Skip to main content
Springer Nature Link
Log in

Sex differences in tobacco withdrawal and responses to smoking reduced-nicotine cigarettes in young smokers

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Policies that establish a standard for reduced nicotine content in cigarettes can decrease the prevalence of smoking in the USA. Cigarettes with nicotine yields as low as 0.05 mg produce substantial occupancy of nicotinic acetylcholine receptors (26%), but women and men respond differently to these cigarettes.

Objective

This study aimed to measure responses to smoking cigarettes that varied widely in nicotine yields, investigating whether sex differences in the effects on craving, withdrawal, and affect would be observed at even lower nicotine yields than previously studied, and in young smokers.

Methods

Overnight abstinent young smokers (23 men, 23 women, mean age 22.18) provided self-reports of craving, withdrawal, and affect before and after smoking cigarettes with yields of 0.027, 0.110, 0.231, or 0.763 mg nicotine, and evaluated characteristics of each cigarette.

Results

Compared to abstinent young men, abstinent young women reported greater negative affect, psychological withdrawal, and sedation, all of which were relieved equally by all cigarettes. Men but not women reported greater craving reduction, perceived nicotine content, and cigarette liking with increasing nicotine dose.

Conclusions

Men may experience less smoking-related relief of craving, and enjoy cigarettes less, if nicotine yields are reduced to very low levels. Conversely, women respond equally well to cigarettes with nicotine yields as low as 0.027 mg as to cigarettes with nicotine yields 28-fold higher (0.763 mg). These differences are relevant for policy regarding reduced nicotine in cigarettes and may influence the efficacy and acceptability of reduced-nicotine cigarettes as smoking cessation aids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Benowitz NL, Henningfield JE (1994) Establishing a nicotine threshold for addiction. The implications for tobacco regulation. N Engl J Med 331:123–125

    Article  CAS  PubMed  Google Scholar 

  • Benowitz NL, Lessov-Schlaggar CN, Swan GE, Jacob P (2006) Female sex and oral contraceptive use accelerate nicotine metabolism. Clin Pharm & Therap 79(5):480–488

    Article  CAS  Google Scholar 

  • Benowitz NL, Nardone N, Dains KM, Hall SM, Stewart S, Dempsey D, Jacob III P (2015) Effect of reducing the nicotine content of cigarettes on cigarette smoking behavior and tobacco smoke toxicant exposure: 2-year follow up. Addiction, 110(10):1667–1675.

  • Britton J (2017) Death, disease, and tobacco. Lancet 389(10082):1861–1862

    Article  PubMed  Google Scholar 

  • Brown AK, Mandelkern MA, Farahi J, Robertson C, Ghahremani DG, Sumerel B, Moallem N, London ED (2012) Sex difference in striatal dopamine D2/D3 receptor availability in smokers and nonsmokers. Int J Neuropsychopharmacol 15(7):989–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Centers for Disease Control and Prevention. (2016) Cigarette smoking among adults—United States, 2005–2015. Morb Mortal Wkly Rep 65(44):1205–1211

  • Cepeda-Benito A, Reynoso JT, Erath S (2004) Meta-analysis of the efficacy of nicotine replacement therapy for smoking cessation: differences between men and women. J Cons & Clin Psych 72(4):712–722

    Article  Google Scholar 

  • Cosgrove KP, Wang S, Kim S-J, McGovern E, Nabulsi N, Gao H, Morris ED (2014) Sex differences in the Brain’s dopamine signature of cigarette smoking. J Neuro 34(50):16851–16855

    Article  Google Scholar 

  • Dallery J, Houtsmuller EJ, Pickworth WB, Stitzer ML (2003) Effects of cigarette nicotine content and smoking pace on subsequent craving and smoking. Psychopharm 165(2):172–180

    Article  CAS  Google Scholar 

  • Doll R, Peto R, Boreham J, Sutherland I (2004) Mortality in relation to smoking: 50 years’ observations on male British doctors. Br Med J 328:1519

    Article  Google Scholar 

  • Donny EC, Denlinger RL, Tidey JW, Koopmeiners JS, Benowitz NL, Vandrey RG, Hatsukami DK (2015) Randomized trial of reduced-nicotine standards for cigarettes. New Eng J Med 373(14):1340–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duriez Q, Crivello F, Mazoyer B (2014) Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly. Front Aging Neurosci 6:299

    Article  PubMed  PubMed Central  Google Scholar 

  • Fagerström K, Russ C, Yu C-R, Yunis C, Foulds J (2012) The Fagerström test for nicotine dependence as a predictor of smoking abstinence: a pooled analysis of varenicline clinical trial data. Nic & Tob Res 14(12):1467–1473

    Article  Google Scholar 

  • Faulkner P, Ghahremani DG, Tyndale RF, Cox CM, Kazanjian AS, Paterson N, London ED (2017) Reduced-nicotine cigarettes in young smokers: impact of nicotine metabolism on nicotine dose effects. Neuropsychopharmacology 42(8):1610–1618

    Article  CAS  PubMed  Google Scholar 

  • Food and Drug Administration (2017). FDA announces comprehensive regulatory plan to shift trajectory of tobacco-related disease, death. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm568923.htm

  • Franklin TR, Wetherill RR, Jagannathan K, Johnson B, Mumma J, Hager N et al (2014) The effects of chronic cigarette smoking on gray matter volume: influence of sex. PLoS One 9(8):e104102

    Article  PubMed  PubMed Central  Google Scholar 

  • Goodchild M, Nargis N, Tursan d'Espaignet E (2017) Global economic cost of smoking-attributable diseases. Tob Con

  • Hatsukami DK, Zhang Y, O’Connor RJ, Severson HH (2013) Subjective responses to oral tobacco products: scale validation. Nic & Toba Res 15(7):1259–1264

  • Johnstone E, Benowitz N, Cargill A, Jacob R, Hinks L, Day I, Walton R (2006) Determinants of the rate of nicotine metabolism and effects on smoking behavior. Clin Pharm & Therap 80(4):319–330

    Article  CAS  Google Scholar 

  • McKee SA, Maciejewski PK, Falba T, Mazure CM (2003) Sex differences in the effects of stressful life events on changes in smoking status. Addiction 98(6):847–855

    Article  PubMed  Google Scholar 

  • Okita K, Petersen N, Robertson CL, Dean AC, Mandlekern MA, London ED (2016) Sex differences in midbrain dopamine d2-type receptor availability and association with nicotine dependence. Neuropsychopharmacology, 41(12):2913–2919. https://doi.org/10.1013/npp.2016.105

  • Okoli C, Greaves L, Fagyas V (2013) Sex differences in smoking initiation among children and adolescents. Public Health 127(1):3–10

    Article  CAS  PubMed  Google Scholar 

  • Perkins K. A. (2008) Sex differences in nicotine reinforcement and reward: influences on the persistence of tobacco smoking. In: Caggiula A., Bevins R. (eds) The Motivational Impact of Nicotine and its Role in Tobacco Use. Nebraska Symposium on Motivation, vol. 55. Springer, New York, NY

  • Perkins KA, Karelitz JL (2015) Sex differences in acute relief of abstinence-induced withdrawal and negative affect due to nicotine content in cigarettes. Nicotine Tob Res 17(4):443–448

    Article  PubMed  PubMed Central  Google Scholar 

  • Perkins KA, Gerlach D, Vender J, Meeker J, Hutchison S, Grobe J (2001) Sex differences in the subjective and reinforcing effects of visual and olfactory cigarette smoke stimuli. Nicotine Tob Res 3(2):141–150

    Article  CAS  PubMed  Google Scholar 

  • Perkins KA, Jacobs L, Sanders M, Caggiula AR (2002) Sex differences in the subjective and reinforcing effects of cigarette nicotine dose. Psychopharmacology 163(2):194–201

    Article  CAS  PubMed  Google Scholar 

  • Rose JE, Behm FM (1995) There is more to smoking than the CNS effects of nicotine. In: Clarke PBS, Quik M, Adlkofer F, Thurau K (eds) Effects of nicotine on biological systems II. Adv Pharmacol Sci Birkhäuser Verlag, Basel

  • Rose JE, Behm FM, Westman EC, Johnson M (2000) Dissociating nicotine and nonnicotine components of cigarette smoking. Pharmacol Biochem Behav 67(1):71–81

    Article  CAS  PubMed  Google Scholar 

  • Shiffman SM, Jarvik ME (1976) Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology 50(1):35–39

    Article  CAS  PubMed  Google Scholar 

  • Smith PH, Zhang J, Weinberger AH, Mazure CM, McKee SA (2017) Gender differences in the real-world effectiveness of smoking cessation medications: findings from the 2010–2011 tobacco use supplement to the current population survey. Drug Alcohol Depend 178:485–491

    Article  PubMed  Google Scholar 

  • Staley JK, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl JP, Maciejewski PK, O’Malley S, Innis RB (2001) Sex differences in [123I] beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse 15(41):275–284

    Article  Google Scholar 

  • Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K, Lancaster T (2008) Nicotine replacement therapy for smoking cessation (Review). Cochrane Database Syst Rev (Online). https://doi.org/10.1002/14651858.CD000146.pub3

  • Tanner JA, Novalen M, Jatlow P, Huestis MA, Murphy SE, Kapiro J et al (2015) Nicotine metabolite ratio (3-hydroxycotinine/cotinine) in plasma and urine by different analytical methods and laboratories: implications for clinical implementation. Cancer Epidemiol Biomark Prev 24:1239–1246

    Article  CAS  Google Scholar 

  • Tidey JW, Colby SM, Xavier EMH (2013) Effects of smoking abstinence on cigarette craving, nicotine withdrawal, and nicotine reinforcement in smokers with and without schizophrenia. Nicotine Tob Res 16(3):326–334

  • United States Congress (2009). Family Smoking Prevention and Tobacco Control and Federal Reform Act. Publ law no. 111–31, 1776 (Jun 22, 2009), Washington, D.C

  • Vogel RI, Hertsgaard LA, Dermody SS, Luo X, Moua L, Allen S, Hatsukami DK (2014) Sex differences in response to reduced nicotine content cigarettes. Addict Behav 39(7):1197–1204

    Article  PubMed  PubMed Central  Google Scholar 

  • Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54(6):1063–1070

    Article  CAS  PubMed  Google Scholar 

  • Wetherill RR, Jagannathan K, Shin J, Franklin TR (2014) Sex differences in resting state neural networks of nicotine-dependent cigarette smokers. Addict Behav 39(4):789–792

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu J, Azizian A, Monterosso J, Domier CP, Brody AL, Fong TW, London ED (2008) Gender effects on mood and cigarette craving during early abstinence and resumption of smoking. Nicotine Tob Res 10(11):1653–1661

    Article  PubMed  PubMed Central  Google Scholar 

  • Zuo Y, Mukhin AG, Garg S, Nazih R, Behm FM, Garg PK, Rose JE (2015) Sex-specific effects of cigarette mentholation on brain nicotine accumulation and smoking behavior. Neuropsychopharmacology, 40(4):884–892.

Download references

Funding

This research was funded by the National Institute on Drug Abuse R01 DA036487 (EDL), the Iris Cantor-UCLA Women’s Health Center/UCLA National Center of Excellent in Women’s Health Pilot Research Project UL1TR000124 (EDL and NP), endowments from the Thomas P and Katherine K Pike Chair in Addiction Studies (EDL) and the Marjorie M Greene Trust, and the Canada Research Chairs Program (Dr. Tyndale, the Canada Research Chair in Pharmacogenomics).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California Los Angeles, 760 Westwood Plaza, Los Angeles, CA, 90025, USA

    Paul Faulkner, Nicole Petersen, Dara G. Ghahremani, Gerhard S. Hellemann & Edythe D. London

  2. Department of Psychology, University of Illinois, Chicago, IL, USA

    Chelsea M. Cox

  3. Department of Pharmacology and Toxicology, and Department of Psychiatry, University of Toronto, 1 King’s College Circle, Toronto, ON, Canada

    Rachel F. Tyndale

  4. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, Canada

    Rachel F. Tyndale

  5. Department of Molecular and Medical Pharmacology, University of California Los Angeles, California, Los Angeles, USA

    Edythe D. London

  6. The Brain Research Institute, University of California Los Angeles, California, Los Angeles, USA

    Edythe D. London

Authors
  1. Paul Faulkner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicole Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dara G. Ghahremani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chelsea M. Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rachel F. Tyndale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerhard S. Hellemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Edythe D. London
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edythe D. London.

Ethics declarations

Conflict of interest

RF Tyndale has consulted for Apotex on issues unrelated to smoking.

Electronic supplementary material

ESM 1

(DOCX 67 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Faulkner, P., Petersen, N., Ghahremani, D.G. et al. Sex differences in tobacco withdrawal and responses to smoking reduced-nicotine cigarettes in young smokers. Psychopharmacology 235, 193–202 (2018). https://doi.org/10.1007/s00213-017-4755-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4755-x

Keywords

Search

Navigation

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy