The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders.
OBJECTIVE
Modafinil (MOD) and its R-enantiomer (R-MOD) are approved medications for narcolepsy and other sleep disorders. They have also been used, off-label, as cognitive enhancers in populations of patients with mental disorders, including substance abusers that demonstrate impaired cognitive function. A debated nonmedical use of MOD in healthy individuals to improve intellectual performance is raising questions about its potential abuse liability in this population.


CONCLUSIONS
MOD has low micromolar affinity for the dopamine transporter (DAT). Inhibition of dopamine (DA) reuptake via the DAT explains the enhancement of DA levels in several brain areas, an effect shared with psychostimulants like cocaine, methylphenidate, and the amphetamines. However, its neurochemical effects and anatomical pattern of brain area activation differ from typical psychostimulants and are consistent with its beneficial effects on cognitive performance processes such as attention, learning, and memory. At variance with typical psychostimulants, MOD shows very low, if any, abuse liability, in spite of its use as a cognitive enhancer by otherwise healthy individuals. Finally, recent clinical studies have focused on the potential use of MOD as a medication for treatment of drug abuse, but have not shown consistent outcomes. However, positive trends in several result measures suggest that medications that improve cognitive function, like MOD or R-MOD, may be beneficial for the treatment of substance use disorders in certain patient populations.
Molecular Targets and Medication Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, DHHS, 251 Bayview Boulevard, NIDA Suite 200, Baltimore, MD, USA.
Maddalena
M
Mereu
Antonello
A
Bonci
Amy Hauck
AH
Newman
Gianluigi
G
Tanda
D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D006801:Humans; D000077408:Modafinil; D015394:Molecular Structure; D009446:Neurobiology; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D056687:Off-Label Use; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects
D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D018697:Nootropic Agents; D000077408:Modafinil; D004298:Dopamine