DOSE-RESPONSE ANALYSIS OF OPIOID CROSS-TOLERANCE AND WITHDRAWAL SUPPRESSION DURING LAAM MAINTENANCE

Levo-alpha-acetylmethadol (LAAM) currently is approved as an opioid ma intenance treatment. This double-blind study was designed to character ize withdrawal suppression and opioid blockade produced by two differe nt LAAM maintenance doses. Outpatient opioid-dependent volunteers were stabilized (5-7 weeks) on 25 (n = 8) or 75 mg (n = 8) LAAM administer ed every-other-day with placebo administered on intervening days. Afte r stabilization, four inpatient, randomly ordered experimental session s 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. Phys iological and subjective indices of opioid withdrawal measured at sess ion base lines increased with time since the last LAAM dose, but did n ot depend on the maintenance dose, Withdrawal symptoms were mild in bo th groups, even at 96 hr after LAAM dosing. Hydromorphone produced dos e-related opioid agonist effects at all intervals in the 25 mg LAAM gr oup; these effects were attenuated substantially in the 75 mg LAAM gro up. Time since last LAAM dose had little influence on hydromorphone ef fects in either group. Thus, 75 mg LAAM provides opioid blockade and w ithdrawal suppression for up to 96 hr, whereas 25 mg LAAM is relativel y ineffective at producing significant opioid blockade.