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Neuropsychiatric disorders affect nearly one billion people worldwide, yet many existing psychopharmacological treatments are limited by adverse effects, drug interactions, and variable efficacy. Ethnopharmacological knowledge embedded in Indigenous health systems offers important perspectives for understanding mental and neurological distress and for informing future research on central nervous system (CNS)-active plants. Colombia, one of the world's most biodiverse countries, harbors a rich medicinal flora that is deeply embedded in Indigenous and rural cultural practices. This review synthesizes published ethnobotanical, phytochemical, and neuropharmacological literature on 42 Colombian plant species reported in Indigenous and local health systems to address conditions that may overlap with what biomedicine classifies as mental and neurological disorders. Within this review, traditional uses were analytically grouped into biomedical categories for comparative purposes, including psychoactive, stimulant, sedative, anxiolytic, and cognitive effects, while recognizing that these categories do not fully capture Indigenous epistemologies. Ayahuasca (locally called yag ) was the most frequently reported preparation, and Nicotiana tabacum, Erythroxylum coca, and Aloysia citrodora were the most commonly cited species. Leaves (38%), stems (14%), and roots (13%) were the most frequently used plant parts, most often prepared as decoctions (21%) and infusions (17%). Across the reviewed taxa, five lack phytochemical characterization, fourteen have demonstrated neuropharmacological activity in preclinical studies, and only seven have been examined in clinical contexts, underscoring substantial evidence gaps. Six species-Iochroma fuchsioides, Brunfelsia grandiflora, Souroubea corallina, Tabernaemontana heterophylla, Psidium guajava, and Dianthera pectoralis-emerged as recurrently cited across ethnobotanical and pharmacological sources, warranting further investigation. Overall, this review highlights both the potential and the limitations of existing evidence on Colombian plants, emphasizing the need for ethically grounded, collaborative research that respects Indigenous knowledge systems while advancing neuropharmacological understanding, cultural preservation, and biodiversity conservation.
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