Introduction and objective:
The endocannabinoid system (ECS) plays a central role in metabolic regulation, immunomodulation, and energy homeostasis. Although absolute circulating endocannabinoid concentrations are commonly used as biomarkers, clinical heterogeneity often persists despite similar absolute levels. The review aims to examine the limitations of absolute-value interpretation and propose a ratio-based framework for understanding cannabinoid signalling dynamics.

Review methods:
A narrative review of peer-reviewed pre-clinical and clinical literature was conducted, focusing on studies examining endocannabinoid signalling, metabolic regulation, insulin sensitivity, and inflammatory tone. Emphasis was placed on studies reporting multiple endocannabinoids concurrently, enabling a comparative or ratio-based interpretation.

Brief description of the state of knowledge:
Current evidence supports the ECS as a coordinated modulatory network rather than a collection of independent signalling molecules. Relative relationships among endocannabinoids appear to better reflect system-level signalling behaviour than single-molecule concentrations alone, although this perspective remains inconsistently applied in clinical interpretation.

Summary:
The review highlights the interpretive limitations of absolute endocannabinoid concentrations and underscores the explanatory value of ratio-based signalling frameworks. The analysis is conservative in scope, synthesizes existing evidence only, and does not propose therapeutic interventions or policy implications.