What topics does this cannabis study cover?

This study covers research on: THC, Endocannabinoid, Inflammation, Neuroprotection.

Where was this research published?

Published in Cell biochemistry and biophysics on September 18, 2026.

THC Endocannabinoid Inflammation Neuroprotection

Endocannabinoids trigger both oxidative stress and antioxidant defenses

Q: What did this research study find?

In cultured *human coronary artery endothelial cells*, *anandamide* and *2-arachidonoyl glycerol* increased **superoxide generation**, indicating greater oxidative stress.

A Potentially Protective Role for NRF2 in Endocannabinoid-Mediated Oxidative Stress in Human Coronary Artery Endothelial Cells.

Cell biochemistry and biophysics • September 18, 2026 • Highly Relevant

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AI Summary

This cell study examined whether the endocannabinoids anandamide and 2-arachidonoyl glycerol—as well as the cannabinoid THC in the study context—could trigger antioxidant defenses in human coronary artery endothelial cells. The researchers exposed the cells to the endocannabinoids or to tunicamycin, an inducer of endoplasmic reticulum (ER) stress, and assessed superoxide generation, lipid peroxidation, and activation of the antioxidant regulator NRF2. The abstract does not report a sample size or exposure duration.

The exposures increased oxidative and ER stress, but they also activated an apparent compensatory response. Anandamide increased expression of the NRF2-responsive genes HO1, TRX1, and NQO1. Blocking or silencing PERK, an ER-stress signaling pathway, prevented NRF2 induction, whereas blocking the ATF6 or IRE1α pathways did not. These findings support cellular cross-talk between ER stress and oxidative stress, but they do not show that cannabis or endocannabinoids protect people from cardiovascular disease. As an in vitro study in cultured cells, this abstract cannot establish effects in animals or humans, clinical benefit, or the long-term consequences of these stress responses. This is an abstract-based summary; the full text was not reviewed.

💡 Key Findings

In cultured human coronary artery endothelial cells, anandamide and 2-arachidonoyl glycerol increased superoxide generation, indicating greater oxidative stress.

Good

70%

The same exposures also increased NRF2 activity and, with anandamide, expression of antioxidant-response genes including HO1, TRX1, and NQO1, suggesting a compensatory antioxidant response.

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70%

Silencing or inhibiting PERK prevented NRF2 induction, while targeting ATF6 or IRE1α did not, identifying PERK-dependent signaling as the pathway linked to this response in the cell model.

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75%

Higher levels of anandamide, 2-arachidonoyl glycerol, and the ER-stress inducer tunicamycin increased lipid peroxidation, so the antioxidant response did not eliminate all measured oxidative-stress signals.

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70%

📄 Original Abstract

Excess oxidative and endoplasmic reticulum (ER) stress disrupt cellular homeostasis and promote cardiovascular disease (CVD). The endocannabinoids anandamide and 2-arachidonoyl glycerol and the potent cannabinoid Δ9-tetrahydrocannabinol increase oxidative stress and ER stress in endothelial cells. However, it remains unclear whether endocannabinoids have intrinsic capacity to ameliorate oxidative stress. In human coronary artery endothelial cells (HCAEC), anandamide, 2-arachidonoyl glycerol, and tunicamycin increased superoxide generation and nuclear factor erythroid 2-related factor 2 (NRF2) mRNA and NRF2-dependent reporter gene activity. High anandamide, 2-arachidonoyl glycerol, and tunicamycin levels also increased lipid peroxidation. Furthermore, anandamide increased NRF2-responsive hemeoxygenase 1 (HO1), thioredoxin reductase 1 (TRX1), and NAD(P)H dehydrogenase quinone 1 (NQO1) mRNA. This effect was mediated by protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK); PERK silencing utilizing siRNA suppressed NRF2 induction by anandamide and tunicamycin. In contrast, activating transcription factor 6 (ATF6) and inositol requiring enzyme 1α (IRE1α ) silencing had no effect on NRF2 mRNA or NRF2 target gene expression in tunicamycin and anandamide-treated cells. Likewise, the PERK inhibitor GSK2606414 prevented NRF2 induction by anandamide and tunicamycin while treatment with Ceapin A7 (an ATF6 inhibitor) or GSK2850163 (an IRE1α inhibitor) did not. In conclusion, endocannabinoid-related ER stress increased superoxide generation accompanied by compensatory increase in production of antioxidant enzymes thereby highlighting the cross talk between ER stress and oxidative stress.

Paper Type

📄 Research

Publication

Journal: Cell biochemistry and biophysics
Published: September 18, 2026
PMID: 42758439
DOI: 10.1007/s12013-026-02169-y

Authors (9)

Michael J Haas Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, Jacksonville, FL, 32209, USA. Michael.haas@jax.ufl.edu.
Kareen Champagne Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, Jacksonville, FL, 32209, USA.
Nidhi Gupta Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, Jacksonville, FL, 32209, USA.
Andrew Velarde Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, Jacksonville, FL, 32209, USA.
Maurice Chakour Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, Jacksonville, FL, 32209, USA.
+4 more authors