Mesoamerican Codices: Prospects for Anxiolytic and Antidepressant Drug Discovery

Background/Objectives: Anxiety and depression are leading causes of disability worldwide. Although current pharmaceuticals are effective, adverse effects reduce adherence, driving the search for alternatives in traditional plant-based medicine. This article analyzes ancient Mesoamerican codices and documents to identify candidate plants, establishing a baseline for pharmacological validation and potential treatment development. Methods: This narrative review analyzes and synthesizes data from specialized databases and physical libraries in Spanish and English. Results: Plants described in Mesoamerican codices demonstrate anxiolytic- and antidepressant-like effects in preclinical models, linked to phytochemicals such as sterols, flavonoids, alkaloids, and terpenes. Mechanisms appear to involve oxytocinergic cells; the GABAergic, serotonergic, noradrenergic, and dopaminergic systems; BDNF activation; and monoamine oxidase regulation. Although translation is complicated by uncertainties in historical interpretation, botanical identification, and reproducibility, these studies remain essential for identifying natural products to inform future drug discovery. Conclusions: Analyzing ancient Mesoamerican medical records helps identify plants with anxiolytic and antidepressant potential. However, characterizing their pharmacokinetic, toxicological, and neurochemical profiles is required before proposing clinical trials to ensure patient safety.