Neural Pathways To Addiction: A Comprehensive Review Of Drug Mechanisms And Effects

Abstract

This comprehensive review examines the mechanisms of action and effects of drugs of abuse through a multidisciplinary lens, integrating neurobiological, cognitive, behavioral, and genetic perspectives. The article details how various substances interact with key neurotransmitter systems—including dopaminergic, glutamatergic, serotonergic, GABAergic, endocannabinoid, and opioid pathways—to produce acute effects and drive long-term neuroadaptations underlying addiction. These adaptations manifest at multiple levels, from molecular signaling to synaptic function to circuit-level reorganization, resulting in tolerance, withdrawal, and compulsive drug-seeking behaviors. Neuroimaging studies reveal substance-specific patterns of structural and functional brain alterations, particularly in regions involved in reward processing, executive function, and cognitive control. Cognitive and behavioral consequences include impaired decision-making, altered risk assessment, deficits in error processing, and neuroinflammatory responses that may persist long after cessation of drug use. Meta-analytic findings highlight significant genetic contributions to addiction vulnerability, with multiple polymorphisms affecting neurotransmitter systems and neural development pathways. The review synthesizes evidence from recent meta-analyses and systematic reviews to provide an updated understanding of how drugs of abuse hijack neural circuits evolved for reward and learning, producing persistent changes that underlie the chronic, relapsing nature of addiction. This knowledge provides a foundation for developing targeted prevention strategies and more effective treatments for substance use disorders.