Caffeine--an atypical drug of dependence

Drug Alcohol Depend. Jun-Jul 1998;51(1-2):199-206. doi: 10.1016/s0376-8716(98)00077-5.


Caffeine has both positive effects that contribute to widespread consumption of caffeine-containing beverages and adverse unpleasant effects if doses are increased. Caffeine has weak reinforcing properties, but with little or no evidence for upward dose adjustment, possibly because of the adverse effects of higher doses. Withdrawal symptoms, although relatively limited with respect to severity, do occur, and may contribute to maintenance of caffeine consumption. Health hazards are small if any and caffeine use is not associated with incapacitation. Thus, although caffeine can be argued to fulfill regulatory criteria as a dependence-producing drug, the extensive use of caffeine-containing beverages poses little apparent risk to the consumer or to society. The positive stimulatory effects of caffeine appear in large measure to be due to blockade of A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum. However, blockade of striatal A1 receptors may also play a role. The mechanisms underlying negative effects of higher doses of caffeine are as yet not well defined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Caffeine / adverse effects
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / pharmacology*
  • Corpus Striatum / chemistry
  • Corpus Striatum / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Interactions
  • Humans
  • Neural Pathways / drug effects
  • Phosphodiesterase Inhibitors / pharmacology
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Purinergic P1 / drug effects
  • Substance Withdrawal Syndrome / physiopathology
  • Substance-Related Disorders / physiopathology*
  • Up-Regulation


  • Central Nervous System Stimulants
  • Phosphodiesterase Inhibitors
  • Receptors, Neurotransmitter
  • Receptors, Purinergic P1
  • Caffeine