Behavioral differentiation of anxiolytic medications: Alone and in combination with alcohol

Twenty-eight healthy male volunteers (mean age, 25.1 years) reporting a history of recreational substance abuse participated in a 4 (drug treatment) x 3 (alcohol levels) mixed-design study to evaluate the acute behavioral effects of commonly prescribed benzodiazepines alone and in combination with alcohol. Drug treatments were diazepam (5 mg), clorazepate (7.5 mg), lorazepam (1.0 mg), and placebo. Alcohol conditions were placebo, 0.54 gm/kg, and 1.08 gm/kg. Drug treatment was a between-groups condition, while alcohol dose was a within-groups factor. Following acute administration of drug alone drug liking and drug effect were rated higher for diazepam and lorazepam than for clorazepate and placebo. As compared with the other drug treatments, lorazepam was associated with poorer performance on fixed-position reaction time and digit symbol substitution task. In the alcohol-drug combination condition, most measures showed strong alcohol-related dose effects. Higher doses of alcohol were associated with higher ratings of drug effect and more dysphoric mood effects for subjects in all treatment groups. Performance deficits observed under the acute drug-dosing condition were maintained. Lorazepam potentiated alcohol-related impairment of short-term recall. This study illustrates that the behavioral effects of benzodiazepines may be differentiated, even at therapeutic dose levels.