Fasoracetam

NFC-1

Fasoracetam (NFC-1) is a cognitive & mood research compound. Upregulates GABA-B and metabotropic glutamate receptors — calmer, anxiolytic-leaning cognition.

How Fasoracetam works

Upregulates GABA-B and metabotropic glutamate receptors — calmer, anxiolytic-leaning cognition.

Proposed benefits

Researched for focus, memory, neuroprotection, mood and stress resilience.

Where to get Fasoracetam

The evidence for Fasoracetam

Graded by what exists behind each claim.

✅ Clinically validated

• Reached phase 2 in humans — trialed by Aevi Genomic Medicine for ADHD in adolescents with specific mGluR gene mutations. The trial missed its primary endpoint, and the company discontinued it.
• Worth noting what was being asked: a genetically stratified ADHD population on a specific rating scale. A miss there is not a general verdict, though it is the only controlled test the compound has had.

📊 Correlative data

• Community use for anxiety and ADHD-adjacent complaints. Reported experience includes a distinctive lack of tolerance, and some users report it restores sensitivity to other racetams.

🧪 Theoretical / extrapolated

• Upregulates metabotropic glutamate receptors and acts on GABA-B — a mechanism unlike any other racetam. The mGluR upregulation is why the ADHD trial selected on mGluR mutations.
• Receptor upregulation rather than direct agonism predicts both the slow onset and the reported absence of tolerance — you are increasing receptor density, not fatiguing it.

How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →

What Fasoracetam actually does

Fasoracetam is (+)-5-oxo-D-prolinepiperidinamide monohydrate, developed as NS-105 Hirouchi 2000. Structurally that is a pyroglutamate — a cyclized glutamate — amidated onto a piperidine ring, which makes it a cousin of the racetams by shape and a relative of glutamate by origin. The second fact predicts the pharmacology better than the first.

What was actually shown, and it is unusually precise for this shelf. Two papers dissected its effect on adenylyl cyclase in rat brain using selective antagonists and antisense knockdown Oka 1997 Hirouchi 2000. In rat cerebrocortical membranes, fasoracetam at 0.1 micromolar inhibited forskolin-stimulated cAMP formation, and that inhibition was blocked by a group II mGlu antagonist and by a group III antagonist (MAP-4) but not by the group I antagonist AIDA. At 1 micromolar, in membranes pretreated with pertussis toxin, it did the opposite — it facilitated cAMP formation — and that facilitation was abolished by AIDA and not by the group II or III antagonists. In cultured mouse cortical neurons, antisense oligonucleotides against mGlu2/mGlu3 and mGlu4/mGlu7 removed the inhibitory action; antisense against mGlu5 did not.

Read what that says. The direction of the effect flips with concentration, and each direction runs through a different family of metabotropic glutamate receptors: Gi-coupled group II and III at the low concentration, Gq-coupled group I at the high one. A bidirectional, concentration-dependent modulator is a genuinely different object from an agonist, and it is the reason this compound is described as tuning glutamatergic signaling rather than driving it.

The honest caveat, which almost every summary of this compound omits. Those experiments show the effect is mGluR-dependent. They do not show that fasoracetam binds a metabotropic glutamate receptor. No published radioligand binding constant exists for fasoracetam at mGlu1 through mGlu8. The molecule could be a direct ligand, an allosteric modulator, or acting upstream on glutamate availability — the antagonist and antisense data cannot distinguish those, and nobody has run the experiment that would.

The other half of the record is cholinergic and GABAergic. Ogasawara 1999 showed antiamnestic action across animal models built on cholinergic dysfunction and implicated both cholinergic and GABAergic systems in the reversal of memory disruption. The widely repeated claim that fasoracetam upregulates GABA-B receptors traces to older work that is not retrievable with an abstract in the indexed literature; what is verifiable is receptor-system involvement, not receptor-number change, and the difference matters for the tolerance-reset story people tell about this compound.

Cell, rodent, human — and where it stops

In membranes and neurons. Rat cerebrocortical membranes and primary cultured mouse cortical neurons, at 0.1 and 1 micromolar, with selective mGluR antagonists and antisense knockdown as the tools Oka 1997 Hirouchi 2000.

In rodents. Antiamnestic effects across several models of induced memory disruption, with cholinergic and GABAergic involvement Ogasawara 1999.

In humans, the positive study — and read its design before its result. Elia 2018 was an open-label, single-blind, fixed placebo-controlled phase 1 trial in 30 adolescents aged 12 to 17 with ADHD selected for mutations in mGluR-network genes (a Tier 1 set of 79 core genes and a Tier 2 set of 200 more). Single doses of 50 to 800 mg were used for the pharmacokinetic phase, then dose escalation at 50, 100, 200 and 400 mg twice daily across five weeks — one week of placebo followed by four weeks of active drug. Clinical Global Impression – Improvement went from 3.79 at baseline to 2.33 at week 5 (p < 0.001), and CGI-Severity from 4.83 to 3.86 (p < 0.001).

In humans, the controlled study — and it failed. The ASCEND trial (AEVI-001-ADHD-202) was a two-part, six-week, double-blind, dose-optimization, parallel-group study in children aged 6 to 17: 69 subjects in Part A and 109 in Part B, dosed at 100 to 400 mg twice daily, with reduction in the ADHD Rating Scale at six weeks as the primary endpoint. It did not achieve statistical significance on the primary endpoint in either part. The sponsor reported the drug was safe and well tolerated, and discontinued the program (company announcement).

The obstacle, and it is the cleanest example on this site of why design beats result. The study that worked had no control arm — a one-week placebo lead-in is not a randomized comparator, and CGI improvement in an open-label adolescent ADHD cohort is exactly the setting in which expectancy produces a point-and-a-half of improvement. The study that had a control arm, at the same doses, in the same genetically selected population, found nothing. The genetic stratification cannot rescue the failure, because it was present in both. And a second obstacle sits underneath: the human doses in both trials were 100 to 400 mg twice daily, while the community dose on this card is 10 to 50 mg — between four and eighty times lower than anything ever studied.

Fasoracetam pharmacokinetics — how much of it actually gets in

The pharmacokinetics are published, in the trial nobody reads past the abstract of. Elia 2018 ran a formal pharmacokinetic phase with single doses from 50 to 800 mg and reported a half-life ranging from 4.06 to 6.99 hours with an average of 4.82 hours. The card on this page says about 5 hours, and for once the card and the primary literature agree exactly.

What clears it, and this is the unusual part. The same paper states that the compound is excreted for the most part unchanged through the kidneys. That single sentence changes the whole interaction profile. There is essentially no hepatic oxidative metabolism to speak of, so the cytochrome P450 interactions that dominate most nootropic stacking advice do not apply. What does apply is renal clearance: reduced kidney function raises exposure proportionally, and so does competition at renal tubular transporters from other renally cleared cations.

What the 4.8-hour half-life implies for dosing. Steady state arrives in about a day — four to five half-lives — and twice-daily dosing, which is what both human trials used, keeps concentrations within roughly a twofold band. Once-daily dosing lets them fall to about a tenth of peak by the following morning. Since the cell-level mechanism is concentration-dependent and changes direction between 0.1 and 1 micromolar Hirouchi 2000, a once-daily schedule may be spending part of each day on one side of that switch and part on the other. That is speculation, clearly labeled, and it is a testable reason why reports of this compound are so inconsistent.

The oral route is not the constraint. It is a small, water-soluble amide; gastrointestinal absorption is adequate at doses up to 800 mg in a single administration, and no food-effect problem has been reported. The constraint on this compound has never been getting it in.

What would have to be true, and how you would know it was not

1. There should be nothing on day one. The mechanism is receptor-system modulation, not an acute agonist effect, and the published human effect was measured over four weeks Elia 2018. Run Trail Making A and B and a MoCA at baseline, day 1 (two hours post-dose, near Tmax) and week 4. Prediction: no day-1 separation. A compound that produces a noticeable acute effect at 10 mg is not producing it by the published mechanism.

2. The prediction that cuts against it, and it is the one this page owes the reader. A double-blind, placebo-controlled trial at 100 to 400 mg twice daily in the genetically selected population this drug was designed for failed its primary endpoint (company announcement). So the prediction is that a properly blinded self-experiment — alternating one-week drug and placebo blocks with a friend holding the code, scored on the same objective task each morning — will show no separation. If it does separate at 10 to 50 mg, that is a result which contradicts a 178-subject randomized trial at eight times the dose, and it deserves a great deal more scrutiny than a forum post.

3. Renal function is the monitoring axis, not liver function. Because the drug leaves unchanged through the kidney Elia 2018, a CMP for creatinine and eGFR at baseline is the relevant screen, particularly for anyone stacking several renally cleared compounds. Prediction: no change in creatinine in normal kidneys, and meaningfully higher exposure — with no way to feel it — in anyone with reduced eGFR.

4. The tolerance-reset claim has a testable shape and nobody has given it one. The community claim is that fasoracetam restores sensitivity to GABA-B agonists. If that is receptor upregulation it should take days to appear and should persist for days after stopping. If it is an acute interaction it should appear within hours and vanish. Those two timelines are trivially distinguishable by anyone keeping a dated log, and the fact that nobody has published one is the reason the claim has survived unexamined for a decade.

What nobody has tested yet

Nobody has tested the dose people actually take. Every human exposure in the literature is 100 to 400 mg twice daily Elia 2018 (company announcement); the dose sold and discussed is 10 to 50 mg. Nobody has established that the community dose produces a plasma concentration in the range where the cell-level effects were observed, and given the bidirectional concentration dependence of those effects Hirouchi 2000, a low dose is not simply a weaker version of a high one — it might be a different effect.

Nobody has asked whether fasoracetam binds an mGlu receptor. The mechanism rests entirely on antagonist-blockade and antisense-knockdown experiments Oka 1997 Hirouchi 2000. A standard radioligand binding panel across mGlu1 to mGlu8, plus a functional assay for allosteric modulation, is routine pharmacology that would turn a twenty-five-year-old inference into a fact.

Nobody has re-run the failed trial with the failure explained. ASCEND is one of very few negative results in this entire corner of the market, which makes it valuable rather than embarrassing. What would advance the question is a published analysis of the Tier 1 subgroup at each dose level, and a plasma concentration–response analysis from the samples that trial already collected. That analysis probably exists inside a company that no longer exists.

And nobody has tested the phenibut-tolerance claim at all. It is the single most repeated statement about this compound and it has never been examined in an animal, let alone a person. A GABA-B tolerance model in rodents with a fasoracetam arm, measuring receptor number and agonist dose-response, would either give the claim a mechanism or retire it — and it is a straightforward study that any pharmacology department could run.

Fasoracetam — its own safety story, not its class's

The safety data on this compound are better than the efficacy data, which is an unusual sentence to write here. A two-part randomized, double-blind trial dosed 178 children and adolescents aged 6 to 17 at 100 to 400 mg twice daily for six weeks and reported the drug safe and well tolerated (company announcement); a phase 1 study took single doses to 800 mg in adolescents Elia 2018. Those doses are four to eighty times the community dose. That is a real, registered, pediatric safety dataset, and it is the strongest thing this compound has.

The monitoring axis is the kidney, and that is specific to this molecule. Fasoracetam is excreted largely unchanged renally Elia 2018. So the drug-interaction advice that applies to most of this shelf — watch the CYP substrates — is the wrong advice here, and the right advice is: exposure scales with reduced kidney function, and a person with an eGFR of 45 taking a standard dose is taking a larger one than they think. Nobody has published a renal-impairment dose adjustment because the drug was never approved.

The interaction that is actually risky is the one the community recommends. Fasoracetam is widely taken specifically to reset tolerance to phenibut, a GABA-B agonist with a documented, serious withdrawal syndrome. Whatever fasoracetam does or does not do to GABA-B signaling Ogasawara 1999, the practice pairs an untested compound with a dependence-producing one, and any apparent ‘reset’ makes it easier to escalate the phenibut dose. That is the concrete harm pathway on this page, and it is behavioral rather than toxicological.

And the regulatory reality. This molecule was developed as an investigational drug — NS-105, later NFC-1 and AEVI-001 — taken into registered pediatric trials, and never approved anywhere (company announcement). It is sold today as a research chemical with no manufacturing standard behind it, which means the pediatric safety data above describe a pharmaceutical-grade material that is not necessarily what is in the bag.

Sources read for this page

• Elia J, Ungal G, Kao C, Ambrosini A, De Jesus-Rosario N, Larsen L, Chiavacci R, Wang T, Kurian C, Titchen K, Sykes B, Hwang S, Kumar B, Potts J, Davis J, Malatack J, Slattery E, Moorthy G, Zuppa A, Weller A, Byrne E, Li YR, Kraft WK, Hakonarson H. Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling.. Nat Commun 2018 · PMID 29339723
• Hirouchi M. Role of metabotropic glutamate receptor subclasses in modulation of adenylyl cyclase activity by a nootropic NS-105.. Eur J Pharmacol 2000 · PMID 10633154
• Oka M. Involvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity induced by a novel cognition enhancer NS-105 in rat brain.. Brain Res 1997 · PMID 9134967
• Ogasawara T. Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer.. Pharmacol Biochem Behav 1999 · PMID 10494996
• Aevi Genomic Medicine Inc. Top-Line Results from Placebo-Controlled ASCEND Trial (Parts A & B) of AEVI-001 in Children with ADHD.. Company announcement, 2 January 2019

Fasoracetam — safety, predicted from mechanism

Fasoracetam — interference & stacking

Bloodwork to run alongside Fasoracetam

Baseline first, then again at 8–12 weeks.

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Fasoracetam — frequently asked questions

Fasoracetam inside a finished plan

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What Fasoracetam is used for

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