Cognitive decline caused by dextromethorphan abuse – a brief review

Objective. To conduct a comprehensive review of the scien­tific literature regarding the current knowledge of the effects of dextromethorphan (DXM) abuse on the de­ve­lo­ping and developed brain, both acute or chronic, with em­pha­sis on the underlying mechanism, clinical mani­fes­ta­tion and population at risk. Materials and method. A lite­ra­ture search was performed across PubMed, MEDLINE, Scopus and Google Scholar to identify relevant research on the matter. After the initial selection, forward and back­ward citation tracking was performed. A total of 32 articles were analyzed, with emphasis on those published within the past ten years. Results. Dextromethorphan abuse causes dose-dependent cognitive impairment mediated mainly through NMDA receptor antagonism and modulation of se­ro­to­ner­gic and dopaminergic pathways. Acute high-dose intake leads to deficits in attention, working memory and episodic memory. On the other hand, chronic abuse is linked to persistent cognitive decline affecting key brain re­gions such as the hippocampus and prefrontal cortex. Ad­di­tio­nal risks include serotonin syndrome, most common in polydrug users, and psychosis. Adolescents, CYP2D6 poor me­ta­bo­li­zers and polydrug users are the most vulnerable po­pu­la­tion subset prone to increased susceptibility to cog­ni­tive toxicity. Conclusions. Dextromethorphan abuse is a silent cause for significant cognitive impairment, with a spectrum of effects that range from reversible acute de­fi­cits to potential prolonged neurocognitive dysfunction. Early identification and targeted prevention strategies are es­sen­tial for high-risk groups, but further research is needed to personalize treatment and characterize the long-term cog­ni­tive outcomes.