Environmental and Endogenous Psychedelics as Adaptive Plasticity Modulators: An Integrative Systems Biology Framework

Abstract

This project develops a full systems biology framework for understanding environmental, endogenous, and synthetic psychedelics as adaptive plasticity modulators that recalibrate biological and psychological set points across multiple levels of organisation. It brings together natural compounds from plants, fungi, and animals, endogenous trace amines, synthetic psychedelics, dissociatives, empathogens, cannabinoids, terpenes, and novel psychoactive substances into one unified scientific structure. The purpose of the project is to resolve fragmentation in the current literature by integrating molecular mechanisms, cellular plasticity, network dynamics, phenomenology, ecological context, clinical evidence, and public health considerations into a single coherent model. The framework explains how psychedelic compounds influence receptor systems, intracellular signalling cascades, neurotrophic pathways, mitochondrial and metabolic processes, and long‑term transcriptional changes. It links these mechanisms to systems‑level effects including changes in network connectivity, predictive processing, thalamic gating, and the dynamics of self‑referential processing. The project treats subjective experience as mechanistic data, connecting phenomenology with measurable neural and behavioural outcomes. A major component of the work examines the evolutionary origins of psychedelic compounds, including biosynthetic pathways, chemical ecology, adaptive functions, and co‑evolution with vertebrate receptor systems. A parallel section traces the origins of synthetic psychedelics, showing how medicinal chemistry and serendipity shaped modern neuroscience and psychopharmacology. The project also provides an exhaustive taxonomy of psychedelic systems, covering natural, endogenous, synthetic, and ecological preparations. Expected outcomes include a complete integrative model of psychedelic action, a detailed research agenda for future mechanistic and clinical studies, and a set of translational pathways for personalised psychedelic medicine, psychoneuroimmunology, and resilience research. The project also delivers extensive supplementary materials, including expanded taxonomies, methodological notes, biomarker panels, safety templates, conservation guidance, and open science resources. These materials support reproducibility, transparency, and interdisciplinary collaboration across neuroscience, pharmacology, anthropology, ecology, ethics, and clinical science. This framework is intended to guide researchers, clinicians, and policy specialists, and to establish a foundation for future experimental work, consortium development, and open access publication. It positions psychedelics as tools for studying adaptive plasticity and homeostatic recalibration across biological and psychological systems.