Transcranial photobiomodulation to enhance sleep by elevating adenosine signaling: a translational study

Sleep disturbances are a significant health concern in modern society, with prevalent treatments often leading to limited efficacy and unwanted side effects. Adenosine, a sleep-promoting molecule in the brain, presents a promising target for innovative therapies, yet strategies to augment intracerebral adenosine have remained largely unexamined. This study explores transcranial photobiomodulation (tPBM) as a potential intervention, employing near-infrared (NIR) light to enhance mitochondrial adenosine triphosphate (ATP) synthesis and facilitate adenosine release. Utilizing fiberoptic cannula and electroencephalographic electrodes implanted in mice, we found that tPBM significantly increased non-rapid eye movement (NREM) sleep during and after stimulation compared to sham controls. Enhanced NREM delta power and elevated adenosine concentration in the frontal cortex were confirmed. In vitro experiments further demonstrated that NIR PBM increased cellular ATP production without inducing cytotoxicity. Additionally, a double-blind randomized controlled trial with 40 subjects demonstrated significant reductions in insomnia severity, sleep disturbances, and sleep latency. These findings provide preliminary clinical and translational evidence that tPBM may represent a promising non-pharmacological approach for short-term improvement of sleep disturbances through increased homeostatic pressure.