Home Ingredients Nefiracetam (DM-9384)
CognitiveMood & Mental Health

Nefiracetam (DM-9384)

Synthetic — pyrrolidone derivative racetam
Evidence Level
Limited
3 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Pyrrolidone racetam developed by Daiichi Pharmaceutical (Japan, 1980s). RCT in poststroke depression with apathy showed positive effects — Starkstein 2016 follow-up RCT FAILED to replicate (very small sample). NIH-funded Phase 2 in Alzheimer's (completed). Marketed in Japan as Translon (withdrawn). Approved Russian indications. Limited rigorous Western evidence.

Studied Dose ROBINSON 2009 (poststroke apathy): 600-900 mg/day × 12 wk. NOOTROPIC: 150-450 mg/day in 2-3 doses. AD NIH: 600-900 mg/day. Half-life ~3-5 hr. Translon withdrawn. NOT FDA-approved.
Active Compound Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, Translon) — pyrrolidone racetam with dimethylphenyl substitution

Benefits

Poststroke depression with apathy (Robinson 2009 small POSITIVE)

Robinson 2009 (, J Neuropsychiatry Clin Neurosci) double-blind treatment of 13 patients with poststroke depression and apathy with nefiracetam. Reported significant improvement in apathy symptoms with nefiracetam vs placebo. POSITIVE small trial supporting potential utility in this specific clinical context. Limited by very small sample size.

Supported by Trial 1

Poststroke apathy RCT

Starkstein 2016 (, J Stroke Cerebrovasc Dis) randomized placebo-controlled double-blind efficacy study designed to replicate Robinson 2009. RESULTS: Treatment with nefiracetam DID NOT prove more efficacious than placebo in ameliorating apathy after stroke. Major limitation: very small randomized sample (of 2514 screened, only 144 confirmed eligible at 8-36 weeks poststroke). Authors concluded: 'pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.' Failed replication of Robinson 2009.

Supported by Trial 2

Alzheimer's disease (NIH-sponsored Phase 2)

NIH/NINDS-sponsored Phase 2 trial (Nefiracetam Therapy of Alzheimer's Type Dementia) completed. Tested whether nefiracetam can safely improve memory, thinking, and ADL in mild-moderate Alzheimer's. Mechanism: enhances acetylcholine-mediated and nicotinic receptor function. Results integrated into broader cholinergic dementia literature with mixed conclusions. Earlier small studies showed ~25% response at low dose, ~50% at higher dose.

Supported by Trial 3

Nicotinic acetylcholine receptor enhancement (mechanism)

Distinguishing feature among racetams: enhances NICOTINIC ACETYLCHOLINE RECEPTOR function. Different from typical racetams (AMPA, HACU) and from cholinesterase inhibitors. Theoretical basis for cognitive enhancement and possibly antiapathy effects. Mechanism interesting but clinical evidence mixed.

Supported by Trial 3

GABA-A modulation (anxiolytic potential)

Animal studies suggest nefiracetam has GABA-A receptor modulatory effects — possible anxiolytic mechanism. Theoretical relevance to combined mood + cognitive effects. Less clinically validated than other racetam mechanisms.

Supported by Trial 2, Trial 3

Mechanism of action

1

Nicotinic acetylcholine receptor enhancement

Nefiracetam enhances NICOTINIC ACh receptor activity — distinguishing it from cholinesterase inhibitors (which prevent ACh breakdown) and other racetams (which affect different mechanisms). Mechanism for proposed cognitive enhancement and antiapathy effects.

2

GABA-A receptor positive modulation

Modulates GABA-A receptors with possible anxiolytic effects. Mechanism for theoretical mood/anxiety benefits. Less robust than dedicated GABAergic anxiolytics (benzodiazepines).

3

Calcium channel modulation

Animal studies suggest nefiracetam modulates voltage-dependent and NMDA-coupled calcium channels — protecting neurons from calcium-mediated excitotoxicity. Mechanism for proposed neuroprotective effects in stroke models.

4

Cholinergic and glutamatergic enhancement

General cognitive enhancement via increased ACh release and modulated glutamatergic transmission. Mechanism similar to other racetams but with nicotinic emphasis.

Clinical trials

1
Robinson 2009 — Nefiracetam in Poststroke Apathy (Small Positive)
PubMed

Double-blind treatment of apathy in poststroke depression (Robinson RG, Jorge RE, Clarence-Smith K, Starkstein S 2009, J Neuropsychiatry Clin Neurosci 21(2):144-151, doi:10.1176/jnp.2009.21.2.144, PMID 19622685).

13 patients with poststroke depression and apathy treated with nefiracetam vs placebo. Apathy and depression scales measured.

Nefiracetam showed SIGNIFICANT IMPROVEMENT in apathy symptoms vs placebo. Foundational small positive trial that motivated larger confirmatory study. Limited by small sample (n=13). Hypothesis-generating evidence for nefiracetam in poststroke apathy specifically.

2
Starkstein 2016 — Larger RCT Replication (NEGATIVE)
PubMed

Randomized placebo-controlled double-blind efficacy study (Starkstein SE, Brockman S, Hatch KK, Bruce DG, Almeida OP, Davis WA, Robinson RG 2016, J Stroke Cerebrovasc Dis 25(5):1119-1127, doi:10.1016/j.jstrokecerebrovasdis.2016.01.032, PMID 26915605).

Of 2514 patients screened, only 377 (15%) eligible after first screening, 233 declined, 144 assessed for apathy at 8-36 weeks poststroke. Final randomized sample very small.

NEFIRACETAM DID NOT prove more efficacious than placebo in ameliorating apathy after stroke. NEGATIVE RCT. Failed replication of Robinson 2009 small positive study. Authors concluded: 'pharmacological studies of apathy in stroke will require large multicenter study and massive sample of patients' — acknowledging trial design challenges. Important counter-evidence to earlier positive findings.

3
NIH Alzheimer's Phase 2 Trial
PubMed

NIH/NINDS-sponsored Phase 2 trial (NCT00001933, Nefiracetam Therapy of Alzheimer's Type Dementia).

Mild-to-moderate Alzheimer's disease patients with caregiver and designated representative. Acute safety and antidementia efficacy tested in double-blind placebo-controlled parallel-groups design.

Nefiracetam enhances activity of nicotinic acetylcholine receptors (in contrast to cholinesterase inhibitors). Earlier small studies showed ~25% improvement at low dose, ~50% at higher dose in mild AD. Comprehensive Phase 2 results integrated into broader literature with mixed conclusions about clinical utility. Did not result in commercial drug approval.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated; safety profile similar to other racetams.
Mild GI upset (nausea, abdominal discomfort).
Headache.
Anxiety, irritability (less common than phenylpiracetam).
Pregnancy/lactation: avoid.
Long-term safety beyond 12 weeks: limited data.
Withdrawn from Japanese market (Translon) — practical availability limited.

Important Drug interactions

Nicotinic agonists/antagonists: theoretical interactions via nAChR modulation.
Cholinesterase inhibitors: theoretical complementary effects but limited evidence for combination.
GABA-active medications (benzodiazepines): theoretical additive effects.
Most medications: compatible at typical doses.
Limited interaction data due to small clinical research base.

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Frequently asked questions about Nefiracetam (DM-9384)

What is Nefiracetam (DM-9384)?

Pyrrolidone racetam developed by Daiichi Pharmaceutical (Japan, 1980s).

What does Nefiracetam (DM-9384) do?

Nefiracetam enhances NICOTINIC ACh receptor activity — distinguishing it from cholinesterase inhibitors (which prevent ACh breakdown) and other racetams (which affect different mechanisms). Mechanism for proposed cognitive enhancement and antiapathy effects. In clinical research, Nefiracetam (DM-9384) has been studied for poststroke depression with apathy (robinson 2009 small positive), poststroke apathy rct, alzheimer's disease (nih-sponsored phase 2).

Who should take Nefiracetam (DM-9384)?

Nefiracetam (DM-9384) may be most relevant for people interested in cognitive, mood & mental health. It has been clinically studied for poststroke depression with apathy (robinson 2009 small positive), poststroke apathy rct, alzheimer's disease (nih-sponsored phase 2). As with any supplement, consult your healthcare provider before starting, especially if you have medical conditions or take prescription medications.

How long does Nefiracetam (DM-9384) take to work?

Most clinical trial effects appear over weeks of consistent use; individual response varies. Acute or same-day effects (where applicable) typically appear within hours, but most cumulative benefits — particularly those affecting biomarkers, mood, sleep quality, or chronic symptoms — require 4-12 weeks of regular use to fully assess. If you don't notice benefit after 12 weeks at the appropriate dose, it may not be your responder.

When is the best time to take Nefiracetam (DM-9384)?

For cognitive goals, Nefiracetam (DM-9384) is typically taken in the morning with breakfast for sustained daytime effects. Avoid late-day dosing if it affects your sleep. Always check product labeling and follow personalized guidance from your healthcare provider.

Is Nefiracetam (DM-9384) worth taking?

Nefiracetam (DM-9384) has limited clinical evidence (Evidence Level 2/5 on NutraSmarts) — preliminary research suggests potential benefit, but more rigorous trials are needed. Whether it's worth taking depends on your specific goals, what you've already tried, your budget, and your overall supplement strategy. The honest framing: no supplement is essential for most people, and lifestyle factors (sleep, exercise, diet, stress management) typically produce larger effects than any single supplement. Nefiracetam (DM-9384) is most worth trying if its evidence-supported uses align with your specific goals.

What is the recommended dosage of Nefiracetam (DM-9384)?

The clinically studied dose for Nefiracetam (DM-9384) is ROBINSON 2009 (poststroke apathy): 600-900 mg/day × 12 wk. NOOTROPIC: 150-450 mg/day in 2-3 doses. AD NIH: 600-900 mg/day. Half-life ~3-5 hr. Translon withdrawn. NOT FDA-approved.. Always follow product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Nefiracetam (DM-9384) used for?

Nefiracetam (DM-9384) is studied for poststroke depression with apathy (robinson 2009 small positive), poststroke apathy rct, alzheimer's disease (nih-sponsored phase 2). Robinson 2009 (, J Neuropsychiatry Clin Neurosci) double-blind treatment of 13 patients with poststroke depression and apathy with nefiracetam. Reported significant improvement in apathy symptoms with nefiracetam vs placebo.