Nefiracetam
Cognition, Memory
Elimination half-life reported at 3-5 h in humans; 4 h is the midpoint.
In short
- A fat-soluble racetam studied in Japan and the US for post-stroke apathy and cognitive impairment.
- Reached phase 2 trials in humans, including in post-stroke depression and apathy.
- Elimination half-life of roughly 3-5 hours.
- Rodent toxicology raised organ-toxicity concerns at high chronic doses — testicular toxicity in dogs was a notable finding that affected development.
- Not approved anywhere.
Structure
How it works
Nefiracetam is reported to act on multiple systems: potentiating cholinergic transmission, enhancing GABAergic signalling, and prolonging opening of calcium channels, with downstream effects on protein kinase C and CaMKII signalling.
Its fat solubility distinguishes it from piracetam-type compounds and is proposed to improve CNS penetration.
The calcium channel activity is the most mechanistically distinctive part and is linked to reported effects on long-term potentiation.
What the research shows
A phase 2 trial in post-stroke apathy reported improvement at higher doses.
A trial in post-stroke depression produced more equivocal results.
Japanese studies explored cognitive impairment after cerebrovascular disease.
Animal work supports anti-amnesic and neuroprotective effects reasonably consistently. Development did not proceed to approval.
Dosing in the literature
Figures below are quoted from published studies, with the species or population they were measured in. They are records of what was studied, not recommendations.
| Studied in | Amount | Route | Source |
|---|---|---|---|
| Human — phase 2 post-stroke apathy trial | 600 mg or 900 mg daily | oral | PubMed |
| Human — pharmacokinetics | Elimination half-life approximately 3–5 h | oral | PubMed |
Commonly reported ranges
These are amounts people report using. They are not from any study, have not been evaluated for safety, and are reproduced here only because they circulate widely and are better seen alongside the evidence than instead of it.
| Reported by | Amount | Route |
|---|---|---|
| Commonly reported | 150–450 mg daily, divided | oral |
Trial doses were higher than typical community use. The relevant caution is not the dose but the animal toxicology: testicular toxicity was observed in dogs at high chronic exposure, and that finding shaped the development programme.
Handling and storage
Oral, as capsules or powder. Fat solubility means administration with a fat-containing meal is commonly described for absorption.
Divided dosing follows from the 3–5 hour half-life.
Side effects
Human trials reported generally acceptable tolerability at studied doses, with mild gastrointestinal effects and headache most common.
The significant finding is preclinical: testicular toxicity in dogs at high chronic doses. This is a genuine animal toxicology signal rather than a theoretical concern, and it is the main reason this compound warrants more caution than its racetam relatives.
Long-term human safety data does not exist.
Combinations
Commonly paired with a choline source (alpha-GPC, citicoline) on the reasoning that racetams increase cholinergic demand and that headache reflects choline depletion. This is a widely repeated community model rather than an established mechanism, and controlled evidence for the pairing is absent.
Research status
Developed in Japan by Daiichi, with phase 2 work in the US on post-stroke apathy and depression. The published human literature is small but real.
Development was discontinued without approval.
Legal status
Not approved in any jurisdiction. Sold as a research chemical. Does not meet the US definition of a dietary supplement.
WADA status
Not specifically named on the Prohibited List. Falls under WADA class S0, which prohibits any pharmacological substance not currently approved by any governmental regulatory health authority for human therapeutic use. Treat it as prohibited in sport.
Conclusion
Nefiracetam has more human data than most racetams and the most concerning animal toxicology of the group.
The testicular finding in dogs is the thing to know about it, and it is rarely mentioned in the places this compound is sold.
Sources
- [1]Nefiracetam in post-stroke apathy — phase 2 trialPubMed
- [2]Nefiracetam pharmacology and mechanismPubMed
- [3]Nefiracetam preclinical toxicologyPubMed
- [4]PubChem CID 71157PubChem
- [5]WADA Prohibited List (current)WADA
Track your own Nefiracetam protocol
Peppers logs your doses, models your levels from this half-life, tracks your vials and tells you when you will run out. Free on iPhone.
Reference and educational information only. Not medical advice. Nothing here diagnoses, treats, or prescribes, and nothing here is a recommendation to use any compound. The compounds described are research chemicals and are not approved for human consumption. Legal and anti-doping status change — the review date above is when these claims were last checked. Talk to a qualified clinician about anything you intend to take.