Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation
Abstract
Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with dextroamphetamine on others. At the doses tested, caffeine, dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performanc…
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Amphetamine restored executive functions and psychomotor vigilance test speed following continuous sleep deprivation.
“AMP restored executive functions (Killgore et al., 2009) and psychomotor vigilance test speed following continuous sleep deprivation (Killgore et al., 2006, 2008; Wesensten et al., 2005).”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Wesensten et al., 2005
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BackgroundInfluentialPharmakologisches Neuroenhancement und „Hirndoping“
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“For the purpose of this analysis, the first 5 PVT sessions (7 pm–11 pm) were used as the baseline, given that 11 pm is often the point at which vigilance changes begin to emerge following a normal day of wakefulness (Wesensten et al., 2005).”
Self-citationEffects of modafinil on cognitive performance and alertness during sleep deprivation.
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“(simulated night shift with 8-hr daytime sleep period) Method: none indicated (no side effects noted) Wesensten et al. (2005) Placebo Caffeine 600 mg Modafinil 400 mg Dextroamphetamine 20 mg 85 hours Method: Symptom Questionnaire* Modafinil 400 mg – excitation, nausea (compared to placebo) * = side…”
BackgroundMethodResultInfluentialSelf-citationEffect of caffeine and taurine on simulated laparoscopy performed following sleep deprivation
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Caffeine Gum Minimizes Sleep Inertia
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Self-citationSleep-Disordered Breathing and Excessive Daytime Sleepiness
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“…(Turner et al., 2004b), methamphetamine dependence (Kalechstein et al., 2010; Ghahremani et al., 2011), schizophrenia (Spence et al., 2005; Hunter et al., 2006), and sleep deprivation (Baranski et al., 2004; Killgore et al., 2009; Wesensten et al., 2005); hence, similar findings were expected here.”
BackgroundResultInfluentialSleep is more sensitive to high doses of caffeine in the middle years of life
Robillard, R., Bouchard, M., Cartier, A., Nicolau, L., & Carrier, J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115575535 · Cited by 53 · see citing works
“These range from increased anxiety, insomnia and higher risk for hypertension to enhanced mood, alertness and cognitive performance in conditions of sleep loss (Charney et al., 1984; Hartley et al., 2000; Killgore et al., 2009; Landolt et al., 1995; Quinlan et al., 2000; Warburton, 1995; Wesensten et al., 2005).”
BackgroundSleep-Wake Regulation and Its Impact on Working Memory Performance: The Role of Adenosine
Reichert, C., Maire, M., Schmidt, C., & Cajochen, C. (2016) · Biology · doi:10.3390/biology5010011 · Cited by 56 · see citing works
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Sleepiness is not the inverse of alertness: evidence from four sleep disorder patient groups
Moller, H., Devins, G., Shen, J., & Shapiro, C. (2006) · Experimental Brain Research · doi:10.1007/s00221-006-0436-4 · Cited by 48 · see citing works
“…agent thought to have a mechanism of action diVering from traditional stimulants has stimulated signiWcant interest in the sleep research Weld through putative eVects on sleepiness (Besset et al. 1993), alertness (Wesensten et al. 2005) as well as fatigue (Kraft and Bowen 2005).”
BackgroundThe Use of Caffeinated Substances by Surgeons for Cognitive Enhancement.
Franke, A., Bagusat, C., McFarlane, C., Tassone-Steiger, T., Kneist, W., & Lieb, K. (2015) · Annals of Surgery · doi:10.1097/sla.0000000000000830 · Cited by 47 · see citing works
The characteristics of recovery sleep when recovery opportunity is restricted.
Jay, S., Lamond, N., Ferguson, S., Dorrian, J., Jones, C. B., & Dawson, D. (2007) · Sleep · doi:10.1093/sleep/30.3.353 · Cited by 46 · see citing works
The influence of stimulants on truck driver crash responsibility in fatal crashes
Gates, J., Dubois, S. J., Mullen, N. W., Weaver, B., & Bédard, M. (2013) · Forensic Science International · doi:10.1016/j.forsciint.2013.02.001 · Cited by 44 · see citing works
Individualized performance prediction of sleep-deprived individuals with the two-process model.
Rajaraman, S., Gribok, A., Wesensten, N., Balkin, T., & Reifman, J. (2008) · Journal of applied physiology · doi:10.1152/japplphysiol.00877.2007 · Cited by 45 · see citing works
“The second data set used to test the proposed approach is based on data collected from a controlled laboratory study in which 48 healthy adults were kept awake for 85 consecutive hours to determine the effects of countermeasures on performance and alertness during prolonged sleep deprivation (40).”
MethodSelf-citationDagan, Y., & Doljansky, J. (2006) · Chronobiology International · doi:10.1080/07420520600920734 · Cited by 45 · see citing works
“All of these drugs enhance vigilance and neurobehavioral performance after sleep deprivation and during sustained wakefulness (Wesensten et al., 2002, 2004, 2005).”
BackgroundIs passive smoking associated with sleep disturbance among pregnant women?
Ohida, T., Kaneita, Y., Osaki, Y., Harano, S., Tanihata, T., Takemura, S., Wada, K., Kanda, H., Hayashi, K., & Uchiyama, M. (2007) · Sleep · doi:10.1093/sleep/30.9.1155 · Cited by 44 · see citing works
Modafinil May Alleviate Poststroke Fatigue: A Randomized, Placebo-Controlled, Double-Blinded Trial
Poulsen, M. B., Damgaard, B., Zerahn, B., Overgaard, K., & Rasmussen, R. (2015) · Stroke · doi:10.1161/strokeaha.115.010860 · Cited by 43 · see citing works
“Effect on reaction time has been demonstrated in healthy sleep deprived individuals.(41) We did not observe an effect or even a trend toward improvement on general cognition as measured by the Montreal Cognitive Assessment test or on reaction time.”
MethodEffects of Modafinil on the Sleep EEG Depend on Val158Met Genotype of COMT
Bodenmann, S., & Landolt, H. (2010) · SLEEP · doi:10.1093/sleep/33.8.1027 · Cited by 49 · see citing works
Modafinil improves rapid shifts of attention
Marchant, N. L., Kamel, F., Echlin, K., Grice, J. E., Lewis, M., & Rusted, J. M. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1395-1 · Cited by 37 · see citing works
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“These effects have been mirrored in the clinical setting, where modafinil has been shown to improve performance in certain cognitive domains in non-sleep/sleep deprived healthy volunteers (Pigeau et al., 1995; Turner et al., 2003; Muller et al., 2004; Wesensten et al., 2005).”
ResultA systematic review of sleep deprivation and technical skill in surgery.
Whelehan, D. F., McCarrick, C. A., & Ridgway, P. (2020) · The Surgeon · doi:10.1016/j.surge.2020.01.004 · Cited by 40 · see citing works
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Effects of modafinil on simulator driving and self‐assessment of driving following sleep deprivation
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“Consequently, this is also the time when countermeasures to the effects of sleep loss are most likely to be initiated (Wesensten et al., 2002; Wesensten et al., 2005).”
BackgroundSleep Deprivation and Cognitive Performance
Killgore, W. D. S., & Weber, M. (2014) · Sleep Deprivation and Disease · doi:10.1007/978-1-4614-9087-6_16 · Cited by 51 · see citing works
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“[11] showed that 600mg of caffeine ingestion improve cognitive performance after 85 h of sleep deprivation.”
Krajewski, J., Sauerland, M., & Wieland, R. (2010) · Journal of Occupational and Organizational Psychology · doi:10.1348/096317910x485458 · Cited by 37 · see citing works
Effects of modafinil on emotional processing in first episode psychosis.
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“It has been shown that dopaminergic psychostimulants enhance the level of arousal (amphetamine and cocaine, Wisor et al. 2001; White and Lambe 2003; Wesensten et al. 2005), whereas antipsychotics, which block dopamine receptors, have sedative effects (Baldessarini and Tarazi 2001; Rye 2004).”
BackgroundDaubner, J., Arshaad, M. I., Henseler, C., Hescheler, J., Ehninger, D., Broich, K., Rawashdeh, O., Papazoglou, A., & Weiergräber, M. (2021) · Journal of Neural Transplantation and Plasticity · doi:10.1155/2021/8823383 · Cited by 35 · see citing works
“Neuropsychological comparative studies with caffeine, dexamphetamine, and modafinil in young, healthy individuals reveal no significant differences in attention and vigilance [206, 207].”
BackgroundAttention deficit/hyperactivity disorder: complexities and controversies
Schonwald, A., & Lechner, E. (2006) · Current opinion in pediatrics · doi:10.1097/01.mop.0000193302.70882.70 · Cited by 35 · see citing works
Doty, T. J., So, C. J., Bergman, E. M., Trach, S. K., Ratcliffe, R. H., Yarnell, A. M., Capaldi, V. F., Moon, J. E., Balkin, T. J., & Quartana, P. J. (2017) · SLEEP · doi:10.1093/sleep/zsx171 · Cited by 33 · see citing works
“Similar effects have been observed on objective measures of sleepiness (polysomnography [PSG]) during or at the end of sleep deprivation: For example, caffeine increases daytime sleep latencies compared to placebo.(11,12) However, the impact of caffeine on measures of self-reported sleepiness are less clear, with some…”
BackgroundSelf-citationPre-existent expectancy effects in the relationship between caffeine and performance.
Elliman, N. A., Ash, J., & Green, M. (2010) · Appetite · doi:10.1016/j.appet.2010.03.016 · Cited by 34 · see citing works
Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation
Ramakrishnan, S., Laxminarayan, S., Wesensten, N. J., Kamimori, G. H., Balkin, T. J., & Reifman, J. (2014) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2014.05.017 · Cited by 33 · see citing works
“In the majority of these studies, caffeine has been administered as a single bolus dose of 600 mg (Wesensten et al., 2002; Wesensten et al., 2005) or as smaller, repeated doses of 50, 100, 200, or 300 mg (Kamimori et al., 2005; LaJambe et al., 2005).”
BackgroundInfluentialSelf-citationKillgore, W. D. S., & Kamimori, G. H. (2020) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2020.100051 · Cited by 34 · see citing works
Self-citation
- Authors
- WESENSTEN, N. J., KILLGORE, W. D. S., & BALKIN, T. J.
- Affiliations
- Walter Reed Army Institute of Research (US)
- Corresponding author
- WESENSTEN, NANCY J.
- Venue
- Journal of Sleep Research
- Publisher
- Wiley
- Published
- 2005-08-25
- Volume
- 14
- Issue
- 3
- Pages
- 255-266
- ISSN
- 0962-1105 (ISSN-L)
- 1365-2869
- OpenAlex
- W1975163395
- Cited by
- 306
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 19 · 2018: 13 · 2017: 8 · 2016: 15 · 2015: 10 · 2014: 22 · 2013: 22 · 2012: 26
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Sleep Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- caffeine, d-amphetamine, modafinil, sleep deprivation, stimulants, alertness, psychomotor performance, executive function, psychomotor vigilance, recovery sleep, drug elimination rate
- MeSH terms
- Modafinil, Adult, Central Nervous System Stimulants, Arousal, Benzhydryl Compounds, Caffeine, Cognition, Dextroamphetamine, Female, Humans, Disorders of Excessive Somnolence, Male, Neuropsychological Tests, Psychomotor Performance, Sleep Deprivation, Wakefulness, Polysomnography, Dopamine Agonists
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