Interactions of diazepam and caffeine: Behavioral and subjective dose effects in humans

The effects of diazepam (DZ) (0, 10, and 20 mg) and caffeine (CAF) (0, 200, 400, and 600 mg) alone and in combination were examined in nine healthy male subjects using a within-subject experimental design in which all subjects received all twelve possible dose combinations. Drug effects were assessed using various psychomotor and cognitive performance tasks, staff (observer) ratings of subject behavior, and subject ratings of mood and drug effect. DZ treatment alone impaired performance on all tasks and produced staff and subject ratings indicative of sedative drug effects. CAF treatment alone facilitated performance on two psychomotor tasks requiring rapid reaction speed and increased staff ratings of subject restlessness and subject ratings of tension, alertness, arousal, and CAF symptoms. CAF generally antagonized the DZ-induced ratings of sedation and impairment of psychomotor performance; however, CAF did not consistently antagonize the DZ impairment of immediate recall or delayed recognition memory performance. DZ antagonized the CAF-induced staff-rated restlessness, and subject-ratings of tension, alterness, arousal and CAF symptoms. The results generally support the hypothesis that DZ and CAF produce antagonistic effects through functionally opposing mechanisms, however, the observed effects of drug combinations are dependent on the specific doses being tested and on the measures of drug effect being examined.