Reinforcing properties of lorazepam in normal volunteers

These experiments were designed to test the positive reinforcing property of a benzodiazepine in normal volunteer subjects. A choice procedure was used to measure preference for lorazepam, a benzodiazepine with a relatively short plasma half-life, over placebo. In separate experiments, subjects were given a choice between three doses of lorazepam (0.5, 1.0 and 2.0 mg, p.o.) and placebo, and in a fourth experiment subjects were given a choice between lorazepam (1.0 mg) and a therapeutically equipotent dose of diazepam (5 mg). Subjective effects of the drugs were monitored using an experimental version of the Profile of Mood States and a shortened version of the Addiction Research Center Inventory. Subjects showed no preference for 0.5 mg lorazepam over placebo (49% drug choice) or for 1.0 mg lorazepam over diazepam (46% lorazepam choice). However, subjects preferred placebo to both 1.0 and 2.0 mg lorazepam (32% and 16% drug choice for 1.0 and 2.0 mg, respectively). Subjective effects were consistent with the drug's known sedative and anxiolytic properties. Relative to diazepam, lorazepam had a longer duration of effect than might be expected from its plasma half-life. Differences in the pharmacokinetic properties of the two drugs account for the results. The results showed that lorazepam is not an effective positive reinforcer in these subjects, suggesting that it also does not have high dependence potential in this population.