Association between A2a receptor gene polymorphisms and caffeine-induced anxiety

Alsene, Karen; Deckert, Jürgen; Sand, Philipp; de Wit, Harriet

doi:10.1038/sj.npp.1300232

Cited by 335Coffee research and impactsNeurotransmitter Receptor Influence on BehaviorAdenosine and Purinergic Signaling

Association between A2a receptor gene polymorphisms and caffeine-induced anxiety

Alsene, Karen, Deckert, Jürgen, Sand, Philipp, de Wit, Harriet·2003·Neuropsychopharmacology

DOI 10.1038/sj.npp.1300232

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Abstract

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.

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Common variants of the gene encoding for the A2a receptor can disrupt sleep or cause anxiety in some individuals after ingesting caffeine.
“For example, common variants of the gene encoding for the A2a receptor can disrupt sleep (51) or cause anxiety in some individuals (52) after ingesting caffeine.”
From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [52]

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Authors: Alsene, K., Deckert, J., Sand, P., & de Wit, H.
Affiliations: University of Chicago (US)
University of Münster (DE)
University of Würzburg (DE)
ORCID: Deckert, Jürgen
Sand, Philipp
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2003-05-14
Volume: 28
Issue: 9
Pages: 1694-1702
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300232
OpenAlex: W2043153453
Cited by: 334
References: 50
Citations by year: 2026: 12 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 18 · 2018: 18 · 2017: 16 · 2016: 19 · 2015: 9 · 2014: 21 · 2013: 11 · 2012: 21
FWCI: 6.86
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (DA 02812, R01DA002812)
Topics: Health Sciences › Medicine › Pharmacology › Coffee research and impacts
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords: caffeine, anxiety, adenosine A2A receptor, adenosine A1 receptor, genetic polymorphism, subjective mood, panic disorder, genetic susceptibility
MeSH terms: Adult, Central Nervous System Stimulants, Animals, Anxiety, Caffeine, Cysteine, Double-Blind Method, Female, Genotype, Humans, Hybrid Vigor, Male, Neuropsychological Tests, Pain Measurement, Personality Inventory, Polymorphism, Genetic, Threonine, Time Factors, Genetic Variation, Sequence Analysis, DNA, Receptors, Purinergic P1, Tandem Repeat Sequences, Receptor, Adenosine A2A

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Association between A2a receptor gene polymorphisms and caffeine-induced anxiety

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