Researchers in China have identified a naturally occurring molecule that appears to play a key role in regulating the body's need for sleep, opening the door to the development of new treatments for insomnia and other sleep disorders. The findings were published in Nature Neuroscience.

Sleep is essential for brain function and overall health, supporting memory consolidation, metabolic waste clearance, and physical recovery. However, many people struggle with insufficient or poor-quality sleep due to conditions such as insomnia, circadian rhythm disorders, anxiety, and depression. Although several medications are available, many are associated with dependence or side effects, including next-day drowsiness and rebound insomnia.

In the new study, researchers from the Chinese Academy of Sciences and collaborating institutions investigated the biological mechanisms that generate "sleep pressure"—the increasing urge to sleep that builds during prolonged wakefulness.

The team identified tryptamine (TrpA) as a naturally occurring molecule whose levels in cerebrospinal fluid rise steadily the longer an individual remains awake. Experiments in both nocturnal mice and diurnal pigs showed that TrpA levels reflected the animals' recent history of wakefulness regardless of the time of day, suggesting that the molecule is linked to the body's internal regulation of sleep rather than the light-dark cycle.

The researchers found that TrpA is released by groups of neurons that are active during wakefulness. Once released, the molecule binds to the G-protein-coupled receptor 139 (GPR139), increasing the activity of sleep-promoting neurons located in the hypothalamic preoptic area of the brain.

Further experiments demonstrated that activating GPR139 with experimental small-molecule compounds significantly increased both sleep duration and sleep quality in mice and pigs. The researchers also showed that TrpA-GPR139 signaling is essential for the normal recovery sleep that follows sleep deprivation.

According to the authors, the findings identify TrpA as a previously unknown signal involved in maintaining sleep homeostasis and highlight GPR139 as a promising therapeutic target. Because the mechanism was observed in two different mammalian species, it may be evolutionarily conserved. If future studies confirm that the same pathway exists in humans, it could lead to the development of safer, non-addictive medications for insomnia and other sleep disorders.