, Volume 193, Issue 4, pp 449–456 | Cite as

Pharmacological effects of naltrexone and intravenous alcohol on craving for cigarettes among light smokers: a pilot study

  • Lara A. Ray
  • Robert MirandaJr.
  • Christopher W. Kahler
  • Adam M. Leventhal
  • Peter M. Monti
  • Robert Swift
  • Kent E. Hutchison
Original Investigation



Although naltrexone has been widely researched in the context of drinking and smoking behaviors, with each substance studied separately, little is known about the effects of naltrexone on craving for cigarettes during alcohol intoxication.


The present study used a within-subjects double-blind placebo-controlled design to (1) examine the effects of alcohol, administered intravenously, on craving for cigarettes; (2) test the effects of naltrexone on cigarette craving during alcohol intoxication; and (3) examine the relationship between craving for alcohol and cigarettes across rising breath alcohol concentrations (BrACs).

Materials and methods

Heavy drinking light smokers completed two counterbalanced intravenous alcohol challenge sessions, one after taking naltrexone (50 mg) for 3 days and one after taking a placebo for 3 days. During each session, participants reported on their craving for alcohol and cigarettes.


Analyses revealed a significant positive effect of BrAC on urge to smoke as well as a BrAC × Medication interaction. Specifically, the linear relationship between BrAC and urge to smoke was significantly weaker in the naltrexone condition, as compared to placebo. There was also a positive association between urge to drink and urge to smoke, and this relationship was moderated by BrAC.


These findings demonstrate that the pharmacological effects of alcohol alone induce craving for cigarettes and that naltrexone blunts the progression of craving for cigarettes during alcohol intoxication. These results highlight the potential clinical utility of naltrexone for heavy drinkers trying to quit smoking.


Alcohol Smoking Naltrexone Craving Urge Pharmacotherapy Laboratory 


  1. Allen JP, Litten RZ, Fertig JB, Babor T (1997) A review of research on the Alcohol Use Disorders Identification Test (AUDIT). Alcohol Clin Exp Res 21:613–619PubMedGoogle Scholar
  2. Anton RF, Moak DH, Waid LR, Latham PK, Malcolm RJ, Dias JK (1999) Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial. Am J Psychiatry 156:1758–1764PubMedGoogle Scholar
  3. Anton RF, Drobes DJ, Voronin K, Durazo-Avizu R, Moak D (2004) Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking. Psychopharmacology 173:32–40PubMedCrossRefGoogle Scholar
  4. Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donavan DM et al (2006) Combined pharmacotherapies and behavioral interventions for alcohol dependence, the COMBINE study: a randomized controlled trial. JAMA 295:2003–2017PubMedCrossRefGoogle Scholar
  5. Balldin J, Berglund M, Borg S, Mansson M, Bendtsen P, Franck J et al (2003) A 6-month controlled naltrexone study: Combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Alcohol Clin Exp Res 27:1142–1149PubMedCrossRefGoogle Scholar
  6. Barrett SP, Tichauer M, Leyton M, Pihl RO (2006) Nicotine increases alcohol self-administration in non-dependent male smokers. Drug Alcohol Depend 81:197–204PubMedCrossRefGoogle Scholar
  7. Bjartveit K, Tverdal A (2005) Health consequences of smoking 1–4 cigarettes per day. Tob Control 14:315–320PubMedCrossRefGoogle Scholar
  8. Burton SM, Tiffany ST (1997) The effect of alcohol consumption on craving to smoke. Addiction 92:15–26PubMedCrossRefGoogle Scholar
  9. Byars JA, Frost-Pineda K, Jacobs WS (2005) Naltrexone augments the effects of nicotine replacement therapy in female smokers. J Addict Dis 24:49–60PubMedCrossRefGoogle Scholar
  10. Covey LS, Glassman AH, Stetner F (1999) Naltrexone effects on short-term and long-term smoking cessation. J Addict Dis 18:31–40PubMedCrossRefGoogle Scholar
  11. Davidson RJ (2003) Affective neuroscience and psychophysiology: toward a synthesis. Psychophysiology 44:655–665CrossRefGoogle Scholar
  12. Davidson D, Swift R, Fitz E (1996) Naltrexone increase the latency to drink alcohol in social drinkers. Alcohol Clin Exp Res 20:732–739PubMedCrossRefGoogle Scholar
  13. Dawson DA (2000) Drinking as a risk factor for sustained smoking. Drug Alcohol Depend 59:235–249PubMedCrossRefGoogle Scholar
  14. Del Boca FK, Kranzler HR, Brown J, Korner PF (1996) Assessment of medication compliance in alcoholics through UV light detection of a riboflavin tracer. Alcohol Clin Exp Res 20:1412–1417PubMedCrossRefGoogle Scholar
  15. Drobes DJ, Anton RF, Thomas SE, Vornin K (2004) Effects of naltrexone and nalmefene on subjective response to alcohol among non-treatment seeking alcoholics and social drinkers. Alcohol Clin Exp Res 28:1362–1370PubMedCrossRefGoogle Scholar
  16. Epstein AM, King AC (2004) Naltrexone attenuates acute cigarette smoking behavior. Pharmacol Biochem Behav 77:29–37PubMedCrossRefGoogle Scholar
  17. Epstein AM, Sher TG, Young MA, King AC (2007) Tobacco chippers show robust increases in smoking urge after alcohol consumption. Psychopharmacology 190(3): 321–329PubMedCrossRefGoogle Scholar
  18. Glautier S, Clements K, White JA, Taylor C, Stolerman IP (1996) Alcohol and the reward value of cigarette smoking. Behav Pharmacol 7:144–154PubMedCrossRefGoogle Scholar
  19. Guardia J, Caso C, Arias F, Gual A, Sanahuja J, Ramirez M et al (2002) A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Alcohol Clin Exp Res 26:1381–1387PubMedGoogle Scholar
  20. Hutchison KE, Monti PM, Rohsenow DJ, Swift R, Colby SM, Gnys M, Niaura RS, Sirota AD (1999) Effects of naltrexone with nicotine replacement on smoking cue-reactivity: preliminary results. Psychopharmacology 142:139–143PubMedCrossRefGoogle Scholar
  21. Kahler CW, Resendes A, Monti PM, Ramsey SE, Abrams DA, Brown RA (2005) Alcohol use and smoking outcomes among heavy drinkers in smoking cessation treatment. In: Society for Research on Nicotine and Tobacco Annual Meeting, Prague, Czech RepublicGoogle Scholar
  22. King AC, Epstein AM (2005) Alcohol dose-dependent increases in smoking urge in light smokers. Alcohol Clin Exp Res 29:547–552PubMedCrossRefGoogle Scholar
  23. King AC, Meyer PJ (2000) Naltrexone alteration of acute smoking response in nicotine-dependent subjects. Pharmacol Biochem Behav 66:563–572PubMedCrossRefGoogle Scholar
  24. King A, de Wit H, Riley RC, Cao D, Niaura R, Hatsukami D (2006) Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Nicotine Tob Res 8:671–682PubMedCrossRefGoogle Scholar
  25. Kouri EM, McCarthy EM, Faust AH, Lukas SE (2004) Pretreatment with transdermal nicotine enhances some of ethanol's acute effects in men. Drug Alcohol Depend 75(1):55–65PubMedCrossRefGoogle Scholar
  26. Lee YS, Joe KH, Sohn IK, Na C, Kee BS, Chae SL (2005) Changes of smoking behavior and serum adrenocorticotropic hormone, cortisol, prolactin, and endogenous opioids levels in nicotine dependence after naltrexone treatment. Prog Neuropsychopharmacol Biol Psychiatry 29:639–647PubMedCrossRefGoogle Scholar
  27. Li T, Yin S, Crabb DW, O’Connor S, Ramchandani VA (2001) Genetic and environmental influences on alcohol metabolism in humans. Alcohol Clin Exp Res 25:136–144PubMedCrossRefGoogle Scholar
  28. Littleton J, Zieglgansberger W (2003) Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence. Am J Addict 12:3–11CrossRefGoogle Scholar
  29. McCaul ME, Wand GS, Stauffer R, Lee SM, Rohde CA (2001) Naltrexone dampens ethanol-induced cardiovascular and hypothalamic–pituitary–adrenal axis activation. Neuropsychopharmacology 25:537–547PubMedCrossRefGoogle Scholar
  30. Mello NK, Mendelson JH, Sellers ML, Kuehnle JC (1980) Effect of alcohol and marijuana on tobacco smoking. Clin Pharmacol Ther 27:202–209PubMedCrossRefGoogle Scholar
  31. Mitchell SH, de Wit H, Zacny JP (1995) Effects of varying ethanol dose on cigarette consumption in healthy normal volunteers. Behav Pharmacol 6:359–365PubMedGoogle Scholar
  32. Monti PM, Rohsenow DJ, Hutchison KE, Swift RM, Mueller TI, Colby SM et al (1999) Naltrexone’s effect on cue-elicited craving among alcoholics in treatment. Alcohol Clin Exp Res 23:1386–1394PubMedGoogle Scholar
  33. Monti PM, Rohsenow DJ, Swift RM, Gulliver SB, Colby SM, Mueller TI et al. (2001) Naltrexone and cue exposure with coping and communication skills training for alcoholics: Treatment process and 1-year outcomes. Alcohol Clin Exp Res 25:1634–1647PubMedCrossRefGoogle Scholar
  34. Ockene JK, Adams A (1995) Screening and intervention for smoking and alcohol use in primary care settings: similarities, differences, gaps, and challenges. In: Fertig JB, Allen JP (eds) Alcohol and tobacco: from basic science to clinical practice. National Institutes of Health, Bethesda, MD, pp 281–294Google Scholar
  35. O’Connor S, Morzorati S, Christian J, Li T (1998) Clamping breath alcohol concentration reduces experimental variance: Application to the study of acute tolerance to alcohol and alcohol elimination rate. Alcohol Clin Exp Res 22:202–210PubMedGoogle Scholar
  36. O’Malley SS, Jaffe AJ, Change G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry 49:881–887PubMedGoogle Scholar
  37. O’Malley SS, Cooney JL, Krishnan-Sarin S, Dubin JA, McKee SA, Cooney NL et al (2006) A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern Med 166:667–674PubMedCrossRefGoogle Scholar
  38. Perkins KA, Sexton JE, DiMarco A, Grobe JE, Scierka A, Stiller RL (1995) Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers. Psychopharmacology 119:205–212PubMedCrossRefGoogle Scholar
  39. Ramchandani VA, Bolane J, Li TK, O’Connor S (1999) A physiologically-based pharmacokinetic (PBPK) model for alcohol facilitates rapid BrAC clamping. Alcohol Clin Exp Res 23:617–623PubMedGoogle Scholar
  40. Ray LA, Hutchison KE (2004) A polymorphism of the mu-opioid receptor gene and sensitivity to the effects of alcohol in humans. Alcohol Clin Exp Res 28:1789–1795PubMedCrossRefGoogle Scholar
  41. Ray LA, Hutchison KE (2007) A double-blind placebo-controlled study of the effects of naltrexone on alcohol sensitivity and genetic moderators of medication response. Arch Gen Psychiatry, in pressGoogle Scholar
  42. Ray LA, McGeary J, Marshall E, Hutchison KE (2006) Risk factors for alcohol misuse: integrating heart rate response to alcohol, alcohol sensitivity, and personality factors. Addict Behav 31:1959–1973PubMedCrossRefGoogle Scholar
  43. Ray LA, Meskew-Stacer S, Hutchison KE (2007) The relationship between prospective self-rating of alcohol sensitivity and craving and experimental results from two alcohol challenge studies. J Stud Alcohol Drugs 68(3)379–384Google Scholar
  44. Rimm EB, Chan J, Stampfer MJ, Colditz GA, Willett WC (1995) Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. Br Med J 310:555–559Google Scholar
  45. Rohsenow DJ, Monti PM, Colby SM, Gulliver SB, Swift RM, Abrams DB (2003) Naltrexone treatment for alcoholics: effect on cigarette smoking rates. Nicotine Tob Res 5:231–236PubMedCrossRefGoogle Scholar
  46. Rohsenow DJ, Monti PM, Hutchison KE, Swift RM, MacKinnon SV, Sirota AD et al (2007) High dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking. Exp Clin Psychopharmacol 15(1):81–92PubMedCrossRefGoogle Scholar
  47. Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D (2002) Potentiation of nicotine reward by alcohol. Alcohol Clin Exp Res 6:930–1931Google Scholar
  48. Rose JE, Brauer LH, Behm FM, Cramblett M, Calkins K, Lawhon D (2004) Psychopharmacological interactions between nicotine and ethanol. Nicotine Tob Res 6:133–144PubMedCrossRefGoogle Scholar
  49. Rubio G, Manzanares J, Lopez-Munoz F, Alamo C, Ponce G, Jimenez-Arriero, MA, Palomo T (2002) Naltrexone improves outcome of a controlled drinking program. J Subst Abuse Treat 23:361–366PubMedCrossRefGoogle Scholar
  50. Rukstalis M, Jepson C, Strasser A, Lynch KG, Perkins K, Patterson F et al (2005) Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm. Psychopharmacology 180:41–48PubMedCrossRefGoogle Scholar
  51. SAS Institute 2003. The SAS system for windows (version 8.2) SAS Institute, Cary, NCGoogle Scholar
  52. Sayette MA, Martin CS, Wertz JM, Perrott MA, Peters AR (2005) The effects of alcohol on cigarette craving in heavy smokers and tobacco chippers. Psychol Addict Behav 19:263–270PubMedCrossRefGoogle Scholar
  53. Schoenborn CA, Adams PF, Barnes PM, Vickerie JL, Schiller JS (2004) Health behaviors of adults: United States, 1999–2001. Vital Health Stat 10(219):1–79Google Scholar
  54. Shiffman S, Fischer LA, Paty JA, Gnys M, Hickcox M, Kassel JD (1994) Drinking and smoking: a field study of their association. Annals Behav Med 16:203–209Google Scholar
  55. Strizke WGK, Breiner MJ, Curtin JJ, Lang AR (2004) Assessment of substance cue reactivity: advances in reliability, specificity, and validity. Psychol Addict Behav 18:148–159CrossRefGoogle Scholar
  56. Sutherland G, Stapleton JA, Russell MA, Feyerabend C (1995) Naltrexone, smoking behaviour and cigarette withdrawal. Psychopharmacology 120:418–425PubMedCrossRefGoogle Scholar
  57. Swift RM, Whelihan W, Kusnetsov O, Buongiorno G, Hsuing H (1994) Naltrexone-induced alterations in human ethanol intoxication. Am J Psychiatry 151:1463–1467PubMedGoogle Scholar
  58. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880PubMedGoogle Scholar
  59. Wewers ME, Dhatt R, Tejwani GA (1998) Naltrexone administration affects ad libitum smoking behavior. Psychopharmacology 140:185–190PubMedCrossRefGoogle Scholar
  60. White HR, Labouvie EW (1989) Towards the assessment of adolescent problem drinking. J Stud Alcohol 50:30–37PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Lara A. Ray
    • 1
    • 2
  • Robert MirandaJr.
    • 2
  • Christopher W. Kahler
    • 2
  • Adam M. Leventhal
    • 2
  • Peter M. Monti
    • 2
    • 3
  • Robert Swift
    • 2
    • 3
  • Kent E. Hutchison
    • 1
  1. 1.Department of PsychologyUniversity of Colorado at BoulderBoulderUSA
  2. 2.Center for Alcohol and Addiction StudiesBrown UniversityProvidenceUSA
  3. 3.Department of Veterans Affairs Medical CenterProvidenceUSA

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