Cognitive enhancement effects of stimulants: a randomized controlled trial testing methylphenidate, modafinil, and caffeine

Psychopharmacology (Berl). 2021 Feb;238(2):441-451. doi: 10.1007/s00213-020-05691-w. Epub 2020 Nov 17.


Rational: At all times humans have made attempts to improve their cognitive abilities by different means, among others, with the use of stimulants. Widely available stimulants such as caffeine, but also prescription substances such as methylphenidate and modafinil, are being used by healthy individuals to enhance cognitive performance.

Objectives: There is a lack of knowledge on the effects of prescription stimulants when taken by healthy individuals (as compared with patients) and especially on the effects of different substances across different cognitive domains.

Methods: We conducted a pilot study with three arms in which male participants received placebo and one of three stimulants (caffeine, methylphenidate, modafinil) and assessed cognitive performance with a test battery that captures various cognitive domains.

Results: Our study showed some moderate effects of the three stimulants tested. Methylphenidate had positive effects on self-reported fatigue as well as on declarative memory 24 hours after learning; caffeine had a positive effect on sustained attention; there was no significant effect of modafinil in any of the instruments of our test battery. All stimulants were well tolerated, and no trade-off negative effects on other cognitive domains were found.

Conclusions: The few observed significant positive effects of the tested stimulants were domain-specific and of rather low magnitude. The results can inform the use of stimulants for cognitive enhancement purposes as well as direct further research to investigate the effects of stimulants on specific cognitive domains that seem most promising, possibly by using tasks that are more demanding.

Keywords: Caffeine; Cognitive enhancement; Methylphenidate; Modafinil; Neuroenhancement.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Attention / drug effects
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Cognition / drug effects*
  • Double-Blind Method
  • Fatigue / prevention & control
  • Humans
  • Male
  • Methylphenidate / pharmacology*
  • Modafinil / pharmacology*
  • Nootropic Agents / pharmacology*
  • Pilot Projects
  • Treatment Outcome
  • Young Adult


  • Central Nervous System Stimulants
  • Nootropic Agents
  • Methylphenidate
  • Caffeine
  • Modafinil