Evidence map›Paper›PMID 26786412›Full record

ReviewPsychopharmacology2016

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders.

Sergi Ferré

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 5 pooled it
18.1field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 5 syntheses or guidelines pooled it, 201 citations in OpenAlex.

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  10. Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020
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  15. Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine AProceedings of the National Academy of Sciences of the United States of America · 2018
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  17. Medicinal Value ofInternational journal of molecular sciences · 2026
    Review
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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Sergi FerréIntegrative Neurobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Triad Technology Building, 333 Cassell Drive, Baltimore, MD, 21224, USA. sferre@intra.nida.nih.gov.
National Institute on Drug Abuse · US

Funding

Neurotransmitter Receptor Heteromers in the Striatal Spine ModuleZIADA000493 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI FERRE, SERGI · 2009 to 2025
$35.6M
Neurotransmitter Receptor Heteromers in the Striatal Spine ModuleZ01DA000493 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI GOLDBERG, STEVEN R · 2006 to 2008
$691k
Intramural NIH HHS Z01 DA000493
6 · The paper itself

Abstract

backgroundThe psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants able to cause substance use disorders (SUD). Caffeine produces psychomotor-activating, reinforcing, and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems.

objectivesA model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. HIGHLIGHTS: The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally, the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives, synthetic cathinones, and energy drinks with alcohol, and the higher sensitivity of children and adolescents to the psychostimulant effects of caffeine and its potential to increase vulnerability to SUD.

conclusionsThe striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.

Indexed as

AnimalsCaffeineCentral Nervous System StimulantsHumansRatsSubstance-Related DisordersCaffeineCentral Nervous System StimulantsAdenosineAlcoholCaffeineDopamineDrug abusePsychostimulantsReceptor heteromer

Identifiers

PMID26786412
PMCPMC4846529
OpenAlexW2283824784

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.