Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans.

Examined the efficacy of lofexidine, an α₂ adrenergic agonist, to suppress opioid withdrawal symptoms in opioid-dependent humans under in-patient laboratory conditions by using a naloxone challenge procedure. A randomized, within-subject, cross-over design was used with drug administration taking place under double-blind and triple-dummy conditions with 8 healthy adult volunteers (mean age 38 yrs) with histories of polysubstance abuse and current physical dependence on opioids. Ss were stabilized onto methadone and maintained on 30 mg/day, throughout the study. Oral placebo, lofexidine and clonidine were each tested as pre-treatments once in combination with each of 3 intramuscular naloxone doses during 18 separate experimental sessions. Lofexidine and clonidine both produced dose-related decreases in blood pressure and heart rate but few subjective effects; naloxone increased opioid withdrawal signs and symptoms in a dose- and time-dependent fashion. Results suggest that lofexidine is well tolerated even at supratherapeutic acute doses. However, its failure to modify most signs and symptoms of opioid withdrawal suggest that its effective use in spontaneous withdrawal will require concomitant medications for improved therapeutic response. (PsycInfo Database Record (c) 2021 APA, all rights reserved)