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Caffeine Self-administration, Withdrawal, and Adverse Effects Among Coffee Drinkers

John R. Hughes, MD; Stephen T. Higgins, PhD; Warren K. Bickel, PhD; William K. Hunt, PhD; James W. Fenwick, PhD; Suzy B. Gulliver, PhD; Gina C. Mireault
Arch Gen Psychiatry. 1991;48(7):611-617. doi:10.1001/archpsyc.1991.01810310029006.
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• Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they selfadminister coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects.

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