Fenethylline (street name, captagon) is a synthetic amphetamine-type stimulant that is emerging as a significant public health and security concern, particularly in the Middle East. This systematic review synthesizes original research articles, epidemiological studies, systematic reviews, policy analyses, and case reports to provide a comprehensive analysis of fenethylline's health impacts, addiction potential, and dynamics of illicit trade. Initially developed for therapeutic use, fenethylline illicit production and use have escalated, raising concern about its physiological, psychological, and socio-economic impacts. This stimulant profoundly affects the central nervous system, enhancing wakefulness, concentration, and physical stamina while inducing euphoria. These effects come at the cost of serious adverse health outcomes, particularly with prolonged or heavy use, including cardiovascular complications, neurological damage, and addiction. The dependence-forming nature of captagon contributes to escalating substance use disorders, impacting healthcare systems. Beyond its biomedical implications, fenethylline trafficking has become a global issue, with supply chains deeply intertwined with politically unstable regions where illicit economies thrive. The geopolitical dimensions of captagon's trade amplify its global security threat, influencing international relations and regional stability. This paper underscores the urgent need for systematic data collection and coordinated efforts to regulate illicit fenethylline production and distribution. Strategies such as improved surveillance, public health interventions, and international cooperation are essential to mitigate its escalating risks. Addressing this issue requires a multidisciplinary approach, integrating public health, law enforcement, and policy development to curb its impact on global health and security.

Department of Agroenvironmental Chemistry and Plant Nutrition Faculty of Agrobiology Food and Natural Resources Czech University of Life Sciences Prague Kamýcká 129 Suchdol Praha 165 00 Czech Republic

Department of Radiology Toxicology and Civil Protection Faculty of Health and Social Studies University of South Bohemia J Boreckého 1167 27 České Budějovice 370 11 Czech Republic

Goodnight Family Department of Sustainable Development Appalachian State University 212 Living Learning Center 305 Bodenheimer Drive Boone NC 28608 United States

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