RT Journal Article
SR Electronic
T1 Dose-Response Analysis of Opioid Cross-Tolerance and Withdrawal Suppression During LAAM Maintenance
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 387
OP 396
VO 285
IS 2
A1 Elisabeth J. Houtsmuller
A1 Sharon L. Walsh
A1 Kory J. Schuh
A1 Rolley E. Johnson
A1 Maxine L. Stitzer
A1 George E. Bigelow
YR 1998
UL http://jpet.aspetjournals.org/content/285/2/387.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics