ArticleBritish journal of pharmacology2020
A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacological inhibition of ENT1 enhances the impact of specific dietary fats on energy metabolism gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants.Plant communications · 2024Article
- Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth.Cell death discovery · 2023Article
- Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment.Journal of neurodevelopmental disorders · 2023Review
- Cannabidiol impairs neural tube closure in mouse whole embryo culture.Birth defects research · 2022Article
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- Effect of Cannabidiol on the Long-Term Toxicity and Lifespan in the Preclinical ModelCannabis and cannabinoid research · 2021Article
- Decanoic Acid Stimulates Autophagy inCells · 2021Article
- In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells.Molecules (Basel, Switzerland) · 2021Review
- Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity.British journal of pharmacology · 2021Article
- UsingFrontiers in cell and developmental biology · 2021Review
- TheFrontiers in cell and developmental biology · 2021Review
- Dictyostelium discoideum as a non-mammalian biomedical model.Microbial biotechnology · 2021Review
- Development of cannabidiol as a treatment for severe childhood epilepsies.British journal of pharmacology · 2020Review
- Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- ABiochemistry and biophysics reports · 2020Article
- A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
Abstract
background and purposeEpidiolex™, a form of highly purified cannabidiol (CBD) derived from Cannabis plants, has demonstrated seizure control activity in patients with Dravet syndrome, without a fully elucidated mechanism of action. We have employed an unbiased approach to investigate this mechanism at a cellular level. EXPERIMENTAL APPROACH: We use a tractable biomedical model organism, Dictyostelium, to identify a protein controlling the effect of CBD and characterize this mechanism. We then translate these results to a Dravet syndrome mouse model and an acute in vitro seizure model. KEY
resultsCBD activity is partially dependent upon the mitochondrial glycine cleavage system component, GcvH1 in Dictyostelium, orthologous to the human glycine cleavage system component H protein, which is functionally linked to folate one-carbon metabolism (FOCM). Analysis of FOCM components identified a mechanism for CBD in directly inhibiting methionine synthesis. Analysis of brain tissue from a Dravet syndrome mouse model also showed drastically altered levels of one-carbon components including methionine, and an in vitro rat seizure model showed an elevated level of methionine that is attenuated following CBD treatment. CONCLUSIONS AND IMPLICATIONS: Our results suggest a novel mechanism for CBD in the regulating methionine levels and identify altered one-carbon metabolism in Dravet syndrome and seizure activity.
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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 Socratic graph.