Evaluating the temporal relationships between withdrawal symptoms and smoking relapse.
Open accessAbstract
Smokers attempting to quit often attribute smoking relapse to negative affect, craving, and other nicotine withdrawal symptoms. In addition, there is evidence that smoking relapse can increase these symptoms, particularly negative affect. To address this issue, we analyzed data from an 11-week smoking cessation clinical trial in which smokers (n = 1,246) were randomized to receive either nicotine replacement therapy (NRT), varenicline, or placebo, combined with behavioral counseling. Using cross-lagged analyses, we examined the temporal bidirectional relationships between self-reported measures of affect, craving, and composite withdrawal symptoms and biochemically verified smoking abstinence. The relative strength of these temporal relationships was examined by comparing the explained variances of the models. The results showed that higher negative affect, craving, and composite withdrawal symptoms increased the likelihood of subsequent smoking relapse, and that smoking relapse led to subsequent increases in these same symptoms. A comparison of the explained variances found symptom predicting subsequent relapse models to be stronger than those where relapse predicted subsequent symptoms. Although the explained variance findings generally support a negative reinforcement conceptualization of nicotine dependence, the bidirectional relationship between symptoms and smoking relapse suggests that struggling with quitting smoking leads to significant negative affect, craving, and other withdrawal symptoms that do not quickly resolve. These findings highlight the importance of addressing specific symptoms within the context of smoking cessation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Relapse is the most common and probable event in the smoking cessation process.
“Relapse is the most common and probable event in the smoking cessation process [10, 11].”
From Relapse prevention among Iranian people who smoke through cognitive behavioral intervention: application of Marlatt’s model (2025) · cites this paper as [11]
The Results (Descriptive statistics of the study sample; page unavailable) say abstinence declined after treatment, but do not establish that relapse was the most common or most probable outcome. Searches for a majority relapsing and for relapse or abstinence rates found no passage in our copy supporting that comparison. (LLM, conf=0.70)
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“slow) metabolizers, as faster nicotine clearance may be associated with greater craving and/or withdrawal symptom severity,(16,17) and greater craving and withdrawal are associated with increased risk of smoking lapse and relapse.(18,19) Among young adult smokers, withdrawal relief from acute smoking depends on nicoti…”
BackgroundSelf-citationNot all smokers are alike: the hidden cost of sustained attention during nicotine abstinence
Deshpande, H. U., Fedota, J. R., Castillo, J., Salmeron, B. J., Ross, T. J., & Stein, E. A. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01275-8 · Cited by 4 · see citing works
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Kypriotakis, G., Bernstein, S. L., Bold, K. W., Dziura, J. D., Hedeker, D., Mermelstein, R. J., & Weinberger, A. H. (2024) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntae005 · Cited by 4 · see citing works
“37,38 This dependency of the longitudinal outcomes and abstinence status is not considered when analyzing each outcome separately.”
BackgroundPeng, H., Lee, L., Huang, B., Lin, C., Chang, Y., Chung, C.-F., & Chen, S. (2021) · Journal of Nursing Scholarship · doi:10.1111/jnu.12719 · Cited by 4 · see citing works
Hajisahneh, S., Rakhshanderou, S., Mehrabi, Y., Razzaghi, E. M., Mazar, L., & Ghaffari, M. (2025) · BMC Psychiatry · doi:10.1186/s12888-024-06373-z · Cited by 2 · see citing works
Characterizing nicotine withdrawal in smokers experiencing homelessness
Sharbin, G. K., & Rash, C. J. (2022) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2022.108748 · Cited by 3 · see citing works
A Quality Review of Smart-Phone Applications for Smoking Cessation
Portelli, P., Bogolyubova, O., Lopez, B. T., & Fernández, A. S.-M. (2022) · Journal of Consumer Health on the Internet · doi:10.1080/15398285.2021.2021372 · Cited by 3 · see citing works
“Although smoking is a modifiable habit and quitting can reduce the risk of developing lung cancer by half (Hall 2016), individuals often try a number of times before finally succeeding in stopping smoking (Robinson et al. 2019).”
BackgroundCircumstances Around Cigarette Use after Enforced Abstinence From Smoking in an American Prison
Martin, R. A., Stein, L. A. R., Kang, A. W. C., Rohsenow, D. J., Bock, B. C., Martin, S. A., & Clarke, J. G. (2022) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000001005 · Cited by 3 · see citing works
Schöttl, S. E., Insam, K., Frühauf, A., Kopp-Wilfling, P., Holzner, B., & Kopp, M. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06506-4 · Cited by 3 · see citing works
“…a strong craving to smoke and withdrawal symptoms such as sleep disturbances, difficulty concentrating, increased appetite, weight gain, restless-ness or negative affect (e.g. depression, irritability) may occur (Yingst et al. 2022; Cheung et al. 2020; Weinberger et al. 2016; Robinson et al. 2019).”
BackgroundMorean, M. E., Rajeshkumar, L., & Krishnan‐Sarin, S. (2024) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntae095 · Cited by 4 · see citing works
Zhao, Y., Li, Y., Shu, Y., Wang, X., Wang, W., & Yang, L. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1642341 · Cited by 2 · see citing works
Zainel, A. A., Mujalli, H. A., Yfakhroo, A. I., Shaheen, S. A., Mohamed, H. A. E., Nuaimi, A. S. A., Syed, M. A., & Syed, M. A. (2025) · Journal of Public Health Research · doi:10.1177/22799036251401951 · Cited by 2 · see citing works
“42 In the first week, withdrawal symptoms are the most intense.”
Bulut, A., Gökhan, A. B. A., KABAK, S., Maraşlı, A., & Akça, B. (2026) · Journal of Ethnicity in Substance Abuse · doi:10.1080/15332640.2025.2610663 · Cited by 2 · see citing works
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“, irritability and trouble sleeping) (18).”
Sancho-Domingo, C., Carballo, J. L., Coloma‐Carmona, A., Román, C. J. V.-D. H., & Sánchez, S. A. (2023) · Addiction Research & Theory · doi:10.1080/16066359.2023.2264773 · Cited by 3 · see citing works
“However, successful attempts to quit still remain low (Garc � ıa-Rodr � ıguez et al. 2013; Robinson et al. 2019) and treatment mechanisms for tobacco cessation need further study.”
Zhang, M. J., Cheung, Y. T. D., Wang, Q., Cheng, C. C. W., Luk, T. T., He, W. J. A., Wang, M. P., & Lam, T. H. (2024) · Tobacco Induced Diseases · doi:10.18332/tid/187839 · Cited by 3 · see citing works
“Withdrawal symptoms due to a deficit of nicotine usually include tobacco craving, stress, anxiety, tension, poor concentration, irritability, negative affect, and restlessness 2,3 .”
BackgroundCigarette Smoking Relapse Among People Who Switched to E-cigarettes or Other Tobacco Products
Sun, R., Méndez, D., & Warner, K. E. (2024) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntae201 · Cited by 2 · see citing works
Vaping to quit smoking: Qualitative study of people receiving opioid agonist treatment
Kypri, K., Austin, E., Jackson, M. A., Wright, K., Shui, A., Li, A., Sathasivam, V., Bonevski, B., & Dunlop, A. J. (2024) · Drug and Alcohol Review · doi:10.1111/dar.13953 · Cited by 2 · see citing works
Robinson, J. D., Kypriotakis, G., Al’Absi, M., Denlinger-Apte, R. L., Drobes, D. J., Leischow, S. J., McClernon, F. J., Pacek, L. R., Severson, H. H., Smith, T. T., et al. (2019) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntz209 · Cited by 2 · see citing works
Self-citationIdentification of the relationship between nicotine dependence levels and cessation fatigue
Bakan, A. B., Aktaş, B., & Aslan, G. (2020) · Perspectives In Psychiatric Care · doi:10.1111/ppc.12715 · Cited by 2 · see citing works
Butler, K., Foll, B. L., & Ciano, P. D. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_392 · Cited by 2 · see citing works
Contextual Factors Associated With Temptations and Lapses Among Smokers Trying to Quit
Elling, J. M., de Vries, H., Candel, M. J. J. M., & Crutzen, R. (2023) · Zeitschrift für Psychologie · doi:10.1027/2151-2604/a000536 · Cited by 2 · see citing works
Adolescent nicotine exposure affects later-life nicotine reward and withdrawal in mice
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The relationship between nicotine craving and state anxiety in daily and non-daily nicotine users
McKinty, A., Hatz, L. E., Liu, W., Andrade, G., Doran, N., & Courtney, K. E. (2025) · Addictive Behaviors · doi:10.1016/j.addbeh.2025.108501 · Cited by 1 · see citing works
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Lespine, L., Rueda‐Delgado, L. M., Vahey, N. A., Ruddy, K. L., Kiiski, H. S. M., Enz, N., Boyle, R. T., Rai, L. A., Pragulbickaite, G., Bricker, J. B., et al. (2025) · European Addiction Research · doi:10.1159/000546112 · Cited by 1 · see citing works
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Time varying connectivity across the brain changes as a function of nicotine abstinence statePreprint
Fedota, J. R., Ross, T. J., Castillo, J., McKenna, M. R., Matous, A. L., Salmeron, B. J., Menon, V., & Stein, E. A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.25.917617
Optimizing digital smoking cessation interventions
Elling, J. M. (2022) · doi:10.26481/dis.20221207je
Wang, J.-H., Yang, Y., Shilei, Z., Liu, H., Xiao, L., Sun, L., Wu, X., Yuan, D., Ma, L., Ju, B., et al. (2022) · doi:10.2196/preprints.44392
Pharmacotherapy for the Treatment of Tobacco Dependence
Fisher, T., & Leone, F. T. (2023) · Respiratory medicine · doi:10.1007/978-3-031-24914-3_4
Sancho-Domingo, C., Carballo, J. L., Coloma‐Carmona, A., Román, C. J. V.-D. H., del Castillo‐López, Á. G., & Sánchez, S. A. (2023) · Substance Use & Misuse · doi:10.1080/10826084.2023.2262021
“During tobacco cessation, the appearance of nicotine withdrawal symptoms (e.g., irritability) or cigarette cravings can increase the risk of relapse in order to reduce discomfort (Garey et al., 2019; J. D. Robinson et al., 2019).”
BackgroundPersonalized Medicine and Personalized Health Promotion Based on Motivation and Reward Proceedings
Michaelsen, M. M. (2023) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202301313
Personalized and One Medicine Coming Together
Stefano, G. B. (2023) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202301311
Stefano, G. B., Kream, R. M., & Esch, T. (2023) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202301312
Hoetger, C., & Schiek, H. (2023) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202301314
Exploring the Details of Body and Mind That Account for a Healthy Life in an Uncertain World
Michaelsen, M. M., Stefano, G. B., & Esch, T. (2023) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202301315
Nicotine use disorder and Neuregulin 3: Opportunities for precision medicine
Elder, T. R., & Turner, J. R. (2024) · Advances in pharmacology · doi:10.1016/bs.apha.2023.10.001
Ahn, Y. M., Jung, S., Lee, H., Cho, J.-A., & Sohn, M. (2025) · Research in Community and Public Health Nursing · doi:10.12799/rcphn.2025.01004
Rabin, R. A., Lerman, C. E., Schnoll, R. A., Tyndale, R. F., & George, T. P. (2025) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2025.112778
“Given that tobacco withdrawal predicts relapse (Robinson et al., 2019), we tested for the first time whether following tobacco cessation, tobacco withdrawal symptoms parallel the trajectory observed with cannabis withdrawal symptoms following cannabis cessation.”
Self-citationPsychometric properties of the Nicotine E-cigarette Withdrawal Scale for use with adults
Morean, M. E., Ouellette, R. R., Li, W., & Sharma, A. (2025) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2025.112968
Kumar, S., Saini, S., Mishra, G., Baishya, A., Sharma, S., Hazarika, D., & Patra, S. (2026) · Cureus · doi:10.7759/cureus.101716
“Despite widespread awareness, many smokers relapse during quit attempts due to nicotine withdrawal symptoms such as persistent craving, irritability, attentional deficits, and negative affect [8].”
Preoperative smoking cessation: Is it a trigger for long-term abstinence?
Shaked, Y., Azuri, J., Tzur, T., & Gildor, O. S. (2026) · Journal of Perioperative Practice · doi:10.1177/17504589261417460
“Relapse remains common, particularly within the first year after quitting (Robinson et al 2019, Rodríguez-Cano et al 2021).”
Brain tract structure predicts relapse to stimulant drug usePreprint
Leong, J. K., Padula, C. B., Knutson, B. D., MacNiven, K. H., & Tisdall, L. (2022) · OSF Preprints (OSF Preprints)
- Authors
- Robinson, J. D., Li, L., Chen, M., Lerman, C., Tyndale, R. F., Schnoll, R. A., Hawk, L. W., George, T. P., Benowitz, N. L., & Cinciripini, P. M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- University of Pennsylvania (US)
- Centre for Addiction and Mental Health (CA)
- University at Buffalo, State University of New York (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- Psychology of Addictive Behaviors
- Published
- 2019-03
- Volume
- 33
- Issue
- 2
- Pages
- 105-116
- ISSN
- 0893-164X (ISSN-L)
- 1939-1501
- PMC
- PMC6405298
- OpenAlex
- W2909063800
- Cited by
- 74
- References
- 55
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 10 · 2023: 19 · 2022: 13 · 2021: 6 · 2020: 9 · 2019: 2
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Psychology of Addictive Behaviors (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (U01DA20830)
- MD Anderson’s Cancer Center (P30CA016672)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Social Sciences › Psychology › Applied Psychology › Behavioral Health and Interventions
- Keywords
- smoking relapse, nicotine withdrawal symptoms, negative affect, nicotine craving, smoking cessation, nicotine replacement therapy, varenicline, negative reinforcement, nicotine dependence, temporal dynamics
- MeSH terms
- Varenicline, Smoking Cessation Agents, Adult, Combined Modality Therapy, Counseling, Female, Humans, Male, Middle Aged, Recurrence, Reinforcement, Psychology, Smoking, Substance Withdrawal Syndrome, Tobacco Use Disorder, Smoking Cessation, Tobacco Use Cessation Devices, Craving
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