Stress is one of the most commonly reported triggers of smoking relapse. It increases frequency of smoking among chronic smokers and accelerates progression towards full relapse among abstinent smokers. This relapse risk is particularly high in the presence of other negative affective states, including anxiety, irritability, depression, and craving, especially in women. Our previous research has demonstrated altered hypothalamic-pituitary-adrenocortical (HPA) axis and endogenous opioid system (EOS) regulation of the stress response in smokers. We found that 1) smokers exhibit enhanced basal HPA activity, 2) they exhibit decreased cortisol responses to multiple acute stress procedures, and 3) early smoking relapse can be predicted by attenuated adrenocorticotropin (ACTH) and cortisol responses to stress. Recent results using an opioid blockade challenge demonstrate blunted opioid regulation of the HPA stress response in smokers relative to nonsmokers; and smoking appears to acutely normalize opioid regulation of the stress response. The clinical significance of altered opioid regulation of the stress response has not been tested in the clinical context of smoking cessation and relapse. Building on previous findings, we plan in this new study to take a novel approach in addiction relapse research by identifying indices of risk for relapse using opioid- HPA stress response patterns. Our hypothesis is that smokers who exhibit blunted HPA stress response to opioid blockade are more likely to relapse early in their cessation attempt. Blunted opioid regulation contributes to inefficient stress response and may exacerbate stress effects on craving and withdrawal symptoms. We will establish the link between altered endogenous opioid regulation of the HPA stress response, withdrawal symptoms, and craving during smoking cessation. We will develop a model to predict early smoking relapse using HPA responses to stress and HPA responses to endogenous opioid blockade. Finally, we will examine sex differences in the HPA response to stress, in the HPA response to opioid blockade, and in predictors of relapse. This research represents a step forward in translating established preclinical neurobiological models of addiction and stress. It is grounded in theory, builds on important preliminary results, and uses rigorous and reproducible procedures. Demonstrating the utility of an opioid challenge in predicting relapse is a novel direction in addiction relapse research that will enable indexing two important stress biological pathways, providing both a novel mechanism of long-term effects of tobacco addiction and a marker of treatment outcome and relapse probability. This will facilitate future efforts targeting those susceptible to effects of stress on their risk for relapse with new or existing behavioral and pharmacological treatments. Reducing relapse rates will reduce tobacco use and its devastating health effects.

Public Health Relevance

Cigarette smoking remains one of the most devastating health challenges in this country and globally. The vast majorly of smokers who attempt to stop ultimately relapse within days to weeks after cessation; and stress is one of the most cited reasons for smoking relapse. There is a critical need to increase intervention efficacy by identifying group and individual differences that are determinants of failed smoking cessation efforts. This will enable enhanced effectiveness of treatments for tobacco addiction, resulting in lower relapse rates and, ultimately, reductions in tobacco use and its devastating health effects. !

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA016351-09A1
Application #
9814462
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Su, Shelley
Project Start
2003-09-30
Project End
2023-07-31
Budget Start
2019-09-30
Budget End
2020-07-31
Support Year
9
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
al'Absi, Mustafa (2018) Stress response pathways, appetite regulation, and drug addiction. Biol Psychol 131:1-4
al?Absi, Mustafa (2018) Stress and Addiction: When a Robust Stress Response Indicates Resiliency. Psychosom Med 80:2-16
Lemieux, Andrine M; al'Absi, Mustafa (2018) Changes in circulating peptide YY and ghrelin are associated with early smoking relapse. Biol Psychol 131:43-48
al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth et al. (2017) Early life adversity influences stress response association with smoking relapse. Psychopharmacology (Berl) 234:3375-3384
Raatz, Susan K; Jahns, Lisa; Johnson, LuAnn K et al. (2017) Smokers report lower intake of key nutrients than nonsmokers, yet both fall short of meeting recommended intakes. Nutr Res 45:30-37
Wiggert, Nicole; Wilhelm, Frank H; Nakajima, Motohiro et al. (2016) Chronic Smoking, Trait Anxiety, and the Physiological Response to Stress. Subst Use Misuse 51:1619-1628
Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro et al. (2016) Life adversity is associated with smoking relapse after a quit attempt. Addict Behav 60:71-7
al'Absi, Mustafa; Nakajima, Motohiro; Allen, Sharon et al. (2015) Sex differences in hormonal responses to stress and smoking relapse: a prospective examination. Nicotine Tob Res 17:382-9
al'Absi, Mustafa; Lemieux, Andrine; Nakajima, Motohiro et al. (2015) Circulating leptin and pain perception among tobacco-dependent individuals. Biol Psychol 107:10-5
Lemieux, Andrine; Nakajima, Motohiro; Hatsukami, Dorothy K et al. (2015) Changes in circulating leptin levels during the initial stage of cessation are associated with smoking relapse. Psychopharmacology (Berl) 232:3355-61

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