Racetam

Fasoracetam

(5R)-5-(Piperidine-1-carbonyl)pyrrolidin-2-one

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

20-100 mg per day

watchEffect Window

Acute effects within 1 hour. GABA-B upregulation over 1-2 weeks.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Fasoracetam is an investigational compound related to racetams that affects glutamate and GABA signaling. It is used for attention and anxiety-related cognitive symptoms, with niche clinical evidence.

Early studies suggest possible benefits for attention and impulsivity in specific ADHD subgroups, including genetically defined cohorts, but replication is limited. Mechanistic work indicates modulation of glutamatergic and GABAergic systems. Minority claims include broader cognitive enhancement and anxiolysis in healthy users, which lack strong controlled evidence. Long-term safety and efficacy remain incompletely characterized.

Agonist of all three mGluR groups. Uniquely upregulates GABA-B receptors after repeated dosing. Glutamatergic and GABAergic dual modulation.

Outcomes

What This Is Expected To Influence

Primary Outcomes

ADHD symptom reduction in adolescents with mGluR gene variants (Phase 2)

Secondary Outcomes

GABA-B receptor upregulation (phenibut tolerance reversal)
Antidepressant/anxiolytic effect in animal models

Safety

Contraindications and Interactions

Contraindications

None established (limited data. Treat as investigational)

Side effects

Headache
Fatigue

Interactions

GABAergic drugs (altered GABA-B sensitivity)
No comprehensive interaction studies

Avoid if

Pregnancy/lactation (no safety data)
Concurrent GABAergic medication without clinician oversight

Evidence

Study-level References

fasoracetam-SRC-001Single-blind, placebo-controlled clinical trial.

Sourceopen_in_new

Elia J, Ungal G, Kao C, et al. Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling. Nat Commun. 2018;9(1):4. doi:10.1038/s41467-017-02244-2. PMID:29339723.

Population: Adolescents aged 12 to 17 years with ADHD carrying mutations in metabotropic glutamate receptor network genes.

Dose protocol: Fasoracetam (NFC-1) up to 400 mg twice daily for 4 weeks in genetically screened adolescents

Key findings: CGI-I scores improved significantly (3.79 to 2.33, P<0.001). Safe and well tolerated across the dose range.

Notes: Single-blind design with placebo lead-in rather than parallel control. Published in Nature Communications.

Paper content

This single-blind, placebo-controlled trial tested fasoracetam (NFC-1) in 30 adolescents with ADHD who carried mutations in metabotropic glutamate receptor genes. Over five weeks (one week placebo, four weeks active treatment up to 400 mg twice daily), CGI-I scores improved significantly. Participants with Tier 1 genetic variants showed the strongest gains on parental Vanderbilt scales. Adverse event rates were comparable between placebo and active weeks. The trial represents one of the first pharmacogenomic-targeting approaches in ADHD, selecting patients by genotype rather than diagnosis alone. The study is small and lacks a parallel randomized control arm, limiting the strength of causal inference.

fasoracetam-SRC-002Systematic review.

Sourceopen_in_new

Nageye F, Cortese S. Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. Expert Rev Neurother. 2019;19(7):707-717. doi:10.1080/14737175.2019.1628640. PMID:31167583.

Population: ADHD patients across included RCTs.

Dose protocol: Systematic review of 28 RCTs of novel non-stimulant ADHD compounds

Key findings: Novel agents including fasoracetam are unlikely to exceed stimulant efficacy but may offer comparable or better tolerability. Supports precision medicine framing.

Notes: Provides independent review context for fasoracetam within the broader ADHD pharmacotherapy landscape.