Evidence map›Paper›PMID 40506434›Full record

ArticleTranslational psychiatry2025

Concentration-dependent effect of delta-9-tetrahydrocannabinol on epigenetic DNA modifiers in human peripheral blood mononuclear cells.

Kerda Pulk, Kelli Somelar-Duracz, Mikk Rooden, Kaili Anier, Anti Kalda

Abstract read
In one paragraph

Article in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

5 authors.

Kerda PulkDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0009-0001-9134-2916
Kelli Somelar-DuraczDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Mikk RoodenDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Kaili AnierDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0001-5039-4771
Anti KaldaDepartment of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. anti.kalda@ut.ee.ORCID http://orcid.org/0000-0003-0605-1303

Funding

Eesti Teadusagentuur (Estonian Research Council) PRG1473
6 · The paper itself

Abstract

Cannabis is among the most used illicit substances in the world, and approximately 10% of regular cannabis users are estimated to be susceptible to developing cannabis use disorder (CUD). We examined the effect of different concentrations of delta-9-tetrahydrocannabinol (THC) on the epigenetic DNA modifiers DNA methyltransferases (DNMTs) and ten-eleven translocation enzymes (TETs); cannabinoid CB1 and CB2 receptors; and the cytokines IL-1β, IL-6, IL-10, and TNF-α. We used two in vitro study designs on human peripheral blood mononuclear cells (PBMCs) collected from healthy donors: (a) repeated THC incubations and (b) repeated THC incubations followed by an "abstinence" period and a THC challenge incubation. We observed no significant effects on DNMTs and TETs mRNA levels, enzymatic activity, or CB1 and CB2 mRNA levels at an average THC concentration (50 ng/ml, n = 8 donors). However, repeated incubations at a high THC concentration (200 ng/ml, n = 16 donors) significantly downregulated DNMTs and upregulated TETs, CB1, and CB2 mRNA levels. Both THC concentrations upregulated the gene expression of IL-1β, IL-6, and IL-10, but had no effect on TNF-α gene expression. At the genome-wide level, repeated THC incubations resulted in a significant number of differentially hydroxymethylated genes being hyperhydroxymethylated. An additional THC challenge shifted the hyperhydroxymethylated state to hypohydroxymethylation. The genes with the strongest associations with THC exposure were found to be functionally significant for various signaling pathways. These findings suggest that repeated incubations with high concentrations of THC may affect the expression of genes critical for the development of CUD through aberrant demethylation.

Indexed as

DronabinolEpigenesis, GeneticLeukocytes, MononuclearAdultCytokinesDNA MethylationDNA Modification MethylasesDose-Response Relationship, DrugFemaleHumansMaleReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2RNA, MessengerYoung AdultCytokinesDNA Modification MethylasesDronabinolReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2RNA, Messenger

Identifiers

PMID40506434
PMCPMC12162825

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.