Ramsey CS, Werchan PM, Isdahl WM, Fischer J, Gibbons JA. Acceleration tolerance at night with acute fatigue and stimulants. Aviat Space Environ Med 2008; 79:769–73.Introduction: The impact of pharmacological agents on aviators concerns all flight surgeons. This study tested the related hypotheses that acute fatigue reduces +G_z tolerance and endurance, and that stimulants can partially reverse this impact. Additionally, the researchers attempted to develop a test battery sensitive enough to detect subtle differences in aviator cognition and performance among conditions. Methods: To determine the effect of fatigue on +G_z tolerance and the impact of stimulant use, 10 male centrifuge subjects, mean age 32, from Brooks City-Base, TX, were tested in a repeated measures study under five nighttime conditions following an average of 22 h of sustained wakefulness during their circadian nadir. Using a within-subject design, subjects received placebo, dextroamphetamine 10 mg, modafinil 200 mg, methylphenidate 10 mg, and pemoline 37.5 mg at night, and were tested during a daytime control session. Cognitive/performance tests were administered before each centrifuge run. Results: No difference in +G_z tolerance or endurance was detected among conditions. The cognitive/performance tests also did not detect any differences. Subject perception that anti-G straining maneuver (AGSM) difficulty was greater during the night placebo condition than during the daytime control, methylphenidate and modafinil night conditions reached statistical significance (P = 0.005, 0.012, 0.022, respectively). Discussion: Physiological changes during the circadian nadir following acute sleep deprivation do not appear to negatively impact +G_z tolerance. A standardized protocol sufficiently sensitive to detect subtle behavioral and performance effects would be useful to test and compare the effect of other pharmacological agents on aviators.