Opioid discrimination in humans: discriminative and subjective effects of progressively lower training dose

The purpose of this study was to examine the extent of covariation of subje ctive and discriminative drug effects as the dose of the discriminated trai ning drug was progressively lowered. Six adult male volunteers with histori es of opioid abuse, who were not currently physically dependent, were train ed to discriminate the mu-receptor agonist hydromorphone (20 mg, oral) from placebo in daily sessions. They received financial reinforcement for corre ct responses. The hydromorphone training dose was then progressively reduce d (20, 14, 10, 7, 5, and 3.5 mg) while the discrimination reinforcement con tingencies remained in effect. Measures of subjective and physiological eff ects were concurrently collected during each discrimination session. As the training dose decreased, discriminative performance was generally well mai ntained, although the percent of drug-appropriate responses to hydromorphon e did decline from 98% to 75%. The magnitude of the subjective and physiolo gical effects of hydromorphone also decreased as the training dose decrease d. At the lowest training dose, there were no physiological effects and few subjective effects of hydromorphone statistically different from placebo, although discrimination behavior remained statistically significant at all doses. These data indicate covariation of subjective effects and discrimina tion performance and suggest that discrimination behavior may be more sensi tive for differentiating among drug conditions than traditional subjective effects measures. Behav Pharmacol 1998; 9:533-543 (C) 1998 Lippincott Willi ams & Wilkins.