GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol
Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security...
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MDPI AG
2022-12-01
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| author | Gabriele Ruffolo Alessandro Gaeta Beatrice Cannata Camilla Pinzaglia Eleonora Aronica Alessandra Morano Pierangelo Cifelli Eleonora Palma |
| author_facet | Gabriele Ruffolo Alessandro Gaeta Beatrice Cannata Camilla Pinzaglia Eleonora Aronica Alessandra Morano Pierangelo Cifelli Eleonora Palma |
| author_sort | Gabriele Ruffolo |
| collection | DOAJ |
| description | Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has been approved for treatment as an add-on therapy in patients afflicted by severe pharmaco-resistant epilepsy, including Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS) and tuberous sclerosis complex (TSC). CBD is pharmacologically considered a “dirty drug”, since it has the capacity to bind different targets and to activate several cellular pathways. GABAergic impairment is one of the key processes during the epileptogenesis period able to induce a generalized hyperexcitability of the central nervous system (CNS), leading to epileptic seizures. Here, by using the microtransplantation of human brain membranes approach in <i>Xenopus</i> oocytes and electrophysiological recordings, we confirm the ability of CBD to modulate GABAergic neurotransmission in human cerebral tissues obtained from patients afflicted by different forms of pharmaco-resistant epilepsies, such as DS, TSC, focal cortical dysplasia (FCD) type IIb and temporal lobe epilepsy (TLE). Furthermore, using cDNAs encoding for human GABA<sub>A</sub> receptor subunits, we found that α1β2 receptors are still affected by CBD, while classical benzodiazepine lost its efficacy as expected. |
| first_indexed | 2024-03-09T16:11:26Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T16:11:26Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-de3c10aeb59841e6b3e2fe084ac303692023-11-24T16:12:34ZengMDPI AGLife2075-17292022-12-011212204210.3390/life12122042GABAergic Neurotransmission in Human Tissues Is Modulated by CannabidiolGabriele Ruffolo0Alessandro Gaeta1Beatrice Cannata2Camilla Pinzaglia3Eleonora Aronica4Alessandra Morano5Pierangelo Cifelli6Eleonora Palma7Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, ItalyDepartment of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Human Neuroscience, University of Rome Sapienza, 00185 Rome, ItalyDepartment of Applied Clinical and Biotechnological Sciences, University of L’Aquila, 67100 L’Aquila, ItalyDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, 00185 Rome, ItalyRecently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has been approved for treatment as an add-on therapy in patients afflicted by severe pharmaco-resistant epilepsy, including Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS) and tuberous sclerosis complex (TSC). CBD is pharmacologically considered a “dirty drug”, since it has the capacity to bind different targets and to activate several cellular pathways. GABAergic impairment is one of the key processes during the epileptogenesis period able to induce a generalized hyperexcitability of the central nervous system (CNS), leading to epileptic seizures. Here, by using the microtransplantation of human brain membranes approach in <i>Xenopus</i> oocytes and electrophysiological recordings, we confirm the ability of CBD to modulate GABAergic neurotransmission in human cerebral tissues obtained from patients afflicted by different forms of pharmaco-resistant epilepsies, such as DS, TSC, focal cortical dysplasia (FCD) type IIb and temporal lobe epilepsy (TLE). Furthermore, using cDNAs encoding for human GABA<sub>A</sub> receptor subunits, we found that α1β2 receptors are still affected by CBD, while classical benzodiazepine lost its efficacy as expected.https://www.mdpi.com/2075-1729/12/12/2042GABA<sub>A</sub> receptorneurophysiologyepilepsy |
| spellingShingle | Gabriele Ruffolo Alessandro Gaeta Beatrice Cannata Camilla Pinzaglia Eleonora Aronica Alessandra Morano Pierangelo Cifelli Eleonora Palma GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol Life GABA<sub>A</sub> receptor neurophysiology epilepsy |
| title | GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol |
| title_full | GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol |
| title_fullStr | GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol |
| title_full_unstemmed | GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol |
| title_short | GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol |
| title_sort | gabaergic neurotransmission in human tissues is modulated by cannabidiol |
| topic | GABA<sub>A</sub> receptor neurophysiology epilepsy |
| url | https://www.mdpi.com/2075-1729/12/12/2042 |
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