The Impact of Caffeine on the Behavioral Effects of Ethanol Related to Abuse and Addiction: A Review of Animal Studies

Abstract

The impact of caffeine on the behavioral effects of ethanol, including ethanol consumption and abuse, has become a topic of great interest due to the rise in popularity of the so-called energy drinks. Energy drinks high in caffeine are frequently taken in combination with ethanol under the popular belief that caffeine can offset some of the intoxicating effects of ethanol. However, scientific research has not universally supported the idea that caffeine can reduce the effects of ethanol in humans or in rodents, and the mechanisms mediating the caffeine-ethanol interactions are not well understood. Caffeine and ethanol have a common biological substrate; both act on neurochemical processes related to the neuromodulator adenosine. Caffeine acts as a nonselective adenosine A₁ and A_2A receptor antagonist, while ethanol has been demonstrated to increase the basal adenosinergic tone via multiple mechanisms. Since adenosine transmission modulates multiple behavioral processes, the interaction of both drugs can regulate a wide range of effects related to alcohol consumption and the development of ethanol addiction. In the present review, we discuss the relatively small number of animal studies that have assessed the interactions between caffeine and ethanol, as well as the interactions between ethanol and subtype-selective adenosine receptor antagonists, to understand the basic findings and determine the possible mechanisms of action underlying the caffeine-ethanol interactions.

FIG. 1.

Schematic showing ethanol regulation of adenosine production (1), release (2), and uptake (3), as well as caffeine blockade of adenosine receptors (4) in the central nervous system. A₁R and A_2AR, adenosine A₁ and A_2A receptors; ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; ATP, adenosine triphosphate; AMP, adenosine monophosphate; CAT-H₂O₂, catalase; CYP-2E1, cytochrome P4502E1; ENT, equilibrative nucleoside transporters.