The effects of caffeine, dextroamphetamine, and modafinil on humor appreciation during sleep deprivation

Sleep. 2006 Jun;29(6):841-7. doi: 10.1093/sleep/29.6.841.


Study objectives: Sleep loss consistently impairs performance on measures of alertness, vigilance, and response speed, but its effects on higher-order executive functions are not well delineated. Similarly, whereas deficits in arousal and vigilance can be temporarily countered by the use of several different stimulant medications, it is not clear how these compounds affect complex cognitive processes in sleep-deprived individuals.

Design: We evaluated the effects of double-blind administration of 3 stimulant medications or placebo on the ability to appreciate humor in visual (cartoons) or verbal (headlines) stimuli presented on a computer screen following 49.5 hours of sleep deprivation.

Setting: In-residence sleep-laboratory facility at the Walter Reed Army Institute of Research.

Participants: Fifty-four healthy adults (29 men, 24 women), ranging in age from 18 to 36 years.

Interventions: Each participant was randomly assigned to 1 of 3 stimulant medication groups, including caffeine, 600 mg, n = 12; modafinil, 400 mg, n = 11; dextroamphetamine, 20 mg, n = 16; or placebo, n = 14.

Measurements and results: Humor appreciation for cartoon stimuli was enhanced by modafinil relative to both placebo and caffeine, but there was no effect of any stimulant medication on the appreciation of verbal humor during sleep loss. In contrast, all 3 stimulants improved psychomotor response speed, whereas only caffeine and dextroamphetamine improved ratings of subjective sleepiness.

Conclusions: Findings suggest that, despite similar alerting and vigilance-promoting effects, these 3 compounds have significantly different effects on those highly complex cognitive abilities mediated by the pre-frontal cortex.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Benzhydryl Compounds / pharmacology*
  • Benzhydryl Compounds / therapeutic use
  • Caffeine / pharmacology*
  • Caffeine / therapeutic use
  • Central Nervous System Stimulants / pharmacology*
  • Central Nervous System Stimulants / therapeutic use
  • Cognition / drug effects*
  • Dextroamphetamine / pharmacology*
  • Dextroamphetamine / therapeutic use
  • Disorders of Excessive Somnolence / diagnosis
  • Disorders of Excessive Somnolence / drug therapy
  • Disorders of Excessive Somnolence / epidemiology
  • Female
  • Humans
  • Male
  • Modafinil
  • Psychological Tests
  • Psychomotor Agitation / diagnosis
  • Sleep Deprivation / diagnosis
  • Sleep Deprivation / drug therapy*
  • Sleep Deprivation / epidemiology
  • Wit and Humor as Topic*


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Caffeine
  • Modafinil
  • Dextroamphetamine