Executive Control Dysfunction and Impairment in Substance Use Disorders: Neurocognitive Mechanisms and Clinical Implications.

Abstract Impaired executive and inhibitory control is increasingly recognized as a core neurocognitive deficit underlying the development, persistence, and relapse vulnerability of substance use disorders (SUDs). Inhibitory control, a central component of executive functioning, enables the suppression of prepotent impulses, maladaptive actions, and intrusive thoughts in favor of goal-directed behavior. Converging evidence from behavioral paradigms, neuroimaging, and neurochemical studies indicates that chronic substance exposure disrupts prefrontal-striatal circuitry, particularly involving the dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), ventrolateral prefrontal cortex, and anterior cingulate cortex (ACC). These disruptions weaken top-down regulatory control over subcortical reward- and habit-related systems, including the ventral and dorsal striatum. Drug-induced dysregulation of dopaminergic and glutamatergic signaling further exacerbates inhibitory dysfunction by altering reward salience, action-outcome evaluation, and response suppression. Across substances, impaired inhibitory control predicts compulsive drug seeking, diminished treatment response, and heightened relapse risk. Developmental factors, particularly adolescent exposure during critical periods of prefrontal maturation, confer additional vulnerability by producing long-lasting alterations in executive circuitry. This article synthesizes current neurocognitive and neurobiological evidence on impaired inhibitory control in SUDs, integrates contemporary models of addiction emphasizing the shift from goal-directed to habitual control, and examines substance-specific and developmental findings. Clinical implications are discussed with emphasis on relapse prediction and intervention targets. Emerging therapeutic approaches, including cognitive remediation, neuromodulation, and pharmacologic strategies, are evaluated as adjuncts to established behavioral treatments. Collectively, the evidence supports inhibitory control dysfunction as a mechanistic driver of addiction pathology and a promising target for precision intervention in addiction neuroscience.