Evidence map›Paper›PMID 21654828›Full record

ArticleCell death & disease2011

Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis.

M P Lim, L A Devi, R Rozenfeld

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 2 pooled it
7.3field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.

  1. The Role of Cannabidiol in Liver Disease: A Systemic Review.International journal of molecular sciences · 2024
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  6. Review
  7. Article
  8. The Cannabinoid System as a Potential Novel Target for Alcohol-Associated Liver Disease: A Propensity-Matched Cohort Study.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  9. A Review of Natural Products Against Alcoholic Liver Fibrosis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Heliyon · 2023
    Article

6 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

3 authors at 1 institution in 1 country.

M P LimDepartment of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
L A Devi
R Rozenfeld
Icahn School of Medicine at Mount Sinai · US

Funding

Regulation Of Opioid Receptor Signaling by Endogenous PeptidesR01DA008863 · NIDA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Lakshmi A Devi, Elyssa Margolis · 1995 to 2026
$6.1M
Post-translational Regulation of Opioid and Cannabinoid Receptors.R37DA008863 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DEVI, LAKSHMI A · 2012 to 2021
$4.6M
Project 2P20AA017067 · NIAAA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FIEL, MARIA ISABEL · 2008 to 2012
$2.5M
Advanced Microscopy Shared Resource FacilityR24CA095823 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FRIEDRICH, VICTOR LOUIS · 2002 to 2006
$1.3M
POST-TRANSLATIONAL REGULATION OF OPIOID RECEPTORSK05DA019521 · NIDA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI DEVI, LAKSHMI A · 2005 to 2014
$1.2M
Post-translational regulation of opioid receptorsR56DA008863 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DEVI, LAKSHMI A · 2007 to 2007
$381k
NCI NIH HHS R24 CA095823NIAAA NIH HHS AA017067NIAAA NIH HHS P20 AA017067NIDA NIH HHS DA019521NIDA NIH HHS DA08863NIDA NIH HHS K05 DA019521NIDA NIH HHS R01 DA008863NIDA NIH HHS R37 DA008863NIDA NIH HHS R56 DA008863
6 · The paper itself

Abstract

The major cellular event in the development and progression of liver fibrosis is the activation of hepatic stellate cells (HSCs). Activated HSCs proliferate and produce excess collagen, leading to accumulation of scar matrix and fibrotic liver. As such, the induction of activated HSC death has been proposed as a means to achieve resolution of liver fibrosis. Here we demonstrate that cannabidiol (CBD), a major non-psychoactive component of the plant Cannabis sativa, induces apoptosis in activated HSCs through a cannabinoid receptor-independent mechanism. CBD elicits an endoplasmic reticulum (ER) stress response, characterized by changes in ER morphology and the initiation of RNA-dependent protein kinase-like ER kinase-, activating transcription factor-6-, and inositol-requiring ER-to-nucleus signal kinase-1 (IRE1)-mediated signaling cascades. Furthermore, CBD induces downstream activation of the pro-apoptotic IRE1/ASK1/c-Jun N-terminal kinase pathway, leading to HSC death. Importantly, we show that this mechanism of CBD-induced ER stress-mediated apoptosis is specific to activated HSCs, as it occurs in activated human and rat HSC lines, and in primary in vivo-activated mouse HSCs, but not in quiescent HSCs or primary hepatocytes from rat. Finally, we provide evidence that the elevated basal level of ER stress in activated HSCs has a role in their susceptibility to the pro-apoptotic effect of CBD. We propose that CBD, by selectively inducing death of activated HSCs, represents a potential therapeutic agent for the treatment of liver fibrosis.

Indexed as

ApoptosisCannabidiolCells, CulturedDose-Response Relationship, DrugEndoplasmic ReticulumHepatic Stellate CellsHumansOxidative StressStructure-Activity RelationshipCannabidiol

Identifiers

PMID21654828
PMCPMC3168994
OpenAlexW2040336212

What OpenQuestion 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 OpenQuestion graph.