Cannabis as a Systems-Level Neuromodulator: Integrating Cannabinoids, Terpenes, and Brain Network Dynamics into a Unified Framework

This record contains the supplementary materials for the forthcoming manuscript Cannabis as a Systems Level Neuromodulator. The supplementary file provides extended mechanistic notes, evolutionary context, conceptual expansions, figure descriptions, and methodological details that support the main systems level framework. The materials include detailed explanations of network level flexibility, synaptic plasticity, microglial modulation, autonomic effects, and creativity related cognitive phenomena. Evolutionary and cultural notes outline the long standing human cannabis interface and chemovar diversification. Safety and toxicology notes summarise LD50 considerations and real world societal functioning in countries with established cannabis use. Supplementary figures are provided as descriptions and cover endocannabinoid system architecture, cannabinoid and terpene target maps, network level shifts, organism level outcomes, and the integrated three layer model. Supplementary tables summarise cannabinoid and terpene targets and evidence strength across behavioural and physiological domains. Methods notes describe the literature search strategy, evidence grading approach, and conceptual model development. Conceptual notes outline the neuromodulatory ecosystem framing and the chemovar state machine concept. Limitations are included to clarify the scope and provisional nature of the framework. This Zenodo record serves as the official supplementary materials package for citation, archiving, and public access. The full manuscript will be released separately as a preprint. Authors: Kaya Genc, James Barkell, Silas Njiru John Version: First release Type: Supplementary Materials Keywords: cannabis, endocannabinoid system, cannabinoids, terpenes, brain networks, neuromodulation, chemovars, synaptic plasticity, creativity, evolution, safety, systems biology