Opioid drug discrimination in humans: Stability, specificity and relation to self-reported drug effect

Non-dependent volunteers with histories of opioid use were trained in a three-choice drug-discrimination procedure to discriminate the effects of i.m. saline, hydromorphone hydrochloride (3 mg/70 kg) and pentazocine lactate (45 mg/70 kg). In daily sessions, monetary reinforcement was contingent upon correctly identifying by letter code, the drug administered; measures of drug discrimination included an operant procedure and a qualitative and a quantitative choice procedure. Drug effects were assessed concurrently on self reports and physiological indices. After acquisition of the discrimination, subjects were tested for generalization to: 1) a range of doses of the training drugs, 2) p.o. doses of the training drugs and 3) novel drugs. The discrimination was readily learned and all three discrimination measures were comparable. Discrimination performance, as well as self reports and physiological effects, remained stable over the course of the study, suggesting that tolerance did not develop in the daily session procedure. Testing with a range of doses of the training drugs resulted in dose-related effects in discrimination performance, physiological effects and self-reported drug effect. Oral doses of the training drugs resulted in partial generalization to the i.m. training doses, compatible with the attenuated subjective effects of the p.o. doses. Novel drugs (d-amphetamine, 10-20 mg p.o.; Lorazepam, 2-4 mg p.o.; and secobarbital, 100-200 mg p.o.) did not generalize to hydromorphone, but showed partial generalization to both pentazocine and saline. In general, drug-discrimination performance paralleled the patterns of self reports.