Evidence map›Paper›PMID 40029368›Full record

ArticleArchives of toxicology2025

7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.

Yuxi Li, Xilin Li, Qiangen Wu, Montserrat Puig, Frederic Moulin, Supratim Choudhuri, Jeremy Gingrich, Lei Guo, Si Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

9 authors.

Yuxi LiDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR, 72079, USA.
Xilin LiDivision of Genetic and Molecular Toxicology, NCTR, U.S. FDA, Jefferson, AR, 72079, USA.
Qiangen WuDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR, 72079, USA.
Montserrat PuigDivision of Biotechnology Review and Research III, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. FDA, Silver Spring, MD, 20993, USA.
Frederic MoulinDivision of Hepatology and Nutrition, Office of New Drugs, Center for Drug Evaluation and Research, U.S. FDA, Silver Spring, MD, 20993, USA.
Supratim ChoudhuriDivision of Food Ingredients, Office of Pre-Market and Additive Safety, Office of Food Chemical Safety, Dietary Supplements, and Innovation, Human Foods Program, U.S. FDA, College Park, MD, 20740, USA.
Jeremy GingrichDivision of Food Ingredients, Office of Pre-Market and Additive Safety, Office of Food Chemical Safety, Dietary Supplements, and Innovation, Human Foods Program, U.S. FDA, College Park, MD, 20740, USA.
Lei GuoDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR, 72079, USA.
Si ChenDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR, 72079, USA. si.chen@fda.hhs.gov.ORCID http://orcid.org/0000-0002-8872-311X

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

Cannabidiol (CBD), a major component of extract from the plant Cannabis sativa L., has demonstrated efficacy in treating childhood-onset epilepsy; however, animal studies and clinical trials have reported elevated liver enzymes after CBD use, suggesting potential liver toxicity. In a previous study, we demonstrated that CBD caused cytotoxicity with apoptosis and endoplasmic reticulum (ER) stress in human hepatic cells. In the present study, we investigated the toxicity profile of the two main metabolites of CBD, 7-hydroxy-CBD and 7-carboxy-CBD, in primary human hepatocytes and HepG2 cells. Our findings indicated that both metabolites induced cellular damage similar to the parent drug in these cells. 7-Hydroxy-CBD and 7-carboxy-CBD also caused cell cycle disturbances, apoptosis, and ER stress in HepG2 cells. Additionally, we explored the role of cytochrome P450 (CYP) in the metabolism of 7-hydroxy-CBD and 7-carboxy-CBD using HepG2 cell lines expressing 14 individual CYPs. We determined that 7-hydroxy-CBD is metabolized by CYP2D6, and CYP2D6-mediated metabolism attenuated the cytotoxicity, apoptosis, and ER stress induced by 7-hydroxy-CBD. The CYPs did not metabolize 7-carboxy-CBD. In summary, our findings highlight the mechanisms underlying cytotoxicity induced by 7-hydroxy-CBD and 7-carboxy-CBD in hepatic cells.

Indexed as

ApoptosisCannabidiolEndoplasmic Reticulum StressHepatocytesCytochrome P-450 Enzyme SystemHep G2 CellsHumans7-hydroxycannabidiolCannabidiolCytochrome P-450 Enzyme System7-Carboxy-CBD7-Hydroxy-CBDApoptosisCYP-overexpressing cellsER stressHepG2Primary human hepatocytes

Identifiers

PMID40029368
PMCPMC12368822

What Socratic holds

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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.