EFFECT OF CLONIDINE PRETREATMENT ON NALOXONE-PRECIPITATED OPIATE WITHDRAWAL

The purpose of this pilot study was to validate a methodology for test ing the opioid withdrawal-attenuating effects of new medications using clonidine as a positive control, Seven heroin-dependent subjects stab ilized on levorphanol received naloxone challenge tests on 4 consecuti ve days in a 2 x 2 design with placebo or clonidine (0.4-0.5 mg) pretr eatment, followed by 0.2 or 0.4 mg of i.v. naloxone. The change in the area-under-the-curve from the preclonidine base line for various meas ures of withdrawal was analyzed in a two-factor (naloxone dose and clo nidine condition) analysis of variance. Clonidine significantly (P < . 05) attenuated systolic and diastolic blood pressure, pulse, lacrimati on, nasal congestion and plasma cortisol, but not subject-rated withdr awal severity. There was a robust dose-dependent adrenocorticotropic h ormone response to naloxone that was not changed by clonidine pretreat ment. The consistency between these results and prior studies of cloni dine's antiwithdrawal efficacy suggests the validity of this methodolo gy for testing medications to treat opiate withdrawal. Studies with la rger samples are needed to refine this methodology.