The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and caffeine metabolites in plasma and urine were assayed. Peak plasma concentrations were observed at 1 to 2 h with an approximate half-life of 5 h. The concentrations of the metabolite 1,7-dimethylxanthine increased during the 5 h. The major urine metabolite was 1-methyluric acid. The EEG showed a dose-related decrease in log 'theta' power and a decrease in log 'alpha' power. Other dose-related effects were an increase in skin conductance level (sweat-gland activity) and self rating of alertness. Ratings of headache and tiredness were decreased by the caffeine. The study illustrates the complexities of studying a drug which is widely taken and which is often associated with withdrawal effects.