Caffeine’s wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. Here we show that evening caffeine consumption delays the human circadian melatonin rhythm in vivo, and chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro primarily via an adenosine receptor/cyclic AMP-dependent mechanism. In a double-blind, placebo controlled, ~49-day long within-subject study, we found the equivalent amount of caffeine as that in a double espresso 3 hours before habitual bedtime induced a phase delay of the circadian melatonin rhythm in humans by ~40 minutes. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3-hours of evening bright-light (~3000 lux; ~7 Watts/m2) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of circadian period by caffeine. By pharmacological dissection and siRNA knockdown we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, is sufficient to account for caffeine’s effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine can influence a core component of the cellular circadian clock. Taken together, our findings demonstrate that caffeine influences human circadian timing and gives new insight into how the world’s most widely consumed psychoactive drug impacts upon human physiology.

Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

Ramelteon improved daytime sleep, perhaps mechanistically in part by reducing core temperature and modulating skin temperature. These findings suggest that ramelteon may have promise for the treatment of insomnia associated with circadian misalignment due to circadian sleep disorders.

Introduction: Quality improvement (QI) is a growing and critical part of perioperative medical practice. However, there are few examples of educational tools to introduce new learners from anesthesiology to QI. This may contribute to a lack of enthusiasm to learn about and apply these concepts. Methods: This problem-based learning discussion (PBLD) was designed to teach anesthesiology residents about QI in a way allowing for the application of core concepts in a group setting. We created this PBLD using available literature on QI in the perioperative setting. Basic concepts and terminology necessary for new learners to communicate about QI were specifically addressed. Feedback from staff anesthesiologists and resident participants in the PBLD was used to tailor it to the needs of the target learners and to reach the educational objectives. Results: We delivered this PBLD in two separate learning sessions both to board-certified anesthesiologists (N = 10) and to resident anesthesiologists (N = 19) at our institution. The exercise was reviewed anonymously, and qualitative feedback was used to improve updated versions. Respondents felt that the PBLD would be improved by avoiding jargon-based humor, considering the systemic implications of QI, and limiting the overall length of the learning tool. The PBLD has been adopted as a starting point for discussions about QI in our training program. Discussion: We feel this PBLD can introduce new learners to the learning objectives. This tool has provided an alternative to lectures or computer-based modules for teaching QI.