Reinforcing effects of caffeine in humans.

The reinforcing and subjective effects of caffeine were studied under double-blind conditions in 12 normal humans. After 2 forced exposure days on which subjects received color-coded capsules containing either caffeine (100, 200, 400 or 600 mg) or placebo, subjects had a choice day on which they chose which one of the two types of color-coded capsules would be ingested. Subjects were exposed to 10 experimentally independent choices (i.e., involving exposure and choice between novel color-coded capsule conditions) at each of several dose levels. All forced exposure and choice opportunities occurred when subjects were overnight abstinent from their normal dietary caffeine intake (mean, 116 mg/day). Significant caffeine positive reinforcement was demonstrated in 5 of 12 subjects at one or more doses. Percentage of selection of caffeine was inversely related to dose, with four subjects showing significant caffeine avoidance at 400 and/or 600 mg. Choice behavior was correlated positively with feelings of contentedness and was correlated negatively with prestudy trait anxiety scores and with ratings of capsule disliking. Compared to placebo, caffeine produced increases in subjective ratings indicating arousal while producing decreases in headache and "craving" for caffeine-containing foods, even at the lowest dose of 100 mg. At higher doses caffeine produced dysphoric anxiety-like subjective effects. Overall, this study provides the first demonstration in humans of the positive reinforcing effects of caffeine alone (i.e., in capsules) and documents individual differences among normal subjects in both caffeine positive reinforcement and caffeine avoidance.