Context-Dependent Cannabinoid Risk and Endocannabinoid System Integrity Allostasis, Adaptive Capacity, and Indication-Aware Frameworks

This record contains a multi-paper research series examining Δ9-tetrahydrocannabinol (THC) exposure through a systems biology and allostatic lens, with emphasis on context-dependent risk, adaptive capacity, and endocannabinoid system (ECS) integrity. Rather than framing THC as inherently beneficial or harmful, the series demonstrates how chronic CB1-dominant signalling can reshape biological systems over time, particularly in metabolically, autonomically, endocrinologically, immunologically, and therapeutically vulnerable states. The primary failure mode explored is not toxicity, but allostatic drift, leading to reduced resilience, impaired immune surveillance, endocrine instability, and altered therapeutic response. The series is non-prescriptive, non-commercial, and does not provide dosing guidance or treatment protocols. Its purpose is to clarify biological failure modes, distinguish symptom relief from system repair, and support indication-aware, time-aware reasoning in cannabinoid-related research and clinical discourse. The work is written from a position that is pro-cannabis but anti-misrepresentation, seeking to prevent avoidable harm caused by conflating THC exposure with physiological ECS support. Papers included Paper 0: Context-Dependent Risks of THC (Series Anchor) Paper I: Metabolic Allostasis and Glycaemic Dysregulation Paper II: Autonomic–Cardiovascular Allostasis Paper III: Endocrine Allostasis and Estrogen-Dependent Cancers Paper IV: Chronic Signalling and Loss of Adaptive Capacity Paper V: Immune Surveillance Failure and Tumour Permissivity Paper VI: THC as a Contextual Interference Agent in Clinical Care Paper VII: Why THC Is a Poor Proxy for Endocannabinoid Medicine Paper VIII: Indication-Aware Cannabinoid Frameworks (CB1/CB2/Time-State Stratification) PDF files are the canonical citation artefacts. DOCX versions are provided for transparency and scholarly review. *Note: This work does not provide medical advice or treatment protocols. It is intended for research, clinical reasoning, and risk-awareness purposes only. Anwar MohamedIndependent ResearcherORCID: https://orcid.org/0009-0000-6043-9275