Acute administration of alprazolam, alcohol and their combination on cognitive performance and mood: A randomised, double-blind, placebo-controlled study

Background: Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population. Methods: In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC). Results: Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported. Conclusions: Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines.