Lorazepam substitutes for the alcohol stimulus in social drinkers

Rationale: The alcohol discriminative stimulus has been extensively studied in animals and demonstrated to be pharmacologically complex. In contrast, however, the alcohol stimulus has been less frequently studied in humans. Objectives: The aim of the experiments reported here was to characterise pharmacologically an alcohol discriminative stimulus in social drinkers. Methods: Volunteers were first trained to discriminate a dose of 0.2 g/kg alcohol from placebo, using an established method. We then investigated the generalisation response and subjective effects following a range of doses of the gamma-amino-butyric acid (GABA)A benzodiazepine-receptor agonist lorazepam (0, 0.5, 1 and 2 mg. PO). Results: Low doses of lorazepam (0.5 and 1 mg) did not cross-generalise with the alcohol stimulus and produced only minimal subjective effects. However, a dose of 2 mg lorazepam substituted (60.8%) for the stimulus (P<0.02) and increased subjective ratings of "lightheaded" (P<0.05). Conclusions: These results are consistent with the pre-clinical literature and indicate the cross-species generality of the GABA(A) component of the alcohol discriminative stimulus.