Editorial: World No-Tobacco: Effects of Tobacco and Nicotine on the Brain

Isis Nem de Oliveira Souza^1*Graciela Noemí Balerio²Vijayapandi Pandy³Massimo Grilli⁴Gilda Angela Neves^1*

• ¹Laboratório de Farmacologia Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Paraná, Brazil
• ²Instituto de Investigaciones Farmacológicas (ININFA-CONICET) and Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
• ³Department of Pharmaceutical Sciences, School of Health Sciences and Technology Dr. Vishwanath Karad, MIT World Peace University, Pune, India
• ⁴Department of Pharmacy, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy

Recent evidence places the earliest human tobacco use around 12,300 years ago (Duke et al., 2021). Among plants with psychoactive compounds, tobacco, and by default nicotine, is arguably the most entrenched in human history, affecting several aspects such as health, culture, and social relations (Castaldelli-Maia et al., 2016). Tobacco smoking remains the world's leading preventable cause of death, responsible for approximately 8 million deaths per year (Reitsma et al., 2021). On World No-Tobacco Day, we are advancing our understanding of tobacco and nicotine use and its impact on human health from various perspectives, with the potential to improve public health.Significant gaps remain in our understanding of sex differences in the development of tobacco and nicotine addiction and relapse (Kcomt et al., 2022;Davis et al., 2023).and co-workers (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1415219/ful l) investigated the operant response to nicotine and the development of addiction in adult rats of both sexes. They also evaluated whether a period of enforced abstinence affected nicotine-seeking behavior. The results showed that nicotine intake was higher in females than in males when they were given prolonged daily access to the drug, highlighting the need for more individualized approaches to tobacco cessation. ) examined the associations between recent nicotine and tobacco product (NTP) use, primarily e-cigarettes, and bilateral hippocampal volume estimates in a sample of adolescents and young adults. Results showed that greater NTP use predicted larger hippocampal volumes but relatively lower memory scores than non-users. These findings suggest that early NTP exposure may alter typical brain-behavior relationships underlying learning and memory. Interestingly, when these findings were examined in the context of cannabis co-use, no interaction between NTP and cannabis was found. However, other studies have shown how one drug exposure can influence the response to another (Laviolette, 2021;Gonçalves et al., 2023). In this context, Carreño and co-workers (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1445303/ful l) investigated sex-and genotype-dependent effects of nicotine-induced methamphetamine self-administration in adolescent rats. They focused on a single-nucleotide polymorphism of the α6 nAChR subunit gene, which is well associated with higher cigarette smoking, adolescent drug experimentation, nicotine dependence, and unsuccessful quit attempts (Carreño et al., 2024). Their findings suggest functional changes in α6 nAChRs in brain regions associated with reward influenced by the CHRNA6 genotype, sex, and drug treatment. These findings provide new insights for future prevention and intervention strategies for nicotine addiction.In addition to e-cigarettes, other unique delivery systems include nicotine pouches, which promise to be less harmful to lung health and aid in smoking cessation (Pluym et al., 2024). Mallock-Ohnesorg and colleagues (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1392027/ful l) evaluated the acute effects of different brands and doses of nicotine pouches in a German cohort of cigarette smokers. Although all pouches successfully reduced cigarette cravings, they were associated with much higher and faster nicotine intake and changes in cardiovascular parameters. These findings emphasize the urgent need for better regulation of new nicotine-releasing products to ensure their safety and effectiveness for tobacco cessation.Returning to the topic of early life tobacco exposure, Proud and colleagues (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1473213/ful l) evaluated prenatal nicotine exposure using an in vitro approach. Their research confirms that nicotine exposure has not only acute but also long-term outcomes on neurogenesis and molecular markers of neural identity, mood disorders, and excitatory/inhibitory balance.Their study demonstrates how sophisticated in vitro approaches can contribute to neurodevelopmental research on nicotine exposure and how this exposure can be detrimental, even if not direct. Furthermore, non-smokers can still be affected by tobacco exposure through second-hand smoke (SHS), also known as passive or environmental tobacco smoke exposure.SHS increases the risk of nine health outcomes, including ischemic heart disease, stroke, diabetes, and lung cancer. Although smoking rates have gradually declined over the past 50 years, ~37% of the world's population is still exposed to smoke emitted from the combustion of tobacco end-products or exhaled by smokers, with higher rates of exposure reported in women and children compared with men (Flor et al., 2024). In their review, Kisby and Raber (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1466332/ful l) address the issue of tobacco exposure from the perspective of pathological risk, including that induced by SHS.Alongside direct deleterious effects, nicotine use is implicated in many comorbidities, although causal or consequential roles are rarely described (CDC-OSH, 2014).People living with HIV are predisposed to an increased risk of developing inflammatory disorders such as HIV-associated neurocognitive disorder (HAND). Moreover, tobacco use has been observed to exacerbate further the risk of neurocognitive symptoms resulting from HIV-associated neuroinflammation (Chang et al., 2020)