Human coffee drinking: reinforcing and physical dependence producing effects of caffeine.

In a residential research ward coffee drinking was studied in nine volunteer human subjects with histories of heavy coffee drinking. The presence or absence of caffeine in the coffee was manipulated under double-blind conditions by using caffeinated (C) or decaffeinated (D) coffee. When subjects were switched alternately for 10 or more consecutive days between C and D, the daily number of cups consumed tended to be relatively stable. In a different experiment, preference for C vs. D was assessed. After experimenter-scheduled exposures, subjects were given choices between C and D. When subjects were presumably caffeine tolerant/dependent, C was rated as being better liked than D and was reliably preferred to D in choice tests. When subjects were not caffeine tolerant/dependent, C was not reliably preferred to D, nor were there pronounced differences in ratings of liking. Under these conditions, some subjects preferred D to C, citing adverse symptoms (suggesting caffeine toxicity) as reasons for avoiding C. The effects of caffeine withdrawal were studied by abruptly substituting D for C for 10 or more days. This resulted in an orderly withdrawal syndrome, having an onset latency of 19 hr, peaking on days 1 and 2, and decreasing progressively over the next 5 or 6 days. The withdrawal syndrome, which was detected on subject-rated, staff-rated and objective behavioral measures, was characterized by increased headache, sleepiness and laziness and decreased alertness and activeness. The present study demonstrates the reinforcing effects of caffeine in humans and also documents the severity of the caffeine withdrawal syndrome. It is concluded that caffeine has the cardinal features of a prototypic drug of abuse.