Skip to main content
Log in

Threshold dose for behavioral discrimination of cigarette nicotine content in menthol vs. non-menthol smokers

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

Abstract

Rationale

The lowest threshold content (or “dose”) of nicotine discriminated in cigarettes may differ due to menthol preference.

Objectives

Menthol and non-menthol Spectrum research cigarettes differing in nicotine content were used to determine discrimination thresholds.

Methods

Dependent smokers preferring menthol (n = 40) or non-menthol (n = 21) brands were tested on ability to discriminate cigarettes (matched for their menthol preference) with nicotine contents of 16–17, 11–12, 5, 2, and 1 mg/g, one per session, from an “ultra-low” cigarette with 0.4 mg/g. Controlled exposure to each cigarette was four puffs/trial, and the number of sessions was determined by the lowest nicotine content they could discriminate on >80% of trials (i.e., ≥5 of 6). We also assessed subjective perceptions and behavioral choice between cigarettes to relate them to discrimination responses.

Results

Controlling for Fagerstrom Test of Nicotine Dependence score, discrimination thresholds were more likely to be at higher nicotine content cigarettes for menthol vs. non-menthol smokers (p < .005), with medians of 16 vs. 11 mg/g, respectively. Compared to the ultra-low, threshold and subthreshold (next lowest) cigarettes differed on most perceptions and puff choice, but menthol preference did not alter these associations. Notably, threshold cigarettes did, but subthreshold did not, increase choice over the ultra-low.

Conclusions

Threshold for discriminating nicotine via smoking may be generally higher for menthol vs. non-menthol smokers. More research is needed to identify why menthol smoking is related to higher nicotine thresholds and to verify that cigarettes unable to be discriminated do not support reinforcement.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ai J, Taylor KM, Lisko JG, Tran H, Watson CH, Holman MR (2016) Menthol content in US marketed cigarettes. Nicotine Tob Res 18:1575–1580

    Article  PubMed  Google Scholar 

  • American Psychiatric Association (APA) (2013) Diagnostic and statistical manual-V. American Psychiatric Association, Washington DC

    Book  Google Scholar 

  • Audrain-McGovern J, Strasser AA, Wileyto EP (2016) The impact of flavoring on the rewarding and reinforcing value of e-cigarettes with nicotine among young adult smokers. Drug Alc Depend 166:263–267

    Article  CAS  Google Scholar 

  • Benowitz NL, Hall SM, Herning RI, Jacob P, Jones RT, Osman A-L (1983) Smokers of low-yield cigarettes do not consume less nicotine. New Engl J Med. 309:139–142

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Benowitz NL, Henningfield JE (2013) Reducing the nicotine content to make cigarettes less addictive. Tob Control 22:i14–i17

    Article  PubMed  PubMed Central  Google Scholar 

  • Biswas L, Harrison E, Gong Y, Avusula R, Lee J, Zhang M et al (2016) Enhancing effect of menthol on nicotine self-administration in rats. Psychopharmacology 233:3417–3427

    Article  CAS  PubMed  Google Scholar 

  • Blank MD, Disharoon S, Eissenberg T (2009) Comparison of methods for measurement of smoking behavior: mouthpiece-based computerized devices versus direct observation. Nicotine Tob Res 11:896–903

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolin BL, Alcorn JL, Reynolds AR, Lile JA, Rush CR (2016) Human drug discrimination: a primer and methodological review. Exp Clin Psychopharmacol 24:214–228

    Article  PubMed  Google Scholar 

  • Breslau N, Kilbey MM, Andreski P (1994) DSM-IIIR nicotine dependence in young adults: prevalence, correlates and associated psychiatric disorders. Addiction 89:743–754

    Article  CAS  PubMed  Google Scholar 

  • Brody AL, Mandelkern MA, Costello MR, Abrams AL, Scheibal D, Farahi J et al (2009) Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette. Int J Neuropsychopharmacol 12:305–312

    Article  CAS  PubMed  Google Scholar 

  • Carter LP, Stitzer ML, Henningfield JE, O’Connor RJ, Cummings KM, Hatsukami DK (2009) Abuse liability assessment of tobacco products including potential reduced exposure products. Cancer Epid Biomarkers Prev 18:3241–3262

    Article  Google Scholar 

  • Chait LE, Evans SM, Grant KA, Kamien JB, Johanson CE, Schuster CR (1988) The discriminative stimulus and subjective effects of smoked marijuana in humans. Psychopharmacology 94:206–212

    Article  CAS  PubMed  Google Scholar 

  • Curtin GM, Sulsky SI, Van Landingham C, Marano KM, Graves MJ, Ogden MW, Swauger JE (2014) Patterns of menthol cigarette use among current smokers, overall and within demographic strata, based on data from four U.S. government surveys. Reg Tox Pharmacol 70:189–196

    Article  CAS  Google Scholar 

  • Delnovo CD, Gundersen DA, Hrywna M et al (2011) Smoking cessation prevalence among U.S. smokers of menthol versus non-menthol cigarettes. Amer J Prev Med 41:357–365

    Article  Google Scholar 

  • Dessirier J, O’Mahony M, Carstens E (2001) Oral irritant properties of menthol: sensitizing and desensitizing effects of repeated application and cross-desensitization to nicotine. Physiol Behav 73:25–36

    Article  CAS  PubMed  Google Scholar 

  • Donny EC, Denlinger RL, Tidey JW et al (2015) Randomized trial of reduced-nicotine standards for cigarettes. New Engl J Med 373:1340–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duke AN, Johson MW, Reissig CJ, Griffiths RR (2015) Nicotine reinforcement in never-smokers. Psychopharmacology 232:4243–4252

    Article  CAS  PubMed  Google Scholar 

  • Farco JA, Grundmann O (2013) Menthol—pharmacology of an important naturally medicinal “cool”. Mini-Rev Med Chem 13:124–131

    Article  CAS  PubMed  Google Scholar 

  • Ferris GF, Carpenter CM (2011) Tobacco industry manipulation of nicotine dosing. In: Henningfield JE, London E, Pogun S (eds) Nicotine psychopharmacology. Springer-Verlag, New York, pp 457–485

    Google Scholar 

  • Fu SS, Okuyemi KS, Partin MR et al (2008) Menthol cigarettes and smoking cessation during an aided quit attempt. Nicotine Tob Res 10:457–462

    Article  PubMed  Google Scholar 

  • Glennon RA, Young R (2011) Drug discrimination: application to medicinal chemistry and drug studies. Wiley, New York

    Book  Google Scholar 

  • Grebenstein PE, Burroughs D, Roiko SA, Pentel PR, LeSage MG (2015) Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy. Drug Alc Depend 151:181–193

    Article  CAS  Google Scholar 

  • Gu X, Lohrenz T, Salas R et al (2015) Belief about nicotine selectively modulates value and reward prediction error signals in smokers. Proc Nat Acad Sci 112:2539–2544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hasenfratz M, Jacober A, Battig K (1993) Smoking-related subjective and physiological changes: pre- to postpuff and pre- to postcigarette. Pharmacol Biochem Behav 46:527–534

    Article  CAS  PubMed  Google Scholar 

  • Hatsukami DK, Heishman SJ, Vogel RI et al (2013) Dose-response effects of Spectrum research cigarettes. Nicotine Tob Res 15:1113–1121

    Article  CAS  PubMed  Google Scholar 

  • Hatsukami DK, Perkins KA, LeSage MG, Ashley DL, Henningfield JE, Benowitz NL, Backinger C, Zeller M (2010) Nicotine reduction revisited: science and future directions. Tob Control 19:436–445

    Article  Google Scholar 

  • Hatsukami DK, Pickens RW, Svikis DS, Hughes JR (1988) Smoking topography and nicotine blood levels. Addict Behav 13:91–95

    Article  CAS  PubMed  Google Scholar 

  • Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom K-O (1991) The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86:1119–1127

    Article  CAS  PubMed  Google Scholar 

  • Hecht SS (2012) Research opportunities related to establishing standards for tobacco products under the Family Smoking Prevention and Tobacco Control Act. Nicotine Tob Res 14:18–28

    Article  CAS  PubMed  Google Scholar 

  • Henningfield JE, Benowitz NL, Slade J, Houston TP, Davis RM, Deitchman SD (1998) Reducing the addictiveness of cigarettes. Tob Control 7:281–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johanson C-E (1991) Discriminative stimulus effects of psychomotor stimulants and benzodiazepines in humans. In: Glennon RA, Jarbe TUC, Frankenheim J (eds) Drug discrimination: applications to drug abuse research, NIDA Research Monograph, vol 116. U.S. Government Printing Office, Washington DC, pp 181–196

    Google Scholar 

  • Kasza KA, Hyland AJ, Bansal-Travers M, Vogl LM, Chen J et al (2014) Switching between menthol and nonmenthol cigarettes: findings from the U.S. cohort of the interational Tobacco Control Four Country survey. Nicotine Tob Res 16:1255–1265

    Article  PubMed  PubMed Central  Google Scholar 

  • Kessler DA (1994) Statement on nicotine-containing cigarettes. Tob Control 3:148–158

    Article  PubMed Central  Google Scholar 

  • King BA, Dube SR, Tynan MA (2012) Current tobacco use among adults in the United States: findings from the National Adult Tobacco Survey. Amer J Public Health 102:e93–e100

    Article  Google Scholar 

  • Kreslake JM, Wayne GF, Connolly GN (2008) The menthol smoker: tobacco industry research on consumer sensory perception of menthol cigarettes and its role in smoking behavior. Nicotine Tob Res 10:705–715

    Article  PubMed  Google Scholar 

  • Marian C, O’Connor RJ, Djordjevic MV, Rees VW, Hatsukami DK, Shields PG (2009) Reconciling human smoking behavior and machine smoking patterns: implications for understanding smoking behavior and the impact on laboratory studies. Cancer Epid Biomarkers Prev. 18:3305–3320

    Article  Google Scholar 

  • Mishina EV, Hoffman AC (2014) Clinical pharmacology research strategy for dissolvable tobacco products. Nicotine Tob Res 16:253–262

    Article  PubMed  Google Scholar 

  • Mooney M, Green C, Hatsukami D (2006) Nicotine self-administration: cigarettes versus nicotine gum diurnal topography. Hum Psychopharmacol 21:539–548

    Article  CAS  PubMed  Google Scholar 

  • Morean ME, Kong G, Cavallo DA, Camenga DR, Krishnan-Sarin S (2016) Nicotine concentration of e-cigarettes used by adolescents. Drug Alc Depend 167:224–227

    Article  CAS  Google Scholar 

  • Perkins KA (2009) Discriminative stimulus effects of nicotine in humans. In: Henningfield JE, London E, Pogun S (eds) Nicotine psychopharmacology. Springer-Verlag, New York, pp 369–400

    Chapter  Google Scholar 

  • Perkins KA (2011). Nicotine discrimination in humans. Chapter 15 in Glennon RA, Young R (eds), Drug discrimination: application to medicinal chemistry and drug studies. New York: Wiley, pp. 463–481

  • Perkins KA, Fonte C, Sanders M, Meeker J, Wilson A (2001) Threshold doses for nicotine discrimination in smokers and nonsmokers. Psychopharmacology 155:163–170

    Article  CAS  PubMed  Google Scholar 

  • Perkins KA, Grobe JE, Weiss D, Fonte C, Caggiula A (1996) Nicotine preference in smokers as a function of smoking abstinence. Pharmacol Biochem Behav 55:257–263

    Article  CAS  PubMed  Google Scholar 

  • Perkins KA, Karelitz JL, Giedgowd GE, Conklin CA (2012) The reliability of puff topography and subjective responses during ad lib smoking of a single cigarette. Nicotine Tob Res 14:490–494

    Article  CAS  PubMed  Google Scholar 

  • Perkins KA, Kunkle N, Michael VC, Karelitz JL, Donny EC (2016a) Assessing discrimination of nicotine in humans via cigarette smoking. Nicotine Tob Res 18:1830–1836

    Article  PubMed  Google Scholar 

  • Perkins KA, Kunkle N, Karelitz JL, Michael VC, Donny EC (2016b) Threshold dose for discrimination of nicotine via cigarette smoking. Psychopharmacology 233:2309–2317

    Article  CAS  PubMed  Google Scholar 

  • Perkins KA, Kunkle N, Karelitz JL (2017) Preliminary test of cigarette nicotine discrimination threshold in non-dependent versus dependent smokers. Drug Alc Depend (in press)

  • Pickworth WB, Moolchan ET, Berlin I, Murty R (2002) Sensory and physiologic effects of menthol and nonmenthol cigarettes with differing nicotine delivery. Pharmacol Biochem Behavior 71:55–61

    Article  CAS  Google Scholar 

  • Rosbrook K, Green BG (2016) Sensory effects of menthol and nicotine in an e-cigarette. Nic Tob Res 18:1588–1595

    Article  Google Scholar 

  • Slade J, Bero LA, Hanauer P, Barnes DE, Glantz SA (1995) Nicotine and addiction: the Brown and Williamson documents. JAMA 274:225–233

    Article  CAS  PubMed  Google Scholar 

  • Smith SS, Fiore MC, Baker TB (2014) Smoking cessation in smokers who smoke menthol and non-menthol cigarettes. Addiction 109:2107–2117

    Article  PubMed  PubMed Central  Google Scholar 

  • Smith JW, Stolerman IP (2009) Recognising nicotine: the neurobiological basis of nicotine discrimination. In: Henningfield JE, London E, Pogun S (eds) Nicotine psychopharmacology. Springer, New York, pp 295–333

    Chapter  Google Scholar 

  • Sofuoglu M, LeSage MG (2012) The reinforcement threshold for nicotine as a target for tobacco control. Drug Alc Depend 125:1–7

    Article  Google Scholar 

  • SRNT subcommittee (2002) Biochemical verification of tobacco use and cessation. Nicotine Tob Res 4:149–159

    Article  Google Scholar 

  • Stolerman IP, Jarvis MJ (1995) The scientific case that nicotine is addictive. Psychopharmacology 117:2–10

    Article  CAS  PubMed  Google Scholar 

  • Strasser AA, Ashare RL, Kaufman M, Tang KZ, Mesaros AC, Blair IA (2013) The effect of menthol on cigarette smoking behaviors, biomarkers and subjective responses. Cancer Epid Biomarkers Prev 22:382–389

    Article  CAS  Google Scholar 

  • Takada K (1996) Drug discrimination studies in humans: a review of methodologies. Meth Find Exp Clin Pharmacol 18(suppl 1):187–196

    Google Scholar 

  • Tobacco Products Scientific Advisory Committee (TPSAC) (2011) Menthol cigarettes and public health: review of the scientific evidence and recommendations. US Food and Drug Administration, Rockville MD

    Google Scholar 

  • Uhl GR, Walther DW, Behm FM, Rose JE (2011) Menthol preference among smokers: association with TRPA1 variants. Nicotine Tob Res 13:1311–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • U.S. Department of Health and Human Services (USDHHS). (2010) How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. A Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.

  • U.S. Govt (2009). Family Smoking Prevention and Tobacco Control Act, Pub. L. No. 111–31; http://www.gpo.gov/fdsys/pkg/PLAW-111publ31/pdf/PLAW-111publ31.pdf

  • Villanti AC, Mowery PD, Delnevo CD, Niaura RS, Abrams DB, Giovino GA (2016) Changes in the prevalence and correlates of menthol cigarette use in the USA, 2004-2014. Tob Control 25(suppl 2):ii14–ii20

    Article  PubMed  Google Scholar 

  • Yerger VB, McCandless PM (2011) Menthol sensory qualities and smoking topography: a review of tobacco industry documents. Tob Control 20(suppl 2):ii37–ii43

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under grant award DA035968. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenneth A. Perkins.

Ethics declarations

These study procedures were approved by the University of Pittsburgh Institutional Review Board and are in accordance with the Helsinki Declaration of 1975.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Perkins, K.A., Kunkle, N. & Karelitz, J.L. Threshold dose for behavioral discrimination of cigarette nicotine content in menthol vs. non-menthol smokers. Psychopharmacology 234, 1255–1265 (2017). https://doi.org/10.1007/s00213-017-4563-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4563-3

Keywords

Navigation