Association between A2a receptor gene polymorphisms and caffeine-induced anxiety

Neuropsychopharmacology. 2003 Sep;28(9):1694-702. doi: 10.1038/sj.npp.1300232. Epub 2003 Jun 25.


The adenosine receptor system, which mediates the psychoactive effects of caffeine, is also thought to be involved in the regulation of anxiety. In this study, we examined the association between variations in anxiogenic responses to caffeine and polymorphisms in the A1 and A2a adenosine receptor genes. Healthy, infrequent caffeine users (N=94) recorded their subjective mood states following a 150 mg oral dose of caffeine freebase or placebo in a double-blind study. We found a significant association between self-reported anxiety after caffeine administration and two linked polymorphisms on the A2a receptor gene, the 1976C>T and 2592C>Tins polymorphisms. Individuals with the 1976T/T and the 2592Tins/Tins genotypes reported greater increases in anxiety after caffeine administration than the other genotypic groups. The study shows that an adenosine receptor gene polymorphism that has been associated with Panic Disorder is also associated with anxiogenic responses to an acute dose of caffeine.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Anxiety / chemically induced
  • Anxiety / genetics*
  • Caffeine / adverse effects*
  • Central Nervous System Stimulants / adverse effects*
  • Cysteine / genetics
  • Double-Blind Method
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Hybrid Vigor / drug effects
  • Male
  • Neuropsychological Tests
  • Pain Measurement / methods
  • Personality Inventory
  • Polymorphism, Genetic*
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / drug effects
  • Receptors, Purinergic P1 / genetics*
  • Sequence Analysis, DNA
  • Tandem Repeat Sequences / drug effects
  • Threonine / genetics
  • Time Factors


  • Central Nervous System Stimulants
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • Threonine
  • Caffeine
  • Cysteine