RT doctoral thesis
T1 Physical fitness and exercise as modulators of the endocannabinoid system in adults with mild-to-moderate depression the sonrie study
T2 Condición física y ejercicio como moduladores del sistema endocannabinoide en adultos con depresión leve a moderada: estudio Sonrie
A1 Ruiz Muñoz, Manuel
A2 Didáctica de la Educación FísicaPlástica y Musical
AB The endocannabinoid system (ES) is a lipid-based signaling network involved inmultiple physiological processes including mood regulation, stress response, andneuroplasticity. The primary and most well studied endogenous ligands areanandamide (AEA) and 2-arachidonoylglycerol (2-AG). These components, alongwith associated analogues interact with CB1 and CB2 receptors. CB1 receptors areabundant in the central nervous system and implicated in cognitive, emotional,and motor functions, whereas CB2 receptors are mainly associated with immuneregulation.Depression is a complex, heterogeneous disorder with multifactorial etiology,ranging from genetic vulnerabilities to environmental stressors. Diagnosticcriteria include persistent mood alterations and cognitive-somatic symptoms,with considerable variability across individuals. Pathophysiological hypotheseshighlight disruptions in neuroendocrine and plasticity-related mechanisms,including ES dysregulation.Preclinical and clinical studies suggest that ES signaling pathway impairment,particularly CB1 receptor dysfunction and altered endocannabinoid tonecontribute to depressive symptoms. Notably, AEA and 2-AG appear to exertcomplementary, stress-buffering roles.Physical exercise has emerged as a promising non-pharmacological strategy tothe depression treatment. Acute exercise, especially at moderate-to-highintensities, appear to elevate AEA and 2-AG. However, the effects of chronicexercise on ES are inconsistent. Importantly, while exercise-induced changes ineCBs ligands are documented, the relationship between physical fitness (e.g.,cardiorespiratory and muscular fitness) and eCBs remains unclear. Given thatfitness reflects sustained physiological adaptations, it may independentlymodulate ES activity, offering a novel perspective in understanding and treatingdepressive disorders. Thus, the main aim of the present Doctoral Thesis is to clarify the extent to which physical exercise behavior and the physical-fitnessadaptations it elicits modulate circulating endocannabinoid biomarkers in adultswith depressive disorders, and to determine whether an internet-deliveredpsycho-physical program can leverage this pathway to improve fitness andbiological profiles. The results in Study I confirmed that moderate-intensityaerobic and high-load resistance exercise reliably increases AEA, with lessconsistent effects on 2-AG, while supramaximal intensities may attenuate the eCBresponse. Chronic exercise appears to normalize eCB dysregulation in stressrelated conditions. Study II we found that higher fitness levels were inverselyassociated with baseline plasma eCBs and their analogues. Study III showed thata structured psycho-physical intervention enhanced cardiorespiratory fitness andinduced directional changes in ES, with partial retention of benefits during followup. These findings demonstrate that physical exercise behavior and fitnessmodulate the ES in individuals with depression and support the role of eCBs aspromising biomarkers of psychophysiological health. Moreover, internetdelivered interventions represent a feasible, non-pharmacological strategy totarget ES dysfunction in depression.
YR 2025
FD 2025
LK http://hdl.handle.net/10498/39607
UL http://hdl.handle.net/10498/39607
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 05-nov-2026