The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain’s extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.

Psychosomatic disorders (PSD), alternatively referred to as psychophysiologic disorders, are characterized by hypothalamic-pituitary-adrenal (HPA) axis activation, posing a substantial challenge in clinical practice. These disorders constitute a collection of intricate medical conditions marked by the considerable impact of psychological and emotional factors on the onset, intensification, or persistence of physical symptoms. The endocannabinoid system, a complex regulatory network consisting of endocannabinoids, cannabinoid receptors, and associated enzymes, emerges as a key player in modulating the body’s stress response, emotional regulation, and immune function. This review delves into the bidirectional relationship between the endocannabinoid system and the HPA axis, elucidating the impact of endocannabinoid system modulation on stress responsiveness, immune modulation, and the intricate interplay between emotional well-being and physical symptoms. Through the synthesis of current scientific knowledge, this review aims to provide a comprehensive understanding of the role of the endocannabinoid system in PSD, offering insights that may pave the way for novel therapeutic approaches.