To show the subjective and cardiovascular effects of khat leaves having a standardized content of cathinone. The main effect of khat is an increase of energy and alertness. This effect is thought to be attributable to the phenylalkylamine cathinone, but no controlled clinical trials have been published. The design was balanced and double blind. Six drug-naïve volunteers received a single dose of khat corresponding to 0.8 mg/kg body weight, as well as alkaloid-free khat as a placebo. Psychologic effects were evaluated by the Addiction Research Center Inventory (ARCI) and visual analog scales. Physiologic measures were systolic blood pressure, diastolic blood pressure, and heart rate. Plasma concentrations of cathinone and its metabolites norephedrine and R,R-(-)norpseudoephedrine were determined by HPLC. Maximal plasma concentrations of cathinone (127 +/- 53 [SD] ng/ml) were attained after 127 +/- 30 minutes. The area under the plasma concentration-time curve from 0 to 9 hours was 415 +/- 207 ng/ml.hr, and the terminal elimination half-life was 260 +/- 102 minutes. An effect of khat was observed in the ARCI scales Abuse Potential (p < 0.01), Motor Stimulation (p < 0.02), Amphetamine-Like Effect (p < 0.005), and Stimulation-Euphoria (p < 0.005), as well as in the visual analog scales Excited-Calm (p < 0.001) and Energetic-Lethargic (p < 0.001). Our results provide objective evidence for the amphetamine-like stimulatory effects of khat leaves. These effects were closely similar to those observed after cathinone, 0.5 mg/kg body weight, although peak plasma concentrations of cathinone after khat were delayed.