Journal of Mental Health Research and Innovation

ABSTRACT

Addiction is a chronic relapsing disorder characterized by compulsive substance use or engagement in rewarding behaviors despite harmful consequences. Contemporary evidence demonstrates that addiction arises from complex interactions among neurobiological, psychological, environmental, and genetic factors that progressively alter brain function and behavior. This review provides an updated synthesis of current knowledge regarding the molecular and neural mechanisms underlying addiction while introducing an integrative conceptual framework that incorporates recent advances in neuroinflammation, gut–brain communication, digital addiction, and precision medicine. A systematic review of peer-reviewed literature published between 2000 and 2026 was conducted using PubMed, Scopus, Web of Science, and Google Scholar. In parallel, secondary epidemiological datasets from international public health agencies were critically evaluated to identify demographic and clinical trends associated with substance use disorders. Evidence indicates that chronic exposure to addictive substances disrupts dopaminergic, glutamatergic, γ-aminobutyric acid (GABA), serotonergic, and endogenous opioid signaling, producing long-term neuroadaptations within mesolimbic reward circuits. Emerging findings further demonstrate that neuroinflammatory responses, epigenetic modifications, and alterations of the gut–brain axis contribute substantially to craving, relapse vulnerability, and treatment resistance. Statistical evidence consistently shows significant associations between addiction, psychiatric comorbidity, socioeconomic disadvantage, and adverse health outcomes. Rather than summarizing established concepts alone, this review proposes an integrated model linking classical reward circuitry with contemporary biological and behavioral mechanisms to better explain addiction progression and recovery. The findings support multidisciplinary treatment strategies combining pharmacological interventions, behavioral therapies, digital health technologies, and biomarker-guided personalized medicine. Future research should prioritize longitudinal studies and precision-based therapeutic approaches to improve prevention, early diagnosis, and individualized treatment of substance use disorders.

Keywords: Addiction; Substance Use Disorder; Dopamine; Neuroinflammation; Glutamate; Gut–Brain Axis; Epigenetics; Digital Addiction; Precision Medicine; Neurobiology