Evidence map›Paper›PMID 25871974›Full record

ArticleTranslational psychiatry2015

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

N D Volkow, G-J Wang, J Logan, D Alexoff, J S Fowler, P K Thanos, C Wong, V Casado, S Ferre, D Tomasi

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06763172 (Measure Striatal Adenosine-dopamine Receptors Interactions), which is not on this map. Cited by 65 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 5 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06763172 phase4recruitingnot on this mapstarted 2023, after this paper: background citation

Measure Striatal Adenosine-dopamine Receptors Interactions: from Molecule to Behaviors

TypeinterventionalSponsorHsiao-Ying WeyRan2023 to 2026Enrolled12ConditionsHealthy, Caffeine, Adenosine, Dopamine D2/3 Receptor AvailabilityArmsCaffeine (200 mg), Placebo
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 5 syntheses or guidelines pooled it, 153 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

N D VolkowIntramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
G-J WangIntramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
J LoganBrookhaven National Laboratory, Upton, NY, USA.
D AlexoffBrookhaven National Laboratory, Upton, NY, USA.
J S FowlerBrookhaven National Laboratory, Upton, NY, USA.
P K ThanosBrookhaven National Laboratory, Upton, NY, USA.
C WongIntramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
V CasadoDepartment of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
S FerreIntramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
D TomasiIntramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
Brookhaven National Laboratory · USNational Institutes of Health · USNational Institute on Alcohol Abuse and Alcoholism · USNational Institute on Drug Abuse · USUniversitat de Barcelona · ES

Funding

Neurobiology of Substance Abuse and AddictionZIAAA000550 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI VOLKOW, NORA D. · 2009 to 2025
$115.1M
Neurotransmitter Receptor Heteromers in the Striatal Spine ModuleZIADA000493 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI FERRE, SERGI · 2009 to 2025
$35.6M
Intramural NIH HHS
6 · The paper itself

Abstract

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

Indexed as

AdultAffectArousalBlood PressureBrainCaffeineCaudate NucleusCentral Nervous System StimulantsDopamineDopamine AntagonistsHeart RateHumansMaleMiddle AgedNeostriatumPositron-Emission TomographyCaffeineCentral Nervous System StimulantsDopamineDopamine AntagonistsDRD2 protein, humanDRD3 protein, humanRacloprideReceptor, Adenosine A2AReceptors, Dopamine D2Receptors, Dopamine D3

Identifiers

PMID25871974
PMCPMC4462609
OpenAlexW1972232046

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.