Cracking the Code of Cravings: Endocannabinoids and the Hypothalamic Appetite Nexus.

Bagri K.; Kumari S.; Deshmukh R. · Prostaglandins & other lipid mediators · 2026

**Background & Methods** This is a narrative review article examining the role of the endocannabinoid system (ECS) in hypothalamic regulation of appetite and feeding behavior. The review synthesizes current literature on how endocannabinoids modulate both homeostatic (physiological need-based) and non-homeostatic (reward-based) food intake through cannabinoid receptors in hypothalamic regions. **Key Findings** • The endocannabinoid system, acting through cannabinoid receptors 1 and 2 (CB1 and CB2), plays a critical modulatory role in appetite regulation within the hypothalamus, particularly the arcuate nucleus, which controls both orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) neural pathways. • Obesity is characterized by dysregulation of eating patterns driven by reward-based cravings rather than physiological hunger signals, involving disrupted ECS signaling that promotes hedonic feeding independent of metabolic need; this is distinct from simple caloric imbalance and involves macrophage infiltration in adipose tissue and adipocyte hypertrophy. • Understanding ECS-hypothalamic interactions is essential for developing targeted interventions for obesity management, as the system integrates metabolic homeostasis with reward-driven feeding behaviors that contribute to the rising prevalence of obesity and associated comorbidities including diabetes, metabolic dysfunction, and cardiovascular disease. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This is a narrative review article, representing Level 5 evidence on the evidence hierarchy. As a review rather than original research, it synthesizes existing literature but does not present new experimental or clinical data. The review focuses on mechanistic understanding of ECS pathways in appetite regulation but lacks discussion of specific clinical trials, adverse effect profiles, or therapeutic dosing strategies. Limitations include the absence of systematic methodology typical of systematic reviews or meta-analyses, reliance on authors' selection of cited literature, and lack of quantitative synthesis of findings. The paper provides theoretical framework for understanding appetite dysregulation in obesity but would require original research studies to establish clinical applicability of ECS-targeted interventions.

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