ArticleFree radical biology & medicine2022
Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors.
Article in Free radical biology & medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Investigation into the oral toxicity profile of TruCBN™.Toxicology reports · 2026Article
- Cannabinol β‑O-Glucoside Inhibitors of the Keap1-Nrf2 Interaction: A Novel Therapeutic Strategy for Parkinson's Disease.ACS medicinal chemistry letters · 2026Article
- Ferroptosis-related stress during aging and its relevance to disease.GeroScience · 2026Review
- Article
- Inhibition of EPAC1 Prevents Neuronal Death Mediated by Diesel Exhaust Particles in Ferroptotic Cell Death Conditions.Antioxidants (Basel, Switzerland) · 2026Article
- Neuroprotective Effect of Cannabidiol Against Rotenone in Hippocampal Neuron Culture.Chemistry, an Asian journal · 2025Article
- Anandamide-Induced Neuroprotection of Cortical Neurons Relies on Metabolic/Redox Regulation and Mitochondrial Dynamics.Molecular neurobiology · 2025Article
- Mitochondrial membrane chromatography: Discovery of mitochondrial targeting modulators.Journal of pharmaceutical analysis · 2025Review
- Interactions Between Iron Metabolism and the Endocannabinoid System in Bacterial Infections.Antibiotics (Basel, Switzerland) · 2025Review
- Affinity-Based Protein Profiling Reveals IDH2 as a Mitochondrial Target of Cannabinol in Receptor-Independent Neuroprotection.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Transcriptomic signatures of oxytosis/ferroptosis are enriched in Alzheimer's disease.BMC biology · 2025Article
- Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms.International journal of molecular sciences · 2025Review
- Neuroprotective and anti-inflammatory activity ofFrontiers in pharmacology · 2025Article
- Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms.Aging and disease · 2024Review
- The Use of Compounds Derived fromInternational journal of molecular sciences · 2024Review
- The Neuroprotective Flavonoids Sterubin and Fisetin Maintain Mitochondrial Health under Oxytotic/Ferroptotic Stress and Improve Bioenergetic Efficiency in HT22 Neuronal Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis-A Systematic Review.Antioxidants (Basel, Switzerland) · 2024Review
- Anti-neuroinflammatory effect of hydroxytyrosol: a potential strategy for anti-depressant development.Frontiers in pharmacology · 2024Article
- The mechanism of ferroptosis and its related diseases.Molecular biomedicine · 2023Review
- Transcriptome Highlights Cannabinol Modulation of Mitophagy in a Parkinson's Disease In Vitro Model.Biomolecules · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis. These protective effects of CBN are at least partly mediated by the promotion of endogenous antioxidant defenses and the activation of AMP-activated protein kinase (AMPK) signaling. Together, our data highlight the potential of mitochondrially-targeted compounds such as CBN as novel oxytotic/ferroptotic inhibitors to rescue mitochondrial dysfunction as well as opportunities for the discovery and development of future neurotherapeutics.
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Registered trials
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.