Psychoactive substances are chemical agents that alter key psychological processes, including cognition, emotion, motivation, and behavior. Pharmacologically, they can be classified as central nervous system depressants, stimulants, hallucinogens, as well as emerging categories such as dissociatives and empathogens. Among these, new psychoactive substances (NPS)—chemically modified variants of traditional drugs— often exhibit higher potency and health risk. Abuse of such substances is associated with drug dependence, psychiatric disorders, and systemic organ damage; however, the underlying cellular and molecular mechanisms and pathology remain incompletely defined.

The nervous system is particularly vulnerable to the effects of psychoactive substances. Substance abuse has been implicated in the pathogenesis of diverse neurological and psychiatric conditions, including depression, anxiety, bipolar disorder, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, Parkinson’s disease, Alzheimer’s disease, epilepsy, migraine, and other forms of neurodegeneration. To advance diagnostic, prognostic, and predictive practice in pathology, there is a pressing need to integrate morphology-based neuropathology with molecular pathology, imaging-pathology correlation, and translational biomarkers in human-relevant systems.

This Research Topic invites Original Research, Case Reports, Clinical Trials and System Review articles that place pathology at the center—emphasizing mechanisms and etiology of disease processes, tissue-based diagnostics, clinicopathological correlation, and molecular pathology in personalized medicine—while synthesizing basic, clinical, and translational research. Potential topics include, but are not limited to:
• Molecular pathology and cellular mechanisms of neuropsychiatric and neurodegenerative disorders induced by substance abuse using experimental models;
• Identification of diagnostic, prognostic, or predictive biomarkers associated with substance-induced neurological damage;
• Novel therapeutic strategies, including pharmacological and non-pharmacological interventions, for substance-related neuropsychiatric disorders;
• Clinical and neuroimaging studies elucidating structural, pathological, functional, and connectivity changes in the brain following substance use;
• Epidemiological and public health research on the burden of substance abuse-related neurological disorders;
• Reviews synthesizing current knowledge on pathological links between substance abuse and neurodegeneration or neuropsychiatric illness.

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Pathology of Substance Abuse and Neural Health: Mechanisms, Morphology-Based Diagnostics, and Molecular Biomarkers