Subjective and behavioral effects of diazepam depend on its rate of onset

This study addressed the assumption that rate of onset affects the euphorigenic effects of drugs. Drugs with rapid onset are commonly thought to be more euphorigenic than drugs with slower onset, but this idea has rarely been studied directly. Nine healthy male social drinkers, with no history of drug- or alcohol-related problems, participated in three sessions. On each session they received oral doses of placebo (PLAC), diazepam in a rapid onset condition (FAST), or diazepam in a slow onset condition (SLOW). In the FAST condition, they received a single 20 mg dose, whereas in the SLOW condition they received six 4 mg doses administered at 30-min intervals. Plasma levels of diazepam and desmethyldiazepam, subjective effects (including measures of euphoria), psychomotor performance and vital signs were monitored throughout each session. Although the FAST and SLOW conditions led to similar peak plasma levels of drug, the peak was attained earlier in the FAST condition (61 min versus 220 min). Subjects' scores on a measure of euphoria (MBG scale of the ARCI) were significantly higher in the FAST condition compared to the SLOW and PLAC conditions. Subjects exhibited significantly more behavioral signs of intoxication and greater psychomotor impairment in the FAST condition. Sedative effects of the drug were similar in magnitude, but the effects lasted slightly longer in the FAST condition. On several measures diazepam produced similar effects in the two conditions (e.g., ratings of strength of drug effect). These data provide limited support for the notion that a faster rate of onset of drug effects is associated with greater euphoria.