Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety ratings in healthy human subjects

In order to investigate possible neurobiologic mechanisms underlying carbon dioxide-induced anxiety, the effects of oral alprazolam 0.75 mg and intravenous clonidine 2 mcg/kg on CO₂-induced increases in ratings of subjective anxiety, pulse rate, and ventilation were measured in healthy human subjects. Pretreatment with alprazolam but not with clonidine significantly reduced the CO₂-induced increase in ratings of anxiety. Neither drug altered CO₂-induced increases in pulse rate or ventilatory responses. Clonidine did produce potent sedative and hypotensive effects. The behavioral data suggest that the mechanisms through which CO₂ induces anxiety-like effects involve neural systems regulated by benzodiazepine receptors and, secondly, that they appear not to require normal functioning of noradrenergic systems. Carbon dioxide may provide a useful model system for identification of new drugs with anxiolytic properties.