Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions

levo-alpha-Acetylmethadol (LAAM) and methadone are full mu-opioid agonists used to treat opioid dependence. Current labeling indicates that LAAM is le ss potent than methadone. Clinical studies have not determined the relative potency of these drugs. This study compared the effects of acute doses of LAAM and methadone and also examined the ability of naloxone to reverse the ir effects. Five occasional opioid users received once weekly doses of eith er placebo, LAAM, or methadone (15, 30, or 60 mg/70 kg p.o.) in agonist exp osure sessions and then received naloxone (1.0 mg/70 kg i.m.) 24, 72, and 1 44 h after agonist exposure. Subject-rated, observer-rated, and physiologic al measures were assessed regularly. Comparisons of physiological and subje ctive measures collected in agonist exposure sessions indicate that LAAM is not less potent than methadone under acute dosing conditions. For some mea sures, LAAM was significantly more potent. Three subjects who entered the s tudy were withdrawn for safety reasons due to greater than anticipated and clinically relevant respiratory depression after receiving 60 mg of LAAM. N aloxone did not fully reverse the pupil constriction produced by 60 mg of L AAM. Acute agonist effects suggest that LAAM may be more potent than methad one and more potent than current labeling indicates. An accurate LAAM:metha done relative potency estimate will aid determination of adequate doses for opioid-dependent patients inducted onto LAAM and for methadone maintenance patients who choose to switch to more convenient thrice-weekly LAAM.