Modafinil and orexin system: interactions and medico-legal considerations

Front Biosci (Landmark Ed). 2019 Jan 1;24:564-575.


Modafinil (Mo) is increasingly being used as an enhancement drug rather than for its therapeutic effects. The effects of this drug have been examined in attention deficit disorders, depression, mental fatigue, and in enhancing concentration. The drug possesses wakefulness-promoting properties which are mediated through the interaction of orexinergic system with the activated sympathetic nervous system. Mo exerts a synergistic effect on the orexin system, controls energy expenditure and strengthens the ability of the individual to exercise. Some view Mo as a drug that enhances sports performance, since it induces a prolonged wakefulness and decreasing the sense of fatigue. These characteristics being similar to conventional stimulants have allowed Mo to emerge as a novel stimulant requiring medico-legal considerations. However, more studies are needed to better understand the mid and long-term effects of the drug on user/abuser.

Publication types

  • Review

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention / physiology
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / physiology
  • Cognition / drug effects
  • Cognition / physiology
  • Humans
  • Modafinil / metabolism
  • Modafinil / pharmacokinetics
  • Modafinil / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology
  • Orexins / metabolism*
  • Wakefulness / drug effects*
  • Wakefulness / physiology
  • Wakefulness-Promoting Agents / metabolism
  • Wakefulness-Promoting Agents / pharmacokinetics
  • Wakefulness-Promoting Agents / pharmacology


  • Orexins
  • Wakefulness-Promoting Agents
  • Modafinil