Fasoracetam

Fasoracetam at a Glance

Fasoracetam is a synthetic racetam — a pyrrolidinone built on a D-pyroglutamic acid scaffold — that modulates metabotropic glutamate receptors (mGluRs) and the GABA-B system. It has an unusually long list of names because it has been repurposed repeatedly: Nippon Shinyaku developed it as NS-105 in the 1990s for vascular dementia and abandoned it, Aevi/Cerecor revived it as NFC-1 / AEVI-001 for ADHD, and it is now NB-001 / SYN-001 in trials for 22q11.2 deletion syndrome.

It does not occur in food, and it is not an approved supplement or medicine anywhere — it is a research chemical sold on the nootropic gray market.

The framing that matters: fasoracetam’s evidence posture is the opposite of its online reputation. An encouraging open-label ADHD result in genetically selected adolescents is the study everyone cites. What almost nobody mentions is that three subsequent double-blind, placebo-controlled trials all failed to beat placebo, and the ADHD program was terminated in January 2019.

The honest bottom line: consistently well tolerated in short supervised trials, and that is genuinely the strongest thing that can be said for it. Tolerability is not efficacy.

What It’s Used For

• 22q11.2 deletion syndrome (DiGeorge) — the only live indication, resting on one small crossover trial where efficacy was a non-significant trend on a secondary endpoint.
• Cognition and memory — 1990s rat anti-amnesia models; no human cognition trial exists.
• Depression — two rat behavioural-despair models and a GABA-B mechanism; never taken into a human depression trial.

ADHD deserves separate mention, because it is the reason most people have heard of this compound — and the controlled answer was no. The positive study was open-label/single-blind ^{1Reference 1Elia J et al. · 2018RCTFasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling — open-label/single-blind, placebo-controlled trialView study →}. Every randomised double-blind placebo-controlled trial that followed missed its primary endpoint, in gene-selected and unselected children alike ^{2,6Reference 2AEVI-001-ADHD-202 (ASCEND) — Phase 2 et al.RCTClinicalTrials.gov NCT03265119View study →Reference 6NFC-1 (SAGA) — Phase 2/3 et al.RCTClinicalTrials.gov NCT02777931View study →}; in one, the drug was numerically worse than placebo on the ADHD rating scale. It is listed here as an honest miss rather than as a benefit, which is why it carries no score in the table below.

Be sceptical of the gray-market claims for mood, anxiety, “GABA-B anxiolysis” and cognitive enhancement in healthy users. None has a supporting human trial; all are extrapolated from rat studies of the NS-105 code name.

How It Works

Fasoracetam’s mechanism is genuinely distinctive among racetams, which is what made it a plausible drug candidate three separate times.

It modulates metabotropic glutamate receptors in both directions depending on the subclass: it inhibits adenylate cyclase through the Gi/Go-coupled group II and III receptors, while facilitating cAMP formation through the Gs-coupled group I receptors ^{8,9Reference 8Oka M et al. · 1997In vitroInvolvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity by NS-105 in rat brain — in vitroView study →Reference 9Hirouchi M et al. · 2000In vitroRole of metabotropic glutamate receptor subclasses in modulation of adenylyl cyclase activity by NS-105 — in vitroView study →}. This bidirectional mGluR activity was the specific rationale for testing it in patients whose ADHD was linked to copy-number variants in the mGluR gene network.

At the GABA-B receptor it does something time-dependent: acute dosing suppresses GABA-B responses, but repeated dosing up-regulates receptor number ^{4,7Reference 4Shimidzu T et al. · 1997AnimalEffect of the cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation — animal studyView study →Reference 7Ogasawara T et al. · 1999Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105 — animal studyView study →}. That up-regulation, rather than any effect on monoamines, is what the rodent antidepressant signal was attributed to — the compound has no action on monoamine uptake or brain monoamine levels at all.

It also facilitates cholinergic signalling, increasing acetylcholine release and high-affinity choline uptake without changing choline acetyltransferase activity ^{7Reference 7Ogasawara T et al. · 1999Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105 — animal studyView study →} — the basis for the anti-amnesia effects in lesioned rats.

Pharmacology & Research

Fasoracetam (NFC-1 / AEVI-001 / NB-001; originally Nippon Shinyaku’s NS-105) is a synthetic racetam — a pyrrolidinone built on a D-pyroglutamic acid (5-oxoproline) scaffold — that modulates metabotropic glutamate receptors (mGluRs) and the GABA-B system, and facilitates cholinergic signalling. It is not an approved supplement or medicine anywhere; it is a research chemical sold on the nootropic gray market. Critically, its evidence posture is the opposite of what its online reputation suggests: an encouraging open-label ADHD signal in genetically selected adolescents was not confirmed — three subsequent double-blind, placebo-controlled trials all failed to beat placebo. Almost everything else (mood, cognition, “GABA-B anxiolysis”) rests on 1990s rat pharmacology, not human trials, and no human pharmacokinetic or long-term safety profile has been formally published.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric. Each application links down to its write-up. Note that fasoracetam’s flagship application (ADHD) is deliberately not scored here — its controlled human data are negative, so it lives in the takeaways above as an honest miss rather than as a benefit.

01DiGeorge syndrome (22q11.2)Shaky30%One small Phase 2 crossover (N≈37); primary was safety, efficacy a non-significant trend; program ongoing

02Cognition & memoryShaky22%Multiple 1990s rat anti-amnesia models; no human cognition trial

03DepressionShaky16%Two rat behavioural-despair models + a GABA-B mechanism; no human trial

Mechanisms

Pharmacokinetics

Human PK has not been formally published beyond single-dose profiling done inside the ADHD trials (50–800 mg, absorption within ~1 h) ^{1Reference 1Elia J et al. · 2018RCTFasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling — open-label/single-blind, placebo-controlled trialView study →}; the detailed PK picture comes from animal studies of NS-105. In rats, dogs and monkeys the compound is rapidly and almost completely absorbed from the small intestine with very limited first-pass metabolism, giving high oral bioavailability (≈97% rat, 90% dog, 79% monkey) ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →}. Plasma protein binding is very low (<3.3%, including in human plasma), and elimination is primarily renal as unchanged drug (~90% rat/monkey), so it is not heavily metabolised by the liver ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →}. Terminal half-life after IV dosing was short in animals — 0.67 h (rat), 1.3 h (monkey), 2.1 h (dog) ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →} — consistent with the twice-daily human dosing used in trials; a firm human half-life has not been published, so gray-market figures should be treated as unverified. Food affects absorption ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →}. In pregnant rats the drug crossed to the fetus (≈66% of maternal plasma) and into milk (≈plasma levels) ^{11Reference 11Mukai H et al. · 1999Pharmacokinetics of NS-105, 2nd communication: distribution and transfer into fetus and milk — animal studyView study →} — directly relevant to the pregnancy and lactation cautions below.

Clinical trials

Fasoracetam has an unusually complete registered-trial record for a “nootropic,” precisely because a pharmaceutical company (Aevi/Cerecor) pursued it — and the controlled results were negative, which is why it was never marketed. Interventional trials clustered in pediatric ADHD (Phase 1 PK plus Phase 2/3 efficacy) and, more recently, 22q11.2 deletion syndrome. A Phase 2b in 22q11.2 (SYN-001) has been announced.

Last checked: August 2026.

Dietary Sources

Not applicable — fasoracetam does not occur in food. It is a fully synthetic racetam, chemically (5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one (fasoracetam monohydrate; C₁₀H₁₆N₂O₂, MW 196.25; CAS 110958-19-5) — a piperidine amide of D-pyroglutamic acid (5-oxo-D-proline). There is no dietary intake, deficiency state, or food-based repletion argument for it; it is only ever encountered as a manufactured research chemical.

It is supplied as the monohydrate; the solid-state forms have been characterised, and there are no meaningfully distinct commercial forms to choose between ^{12Reference 12Harmsen B et al. · 2017A study of fasoracetam’s solid state forms — chemistryView study →}.

Dosage

There is no established supplement dose and no reference intake — fasoracetam is not a nutrient and has no RDA/AI or Tolerable Upper Intake Level.

The only human dosing on record is the research protocol used in the ADHD trials: single-dose PK profiling from 50–800 mg, then titration up to 400 mg twice daily under medical supervision ^{1Reference 1Elia J et al. · 2018RCTFasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling — open-label/single-blind, placebo-controlled trialView study →}. Because oral absorption is high and largely first-pass-independent but the terminal half-life appears short (≈1–2 h in animals), the trials used twice-daily dosing; food alters absorption ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →}.

These are doses studied in research, not a personal recommendation — and they were administered to a clinical population under supervision, never validated for self-directed use in healthy adults. It is worth restating that the trials which used these doses did not meet their endpoints, so this is a dose that failed, not a dose that worked.

Safety

Across short controlled trials fasoracetam was well tolerated — which is genuinely the strongest finding here, and also the most easily over-read.

Safety at a Glance

❔ Toxicity unknownDrug interactions

• Well tolerated in short supervised trials. No serious adverse events, and an overall adverse-event rate similar to placebo ^{1,2Reference 1Elia J et al. · 2018RCTFasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling — open-label/single-blind, placebo-controlled trialView study →Reference 2AEVI-001-ADHD-202 (ASCEND) — Phase 2 et al.RCTClinicalTrials.gov NCT03265119View study →}.
• Fatigue and weight increase were the two events more common on drug than placebo in the largest RCT (7/47 vs 3/50, and 7/47 vs 2/50) ^{6Reference 6NFC-1 (SAGA) — Phase 2/3 et al.RCTClinicalTrials.gov NCT02777931View study →}.
• A research chemical, not an approved supplement or drug. Long-term safety in self-dosing adults is entirely unstudied.
• Crosses the placenta and enters milk in animals — fetal levels ≈66% of maternal plasma ^{11Reference 11Mukai H et al. · 1999Pharmacokinetics of NS-105, 2nd communication: distribution and transfer into fetus and milk — animal studyView study →}.
• Interactions untested. Theoretical caution with GABA-B agents (baclofen), cholinergics/anticholinergics and glutamatergic drugs.
• Renally eliminated as unchanged drug ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →} — renal impairment could raise exposure.

Full Safety & Interactions Detail

Across short (≤6-week) controlled trials, fasoracetam was safe and well tolerated, with no serious adverse events and an adverse-event rate similar to placebo ^{1,2Reference 1Elia J et al. · 2018RCTFasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling — open-label/single-blind, placebo-controlled trialView study →Reference 2AEVI-001-ADHD-202 (ASCEND) — Phase 2 et al.RCTClinicalTrials.gov NCT03265119View study →}.

In the largest RCT the events more common on drug than placebo were fatigue (7/47 vs 3/50) and weight increase (7/47 vs 2/50); headache and gastrointestinal complaints did not differ from placebo ^{6Reference 6NFC-1 (SAGA) — Phase 2/3 et al.RCTClinicalTrials.gov NCT02777931View study →}.

This tolerability is the strongest thing that can be said about the compound — but it is short-term data from supervised pediatric trials, not evidence of long-term safety in self-dosing adults.

Interactions: not studied in humans. Mechanistically, fasoracetam modulates glutamatergic (mGluR) and GABA-B signalling and facilitates cholinergic tone; theoretical caution is warranted with other centrally acting agents — GABA-B agonists such as baclofen, cholinergics and anticholinergics, and glutamatergic drugs — but no clinical interaction data exist. Renal elimination of unchanged drug ^{10Reference 10Mukai H et al. · 1999AnimalPharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal studyView study →} means renal impairment could raise exposure.

Scope disclosure. Interactions assessed? No — no human drug-interaction studies exist; only mechanistic inference. Pregnancy/lactation assessed? Partially — no human data, but animal data show placental and milk transfer, so it should be avoided. Upper limit established? No. Do not read “well tolerated for 6 weeks” as “safe.”

Pregnancy & Lactation

⚠ Avoid in pregnancy⚠ Avoid while breastfeeding

Avoid. No human data exist. In rats, fasoracetam crosses the placenta (fetal levels ≈66% of maternal plasma) and transfers into milk at concentrations similar to plasma ^{11Reference 11Mukai H et al. · 1999Pharmacokinetics of NS-105, 2nd communication: distribution and transfer into fetus and milk — animal studyView study →}. Combined with its unapproved research-chemical status, there is no basis for use in pregnancy or breastfeeding.

Related racetams: piracetam, aniracetam, oxiracetam, pramiracetam, phenylpiracetam, nefiracetam and coluracetam.

References

1. Elia J, Ungal G, Kao C, et al. (2018). Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling — open-label/single-blind, placebo-controlled trial. Nature Communications. https://pubmed.ncbi.nlm.nih.gov/29339723/
2. AEVI-001-ADHD-202 (ASCEND) — Phase 2, double-blind, randomised, placebo-controlled trial of AEVI-001 in children and adolescents with ADHD, with (Part A, N=69) and without (Part B, N=109) mGluR copy-number variants; primary endpoint (ADHD-RS-5) not met in either part. ClinicalTrials.gov NCT03265119. https://clinicaltrials.gov/study/NCT03265119
3. NB-001 in children and adolescents with 22q11.2 deletion syndrome — Phase 2, randomised, placebo-controlled crossover (N≈37); primary endpoint safety/tolerability, CGI-I trend p≈0.067. ClinicalTrials.gov NCT05290493. https://clinicaltrials.gov/study/NCT05290493
4. Shimidzu T, Itoh Y, Oka M, et al. (1997). Effect of the cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation — animal study. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/9424016/
5. Nageye F, Cortese S. (2019). Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD — systematic review. Expert Review of Neurotherapeutics. https://pubmed.ncbi.nlm.nih.gov/31167583/
6. NFC-1 (SAGA) — Phase 2/3, double-blind, randomised, placebo-controlled trial in adolescents with mGluR-network genetic variants and ADHD (N=101); primary endpoint not met. ClinicalTrials.gov NCT02777931. https://clinicaltrials.gov/study/NCT02777931
7. Ogasawara T, Itoh Y, Tamura M, et al. (1999). Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105 — animal study. Pharmacology, Biochemistry, and Behavior. https://pubmed.ncbi.nlm.nih.gov/10494996/
8. Oka M, Itoh Y, Shimidzu T, et al. (1997). Involvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity by NS-105 in rat brain — in vitro. Brain Research. https://pubmed.ncbi.nlm.nih.gov/9134967/
9. Hirouchi M, Oka M, Itoh Y, et al. (2000). Role of metabotropic glutamate receptor subclasses in modulation of adenylyl cyclase activity by NS-105 — in vitro. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/10633154/
10. Mukai H, Sugimoto T, Ago M, Morino A. (1999). Pharmacokinetics of NS-105, 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys — animal study. Arzneimittel-Forschung. https://pubmed.ncbi.nlm.nih.gov/10604039/
11. Mukai H, Sugimoto T, Ago M, et al. (1999). Pharmacokinetics of NS-105, 2nd communication: distribution and transfer into fetus and milk — animal study. Arzneimittel-Forschung. https://pubmed.ncbi.nlm.nih.gov/10635441/
12. Harmsen B, Robeyns K, Wouters J, Leyssens T. (2017). A study of fasoracetam’s solid state forms — chemistry. Journal of Pharmaceutical Sciences. https://pubmed.ncbi.nlm.nih.gov/28109793/

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