Evidence map›Paper›PMID 39004336›Full record

ArticleToxicology2024

Investigation of cannabidiol-induced cytotoxicity in human hepatic cells.

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

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
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  9. 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

9 authors.

Si ChenDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR 72079, USA. Electronic address: si.chen@fda.hhs.gov.
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), Jefferson, AR 72079, USA.
Yuxi LiDivision of Biochemical Toxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), 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 Food Additive Safety, Center for Food Safety and Applied Nutrition, U.S. FDA, College Park, MD 20740, USA.
Jeremy GingrichDivision of Food Ingredients, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, 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), Jefferson, AR 72079, USA. Electronic address: lei.guo@fda.hhs.gov.

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

Cannabidiol (CBD) is one of the primary cannabinoids present in extracts of the plant Cannabis sativa L. A CBD-based drug, Epidiolex, has been approved by the U.S. FDA for the treatment of seizures in childhood-onset epileptic disorders. Although CBD-associated liver toxicity has been reported in clinical studies, the underlying mechanisms remain unclear. In this study, we demonstrated that CBD causes cytotoxicity in primary human hepatocytes and hepatic HepG2 cells. A 24-h CBD treatment induced cell cycle disturbances, cellular apoptosis, and endoplasmic reticulum (ER) stress in HepG2 cells. A potent ER stress inhibitor, 4-phenylbutyrate, markedly attenuated CBD-induced apoptosis and cell death. Additionally, we investigated the role of cytochrome P450 (CYP)-mediated metabolism in CBD-induced cytotoxicity using HepG2 cell lines engineered to express 14 individual CYPs. We identified CYP2C9, 2C19, 2D6, 2C18, and 3A5 as participants in CBD metabolism. Notably, cells overexpressing CYP2C9, 2C19, and 2C18 produced 7-hydroxy-CBD, while cells overexpressing CYP2C9, 2C19, 2D6, and 2C18 generated 7-carboxy-CBD. Furthermore, CBD-induced cytotoxicity was significantly attenuated in the cells expressing CYP2D6. Taken together, these data suggest that cell cycle disturbances, apoptosis, and ER stress are associated with CBD-induced cytotoxicity, and CYP2D6-mediated metabolism plays a critical role in decreasing the cytotoxicity of CBD.

Indexed as

ApoptosisCannabidiolEndoplasmic Reticulum StressHepatocytesCell CycleCell SurvivalCytochrome P-450 Enzyme SystemHep G2 CellsHumansCannabidiolCytochrome P-450 Enzyme SystemApoptosisCBDCYPsER stressLiver toxicityTopoisomerases

Identifiers

PMID39004336
PMCPMC11648445

What Socratic 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 Socratic graph.