ArticleThe Journal of general physiology2021
Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.
Article in The Journal of general physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Sex-specific association between low oral doses of cannabidiol (CBD) and plasma concentration of anandamide (AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) in healthy occasional cannabis users.Journal of cannabis research · 2026Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Drugs exhibit diverse binding modes and access routes in the Nav1.5 cardiac sodium channel pore.The Journal of general physiology · 2025Article
- Pharmacological therapy of non-dystrophic myotonias.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Treatment Strategies for Painful Pelvic Floor Conditions: A Focus on the Potential Benefits of Cannabidiol.Biomolecules · 2024Review
- Effects of Hemp-Derived Cannabidiol Supplementation on Blood Variables, Carcass Characteristics, and Meat Quality of Goats.Animals : an open access journal from MDPI · 2024Article
- Cannabidiol potentiates hyperpolarization-activated cyclic nucleotide-gated (HCN4) channels.The Journal of general physiology · 2024Article
- Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore region.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular Pharmacology of Selective NaACS chemical neuroscience · 2024Article
- Article
- Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol.Communications biology · 2024Article
- Functional effects of drugs and toxins interacting with NaFrontiers in pharmacology · 2024Review
- Endocannabinoid regulation of inward rectifier potassium (Kir) channels.Frontiers in pharmacology · 2024Article
- Informing the Cannabis Conjecture: From Life's Beginnings to Mitochondria, Membranes and the Electrome-A Review.International journal of molecular sciences · 2023Review
- Usage of Cell-Free Protein Synthesis in Post-Translational Modification of μ-Conopeptide PIIIA.Marine drugs · 2023Article
- Cannabidiol inhibits NaNature communications · 2023Article
- Molecular Dynamics Simulations of Ion Permeation in Human Voltage-Gated Sodium Channels.Journal of chemical theory and computation · 2023Article
- High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons.Cell reports methods · 2023Article
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD's localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability.
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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.