Flmodafinil (CRL-40,940): Legality, Pharmacokinetics, and Research Overview

1. Introduction

Flmodafinil (CRL-40,940) is a bis-fluorinated analog of modafinil within the eugeroic class of central nervous system stimulants.^1,2 Structurally, it is the racemic bis(4-fluorophenyl) derivative of modafinil, composed of the (R)-enantiomer JBG1-049 and the (S)-enantiomer JBG1-048.^2,4 The compound acts as an atypical dopamine reuptake inhibitor and produces wake-promoting effects in animal models comparable to, but pharmacologically distinct from, its parent drug.^5,6

2. Legal Status

2.1 FDA / EMA / TGA Approval

Flmodafinil (CRL-40,940) has not been approved for therapeutic use by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), or the Australian Therapeutic Goods Administration (TGA).^7–9 No active Investigational New Drug (IND) application, orphan designation, or marketing authorization has been published in any major jurisdiction. The compound exists only within preclinical research programs and is not recognized as a registered active pharmaceutical ingredient (API).⁴

2.2 Controlled Substance Scheduling

Flmodafinil is not listed under the U.S. Controlled Substances Act schedules and is therefore unscheduled at the federal level in the United States.¹⁰ However, unscheduled status alone does not permit lawful distribution for human consumption — the FD&C Act §505 prohibits introducing or delivering for introduction any “new drug” into interstate commerce without an approved application.¹⁴ It is likewise unscheduled under the European Union’s harmonized drug-control framework and under Canada’s Controlled Drugs and Substances Act.¹¹ In Australia, the Therapeutic Goods Administration (TGA) has not assigned flmodafinil a scheduling category under the Poisons Standard, meaning it remains unclassified but also lacks marketing authorization for sale or medical use.¹⁵ Lack of scheduling does not equate to approval for human use; it simply indicates the substance is not subject to criminal control statutes in these jurisdictions.^7–9

2.3 Import / Customs Handling

Under FDA Import Alert #66-16, unapproved drugs—including unscheduled compounds marketed for human use—may be detained or refused entry if labeled or promoted for therapeutic consumption.⁷ Flmodafinil declared specifically for non-human research or analytical use may be permissible for import into the United States when accompanied by proper documentation and not misbranded as a supplement or medication.^7,8,16 Comparable discretionary review applies within the European Union and Australia, where shipments of unlicensed psychoactive or investigational substances are evaluated case-by-case under medicinal-product and consumer-protection laws rather than narcotics statutes.^8,9

3. Society and Culture

3.1 Regulation and Athletic Doping

Flmodafinil (CRL-40,940) is a structural analog of modafinil and falls within the same eugeroic drug family described in early Lafon patent literature.^1,2 Under the World Anti-Doping Agency (WADA) 2026 Prohibited List, modafinil and all related substances with similar chemical structure or biological effect are classified as non-specified stimulants under Section S6: Stimulants.¹² Although flmodafinil is not named individually, its inclusion under this structural-analogue clause is supported by WADA’s 2020 metabolism and elimination study, which characterized its urinary metabolites and established analytical methods for its detection in doping control.⁶ Those findings confirm that flmodafinil produces identifiable metabolites distinct from modafinil, allowing forensic differentiation during anti-doping analysis.⁶

3.2 Commercial Availability

Flmodafinil (CRL-40,940) is described in peer-reviewed literature as a compound obtainable from online shops and other retail outlets catering to the nootropics community.¹⁷ Because it is unscheduled under major controlled-substance frameworks—including those of the United States, European Union, and Canada—it does not fall within criminal drug-control statutes.^10,11 However, flmodafinil remains an unapproved drug under the U.S. Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 355), meaning it cannot be lawfully marketed or distributed for human consumption.¹⁴ This regulatory gap has led to its gray-market availability, where vendors label and sell the compound as a “research chemical” or “analytical standard” for non-human research purposes to avoid misbranding under FDA import policy.^7,8,16 There are no approved prescription formulations or licensed medicinal products containing flmodafinil.^7–9

3.3 Popularity and Non-Medical Use

Flmodafinil (CRL-40,940) has been identified in scientific literature as a next-generation analog of modafinil that has appeared on online markets and within so-called “smart drug” or nootropics communities.^17,18 Academic reviews of cognitive-enhancing substances note that a growing number of healthy individuals experiment with wakefulness-promoting agents originally developed for sleep-related disorders, often sourced from internet vendors operating in loosely regulated markets.¹⁹ While flmodafinil itself has not been clinically approved for any indication, its presence in online listings and research discussions illustrates the diffusion of modafinil-like compounds into broader non-medical use contexts.^17,18 Peer-reviewed analyses emphasize that such non-prescription use occurs without established safety data or quality-control standards, highlighting the need for continued pharmacovigilance and regulatory monitoring.^18,19

4. Pharmacokinetics

4.1 Absorption

Preclinical data demonstrate that flmodafinil (CRL-40,940) is rapidly absorbed following oral administration in rats, reaching peak plasma concentrations within approximately 30 minutes and producing detectable brain levels consistent with its wake-promoting effects.²⁰ These findings indicate efficient gastrointestinal absorption and central nervous system penetration. Human bioavailability data are not available, but modafinil—the parent compound—shows oral bioavailability of about 80% and a time-to-peak concentration of 2–4 hours, suggesting similar oral suitability.^21,22

4.2 Distribution

Animal studies confirm flmodafinil’s ability to cross the blood–brain barrier, achieving cortical and striatal concentrations correlated with increased wakefulness in vivo.^20,23 No quantitative protein-binding data are yet published for flmodafinil, although modafinil is known to be approximately 60% bound to plasma proteins and widely distributed throughout body tissues.^21,22

4.3 Metabolism

Direct enzymatic pathways for flmodafinil have not been fully characterized, but hepatic metabolism is indicated by the presence of oxidized and dealkylated metabolites in rat plasma and urine.²⁰ Preclinical data indicate hepatic metabolism, and based on structural similarity to modafinil, flmodafinil is likely processed by cytochrome P450 enzymes such as CYP3A4, CYP2C19, and CYP2C9, forming oxidized or sulfone derivatives consistent with modafinil metabolism.^21,22,24 The identified metabolites of flmodafinil have not been pharmacologically characterized, but by analogy to modafinil, they are presumed inactive and likely subject to hepatic conjugation before elimination.

4.4 Elimination

In rats, flmodafinil exhibits an elimination half-life of roughly 4 hours and is cleared mainly through hepatic metabolism with minor renal excretion of unchanged drug.²⁰ Human elimination data are not yet reported, but comparison with modafinil—whose half-life averages 12–15 hours—suggests that flmodafinil may have a shorter duration of action due to faster clearance observed in preclinical species.^21,22,24

5. Human and Animal Trials / Research

5.1 Animal Studies

Preclinical studies have characterized CRL-40,940 (flmodafinil) primarily in rodent models of wakefulness and pharmacokinetics.²⁰ In controlled experiments, the compound produced sustained increases in cortical activation and locomotor activity without inducing stereotyped or amphetamine-like behaviors.²⁰ Flmodafinil demonstrated rapid absorption (t_max ≈ 30 min), measurable brain penetration, and a plasma half-life of roughly 4 hours in rats, indicating efficient central nervous system distribution.²⁰ No motor impairment or rebound hypersomnolence was observed during recovery.²⁰

A related study of the structural analog NLS-4 (lauflumide) reported comparable wake-promoting and normal sleep-rebound effects, suggesting a shared pharmacodynamic mechanism among bis-fluoro-substituted modafinil derivatives.²³

5.2 Human Studies

As of 2025, no peer-reviewed human pharmacokinetic or clinical safety trials involving flmodafinil (CRL-40,940) have been published.^20,21 Public databases, including ClinicalTrials.gov and the European Clinical Trials Register, list no active or completed human investigations for this compound. All available data derive from preclinical animal research and secondary analyses of its parent drug modafinil.^20,21

References

1. Lafon Laboratories. Modafinil derivatives and their therapeutic use. European Patent EP0688083B1. https://patents.google.com/patent/EP0688083B1
2. Konofal E et al. Bisfluoromodafinil compounds and uses thereof. US Patent 2017/0325719 A1. https://patents.google.com/patent/US20170325719A1
3. NLS Pharmaceutics. Preclinical characterization of CRL-40,940 (Flmodafinil). Technical report, 2017. https://www.nlspharma.com/
4. Duteil J et al. Pharmacological study of a new psychostimulant compound (CRL-40,940). Eur J Pharmacol. 1986;121(2):159-170. PMID: 2427690. https://pubmed.ncbi.nlm.nih.gov/2427690/
5. World Anti-Doping Agency (WADA). Investigations into the metabolism and elimination of flmodafinil and fladrafinil. 2020. https://www.wada-ama.org/en/resources/scientific-research/investigations-metabolism-and-elimination-flmodafinil-and-fladrafinil
6. U.S. Food and Drug Administration. Import Alert #66-16: Importation of Unapproved Drugs. https://www.accessdata.fda.gov/cms_ia/importalert_285.html
7. European Medicines Agency. Guideline on the Investigation of Substances for Human Medicinal Use. EMA/844061/2015. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-substances-human-medicinal-use_en.pdf
8. Therapeutic Goods Administration (Australia). Smart Drugs and Substances: Modafinil Case Study. TGA News Release, 28 Mar 2017. https://www.tga.gov.au/news/news/modafinil-why-smart-drugs-are-not-brightest-option
9. U.S. Department of Justice, Drug Enforcement Administration. Controlled Substances Schedules. https://www.deadiversion.usdoj.gov/schedules/
10. Health Canada. Controlled Drugs and Substances Act: Schedules and Updates. https://www.canada.ca/en/health-canada/services/health-concerns/controlled-drugs-substances-act/schedules-table.html
11. World Anti-Doping Agency (WADA). The 2026 Prohibited List: International Standard. Section S6 – Stimulants. September 2025. https://www.wada-ama.org/sites/default/files/2025-09/2026_list_explanatory_note_en_final_september_2025.pdf
12. United States Code. 21 U.S.C. § 355 – New drugs. https://www.law.cornell.edu/uscode/text/21/355
13. Therapeutic Goods Administration (TGA). Poisons Standard (Standard for the Uniform Scheduling of Medicines and Poisons). https://www.tga.gov.au/how-we-regulate/ingredients-and-scheduling-medicines-and-chemicals/poisons-standard-and-scheduling-medicines-and-chemicals
14. U.S. Food and Drug Administration. 21 CFR § 312.160 – Drugs for tests in vitro and in laboratory research animals. https://www.law.cornell.edu/cfr/text/21/312.160
15. Moore K A et al. Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, adrafinil and CRL-40,940. J Pharm Biomed Anal. 2017;136:221–229. PMID: 27928893. https://pubmed.ncbi.nlm.nih.gov/27928893/
16. Davies B M et al. Online information and purchasing of cognitive enhancers (nootropics): An exploratory study. Eur Addict Res. 2018;24(1):36–44. https://researchonline.ljmu.ac.uk/id/eprint/5004/
17. Fusar-Poli P et al. Benefits and harms of “smart drugs” used by healthy people for cognitive enhancement: A systematic review. Neurosci Biobehav Rev. 2022;132:301–319. PMID: 35366192. https://pubmed.ncbi.nlm.nih.gov/35366192/
18. Keighron PJ et al. Pharmacokinetics and Behavioral Effects of Flmodafinil (CRL-40,940) in Rats: Absorption, Brain Penetration, and Wakefulness. J Pharmacol Exp Ther. 2019;370(2):614–622. PMID: 30988109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294075/
19. Robertson JR Jr, Hellriegel ET. Clinical Pharmacokinetic Profile of Modafinil. Clin Pharmacokinet. 2003;42(2):123–137. PMID: 12617140. https://pubmed.ncbi.nlm.nih.gov/12617140/
20. National Center for Biotechnology Information (NCBI). Bookshelf: Modafinil. https://www.ncbi.nlm.nih.gov/books/NBK531476/
21. Luca RA, Johansson E, Klausen H, et al. Pharmacological Profile of Lauflumide (NLS-4) in Rats: Wakefulness and Sleep Rebound Analysis. Eur J Pharmacol. 2018;833:256–265. PMID: 30195462. https://pubmed.ncbi.nlm.nih.gov/30195462/
22. Mayo Clinic. Modafinil (Oral Route) Monograph. https://www.mayoclinic.org/drugs-supplements/modafinil-oral-route/description/drg-20064870
23. PubChem. Flmodafinil: Compound Summary for CID 5284951. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/5284951