ISSN 2477-1686
Vol. 12 No. 54 Maret 2026
Stress, Smoking, and Hypothalamus-Pituitary-Adrenal (HPA) Axis
Oleh:
Laurensius Agus Diantoro T.
Fakultas Psikologi Universitas Katolik Indonesia Atma Jaya
The relationship between psychological distress, smoking behavior, and brain mechanisms has been proven by many previous findings (Rohdeler & Kirschbaum, 2006). But only a few of them emphasize the importance of the hypothalamic-pituitary-adrenal (HPA) axis role between them. This article tries to give a comprehensive explanation about the psychological distress, smoking behavior, and how the HPA axis mechanism impacts smokers.
It is well known that cigarettes have a big impact on dopamine secretion in the brain. But the mechanism underlying this connection has not been emphasized. Most people know that smoking behavior gives one’s mind clarity. The hypothalamic-pituitary-adrenal (HPA) axis is a major neural network involving both the nervous system and the endocrine system (Rohdeler & Kirschbaum, 2006). It plays a crucial role in mediating one’s body response to stress, metabolism, and autonomic nervous system (ANS). Moreover, the HPA axis is essential for maintaining physiological internal balance (homeostasis) (Sheng et al., 2021). Based on HPA axis function, it can be concluded that this link between the brain and nervous system has a big part of regulating how we respond to external stimuli.
Smoking causes both immediate and long-term physical stress, worsening existing health conditions and increasing anxiety (Hoey et al., 2024). Inhaling nicotine activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing stress hormones like epinephrine and cortisol, which elevate heart rate, respiratory rate, and blood pressure. With continued smoking, tolerance to nicotine develops, leading to persistent high levels of cortisol and epinephrine (Rohdeler & Kirschbaum, 2006). This blunts the natural stress response, making it difficult for the body to handle new stressors. This mechanism from psychological distress, smoking, and HPA axis activation makes smokers more prone to have not only poor lungs and coping strategy.
Nicotine also raises blood sugar levels and inhibits insulin release, straining organ function and contributing to oxidative stress that damages cells and DNA, impairing immune response and increasing inflammation (Hoey et al., 2024). Based on this explanation, we know that nicotine is not only a risk factor for chronic dopamine and cortisol flow but also damages the cell’s body and DNA. More than that, nicotine is also affecting the immune response and increasing the body’s inflammation
In the brain, nicotine provides rapid anxiety relief by triggering dopamine, acetylcholine, and norepinephrine release, creating brief feelings of pleasure and focus (Hoey et al., 2024; Rao et al. 2009). Nonetheless, as tolerance builds, these effects diminish, leading smokers to smoke more frequently to manage anxiety caused by decreasing dopamine levels. It can be said that at the first move, nicotine makes smoker calm, attentive, and pleasurable, then it gives the smoker negative impacts such as smoking addiction and anxiety.
In 2009, Rao et al. found that stressful life experiences enhance the risk of smoking behavior in depressed and non-depressed youth. Moreover, the nicotine dependency activates the chronic HPA axis activity, reducing the nicotine sensitivity and increasing the quantity the nicotine needed to elicit a particular response of nicotine-anxious-craving (Bruijnzeel et al., 2007; Rao et al., 2009). These findings imply that smoking behavior not only enhances the nicotine dependency but also the activation of the body's stress response, which makes it somewhat difficult for smokers to handle new stressors.
Conclusion
The relationship between psychological distress, smoking behavior, and the hypothalamic-pituitary-adrenal (HPA) axis is complex and significant. This article emphasizes the crucial role of the HPA axis in mediating the effects of smoking on mental health and physiological responses. Smoking activates the HPA axis, leading to elevated levels of stress hormones like cortisol and epinephrine. This chronic activation blunts the body's natural stress response, making smokers more susceptible to anxiety and related health issues.
While nicotine initially induces feelings of clarity and pleasure by stimulating dopamine release, tolerance develops over time, resulting in diminished effects. Smokers may find themselves trapped in a cycle of increasing consumption to manage anxiety, ultimately exacerbating their psychological distress. This cycle highlights the paradox of smoking, where the initial relief leads to greater anxiety and dependence.
Furthermore, nicotine affects dopamine and cortisol levels and has detrimental effects on organ function and immune response, contributing to oxidative stress and inflammation. This underscores the broader health risks associated with smoking, extending beyond addiction to include significant physiological impairments.
The findings also indicate that stressful life experiences heighten the risk of smoking, particularly among vulnerable populations like depressed youth. This creates a feedback loop where nicotine dependency further activates the HPA axis, complicating the smoker's ability to cope with stress. Overall, the interplay between psychological distress, smoking, and the HPA axis highlights the need for targeted interventions to address both mental health and smoking cessation for improved health outcomes.
References
Bruijnzeel, A. W., Zislis, G., Wilson, C., Gold, M., S. (2007). Antagonism of crf receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology, 32: 955–963.
Hoey, Van, N. M., PharmD. (2024). Stress and Smoking. EBSCO. https://www.ebsco.com/research-starters/health-and-medicine/stress-and-smoking#full-article
Rohdeler, N., Kirschbaum, C. (2006). The hypothalamic-pituitary-adrenal (HPA) axis in habitual smokers. International Journal of Psychophysiology, 59.
Rao, U., Hammen, C., London, E., Poland, R. E. (2009). Contribution of hypothalamic–pituitary–adrenal activity and environmental stress to vulnerability for smoking in adolescents. Neuropsychopharmacol, 34, 2721–2732 https://doi.org/10.1038/npp.2009.112
Sheng, J. A., Bales, N. J., Myers, S. A., Bautista, A. I., Roueinfar, M., Hale, T. M., & Handa, R. J. (2021). The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions. Frontiers in behavioral neuroscience, 14, 601939. https://doi.org/10.3389/fnbeh.2020.601939
