Smoking in Schizophrenia: New Insights into Mechanisms, Clinical Manifestations, and Treatment Strategies

Abstract: People with schizophrenia smoke much more than the general population. Biological evi-dence shows that the main addictive component in tobacco is nicotine, which binds to nicotinic ace-tylcholine receptors (nAChRs) and can modulate dopaminergic and glutamatergic neurotransmis-sion. On one hand, nicotine may alleviate negative symptoms while exacerbating positive symp-toms. It can also reduce the plasma concentration of medications, which decreases their efficacy and leads to unpredictable treatment outcomes. Moreover, it contributes to addiction and long-term neu-robiological changes in the brain. Smoking also worsens cardiovascular and respiratory comorbidi-ties and increases the risk of cardiovascular mortality and all-cause mortality in this population. This review examines the neurobiological mechanisms, clinical implications, and sociocultural factors underlying smoking in schizophrenia. We also discuss strategies to help people quit smoking, in-cluding current effective cessation methods such as cognitive behavioral therapy (CBT), pharma-cotherapy (e.g., varenicline, bupropion, nicotine replacement therapy), combined treatments, and digital health tools (e.g., mobile apps). These therapies have been assessed for their efficacy and safety in this clinically complex group. We also note that relying solely on self-reported smoking measures may be insufficient; therefore, we recommend using objective biomarkers, such as serum cotinine, in future research. A personalized approach that considers cognitive profiles, pharmacoki-netic differences, and other substance use may improve cessation outcomes. Supporting people with schizophrenia to quit smoking is very important, as it can reduce cardiovascular risk, enhance the effectiveness of medications, and improve overall recovery.