Discrimination of agonist-antagonist opioids in humans trained on a two-choice saline-hydromorphone discrimination

The stimulus properties of four opioid agonist-antagonists were assessed in postaddict volunteers trained in a two-choice drug discrimination procedure to discriminate between the effects of i.m. saline and hydromorphone (3 mg/70 kg). Behavioral, subjective and physiological measures were concurrently collected. After training, generalization curves were determined for hydromorphone, pentazocine, butorphanol, nalbuphine and buprenorphine. In generalization testing, hydromorphone produced dose-related increases in hydromorphone-appropriate responses and in characteristic opioid agonist-like subjective effects measures. In general, each of the study drugs produced a profile of subjective and physiological effects similar to that reported in other human studies. These subjective indices showed the study drugs to be heterogeneous. However, in this two-choice drug discrimination procedure, they were discriminated as homogeneous (i.e., all were discriminated as hydromorphone-like). The present study also found that all test drugs were subjectively identified as being opiates, and all were subjectively rated as similar to the hydromorphone training condition. A previous three-choice discrimination was sensitive to the heterogeneity among these drugs on both the discrimination measures and subjective ratings of similarity to the hydromorphone training condition. Thus, the specific procedures of drug discrimination studies may have an effect on some subjective indices, although this interaction is not apparent for the majority of subjective effect measures. Also, the characterization of opioids in drug discrimination testing appears to depend upon the specific training subjects receive; this is most clear with discrimination measures, and to a more limited extent, with subjective measures.