, Volume 123, Issue 1, pp 1–8

Alcohol pretreatment increases preference for cocaine over monetary reinforcement

  • S. T. Higgins
  • J. M. Roll
  • W. K. Bickel
Original Investigation


Non-dependent cocaine users participated in a two-phase experiment conducted under controlled laboratory conditions. During phase 1, subjects sampled intranasal cocaine (100 mg) and placebo (96 mg lactose +4 mg cocaine) in separate sessions and under double-blind conditions. Sampling sessions were followed by a single choice session in which subjects made a maximum of ten choices between 10 mg unit doses of cocaine or placebo. Only subjects who reliably (≥70%) chose cocaine over placebo in phase 1 participated in phase 2. During phase 2, subjects participated in a series of nine experimental sessions conducted on different days in which they were pretreated with varying doses of alcohol (placebo, 0.5, and 1.0 g/kg) and made a maximum of ten choices between 10 mg unit doses of cocaine and an alternative reinforcer (i.e., varying amounts of money). Visual-analog ratings of drug effects and cardiac function were monitored across all experimental sessions. Cocaine was reliably chosen over placebo by the majority (9 of 11) of subjects during phase 1, demonstrating that the drug functioned as a reinforcer. During phase 2, alcohol pretreatment significantly increased choice of cocaine over the alternative reinforcer, while increasing monetary value decreased cocaine choice. Ratings on some visual-analog scales (e.g., good effects) paralleled cocaine choice, with alcohol pretreatment increasing ratings and greater monetary value decreasing them. Cardiac output increased above baseline levels across all alcohol and monetary conditions, but maximal effects were observed during sessions involving pretreatment with the active alcohol doses. Overall, these results demonstrate (a) that alcohol can increase preference for cocaine over alternative reinforcers and thereby may thwart efforts to reduce or abstain from cocaine use, (b) that availability of an alternative, non-drug reinforcer can effectively decrease preference for cocaine, and (c) that combined use of alcohol and cocaine increases cardiac risk compared to use of cocaine alone.

Key words

Cocaine Alcohol Self-administration Choice Heart rate Cardiac function Humans 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bigelow GE, Griffiths RR, Liebson IA (1977) Pharmacological influences upon ethanol self-administration. In: Gross EM (ed) Alcohol intoxication and withdrawal. Plenum, New York, N.Y. pp 523–538Google Scholar
  2. Budney AJ, Higgins ST, Hughes JR, Bickel WK (1993) Nicotine and caffeine use in cocaine-dependent individuals. J Subst Abuse 5:117–130Google Scholar
  3. Carroll ME, Lac ST, Nygaard SL (1989) A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforced behavior. Psychopharmacology 97:23–29Google Scholar
  4. Carroll KM, Rounsaville BJ, Bryant KJ (1993a) Alcoholism in treatment-seeking cocaine abusers: clinical and prognostic significance. J Stud Alcohol 54:199–208Google Scholar
  5. Carroll K, Ziedonis D, O'Malley S, McCance-Katz E, Gordon L, Rounsaville B (1993b) Pharmacologic interventions for alcohol- and cocaine-abusing individuals. Am J Addict 2:77–79Google Scholar
  6. Chutuape MD, Mitchell SH, de Wit H (1994) Ethanol preloads increase ethanol preference under concurrent random-ratio schedules in social drinkers. Exp Clin Psychopharmacol 2:310–318Google Scholar
  7. Farre M, De La Torre R, Llorente M, Lamas X, Ugena B, Segura J, Cami J (1993) Alcohol and cocaine interactions in humans. J Pharmacol Exp Ther 266:1364–1373Google Scholar
  8. Fischman MW, Foltin RW, Nestadt G, Pearlson GD (1990) Effects of desipramine maintenance on cocaine self-administration by humans. J Pharmacol Exp Ther 253:760–770Google Scholar
  9. Foltin RW, Fischman MW (1989) Ethanol and cocaine interactions in humans: cardiovascular consequences. Pharmacol Biochem Behav 31:877–883Google Scholar
  10. Foltin RW, Fischman MW (1994) Effects of buprenorphine on the self-administration of cocaine by humans. Behav Pharmacol 5:79–89Google Scholar
  11. Grant BF, Harford TC (1990) Concurrent and simultaneous use of alcohol with cocaine: results of national survey. Drug Alcohol Depend 25:97–104Google Scholar
  12. Griffiths RR, Bigelow G, Liebson I (1975) Effect of ethanol self-administration on choice behavior: money vs. socializing. Pharmacol Biochem Behav 3:443–446Google Scholar
  13. Griffiths RR, Bigelow GE, Liebson I (1976) Facilitation of human tobacco self-administration by ethanol: a behavioral analysis. J Exp Anal Behav 25:279–292Google Scholar
  14. Hatsukami DK, Thompson TN, Pentel PR, Flygare BK, Carroll ME (1994) Self-administration of smoked cocaine. Exp Clin Psychopharmacology 2:115–125Google Scholar
  15. Higgins ST, Bickel WK, Hughes JR, Lynn M, Capeless MA, Fenwick JW (1990) Effects of intranasal cocaine on human learning, performance, and physiology. Psychopharmacology 102:451–458Google Scholar
  16. Higgins ST, Delaney D, Budney AJ, Bickel WK, Hughes JR, Foerg F, Fenwick JW (1991) A behavoral approach to achieving initial cocaine abstinence. Am J Psychiatry 148:1218–1224Google Scholar
  17. Higgins ST, Rush CR, Hughes JR, Bickel WK, Lynn M, Capeless MA (1992) Effects of cocaine and alcohol, alone and in combination, on human learning and performance. J Exp Anal Behav 58:87–105Google Scholar
  18. Higgins ST, Budney AJ, Bickel WK, Hughes JR, Foerg F, Badger G (1993a) Achieving cocaine abstinence with a behavioral approach. Am J of Psychiatry 150:763–769Google Scholar
  19. Higgins ST, Rush CR, Bickel WK, Hughes JR, Lynn M, Capeless MA (1993b) Acute behavioral and cardiac effects of cocaine and alcohol combinations in humans. Psychopharmacology 11:285–294Google Scholar
  20. Higgins ST, Budney AJ, Bickel WK, Hughes JR, Foerg F (1993c) Disulfiram therapy in patients abusing cocaine and alcohol. Am J Psychiatry 150:675–676Google Scholar
  21. Higgins ST, Budney AJ, Hughes JR, Bickel WK, Lynn M, Mortensen A (1994a) Influence of cocaine use on cigarette smoking. JAMA 272:1724Google Scholar
  22. Higgins ST, Budney AJ, Bickel WK (1994b) Applying behavioral concepts and principles to the treatment of cocaine dependence. Drug Alcohol Depend 34:87–97Google Scholar
  23. Higgins ST, Budney AJ, Bickel WK, Foerg FE, Donham R, Badger GJ (1994c) Incentives improve outcome in outpatient behavioral treatment of cocaine dependence. Arch Gen Psychiatry 54:568–576Google Scholar
  24. Higgins ST, Bickel WK, Hughes JR (1994d) Influence of an alternative reinforcer on human cocaine self-administration. Life Sci 55:179–187Google Scholar
  25. Javaid JI, Fischman MW, Schuster CR, Dekirmenjian H, Davis JM (1978) Cocaine plasma concentration: relation to physiological and subjective effects in humans. Science 202:227–228Google Scholar
  26. Johanson C-E, Fischman MW (1989) The pharmacology of cocaine related to its abuse. Pharm Rev 41:3–52Google Scholar
  27. Katz, JL, Terry P, Witkin JM (1992) Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene). Life Sci 50:1351–1361Google Scholar
  28. McLellan AT, Arndt IO, Metzger DS, Woody G., O'Brien CP (1993) The effects of psychosocial services in substance abuse treatment. JAMA 269:1953–1959Google Scholar
  29. Miller NS, Millman RB, Keskinen S (1989) The diagnosis of alcohol, cocaine, and other drug dependence in an inpatient treatment population. J Subst Abuse Treat 6:37–40Google Scholar
  30. Moliterno DJ, Willard JE, Lange RA, Negus BH, Boehrer JD, Glamann B, Landau C, Rossen JD, Winniford MD, Hillis LD (1994) Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both. New Eng J Med 330:454–459Google Scholar
  31. Nader MA, Woolverton WL (1991) Effects of increasing the magnitude of an alternative reinforcer on drug choice in a discretetrials choice procedure. Psychopharmacology 105:169–174Google Scholar
  32. Perez-Reyes M (1993) Subjective and cardiovascular effects of cocaethylene in humans. Psychopharmacology 113:144–147Google Scholar
  33. Preston KL, Sullivan JT, Berger P, Bigelow GE (1993) Effects of cocaine alone and in combination with mazidol in human cocaine abusers. J Pharmacol Exp Ther 267:296–307Google Scholar
  34. Silverman K, Higgins ST, Brooner RK, Montoya ID, Cone EJ, Schuster CR, Preston KL (1996) Sustained cocaine abstinence in methadone maintenance patients through voucher-based reinforcement therapy. Arch Gen Psychiatry (in press)Google Scholar
  35. Stitzer ML, Iguchi MY, Felch LJ (1992) Contingent take-home incentive: effects on drug use of methadone maintenance patients. J Consult Clin Psychol 60:927–934Google Scholar
  36. Tusel DJ, Piotrowski NA, Sees KL, Reilly PM, Banys P, Meek P, Hall SM (1995) Contingency contracting for illicit drug use with opioid addicts in methadone treatment. In: Harris LS, (ed) Problems of Drug Dependence. US Government Printing Office; National Institute on Drug Abuse research monograph 153 Washington, D.C., p 155.Google Scholar
  37. Washton AM, Gold MS (1987) Cocaine: A clinician's handbook The Guilford Press, New YorkGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • S. T. Higgins
    • 1
  • J. M. Roll
    • 1
  • W. K. Bickel
    • 1
  1. 1.Human Behavioral Pharmacology Laboratory, Department of PsychiatryUniversity of VermontBurlingtonUSA

Personalised recommendations