| Description: |
Background Optimizing human performance under stressful physical and cognitive conditions is paramount during high-stakes military operations. As such, interventions to improve warfighter performance by mitigating task-induced cognitive performance deficits are necessary. While caffeine is the most widely consumed psychoactive substance in the world, common side effects (i.e. anxiousness, micro-saccades, irritability) may be detrimental to warfighter operations. Theacrine, a purine alkaloid similar in structure to caffeine but with a longer half-life, less habituation, and fewer side effects, is proposed as a caffeine-alternative to enhance cognitive resilience.Methods Tactically trained participants (n = 20; F = 5; M = 16; age = 21.5 ± 3.8 y) completed one baseline and three experimental visits. Baseline included familiarization with cognitive tasks and a graded exercise test to determine VO2max. Experimental sessions, separated by ≥96 hours, were double-blind, placebo-controlled, and randomized. Participants completed cognitive testing (Dynavision, Trazer, Object Hit and Avoid, Anti-Saccade, Two-Back), consumed either 300 mg caffeine (CAF), 150 mg caffeine +150 mg theacrine (CTC), or placebo (PLA), and repeated cognitive tests 60-min post supplementation. After a high-intensity interval exercise session (10 intervals at >90% VO2max with recovery), reaction time (RT) tests were repeated after the 4th and 8th intervals, as well as immediately and 30-min post-exercise. Heart rate was measured continuously. Change scores were calculated from baseline, and data analyzed using repeated measures ANOVA (α = 0.05) with Bonferroni correction.Results Both CAF and CTC consistently enhanced cognitive and physical performance compared to PLA. In the Two-Back task, CTC showed significantly higher total accuracy (p < 0.01), while both CAF and CTC had fewer target (p < 0.01) and non-target errors (CAF: p = 0.03; CTC: p < 0.01) than PLA. CTC also had significantly faster RTs (p = 0.03) and lower RT variability for ... |