Caffeine helps restore memory function after sleep loss, NUS Medicine study shows

Researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have demonstrated that caffeine can restore social memory­­­ impaired by sleep deprivation by targeting a defined brain pathway. Social memory enables us to recognise and differentiate familiar individuals, such as people we have met before. Published in Neuropsychopharmacology, the study offers insights into the effect of caffeine on cognitive function and memory.

The study, led by Associate Professor Sreedharan Sajikumar and first author Dr Lik-Wei Wong, both from the Department of Physiology and Healthy Longevity Translational Research Programme at NUS Medicine, investigated the effects of sleep deprivation in the hippocampal CA2 region of the brain. The hippocampus plays an essential role in memory and learning processes, and its CA2 region contributes significantly to social memory formation. The CA2 area also receives signals linked to the regulation of the sleep and wake cycle.

In their laboratory studies, researchers induced five hours of sleep deprivation, and subsequently provided caffeine mixed into drinking water for unrestricted consumption for seven days. Caffeine is a known stimulant. At the molecular level, it blocks adenosine receptor signalling pathways that accumulate during wakefulness and dampen brain activity. Electrophysiological recordings were subsequently performed on hippocampus samples to measure synaptic plasticity, which refers to the brain’s ability to strengthen or weaken connections between nerve cells based on experience and learning.

The study findings revealed that sleep deprivation disrupted the maintenance of synaptic plasticity, weakening communication between neurons in the hippocampal CA2 region of the brain. A reduced capacity for synaptic strengthening in the brain was observed, alongside clear deficits in social recognition memory. Overall, sleep loss disrupted both neural function and behaviour in a targeted and circuit-specific manner.

However, the researchers discovered that taking caffeine prior to sleep deprivation led to a recovery of synaptic communication in the CA2 region and plasticity returned to normal levels. Specifically, social memory deficits were reversed and the effects of caffeine were pathway specific, selectively restoring the disrupted brain circuit rather than globally increasing neural activity. This meant the control group that was not sleep-deprived did not exhibit signs of overstimulation despite caffeine exposure.

“Sleep deprivation does not just make you tired. It selectively disrupts important memory circuits,” noted Dr Wong. “We found that caffeine can reverse these disruptions at both the molecular and behavioural levels. Its ability to do so suggests that caffeine’s benefits may extend beyond simply helping us stay awake.”

Assoc Prof Sajikumar said, “Our findings position the CA2 region as a critical hub linking sleep and social memory. This research enhances our understanding towards the biological mechanisms underlying sleep-related cognitive decline. This could inform future approaches to preserving cognitive performance.”

The study underscores the fundamental role of sleep in supporting healthy cognition and memory. By demonstrating that caffeine can restore selective neural pathways impaired by sleep deprivation, the study strengthens insights into potential targeted molecular therapies for cognitive conditions. Building on these findings, the researchers aim to further examine the effect of caffeine on memory consolidation and retrieval, as well as employing targeted circuit manipulations to explore causality with neural pathways.

Reference:

Wong, LW., Bin Ibrahim, M.Z., Kannan, A.L. et al. Caffeine reverses sleep deprivation-induced synaptic and social memory deficits via adenosine receptor modulation in the male mouse hippocampal CA2 region. Neuropsychopharmacol. (2026). https://doi.org/10.1038/s41386-026-02362-w