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Enhancement of cocaine's abuse liability in methadone maintenance patients

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Abstract

The present study was conducted to determine whether methadone maintenance alters the pharmacodynamic effects of single doses of cocaine. Twenty-two current users of IV cocaine who were not seeking treatment for their illicit cocaine use participated while living on a research unit. Eleven were maintained on methadone 50 mg PO daily as treatment for their opioid abuse; 11 were opioid abusers who were not physically dependent on opioids and who provided opioid-free urines throughout the study. Each subject received acute cocaine challenge doses of 0, 12.5, 25, and 50 mg intravenously in random order under double-blind conditions in separate test sessions. Physiologic and subject-rated responses were measured before injection and for 2 h after. In the methadone maintenance group, cocaine challenge sessions occurred 15.5 h after the daily methadone dose. There were significant differences between the methadone-dependent and nondependent groups: 1) baseline differences related to chronic methadone administration and not associated with cocaine administration (lower respiration rates and pupil diameter; higher skin temperature) and 2) differences in response to cocaine administration; cocaine-induced increases in subject ratings of Drug Effect, Rush, Good Effects, Liking, and Desire for Cocaine and in heart rate were greater in the methadone maintenance patients compared to the non-dependent group. These results indicate that the positive subjective effects and some physiological effects of cocaine are enhanced in methadone-maintained individuals, suggesting a pharmacological basis for the high rates of cocaine abuse among methadone maintenance patients.

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References

  • Ball JC, Ross A (1991) The effectiveness of methadone maintenance treatment. Springer, New York

    Google Scholar 

  • Black JL, Dolan MP, Penk WE, Robinowitz R, DeFord HA (1987) The effect in increased cocaine use on drug treatment. Addict Behav 12:289–292

    Google Scholar 

  • Blumberg H, Ikeda C (1978) Naltrexone, morphine and cocaine interactions in mice and rats. J Pharmacol Exp Ther 206:303–310

    Google Scholar 

  • Chaisson RE, Bacchetti P, Osmond D, Brodie B, Sande MA, Moss AR (1989) Cocaine use and HIV infection in intravenous drug users in San Francisco. JAMA 261:561–565

    Google Scholar 

  • Condelli WS, Fairbank JA, Dennis ML, Rachal JV (1991) Cocaine use by clients in methadone programs: Significance, scope, and behavioral interventions. J Subst Abuse 8:203–212

    Google Scholar 

  • Cooper JR (1989) Methadone treatment and acquired immuno-deficiency syndrom JAMA 262:1664–1668

    Google Scholar 

  • Cushman P (1988) Cocaine use in a population of drug abusers on methadone. Hosp Commun Psychiatry 39:1205–1207

    Google Scholar 

  • Dole VP (1988) Implications of methadone maintenance for theories of narcotic addiction. JAMA 260:3025–3029

    Google Scholar 

  • Downs DA (1979) Interactions of acetylmethadol or methadone with other drugs in rhesus monkeys. Pharmacol Biochem Behav 10:407–414

    Google Scholar 

  • Fischman MW, Schuster CR (1980) Cocaine effects in sleep-deprived humans. Psychopharmacology 72:1–8

    Google Scholar 

  • Foltin RW, Fischman MW (1992) The cardiovascular and subjective effects of intravenous cocaine and morphine combinations in humans. J Pharmacol Exp Ther 261:623–632

    Google Scholar 

  • Foltin RW, Fischman MW (1994) Effects of buprenorphine on the self-administration of cocaine by humans. Behav Pharmacol 5:79–89

    Google Scholar 

  • Forman LJ, Estilow S (1988) Cocaine influences beta-endorphin levels and release. Life Sci 43:309–315

    Google Scholar 

  • Gottheil E, Sterling RC, Weinstein SP (1993) Diminished illicit drug use as a consequence of long-term methadone maintenance. J Addict Dis 12:45–57

    Google Scholar 

  • Houdi AA, Bardo MT, Van Loon GR (1989) Opioid medication of cocaine-induced hyperactivity and reinforcement. Brain Res 497:195–198

    Google Scholar 

  • Hunt DE, Strug DL, Goldsmith DS, Lipton DS, Spunt B, Truitt L, Robertson KA (1984) An instant shot of “Aah”: cocaine use among methadone clients. J Psychoact Drugs 16:217–227

    Google Scholar 

  • Kidorf M, Stitzer ML (1993a) Descriptive analysis of cocaine use of methadone patients. Drug Alcohol Depend 32:267–275

    Google Scholar 

  • Kidorf M, Stitzer ML (1993b) Contingent access to methadone maintenance treatment: effects on cocaine use of mixed opiate-cocaine abusers. Exp Clin Psychopharmacol 1:200–206

    Google Scholar 

  • Kolar AF, Brown BS, Weddington WW, Ball JC (1990) A treatment crisis: cocaine use by clients in methadone maintenance programs. J Subst Abuse Treat 7:101–107

    Google Scholar 

  • Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723

    Google Scholar 

  • Kosten TR, Rounsaville BJ, Kleber HD (1987a) A 2.5-year follow-up of cocaine use among treated opioid addicts. Arch Gen Psychiatry 44:281–284

    Google Scholar 

  • Kosten TR, Kreek MJ, Swift C, Carney MK, Ferdinands L (1987b) Beta endorphin levels in CSF during methadone maintenance. Life Sci 41:1071–1076

    Google Scholar 

  • Leander JD, Lucot JB (1977) Toxic interactions of stimulants, narcotics and narcotic antagonists. Res Commun Chem Pathol Pharmacol 17:255–264

    Google Scholar 

  • Martin WR, Sloan JW, Sapiro JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine and methylphenidate in man. Clin Pharmacol Ther 12:245–258

    Google Scholar 

  • Martin WR, Jasinski DR, Haertzen CA, Kay DC, Jones BE, Mansky PA, Carpenter RW (1973) Methadone — A reevaluation. Arch Gen Psychiatry 28:286–295

    Google Scholar 

  • McLellan AT, Arndt IO, Metzger DS, Woody GE, O'Brien CP (1993) The effects of psychosocial services in substance a base treatment. JAMA 269:1953–1959

    Google Scholar 

  • Mello NK, Mendelson JH, Bree MP, Lukasse SE (1989) Buprenorpkine suppresses cocaine self-administration by rhesus monkeys. Science 245:859–862

    Google Scholar 

  • Mello NK, Mendelson JH, Bree MP, Lukas SE (1990) Buprenorphine and naltrexone effects on cocaine self-administration by rhesus monkeys. J Pharmacol Exp Ther 254:926–939

    Google Scholar 

  • Plunkett LM, Seifen E, Kennedy RH (1989) Effects of morphine pretreatment on cocaine cardiotoxicity in anesthetized guineapigs. Arch Int Pharmacodyn Ther 297:60–67

    Google Scholar 

  • Preston KL, Sullivan JT, Strain EC, Bigelow GE (1992) Effects of cocaine alone and in combination with bromocriptine in human cocaine abusers. J Pharmacol Exp Ther 262:279–291

    Google Scholar 

  • Preston KL, Sullivan JT, Berger P, Bigelow GE (1993) Effects of cocaine alone and in combination with mazindol in human cocaine abusers. J Pharmacol Exp Ther 267:296–307

    Google Scholar 

  • Shimada A, Tsuda T, Yanagita T (1988) Mode of potentiating action of cocaine in morphine analgesia. Jpn J Pharmacol 48:185–193

    Google Scholar 

  • Sierra V, Duttaroy A, Lutfy K, Candido J, Billings B, Zito SW, Yoburn BC (1992) Potentiation of opioid analgesia by cocaine: the role of spinal and supraspinal receptors. Life Sci 50:591–597

    Google Scholar 

  • Sivam SP (1989) Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism. J Pharmacol Exp Ther 250:818–824

    Google Scholar 

  • Spealman RD, Bergman J (1992) Modulation of the discriminative stimulus effects of cocaine bymu andkappa opioids. J Pharmacol Exp Ther 261:607–615

    Google Scholar 

  • Stitzer ML, Iguchi MY, Felch LJ (1992) Contingent take-home incentive: Effects on drug use of methadone maintenance patients. J Consult Clin Psychol 60:927–934

    Google Scholar 

  • Strain EC, Stitzer ML, Liebson IA, Bigelow GE (1993) Doseresponse effects of methadone in the treatment of opioid dependence. Ann Int Med 119:23–27

    Google Scholar 

  • Strain EC, Preston KL, Stitzer ML, Liebson IA, Bigelow GE (1994) The effects of cocaine in buprenorphine-maintained outpatient volunteers. Am J Addict 3:129–143

    Google Scholar 

  • Strug DL, Hunt DE, Goldsmith DS, Lipton DS, Spunt B (1985) Patterns of cocaine use among methadone clients. Int J Addict 20:1163–1175

    Google Scholar 

  • Teoh SK, Mello NK, Mendelson JH, Kuehnle J, Gastfriend DR, Rhoades E, Sholar W (1994) Buprenorphine effects on morphine-and cocaine-induced subjective responses by drug-dependent men. J Clin Psychopharmacol 14:15–27

    Google Scholar 

  • Wenger GR, Wright DW (1990) Behavioral effects of cocaine and its interaction withd-amphetamine and morphine in rats. Pharmacol Biochem Behav 35:595–600

    Google Scholar 

  • Willenbring ML, Morley JE, Krahn DD, Carlson GA, Levine AS, Shafer RB (1989) Psychoneuroendocrine effects of methadone maintenance. Psychoneuroendocrinology 14:371–391

    Google Scholar 

  • Winger G, Skjoldager P, Woods JH (1992) Effects of buprenorphine and other opioid agonists and antagonists on alfentanil- and cocaine-reinforced responding in rhesus monkeys. J Pharmacol Exp Ther 261:311–317

    Google Scholar 

  • Wise RA (1988) The neurobiology of craving: implications for the understanding and treatment of addiction. J Abnorm Psychol 97:118–132

    Google Scholar 

  • Witkin JM, Johnson RE, Jaffe JH, Goldberg SR, Grayson NA, Rice KC, Katz JL (1991) The partial opioid agonist, buprenorphine, protects against lethal effects of cocaine. Drug Alcohol Depend 27:177–184

    Google Scholar 

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Preston, K.L., Preston, K.L., Strain, E.C. et al. Enhancement of cocaine's abuse liability in methadone maintenance patients. Psychopharmacology 123, 15–25 (1996). https://doi.org/10.1007/BF02246276

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  • DOI: https://doi.org/10.1007/BF02246276

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