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OtherANALGESIA AND DRUGS OF ABUSE

Dose-Response Analysis of Opioid Cross-Tolerance and Withdrawal Suppression During LAAM Maintenance

Elisabeth J. Houtsmuller, Sharon L. Walsh, Kory J. Schuh, Rolley E. Johnson, Maxine L. Stitzer and George E. Bigelow
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 387-396;
Elisabeth J. Houtsmuller
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Sharon L. Walsh
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Kory J. Schuh
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Rolley E. Johnson
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Maxine L. Stitzer
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George E. Bigelow
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Abstract

Levo-α-acetylmethadol (LAAM) currently is approved as an opioid maintenance treatment. This double-blind study was designed to characterize withdrawal suppression and opioid blockade produced by two different LAAM maintenance doses. Outpatient opioid-dependent volunteers were stabilized (5–7 weeks) on 25 (n = 8) or 75 mg (n = 8) LAAM administered every-other-day with placebo administered on intervening days. After stabilization, four inpatient, randomly ordered experimental sessions were conducted at 24, 48, 72 and 96 hr after LAAM dosing; the timing of these sessions corresponds to intervals that occur during typical thrice-weekly treatment and after a missed dose. During each session, after baseline assessments, ascending doses of hydromorphone (0, 6 and 12 mg i.m.) were administered 45 min apart; physiological, subjective and observer-rated effects were recorded throughout the session. Physiological and subjective indices of opioid withdrawal measured at session base lines increased with time since the last LAAM dose, but did not depend on the maintenance dose. Withdrawal symptoms were mild in both groups, even at 96 hr after LAAM dosing. Hydromorphone produced dose-related opioid agonist effects at all intervals in the 25 mg LAAM group; these effects were attenuated substantially in the 75 mg LAAM group. Time since last LAAM dose had little influence on hydromorphone effects in either group. Thus, 75 mg LAAM provides opioid blockade and withdrawal suppression for up to 96 hr, whereas 25 mg LAAM is relatively ineffective at producing significant opioid blockade.

Footnotes

  • Send reprint requests to: Sharon L. Walsh, Ph.D., BPRU, Behavioral Biology Research Center, Johns Hopkins Bayview Campus, 5510 Nathan Shock Drive, Baltimore, MD 21224-6823.

  • ↵1 This research was supported by U.S. Public Health Service Research Grants P50 DA05273, K05 DA00050 and T32 DA07209 from the National Institute on Drug Abuse.

  • ↵2 Current address: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48207.

  • Abbreviations:
    LAAM
    levo-α-acetylmethadol (levomethadyl acetate)
    Amph
    amphetamine scale
    ANOVA
    analysis of variance
    ARCI
    Addiction Research Center Inventory
    BG
    benzedrine group scale
    LSD
    lysergic acid diethylamide (“dysphoria”) scale
    MBG
    morphine-benzedrine group (“euphoria”) scale
    PCAG
    pentobarbital-chlorpromazine-alcohol group (“sedation”) scale
    S.E.M.
    standard error of the mean
    WOW
    weak opiate withdrawal scale
    • Received September 2, 1997.
    • Accepted January 2, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 2
1 May 1998
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OtherANALGESIA AND DRUGS OF ABUSE

Dose-Response Analysis of Opioid Cross-Tolerance and Withdrawal Suppression During LAAM Maintenance

Elisabeth J. Houtsmuller, Sharon L. Walsh, Kory J. Schuh, Rolley E. Johnson, Maxine L. Stitzer and George E. Bigelow
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 387-396;

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OtherANALGESIA AND DRUGS OF ABUSE

Dose-Response Analysis of Opioid Cross-Tolerance and Withdrawal Suppression During LAAM Maintenance

Elisabeth J. Houtsmuller, Sharon L. Walsh, Kory J. Schuh, Rolley E. Johnson, Maxine L. Stitzer and George E. Bigelow
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 387-396;
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