THC, Metabolic Allostasis, and Glycaemic Dysregulation (Volume 2: Context-Dependent Risks of Chronic THC Exposure)

This paper examines how chronic Δ9-tetrahydrocannabinol (THC) exposure reshapes metabolic regulation through CB1-dominant allostatic mechanisms. Rather than treating insulin resistance and glycaemic instability as isolated pathological defects, the analysis reframes them as predictable system-level adaptations to sustained cannabinoid signalling within metabolically constrained states. Focusing on glucose homeostasis, insulin sensitivity, pancreatic β-cell stress, immune–metabolic coupling, and regulatory flexibility, the paper demonstrates how early metabolic stability or symptomatic relief can coexist with progressive loss of adaptive capacity under chronic exposure. Particular attention is given to population-specific vulnerability in individuals with insulin resistance, obesity, type 2 diabetes, and chronic inflammatory burden. Serving as Volume 2 in the Context-Dependent Risks of THC series, this work provides the first domain-specific instantiation of a systems-level framework grounded in allostasis, adaptive capacity, and regulatory architecture. The analysis is descriptive and non-prescriptive, intended to support indication-aware clinical reasoning and consistent regulatory evaluation rather than protocol guidance.