Alprazolam attenuates the behavioral effects of D-amphetamine in humans

The results of preclinical behavioral pharmacology studies suggest that γ-aminobutyric acid_A (GABA_A) receptor modulators attenuate the behavioral effects of commonly abused stimulants such as amphetamines and cocaine under a variety of behavioral arrangements including drug discrimination and self-administration. In the present experiment, 6 healthy humans learned to discriminate 15-mg oral D-amphetamine. After acquiring the discrimination (ie, ≥80% correct responding on 4 consecutive days), the effects of a range of doses of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and following pretreatment with alprazolam (0 and 0.5 mg), a GABA_A receptor modulator, were assessed. D-Amphetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported drug effects (eg, increased scores on a Stimulant-Sensitive Adjective-Rating Scale). These effects were generally a function of dose. Alprazolam alone did not occasion D-amphetamine-like discriminative stimulus effects, nor did it increase ratings of sedation or impair performance. Alprazolam pretreatment significantly attenuated the discriminative stimulus effects of D-amphetamine, and some of the self-reported drug effects. Future human laboratory experiments should compare the behavioral effects of D-amphetamine alone and following pretreatment with alprazolam using other behavioral arrangements such as drug self-administration. Future laboratory experiments with humans should also determine if benzodiazepines with lower abuse potential (eg, oxazepam) might also attenuate the behavioral effects of D-amphetamine.