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Nefiracetam is a nootropic compound of the racetam family with similarities to Aniracetam. It seems to enhance both GABAergic and cholinergic signalling, and long term usage appears to be both neuroprotective and nootropic in research animals (similar trends in human studies).

Our evidence-based analysis on nefiracetam features 95 unique references to scientific papers.

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Summary of Nefiracetam

Primary information, health benefits, side effects, usage, and other important details

Nefiracetam is a cognitive enhancer (nootropic) of the racetam class, derived initially from the parent molecule piracetam but it shares most structurally similarity to aniracetam. Both nefiracetam and aniracetam are fat soluble racetam drugs for the purpose of memory enhancement or the treatment of cognitive decline.

In regards to acute usage, a single dosage of nefiracetam does not appear to significantly affect memory formation. Nefiracetam appears to be able to increase memory formation when taken daily over a prolonged period of time (7 days or longer), which has been repeatedly shown in animal studies with some limited human evidence suggesting the same. Prolonged supplementation is also associated with a higher rate of neurogenesis, which is not seen acutely.

The mechanisms of nefiracetam seem to be linked back to two pathways. One of these pathways is prolonging the opening of calcium channels (tied into PKA and a Gi/o protein) which enhances signalling of a receptor independent of the synapse, and the other pathway seems to be tied into PKC and CAMKII which then augments signalling through cholinergic receptors (which then releases most excitatory neurotransmitters from the presynaptic level in a manner similar to nicotine).

The former pathway (calcium channels) appears to be critical for long-term potentiation, whereas the latter pathway (PKC/CAMKII) appears to be vital for neuronal signal enhancement.

Some other minor pathways include being a partial agonist at the glycine binding site of the NDMA receptor (may enhance signalling when there are subpar levels of glycine, but attenuates excessive signalling) and increasing affinity of the muscarinic acetylcholine receptors for its ligand, acetylcholine.

Nefiracetam is a cogntive enhancer that appears to promote memory formation, and it does so via enhancing signalling of acetylcholine and glutamate at the synapse and then prolonging the calcium in the activated neuron. It does not appear to work acutely, but requires daily supplementation

In regards to the potential toxicity of nefiracetam, it does appear to be reliably toxic in dogs at doses that are much higher than the recommended supplemental dosage; lower doses seem to be free from toxicity, and these lower doses barely fit into the recommended dosage range.

That being said, there is evidence to suggest that this toxicity is exclusive to canines as it has not been detected in rats nor monkeys. There is insufficient human testing to absolutely confirm that it isn't a concern for humans, but the limited human evidence at this point in time using the recommended nefiracetam dosages do not find any significant complications.

Nefiracetam is highly toxic to dogs, but this does not appear to extend to monkeys nor rodents. While it has not been completely confirmed to be harmful or harmless in humans, the standard supplemental dosages do not appear to be associated with overt toxicity in preliminary studies

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How to Take

Recommended dosage, active amounts, other details

Supplementation of nefiracetam appears to be in the 150-450mg range over the course of a day (usually divided into three even doses). Animal studies using acute doses tend to note most benefits in the 3-10mg/kg range, and this correlates to a human dose of 0.48-1.6mg/kg (for a 150lb person, 33-110mg) which is similar to the aforementioned human doses.

Although single doses of nefiracetam do not appear to promote cognition, it is able to affect the brain within 30-60 minutes following oral ingestion. It is not certain whether nefiracetam needs to be taken prior to cognitive training.

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Human Effect Matrix

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The Human Effect Matrix summarizes human studies to tell you what effects Nefiracetam has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
grade-c - - See study
grade-c - - See study
grade-c - - See study
No significant influence on the recovery rates from stroke has been noted.

Studies Excluded from Consideration

  • Duplication of a study already in the Human rubricreference|url=http://www.ncbi.nlm.nih.gov/pubmed/18451188|title=Double-blind randomized treatment of poststroke depression using nefiracetam|published=2008 Spring|authors=Robinson RG, Jorge RE, Clarence-Smith K|journal=J Neuropsychiatry Clin Neurosci]

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Things to Note

Is a Form Of

Also Known As

DM-9384, N-(2, 6-dimethylphenyl)-2-(2-oxopyrrolidine-1-yl)-acetamide

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Click here to see all 95 references.