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Psychopharmacology

, Volume 233, Issue 12, pp 2309–2317 | Cite as

Threshold dose for discrimination of nicotine via cigarette smoking

  • Kenneth A. Perkins
  • Nicole Kunkle
  • Joshua L. Karelitz
  • Valerie C. Michael
  • Eric C. Donny
Original Investigation

Abstract

Rationale

The lowest nicotine threshold “dose” in cigarettes discriminated from a cigarette containing virtually no nicotine may help inform the minimum dose maintaining dependence.

Objectives

Spectrum research cigarettes (from NIDA) differing in nicotine content were used to evaluate a procedure to determine discrimination thresholds.

Methods

Dependent smokers (n = 18; 13 M, 5 F) were tested on ability to discriminate cigarettes with nicotine contents of 11, 5, 2.4, and 1.3 mg/g, one per session, from the “ultralow” cigarette with 0.4 mg/g, after having discriminated 16 mg/g from 0.4 mg/g (all had 9–10 mg “tar”). Exposure to each was limited to 4 puffs/trial. All subjects were abstinent from smoking overnight prior to each session, and the number of sessions was determined by the participant’s success in discrimination behavior on >80 % of trials. Subjective perceptions and behavioral choice between cigarettes were also assessed and related to discrimination behavior.

Results

The median threshold was 11 mg/g, but the range was 2.4 to 16 mg/g, suggesting wide variability in discrimination threshold. Compared to the ultralow, puff choice was greater for the subject’s threshold dose but only marginal for the subthreshold (next lowest nicotine) cigarette. Threshold and subthreshold also differed on subjective perceptions but not withdrawal relief.

Conclusions

Under these testing conditions, threshold content for discriminating nicotine via cigarettes may be 11 mg/g or greater for most smokers, but some can discriminate nicotine contents one-half or one-quarter this amount. Further study with other procedures and cigarette exposure amounts may identify systematic differences in nicotine discrimination thresholds.

Keywords

Nicotine Discrimination Cigarette smoking Threshold Choice Subjective effects 

Notes

Acknowledgment

Research reported in this publication was supported by the National Institute on Drug Abuse and Food and Drug Administration Center for Tobacco Products (CTP) (U54 DA031659). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

Compliance with ethical standard

Conflict of interests

No authors have any potential conflicts of interest to report.

References

  1. American Psychiatric Association (APA) (2013) Diagnostic and statistical manual—v. American Psychiatric Association, Washington DCGoogle Scholar
  2. Benowitz NL, Henningfield JE (1994) Establishing a nicotine threshold for addiction. New Engl J Med 331:123–125CrossRefPubMedGoogle Scholar
  3. 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 309:139–142CrossRefPubMedGoogle Scholar
  4. 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 11:896–903CrossRefPubMedPubMedCentralGoogle Scholar
  5. Breslau N, Kilbey MM, Andreski P (1994) DSM-IIIR nicotine dependence in young adults: prevalence, correlates and associated psychiatric disorders. Addiction 89:743–754CrossRefPubMedGoogle Scholar
  6. 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 12:305–312CrossRefPubMedPubMedCentralGoogle Scholar
  7. Butschky MF, Bailey D, Henningfield JE, Pickworth WB (1995) Smoking with nicotine delivery decreases withdrawal in 12-hour abstinent smokers. Pharmacol Biochem Behav 50:91–96CrossRefPubMedGoogle Scholar
  8. 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 (Berl) 94:206–212CrossRefGoogle Scholar
  9. Donny EC, Houtsmuller E, Stitzer ML (2007) Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days. Addiction 102:324–334CrossRefPubMedGoogle Scholar
  10. Donny EC, Denlinger RL, Tidey JW et al (2015) Randomized trial of reduced-nicotine standards for cigarettes. New Engl J Med 373:1340–1349CrossRefPubMedPubMedCentralGoogle Scholar
  11. Duke AN, Johson MW, Reissig CJ, Griffiths RR (2015) Nicotine reinforcement in never-smokers. Psychopharmacology (Berl) 232:4243–4252CrossRefGoogle Scholar
  12. Glennon RA, Young R (2011) Drug discrimination: application to medicinal chemistry and drug studies. Wiley, New YorkCrossRefGoogle Scholar
  13. Goodwin AK, Hiranita T, Paule MG (2015) The reinforcing effects of nicotine in humans and nonhuman primates: a review of intravenous self-administration evidence and future directions for research. Nicotine Tob Res 17:1297–1310CrossRefPubMedGoogle Scholar
  14. 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
  15. 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 151:181–193CrossRefGoogle Scholar
  16. Gu X, Lohrenz T, Salas R et al (2015) Belief about nicotine selectively modulates value and reward prediction error signals in smokers. Proc Natl Acad Sci USA 112:2539–2544CrossRefPubMedPubMedCentralGoogle Scholar
  17. Harvey DM, Yasar S, Heishman SJ, Panlilio LV, Henningfield JE, Goldberg SR (2004) Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Psychopharmacology (Berl) 175:134–142CrossRefGoogle Scholar
  18. Hasenfratz M, Jacober A, Battig K (1993) Smoking-related subjective and physiological changes: pre- to postpuff and pre- to postcigarette. Pharmacol Biochem Behav 46:527–534CrossRefPubMedGoogle Scholar
  19. Hatsukami DK, Pickens RW, Svikis DS, Hughes JR (1988) Smoking topography and nicotine blood levels. Addict Behav 13:91–95CrossRefPubMedGoogle Scholar
  20. 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 19:436–445CrossRefGoogle Scholar
  21. Hatsukami DK, Biener L, Leischow SJ, Zeller MR (2012) Tobacco and nicotine product testing. Nicotine Tob Res 14:7–17CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hatsukami DK, Benowitz NL, Donny E, Henningfield J, Zeller MR (2013a) Nicotine reduction: Strategic research plan. Nicotine Tob Res 15:1003–1013CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hatsukami DK, Heishman SJ, Vogel RI, Denlinger RL et al (2013b) Dose-response effects of Spectrum research cigarettes. Nicotine Tob Res 15:1113–1121CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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 86:1119–1127CrossRefPubMedGoogle Scholar
  25. Hecht SS (2012) Research opportunities related to establishing standards for tobacco products under the Family Smoking Prevention and Tobacco Control Act. Nicotine Tob Res 14:18–28CrossRefPubMedPubMedCentralGoogle Scholar
  26. Henningfield JE, Keenan RM (1993) Nicotine delivery kinetics and abuse liability. J Consult Clin Psychol 61:743–750CrossRefPubMedGoogle Scholar
  27. Henningfield JE, Kozlowski LT, Benowitz NL (1994) A proposal to develop meaningful labeling for cigarettes. JAMA 272:312–314CrossRefPubMedGoogle Scholar
  28. Hoffmann AC, Evans SE (2013) Abuse potential of non-nicotine tobacco smoke constituents: acetaldehyde, nornicotine, cotinine, and anabasine. Nicotine Tob Res 15:622–632CrossRefGoogle Scholar
  29. Holtzman SG (1990) Discriminative stimulus effects of drugs: relationship to potential for abuse. In: Modern Methods in Pharmacology, vol 6. Wiley-Liss, Inc, New York, pp 193–210Google Scholar
  30. Hughes JR, Hatsukami DK (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43:289–294CrossRefPubMedGoogle Scholar
  31. Jackson A, Stephens DN, Duka T (2001) A low dose alcohol drug discrimination in social drinkers: relationship with subjective effects. Psychopharmacology (Berl) 157:411–420CrossRefGoogle Scholar
  32. Jarvis MJ, Boreham R, Primatesta P, Feyerabend C, Bryant A (2001) Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population. J of NCI 93:134–138Google Scholar
  33. 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, vol 116, NIDA Research Monograph. U.S. Government Printing Office, Washington DC, pp 181–196Google Scholar
  34. June KM, Norton KJ, Rees VW, O’Connor RJ (2012) Influence of measurement setting and home smoking policy on smoking topography. Addict Behav 37:42–46CrossRefPubMedPubMedCentralGoogle Scholar
  35. 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 18:3305–3320CrossRefGoogle Scholar
  36. Mooney M, Green C, Hatsukami D (2006) Nicotine self-administration: cigarettes versus nicotine gum diurnal topography. Hum Psychopharmacol 21:539–548CrossRefPubMedGoogle Scholar
  37. Mumford GK, Evans SM, Kaminski BJ, Preston KL, Sannerud CA, Silverman K, Griffiths RR (1994) Discriminative stimulus and subjective effects of theobromine and caffeine in humans. Psychopharmacology (Berl) 115:1–8CrossRefGoogle Scholar
  38. 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 369–400CrossRefGoogle Scholar
  39. Perkins KA (2011) Nicotine discrimination in humans. Chapter 15. In: Glennon RA, Young R (eds) Drug discrimination: application to medicinal chemistry and drug studies. Wiley, New York, pp 463–481CrossRefGoogle Scholar
  40. Perkins KA, DiMarco A, Grobe JE, Scierka A, Stiller RL (1994) Nicotine discrimination in male and female smokers. Psychopharmacology (Berl) 116:407–413CrossRefGoogle Scholar
  41. Perkins KA, Grobe JE, Weiss D, Fonte C, Caggiula A (1996) Nicotine preference in smokers as a function of smoking abstinence. Pharmacol Biochem Behav 55:257–263CrossRefPubMedGoogle Scholar
  42. Perkins KA, Fonte C, Sanders M, Meeker J, Wilson A (2001) Threshold doses for nicotine discrimination in smokers and nonsmokers. Psychopharmacology (Berl) 155:163–170CrossRefGoogle Scholar
  43. 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 14:490–494CrossRefPubMedPubMedCentralGoogle Scholar
  44. Perkins KA, Kunkle N, Michael VC, Karelitz JL, Donny EC (in press). Assessing discrimination of nicotine in humans via cigarette smoking. Nicotine Tob Res. (in press).Google Scholar
  45. Pittenger ST, Bevins RA (2013) Interoceptive conditioning in rats: effects of using a single training dose or a set of 5 different doses of nicotine. Pharmacol Biochem Behav 114:82–89CrossRefPubMedGoogle Scholar
  46. Preston KL (1991) Drug discrimination methods in human drug abuse liability evaluation. Br J Addiction 86:1587–1594CrossRefGoogle Scholar
  47. Preston KL, Bigelow GE (1998) Opioid discrimination in humans: discriminative and subjective effects of progressively lower training dose. Behav Pharmacol 9:533–543CrossRefPubMedGoogle Scholar
  48. Rose JE (2006) Nicotine and nonnicotine factors in cigarette addiction. Psychopharmacology (Berl) 184:274–285CrossRefGoogle Scholar
  49. Rush CR, Critchfield TS, Troisi JR, Griffiths RR (1995) Discriminative stimulus effects of diazepam and buspirone in normal volunteers. J Exper Anal Behav 63:277–294CrossRefGoogle Scholar
  50. Shoaib M, Stolerman IP (1996) Brain sites mediating the discriminative stimulus effects of nicotine in rats. Behav Brain Res 78:183–188CrossRefPubMedGoogle Scholar
  51. Smith JW, Stolerman IP (2009) Recognising nicotine: the neurobiological basis of nicotine discrimination. In: Henningfield JE, London E, Pogun S (eds) Nicotine Psychopharmacology. Springer-Verlag, New York, pp 295–333CrossRefGoogle Scholar
  52. Sofuoglu M, LeSage MG (2012) The reinforcement threshold for nicotine as a target for tobacco control. Drug Alc Depend 125:1–7CrossRefGoogle Scholar
  53. Sofuoglu M, Yoo S, Hill KP, Mooney M (2008) Self-administration of intravenous nicotine in male and female cigarette smokers. Neuropsychopharmacol 33:715–720CrossRefGoogle Scholar
  54. SRNT subcommittee (2002) Biochemical verification of tobacco use and cessation. Nicotine Tob Res 4:149–159CrossRefGoogle Scholar
  55. St. Charles FK, Kabbani AA, Borderding MF (2010) Estimating tar and nicotine exposure: human smoking versus machine generated smoke yields. Reg Tox Pharmacol 56:100–110CrossRefGoogle Scholar
  56. Stolerman IP (1989) Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Psychopharmacology (Berl) 97:131–138CrossRefGoogle Scholar
  57. Strasser AA, Ashare RL, Kozlowski LT, Pickworth WB (2005) The effect of filter vent blocking and smoking topography on carbon monoxide levels in smokers. Pharmacol Biochem Behav 82:320–329CrossRefPubMedGoogle Scholar
  58. 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 22:382–389CrossRefGoogle Scholar
  59. Takada K (1996) Drug discrimination studies in humans: a review of methodologies. Meth Find Exp Clin Pharmacol 18(suppl 1):187–196Google Scholar
  60. 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. 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, AtlantaGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Kenneth A. Perkins
    • 1
  • Nicole Kunkle
    • 1
  • Joshua L. Karelitz
    • 1
  • Valerie C. Michael
    • 1
  • Eric C. Donny
    • 2
  1. 1.Western Psychiatric Institute and Clinic, University of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of PsychologyUniversity of PittsburghPittsburghUSA

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