Evidence map›Paper›PMID 40381619›Full record

ArticleCell reports. Medicine2025

Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: Implications for nociception.

Michaela Dvorakova, Taryn Bosquez-Berger, Jenna Billingsley, Natalia Murataeva, Taylor Woodward, Emma Leishman, Anaëlle Zimmowitch, Anne Gibson, Jim Wager-Miller, Ruyi Cai and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Acetaminophen's Role in Autism and ADHD: A Mitochondrial Perspective.International journal of molecular sciences · 2025
    Review
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

17 authors.

Michaela DvorakovaDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA; Gill Institute for Neuroscience, Indiana University, Bloomington, IN 47405, USA.
Taryn Bosquez-BergerDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Jenna BillingsleyDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Natalia MurataevaDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Taylor WoodwardDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Emma LeishmanDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Anaëlle ZimmowitchDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Anne GibsonDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Jim Wager-MillerDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Ruyi CaiState Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
Shangxuan CaiState Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
Tim WareDepartment of Chemistry, University of Virginia, Charlottesville, VA 22904, USA.
Ku-Lung HsuDepartment of Chemistry, University of Texas at Austin, Austin, TX 78712, USA.
Yulong LiState Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Beijing 100871, China.
Heather BradshawDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Ken MackieDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA; Gill Institute for Neuroscience, Indiana University, Bloomington, IN 47405, USA.
Alex StraikerDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA; Gill Institute for Neuroscience, Indiana University, Bloomington, IN 47405, USA. Electronic address: straiker@iu.edu.

Funding

Modulation of pain mechanisms by cannabis-derived phytochemicals.R01AT011162 · NCCIH · QUEEN'S MEDICAL CENTER · 2022 to 2025
$2.5M
Multi-Scale Imaging Core (MSIC)P30DA056410 · TRUSTEES OF INDIANA UNIVERSITY · 2025 to 2025
$1.4M
NCCIH NIH HHS R01 AT011162NIDA NIH HHS P30 DA056410
6 · The paper itself

Abstract

Acetaminophen (paracetamol) is a common analgesic, but its mechanism of action remains unknown. Despite causing around 500 deaths annually in the US, safer alternatives have not been developed. Because endocannabinoids may have a role in acetaminophen action, we examine interactions between the two. We report that acetaminophen inhibits the activity of diacylglycerol lipase α (DAGLα), but not DAGLβ, decreasing the production of the endocannabinoid 2-arachidonoyl glycerol. This gives rise to the counterintuitive hypothesis that decreasing endocannabinoid production by DAGLα inhibition may be antinociceptive in certain settings. Supporting this hypothesis, we find that diacylglycerol lipase (DAGL) inhibition by RHC80267 is antinociceptive in wild-type but not CB1 knockout mice in the hot-plate test. We propose (1) that activation of DAGLα may exacerbate some forms of nociception and (2) a mechanism for the antinociceptive actions of acetaminophen, whereby acetaminophen inhibits a DAGLα/CB1-based circuit that plays a permissive role in at least one form of nociception.

Indexed as

AcetaminophenArachidonic AcidsGlyceridesLipoprotein LipaseNociceptionAnalgesics, Non-NarcoticAnimalsEndocannabinoidsHumansMaleMiceMice, Inbred C57BLMice, KnockoutReceptor, Cannabinoid, CB1AcetaminophenAnalgesics, Non-NarcoticArachidonic AcidsEndocannabinoidsGlyceridesglyceryl 2-arachidonateLipoprotein LipaseReceptor, Cannabinoid, CB12-arachidonoyl glycerolacetaminophenantinociceptioncannabinoid receptordiacylglycerol lipaseparacetamol

Identifiers

PMID40381619
PMCPMC12208326

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.