Context-Dependent Risks of THC: Why Indication-Aware Framing Is Essential in Cannabinoid Medicine

This paper establishes a systems-level framework for evaluating Δ9-tetrahydrocannabinol (THC) exposure in cannabinoid medicine. Rather than treating THC as a universal therapeutic agent or surrogate for endocannabinoid system (ECS) support, it examines how sustained CB1-dominant signalling reshapes biological regulation through allostatic mechanisms. The analysis reframes THC-associated risk as context-dependent, time-dependent, and state-dependent. It introduces adaptive capacity as a governing metric and shows how early symptom relief can coexist with progressive loss of regulatory flexibility in biologically vulnerable states. Serving as the conceptual gateway to a multi-paper series, this work replaces reductionist benefit–risk narratives with indication-aware, systems-level reasoning grounded in regulatory architecture rather than isolated outcomes.