Toward a Nutritionally Complete Model of the Endocannabinoid System

The endocannabinoid system (ECS) has been extensively mapped at the level of receptors, ligands, enzymes, and signaling pathways, forming a detailed component inventory of a major homeostatic network. However, prevailing ECS models largely omit the nutritional substrates required to sustain ligand synthesis, membrane composition, signaling capacity, and regenerative function, leaving the system operationally incomplete from a systems-biology perspective. This Hypothesis identifies this gap by integrating evidence from nutritional biochemistry, lipid metabolism, and regenerative physiology, and argues that inclusion of dietary inputs is necessary to advance toward a nutritionally complete model of the ECS.By reframing the ECS as a metabolically sustained regulatory network rather than a purely signaling system, this framework has implications for understanding resilience, regeneration, and system failure under chronic stress, nutritional insufficiency, and environmental disruption. This synthesis is intended as a hypothesis-generating foundation to guide future experimental and clinical investigation.