Three-choice discrimination in methadone maintenance patients: Hydromorphone, naloxone, and saline

Recent data indicate that drugs acting at the various opioid receptors produce discriminable stimulus effects which make it possible to use behavioral drug discrimination testing procedures as a basis for classifying drugs with respect to the similarity of their pharmacological actions. The purpose of the present study was to develop drug discrimination procedures for use in human volunteers. Although subjective effect measures such as true/false questionnaires, adjective rating scales, and questionnaires concerning similarity of a test drug to previously used street drugs have been very useful in describing the effects of various drug classes, it appears likely that a drug discrimination paradigm could be successfully combined with the collection of these traditional subjective effect measures to obtain finer and more complete descriptions of the subjective effects of psychoactive drugs. The addition of drug discrimination to human behavioral pharmacological studies could provide direct comparison of the effects of study drugs to standard drugs with less dependence on each subject's own unknown and unique street drug history. In this initial pilot study we trained methadone maintenance volunteers in a three-way drug discrimination procedure to discriminate between the effects of saline, hydromorphone, and naloxone - i.e., between no pharmacological effect, an opioid/mu-agonist effect, and a withdrawal/mu-antagonist effect. Following this discrimination training dose-effect functions were determined for the two active training compounds.