ArticleBritish journal of pharmacology2021
Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity.
Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Cannabis and Cannabidiol, GLP-1 Receptors, and Autophagy: The Burgeoning Link Between Cognitive Neurodegeneration With Alzheimer's Disease and Metabolic Disorders.Discovery medicine · 2026Article
- Cannabis and Cannabidiol: Pioneering Treatment for the Nervous System with Alzheimer's Disease and Peripheral Organ Involvement with Nonalcoholic Fatty Liver Disease (NAFLD).Current neurovascular research · 2025Article
- Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma.International journal of molecular sciences · 2024Article
- Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants.Plant communications · 2024Article
- Mutation Screening of Dictyostelium Restriction Enzyme-Mediated Integration (REMI) Libraries.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
- Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth.Cell death discovery · 2023Article
- Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.Biomolecules · 2023Review
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
- The Inositol Phosphate System-A Coordinator of Metabolic Adaptability.International journal of molecular sciences · 2022Review
- Review
- The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis.Advances in biological regulation · 2022Article
- Editorial:Frontiers in cell and developmental biology · 2022Article
- Decanoic Acid Stimulates Autophagy inCells · 2021Article
- Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm.Frontiers in bioscience (Landmark edition) · 2021Review
- Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways.Biomolecules · 2021Review
- Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity.British journal of pharmacology · 2021Article
- Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism.Frontiers in cell and developmental biology · 2021Article
- UsingFrontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
background and purposeCannabidiol (CBD) has been shown to differentially regulate the mechanistic target of rapamycin complex 1 (mTORC1) in preclinical models of disease, where it reduces activity in models of epilepsies and cancer and increases it in models of multiple sclerosis (MS) and psychosis. Here, we investigate the effects of phytocannabinoids on mTORC1 and define a molecular mechanism. EXPERIMENTAL APPROACH: A novel mechanism for phytocannabinoids was identified using the tractable model system, Dictyostelium discoideum. Using mouse embryonic fibroblasts, we further validate this new mechanism of action. We demonstrate clinical relevance using cells derived from healthy individuals and from people with MS (pwMS). KEY
resultsBoth CBD and the more abundant cannabigerol (CBG) enhance mTORC1 activity in D. discoideum. We identify a mechanism for this effect involving inositol polyphosphate multikinase (IPMK), where elevated IPMK expression reverses the response to phytocannabinoids, decreasing mTORC1 activity upon treatment, providing new insight on phytocannabinoids' actions. We further validated this mechanism using mouse embryonic fibroblasts. Clinical relevance of this effect was shown in primary human peripheral blood mononuclear cells, where CBD and CBG treatment increased mTORC1 activity in cells derived from healthy individuals and decreased mTORC1 activity in cells derived from pwMS. CONCLUSION AND IMPLICATIONS: Our findings suggest that both CBD and the abundant CBG differentially regulate mTORC1 signalling through a mechanism dependent on the activity of the upstream IPMK signalling pathway, with potential relevance to the treatment of mTOR-related disorders, including MS.
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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.