ArticleFrontiers in behavioral neuroscience2020
Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions.
Article in Frontiers in behavioral neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Subchronic Cannabidiol (CBD) Treatment During the Silent Period Fails to Prevent Increased Seizure Susceptibility Following Lithium-Pilocarpine-Induced Status Epilepticus.Brain sciences · 2026Article
- Editorial: Cannabidiol: perspectives on drug-resistant epilepsy management.Frontiers in pharmacology · 2026Article
- Entry of cannabidiol into the fetal, postnatal and adult rat brain.Cell and tissue research · 2024Article
- CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions.Pharmaceutics · 2024Review
- Human Data on Pharmacokinetic Interactions of Cannabinoids: A Narrative Review.Current pharmaceutical design · 2024Review
- Article
- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?Epilepsia open · 2022Review
- In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells.Molecules (Basel, Switzerland) · 2021Review
- Cannabidiol (CBD) Alters the Functionality of Neutrophils (PMN). Implications in the Refractory Epilepsy Treatment.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Glial Cells and Their Contribution to the Mechanisms of Action of Cannabidiol in Neuropsychiatric Disorders.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the constant development of new antiepileptic drugs (AEDs), more than 30% of patients develop refractory epilepsy (RE) characterized by a multidrug-resistant (MDR) phenotype. The "transporters hypothesis" indicates that the mechanism of this MDR phenotype is the overexpression of ABC transporters such as P-glycoprotein (P-gp) in the neurovascular unit cells, limiting access of the AEDs to the brain. Recent clinical trials and basic studies have shown encouraging results for the use of cannabinoids in RE, although its mechanisms of action are still not fully understood. Here, we have employed astrocytes and vascular endothelial cell cultures subjected to hypoxia, to test the effect of cannabidiol (CBD) on the P-gp-dependent Rhodamine-123 (Rho-123) efflux. Results show that during hypoxia, intracellular Rho-123 accumulation after CBD treatment is similar to that induced by the P-gp inhibitor Tariquidar (Tq). Noteworthy, this inhibition is like that registered in non-hypoxia conditions. Additionally, docking studies predicted that CBD could behave as a P-gp substrate by the interaction with several residues in the α-helix of the P-gp transmembrane domain. Overall, these findings suggest a direct effect of CBD on the Rho-123 P-gp-dependent efflux activity, which might explain why the CBD add-on treatment regimen in RE patients results in a significant reduction in seizure frequency.
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