The Caffeinated Brain Part 2: The Effect of Caffeine on Sleep-Related Electroencephalography (EEG)—A Systematic and Mechanistic Review

Introduction: Caffeine is the most widely consumed psychoactive stimulant worldwide and acts primarily through antagonism of adenosine A1 and A2A receptors, thereby reducing sleep pressure and promoting wakefulness. Although its alerting and performance-enhancing effects are well established, its influence on sleep-related electroencephalography (EEG) has been investigated across diverse paradigms with substantial methodological heterogeneity. This systematic and mechanistic review aimed to synthesize human evidence on how caffeine affects sleep architecture, quantitative sleep EEG, and neurophysiological markers of sleep homeostasis, and to interpret these findings within current models of adenosine-mediated sleep–wake regulation. Materials and methods: A systematic search of PubMed/MEDLINE, Web of Science, Scopus, Embase, PsycINFO, ResearchGate, and Google Scholar was conducted for studies published between January 1980 and January 2026, with the final search performed on 10 January 2026. Eligible studies were original human investigations examining caffeine exposure or administration and reporting sleep-related EEG outcomes, including polysomnographic sleep staging, spectral EEG analyses, or other EEG-derived sleep metrics. Two reviewers independently screened records and assessed eligibility, with disagreements resolved by consensus. Data on study design, participant characteristics, caffeine interventions, EEG methodology, and outcomes were extracted using a predefined form. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Owing to marked heterogeneity across studies, findings were synthesized narratively within a mechanistic interpretive framework. Results: Thirty-two studies were included. Across highly heterogeneous paradigms—including acute bedtime or evening dosing, daytime or repeated caffeine use before nocturnal sleep, administration during prolonged wakefulness followed by recovery sleep, withdrawal protocols, and ambulatory/home EEG monitoring—the most consistent finding was suppression of low-frequency NREM EEG activity, particularly slow-wave activity and the lowest delta frequencies. Caffeine frequently increased faster EEG activity, including sigma/spindle and beta ranges, producing a lighter, more aroused, and more wake-like sleep EEG profile. These effects were especially prominent during early-night NREM sleep and in recovery sleep after sleep deprivation, where caffeine attenuated the expected homeostatic rebound in low-frequency power. REM-related effects were less consistent, but some studies reported delayed REM timing and subtler alterations in REM EEG. Emerging evidence further suggests that caffeine increases EEG complexity and shifts sleep dynamics toward a more excitation-dominant state. Several studies indicated that quantitative EEG measures were more sensitive than conventional sleep-stage variables in detecting caffeine-related sleep disruption. Dose, timing, habitual caffeine use, withdrawal state, age, circadian context, and adenosinergic genetic variation, particularly involving ADORA2A, moderated the magnitude of effects. We also highlighted the connection between current results and sports and sports science. Conclusions: Caffeine reliably alters the neurophysiological architecture of human sleep in a direction consistent with reduced sleep depth and weakened homeostatic recovery. The overall evidence supports a mechanistic model centered on adenosine receptor antagonism, attenuation of sleep-pressure build-up and expression, and a shift toward greater cortical arousal during sleep. Sleep EEG appears to be a sensitive marker of these effects, often revealing physiological disruption even when conventional sleep architecture changes are modest. Future research should prioritize larger and more diverse samples, pharmacokinetic and pharmacogenetic characterization, and ecologically valid high-resolution sleep monitoring to clarify the real-world and functional consequences of caffeine-induced EEG changes.