dosages and timing

Typical
40-80 mg/day
Not a recommendation
Lower bound
40 mg
Profile value
Upper bound
80 mg
Profile value
Published phase 2 context240-80 mg/day

The trial used two six-week stages with monitored oral phosphate. This is a study-dose range, not an established consumer regimen or a conversion for free-base products.

Phase 1b context140-120 mg/day

The small 28-day inpatient study used once-, twice- or three-times-daily administration. Escalation was reviewed by a safety board; these data do not validate increasing a retail-product dose.

06

Timing & effect horizon

Effect horizonUnknown
Unknown
Plasma peak1Acute
1-2 hours
Half-life1Acute
17.4-20.5 hours
Study window2Cumulative
12 weeks
Plasma timing versus felt effects1

The phase 1b phosphate study measured plasma peak and The time for blood levels to fall by half during the final elimination phase.Source. Plasma peak means the highest measured blood concentration; half-life means the time for concentration to fall by half. Neither establishes when a cognitive effect begins or how long it lasts.

Duration and cycling2

The featured study window describes observation time. The cited trials establish neither a healthy-user onset nor an evidence-based cycle, washout schedule or single-dose effect duration.

07

Safety, side effects and risk profile

How to read the low risk rating1
Somnolence in the small early trial can affect alertness, making a minimal rating insufficient despite generally favorable short-term tolerability. Low is a provisional assessment for ordinary oral phosphate exposure in adults without major comorbidity; it is not a safety endorsement for unverified products, free-base formulations or extended use.
Legal / regulatory risk6
Confidence: High

U.S., as of 14 October 2026: ALTO-100 remains investigational under the developer's FDA approval disclaimer.

Note Approval status does not establish a global purchase or import ban. Regulatory caution is separate from base pharmacological risk.

2/5
C
Evidence uncertainty2
Confidence: High

Healthy-user benefits and long-term consumer safety are not established by the cited short-term patient trials.

Note Uncertainty is a limitation, not evidence of severe toxicity.

2/5
C
Interaction risk2
Confidence: Low

A complete consumer interaction profile is unavailable; trial eligibility rules constrain what combinations were evaluated.

Note The older trial excluded antidepressants, antipsychotics, buspirone and lithium, while allowing several stable concomitant medicines. Exclusion is not proof of a harmful interaction.

2/5
C
Pregnancy / lactation caution2
Confidence: High

Pregnant and lactating participants were excluded from the published phase 2 study; their safety cannot be inferred from its results.

Note Precaution based on missing reproductive data, not a demonstrated reproductive toxicity rate.

2/5
C
Headache / dizziness1
Confidence: Medium

Headache and dizziness were reported in the small phase 1b trial; headache was equally common in active and placebo groups.

Note Small cohorts make frequencies imprecise. The 2024 sponsor report found common adverse events at rates similar to placebo.

1/5
C
Sedation / impairment1
Confidence: Low

Somnolence occurred in 5 of 18 active participants and 1 of 6 placebo participants in phase 1b.

Note This small-sample alertness concern supports low short-term concern; it does not establish severe toxicity or safety of retail free-base products.

2/5
C
Trial safety has limits2

The larger published trial reported no serious adverse events in active groups and one later-stage discontinuation for intolerance. Pregnancy, lactation, major medical illness and several psychiatric histories were excluded. Retail purity and long-term safety were not assessed.

08

Interactions and cautions

Incomplete interaction data2

The older monotherapy trial excluded some psychiatric medicines and allowed others only at stable doses. Later adjunctive development does not validate arbitrary combinations with alcohol, stimulants or other research compounds.

09

Legal and regulatory status

As of 14 October 20266

Alto lists ALTO-100 as an investigational candidate and carries a U.S. FDA approval/indication disclaimer. This documents U.S. development status, not a global controlled-substance classification or a determination that any retail product may lawfully be imported. Other jurisdictions and product claims require separate checks.

10

Practical buying and quality notes

  • Phosphate is a salt containing the free-base molecule plus phosphoric acid. Equal labeled masses of salt and free base are not equal amounts of the parent molecule. Check whether a label states salt mass or base-equivalent mass before comparing price per gram; chemical arithmetic alone does not establish bioequivalence.8
  • A label stating 60 capsules at 20 mg each implies 1,200 mg, or 1.2 g, of labeled content. Compare package price divided by that total only with the same form and labeling basis. Add shipping and check lot-specific identity/purity testing; a certificate of analysis (COA) does not establish clinical safety.8
11

FAQ

What is the latest ALTO-100 status?

9

In its 12 August 2026 update, Alto said bipolar-depression enrollment remained ongoing and expected topline data in mid-2027. That forecast is not a positive clinical result.

Is there an established NSI-189 dosage?

2

The dose rows give published phosphate research exposure, not a recommended consumer dose. They do not validate free-base substitution, personal titration or a healthy-user regimen.

How long does NSI-189 take to work, and should it be cycled?

2

A reproducible healthy-user onset and cycle schedule have not been established. The study window and plasma measurements answer different questions and cannot supply a cycle length.

What should I compare before following an offer?

8

Start with chemical form, salt-versus-base labeling, total content and final delivered price. Check the testing laboratory, lot/date and identity evidence, then review the jurisdiction-specific legal context above. A retailer listing does not demonstrate efficacy or product quality.

12

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. Molecular Psychiatry. 2016;21:1372-1380.
  2. Papakostas GI, Johe K, Hand H, et al. A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate among outpatients with major depressive disorder. Molecular Psychiatry. 2020;25:1569-1579.
  3. ClinicalTrials.gov. Study of NSI-189 for Major Depressive Disorder. NCT02695472.
  4. ClinicalTrials.gov. Effect of NSI-189 Phosphate in Depression Patient Subjects. NCT01520649.
  5. Alto Neuroscience. Topline results from the Phase 2b ALTO-100 trial in major depressive disorder. 22 October 2024.
  6. Alto Neuroscience. Pipeline: ALTO-100.
  7. PubChem. NSI-189 free base, CID 50922681.
  8. PubChem. NSI-189 phosphate, CID 50922680.
  9. Alto Neuroscience. Second Quarter 2026 Financial Results and Recent Business Highlights. 12 August 2026.
  10. Palisade Bio. Form 10-Q for the quarter ended 31 March 2026: NSI-189 asset transfer and ALTO-100.
Note

This page is informational and summarizes available evidence. It is not medical advice, a recommendation, or a substitute for guidance from a qualified clinician.