The endocannabinoid system (ECS) is increasingly recognized as a master regulator of homeostasis, yet the field that studies it operates with a structural blind spot: the dominant research paradigm focuses overwhelmingly on cannabinoid ligands—phytocannabinoids such as THC and CBD—while treating the receptor architecture, endogenous tone, and nutritional substrate availability as secondary concerns. This paper argues that such a ligand-centric view represents the study of, at best, half a system. We present a sex-stratified dataset derived from hemp seed nutritional pharmacology that demonstrates how ECS receptor density, hormonal modulation, and downstream signaling differ profoundly between female and male physiology across fifteen distinct system/effect pairs. These differences are systematically mediated by the interaction of sex hormones (estrogen, testosterone) with CB1 and CB2 receptor expression and by the availability of specific nutritional precursors including gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), arginine, zinc, and magnesium. The disconnect within the ECS field mirrors a broader epistemic problem: sub-field experts understand their component but no integrative framework exists that maps the full system—its hormonal regulation, nutritional dependencies, and sex-based dimorphism simultaneously. We propose that without such a framework, ECS research will continue to produce findings that are reproducible within a sex but inconsistent across studies that pool or ignore sex stratification, and therapeutic interventions that are effective for one population while neutral or counterproductive in another. This paper constitutes a call for the field to recognize nutritional completeness and sexual dimorphism as foundational—not peripheral—variables in ECS research design, interpretation, and clinical translation. Keywords: endocannabinoid system; ECS vitamers; hemp seed nutrition; acidic phytocannabinoids; clinical endocannabinoid deficiency; environmental stress; hormonal expression; sex differences; nutritional modulation; hemp seed; CB1; CB2; phytocannabinoids; anandamide; 2-AG; GLA; ALA; sexual dimorphism.
Floyd et al. (2026) studied this question.