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Psychopharmacology

, Volume 119, Issue 3, pp 268–276 | Cite as

Effects of buprenorphine and methadone in methadone-maintained subjects

  • S. L. Walsh
  • H. L. June
  • K. J. Schuh
  • K. L. Preston
  • G. E. Bigelow
  • M. L. Stitzer
Original Investigation

Abstract

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n=7) or 60 (n=6) mg/day oral methadone. Test doses of placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorphine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pupils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenance condition. Buprenorphine, but not methadone, precipitated opioid withdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce patient discomfort that is positively related to both methadone maintenance dose and buprenorphine transition dose.

Key words

Buprenorphine Methadone Opioid Dependence Withdrawal 

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References

  1. Aceto MD (1984) Characterization of prototypical opioid antagonists, agonist-antagonists, and agonists in the morphine dependent rhesus monkey. Neuropeptides 5:15–18CrossRefPubMedGoogle Scholar
  2. Amass L, Bickel WK, Higgins ST, Badger G (1994) Alternate-day dosing during buprenorphine treatment of opioid dependence. Life Sci 17:1215–1228CrossRefGoogle Scholar
  3. Bickel WK, Stitzer ML, Bigelow GE, Liebson IA, Jasinski DR, Johnson RE (1988a) Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans. J Pharmacol Exp Ther 247:47–53PubMedGoogle Scholar
  4. Bickel WK, Stitzer ML, Bigelow GE, Liebson IA, Jasinski DR, Johnson RE (1988b) A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts. Clin Pharmacol Ther 43:72–78PubMedGoogle Scholar
  5. Bickel WK, Stitzer ML, Liebson IA, Bigelow GE (1988c) Acute physical dependence in man: Effects of naloxone after brief morphine exposure. J Pharmacol Exp Ther 244:126–132PubMedGoogle Scholar
  6. Bullingham RES, McQuay HJ, Moore A, Bennett MRD (1980) Buprenorphine kinetics. Clin Pharmacol Ther 28:667–672PubMedGoogle Scholar
  7. Cowan A, Lewis JW, MacFarlane IR (1977) Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br J Pharmacol 60:537–545PubMedGoogle Scholar
  8. Dum JE, Herz A (1981) In vivo receptor binding of the opiate partial agonist, buprenorphine, correlated with its agonistic and antagonistic actions. Br J Pharmacol 74:627–633PubMedGoogle Scholar
  9. Fudala PJ, Jaffe JH, Dax EM, Johnson RE (1989) Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal. Clin Pharmacol Ther 47:525–534Google Scholar
  10. GAO United States General Accounting Office Report (1990) Methadone maintenance: Some treatment programs are not effective; greater federal oversight needed. Washington, DCGoogle Scholar
  11. Haertzen CA (1974) An overview of the Addiction Research Center Inventory (ARCI): an appendix and manual of scales. DHEW Pub No (ADM) 79, Department of Health Education and Welfare, Washington, DCGoogle Scholar
  12. Haertzen CA, Meketon MJ, Hooks NT (1970) Subjective experiences produced by the withdrawal of opiates. Br J Addict 65:245–255Google Scholar
  13. Hambrook JM, Rance MJ (1976) The interaction of buprenorphine with the opiate receptor: lipophilicity as a determining factor in drug-receptor kinetics. In: Kosterlitz HW (ed) Opiates and endogenous opioid peptides. Elsevier/North Holland, Biomedical Press, Amsterdam, pp 295–301Google Scholar
  14. Heishman SJ, Stitzer ML, Bigelow GE, Liebson IA (1989) Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure. J Pharmacol Exp Ther 248:127–134PubMedGoogle Scholar
  15. Jasinski DR, Henningfield JE, Hickey JE, Johnson RE (1983) Progress report of the NIDA Addiction Research Center, Baltimore, Maryland, 1982. In: Harris LS (ed) Problems of drug dependence, 1982. National Institute on Drug Abuse Research Monograph 43, DHHS (ADM) 83-1264, Washington DC, pp 92–98Google Scholar
  16. Jasinski DR, Martin WR, Hoeldtke R (1971) Studies of the dependence-producing properties of GPA-1657, profadol, and propiram in man. Clin Pharmacol Ther 12:613–649PubMedGoogle Scholar
  17. Jasinski DR, Pevnick JS, Griffith JD (1978) Human pharmacology and abuse potential of the analgesic buprenorphine. Arch Gen Psychiatry 35:501–506PubMedGoogle Scholar
  18. Johnson RE, Jaffe JH, Fudala PJ (1992) A controlled trial of buprenorphine treatment for opioid dependence. JAMA 267[20]:2750–2755CrossRefPubMedGoogle Scholar
  19. Kirby KC, Stitzer ML, Heishman SJ (1990) Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval II. J Pharmacol Exp Ther 255:730–737PubMedGoogle Scholar
  20. Kolb L, Himmelsbach CK (1938) Clinical studies of drug addiction, III. A critical review of the withdrawal treatments with methods of evaluating abstinence syndromes. Am J Psychiatry 94:759–797Google Scholar
  21. Lewis JW (1985) Buprenorphine. Drug Alcohol Depend 14:363–372CrossRefPubMedGoogle Scholar
  22. Martin WR, Jasinski DR, Haertzen CA, Kay DC, Jones BE, Mansky PA, Carpenter RW (1973) Methadone—a reevaluation. Arch Gen Psychiatry 28:286–295PubMedGoogle Scholar
  23. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 197:517–532PubMedGoogle Scholar
  24. McLeod D, Griffiths RR, Bigelow GE, Yingling J (1982) An automated version of the digit symbol substitution test (DSST). Behav Res Methods Instrum 14:463–466Google Scholar
  25. Mello NK, Mendelson JH (1980) Buprenorphine suppresses heroin use by heroin addicts. Science 207:657–659Google Scholar
  26. Mello NK, Mendelson JH, Kuehlne JC (1982) Buprenorphine effects on human heroin self-administration: an operant analysis. J Pharmacol Exp Ther 223:30–39PubMedGoogle Scholar
  27. Preston KL, Bigelow GE, Liebson IA (1988a) Butorphanol-precipitated withdrawal in opioid-dependent human volunteers. J Pharmacol Exp Ther 246[2]:441–448PubMedGoogle Scholar
  28. Preston KL, Bigelow GE, Liebson IA (1988b) Buprenorphine and naloxone alone and in combination in opioid-dependent humans. Psychopharmacology 94:484–490CrossRefPubMedGoogle Scholar
  29. Preston KL, Bigelow GE, Liebson IA (1989) Antagonist effects of nalbuphine in opioid-dependent human volunteers. J Pharmacol Exp Ther 248[3]:929–937PubMedGoogle Scholar
  30. Stitzer ML, Bigelow GE, Liebson IA (1984) Single-day methadone dose-alteration: detectability and symptoms. Clin Pharmacol Ther 36[2]:244–250PubMedGoogle Scholar
  31. Strain EC, Preston KL, Liebson IA, Bigelow GE (1992) Acute effects of buprenorphine, hydromorphone and naloxone in methadone-maintained volunteers. J Pharmacol Exp Ther 261[3]:985–993PubMedGoogle Scholar
  32. Strain EC, Preston KL, Liebson IA, Bigelow GE (1993) Precipitated withdrawal by pentazocine in methadone-maintained volunteers. J Pharmacol Exp Ther 267[2]:624–634PubMedGoogle Scholar
  33. Strain EC, Stitzer ML, Liebson IA, Bigelow GE (1994) Comparison of buprenorphine to methadone in the treatment of opioid dependence. Am J Psychiatry 151:1025–1030Google Scholar
  34. Strain EC, Preston KL, Liebson IA, Bigelow GE (1995) Buprenorphine effects in methadone-maintained volunteers: effects at two hours after methadone. J Pharmacol Exp Ther 272:428–438Google Scholar
  35. Takemori AE, Ikeda M, Portoghese PS (1986) Theμ, κ, andδ properties of various opioid agonists. Eur J Pharmacol 123:357–361CrossRefPubMedGoogle Scholar
  36. Verebely K, Volavka J, Mule S, Resnick R (1975) Methadone in man: Pharmacokinetic and excretion studies in acute and chronic treatment. Clin Pharmacol Ther 18:180–190PubMedGoogle Scholar
  37. Walsh SL, Preston KL, Stitzer ML, Liebson I, Bigelow GE (1992) Comparison of the acute effects of buprenorphine and methadone in non-dependent humans. In: Harris LS (ed) Problems of drug dependence 1992. Proceedings of the 54th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, NIDA Research Monograph 132:333Google Scholar
  38. Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE (1994) Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 55:569–580PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • S. L. Walsh
    • 1
  • H. L. June
    • 1
  • K. J. Schuh
    • 1
  • K. L. Preston
    • 1
  • G. E. Bigelow
    • 1
  • M. L. Stitzer
    • 1
  1. 1.Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral ScienceJohns Hopkins University School of MedicineBaltimoreUSA

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