The compared effects of an acute and subacute treatment by fresh cola extract and caffeine on the caffeine pharmacokinetics and on cortical activities by spectral analysis of the electroencephalogram (EEG) are studied in rats. After acute cola administration, we observed an increase in half-life elimination of caffeine and a stabilization of its plasma/erythrocyte ratio. Chronic administration revealed differences in cola-caffeine penetration in erythrocytes and a reduction of the area under the curve (AUC) and plasma/erythrocyte ratio. We also noted a significant difference in the binding of the caffeine on plasma proteins after subacute administration of cola seed extract. Cola seed treatment induces an increase in the cortical activity with a widening of the dominant frequency spectrum 7-to 10-Hz band of EEG, whereas caffeine alone induces a shift of the dominant frequency band toward higher frequencies. The observed delay to obtain the greatest EEG effect related to the caffeine contained in cola seeds can be partially explained by the pharmacokinetic data.