The endocannabinoid system (ECS) is a fundamental regulator of brain and body homeostasis, integrating neural, immune, and stress-related signaling pathways. Dysregulation of ECS components, including cannabinoid receptors (CB1 and CB2), endocannabinoids such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes (FAAH and MAGL), has been increasingly implicated in the pathophysiology of neuropsychiatric disorders, including mood, anxiety, psychotic, stress-related, and eating disorders. Altered endocannabinoid signaling contributes to maladaptive stress responses, emotional dysregulation, and impaired synaptic plasticity, highlighting the role of the ECS as a core integrative mechanism. Therapeutic strategies targeting ECS, particularly through FAAH inhibition and the use of plant-derived cannabinoids, such as cannabidiol (CBD), show promise in restoring endogenous homeostasis while minimizing the adverse cognitive and affective effects associated with direct CB1 activation. ECS function and treatment response are further influenced by genetic polymorphisms in CNR1, CNR2, FAAH, and MGLL, as well as epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation. Despite these advances, clinical translation remains limited by interindividual variability, the complexity of ECS interactions, and the relatively small size of existing clinical studies. Future research integrating longitudinal clinical trials with multi-omics approaches is essential to support the development of evidence-based, personalized interventions. Overall, understanding ECS mechanisms and dysregulation provides a valuable framework for the development of targeted therapies in neuropsychiatric disorders.

Introduction and aim. Arterial stiffness reflects vascular properties that can influence blood pressure (BP) and heart rate (HR) responses to exercise, but its association with post-exercise autonomic recovery in healthy young adults remains unclear. This exploratory pilot study investigated the relationship between baseline aortic stiffness and post-exercise hemodynamic and autonomic recovery following graded submaximal aerobic exercise. Material and methods. Thirty healthy young adults (17 women, 13 males; mean age 22.7±2.5 years) underwent baseline evaluation of carotid–femoral pulse wave velocity (cf-PWV), central BP, and pulse wave analysis. Participants completed a graded submaximal cycling protocol from 20 to 80% of the maximum oxygen uptake in 3-minute stages, followed by 5 minutes of seated recovery. HR was continuously recorded and BP measured at 1, 3, and 5 minutes of recovery. Autonomic recovery was assessed using heart rate recovery (HRR) and heart rate variability (HRV) indices. Associations were analyzed using correlation and multivariate linear regression adjusted for age, sex, and body mass index. Results. Higher baseline cf-PWV was associated with higher peak HR and systolic BP during exercise (p<0.01), and slower HRR at 1 min (r=-0.517, p=0.002). Cf-PWV independently predicted early HRR after adjustment. Conclusion. In this pilot sample of healthy young adults, greater aortic stiffness was associated with higher BP responses during exercise and slower early autonomic recovery. These findings suggest an association between vascular properties and early postexercise recovery, which should be confirmed in larger studies.

Cancer predominantly affects older adults, who frequently present with frailty, sarcopenia, cachexia, multimorbidity, and functional decline that limit tolerance to conventional exercise interventions. Blood flow restriction (BFR) training has emerged as a potential low-load exercise strategy capable of promoting muscular adaptations while reducing mechanical stress. This narrative review synthesizes current evidence on the physiological rationale, clinical applications, safety considerations, and implementation of BFR training in older adults with cancer. Literature from PubMed, Scopus, and Web of Science was reviewed, with emphasis on studies investigating BFR, exercise interventions, geriatric syndromes, and oncology rehabilitation. Evidence from older adult populations demonstrates that low-load BFR training may improve muscle strength, muscle mass, and functional performance while maintaining a generally favorable safety profile when individualized and appropriately supervised. Although oncology-specific evidence remains limited, preliminary studies suggest that BFR is feasible, acceptable, and may attenuate treatment-related declines in physical function, particularly in patients with sarcopenia, frailty, and reduced exercise tolerance. However, substantial heterogeneity in study populations and intervention protocols, together with limited long-term safety data, precludes definitive clinical recommendations. BFR training represents a promising adjunct to individualized exercise programs for older adults with cancer, particularly when conventional high-load exercise is poorly tolerated. Nevertheless, adequately powered oncology-specific trials are needed to establish standardized protocols, confirm safety, and define its role in routine geriatric oncology care.

Orthostatic intolerance represents a broad clinical continuum encompassing orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS). Although both entities share overlapping manifestations, such as dizziness, presyncope, and palpitations, their underlying autonomic mechanisms differ substantially. Distinguishing between these disorders is crucial yet often diagnostically challenging, particularly in older adults and those with multimorbidity. We report the case of a 78-year-old woman with recurrent episodes of dizziness and presyncope, initially suspected to have orthostatic hypotension and possible arrhythmic etiology. During active standing, her heart rate increased by more than 30 bpm without a significant fall in blood pressure, fulfilling diagnostic criteria for POTS. Continuous 24-hour Holter electrocardiography revealed a tachycardic response to orthostasis without arrhythmogenic events. Comprehensive cardiovascular, neurological and endocrine evaluations were unremarkable, excluding secondary causes of orthostatic intolerance such as anemia, hypovolemia, endocrine disorders, or structural heart disease. The patient’s symptoms improved markedly with non-pharmacological measures, gradual mobilization and low-dose beta-blocker therapy. This case underscores the diagnostic complexity within the orthostatic intolerance spectrum and highlights the need for meticulous assessment of autonomic responses. OH and POTS may appear clinically similar but differ fundamentally in pathophysiology. OH is characterized by impaired vasoconstriction and an inadequate, often blunted heart rate response due to autonomic dysfunction, whereas POTS involves excessive sympathetic activation with a pronounced tachycardic response. Recognition of POTS in the older adults is critical, as misclassification can delay management. Comprehensive autonomic testing and individualized therapy remain key to optimizing outcomes.

Vasomotion refers to spontaneous rhythmic oscillations in microvascular tone that are independent of cardiac and respiratory cycles and contribute to the regulation of tissue perfusion. These oscillations arise from intrinsic vascular mechanisms and are modulated by autonomic, cardiometabolic and neuroendocrine signals. Although traditionally considered a local vascular phenomenon, emerging evidence suggests that microvascular oscillations may exhibit temporal relationships across different vascular beds. Whether shared physiological inputs contribute to the coordination of vasomotion between cerebral and systemic microcirculation remains largely unexplored. This review covers the cellular basis of vasomotion and the potential contributors of autonomic nervous system, cardiometabolic signals and neuroendocrine mediators in cerebral-systemic microvascular interactions. We propose that these extrinsic influences constitute a superimposed regulatory layer that may modulate the amplitude, frequency, and phase of locally generated vasomotor oscillations, potentially contributing to coordination across distributed vascular networks while preserving vascular bed-specific regulation. We further discuss experimental approaches for investigating vasomotion across spatial and temporal scales, including intravital imaging, wavelet analysis, phase-coherence assessment, and simultaneous measurements of cerebral and peripheral hemodynamic signals. Methodological limitations, including the difficulty of assigning specific mechanisms to individual frequency bands and inability to establish causality from coherence alone, are also considered. This integrative framework identifies key questions for determining whether coordinated vasomotion contributes to functional coupling between cerebral and systemic microcirculation and helps maintain microvascular homeostasis.