The dependence potential of benzodiazepines.

A series of studies has been carried out using a choice procedure to investigate the reinforcing properties of benzodiazepines in adult volunteer subjects. Amphetamine and other drugs with undisputed dependence potential are clearly preferred by the majority of subjects using this procedure. However, diazepam has not been found to be an effective reinforcer across a range of doses, using various subject populations and under different experimental conditions. In the present study, lorazepam, a benzodiazepine with a shorter half-life than diazepam, was tested. Twelve normal volunteer subjects were tested in 4 separate experiments in which three doses of lorazepam (0.5, 1.0 and 2.0 mg) were each compared to placebo, and in a separate experiment, 1.0 mg lorazepam was compared to 5.0 mg diazepam. Subjects showed no preference between 0.5 mg lorazepam and placebo or between 1.0 mg lorazepam and 5.0 mg diazepam, but at the 1.0 and 2.0 mg doses of lorazepam they showed a clear preference for placebo. Subjective effects of the drugs were also monitored, and showed changes consistent with the anxiolytic and sedative effects of the drugs. The duration of the effects of lorazepam was unexpectedly long (as long as 6 hours), so the question whether a shorter-acting benzodiazepine would be a more effective reinforcer in this situation remains unanswered.