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Life (Basel)
2022 Dec 06;1212:. doi: 10.3390/life12122042.
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GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol.
Ruffolo G
,
Gaeta A
,
Cannata B
,
Pinzaglia C
,
Aronica E
,
Morano A
,
Cifelli P
,
Palma E
.
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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 Xenopus 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 GABAA receptor subunits, we found that α1β2 receptors are still affected by CBD, while classical benzodiazepine lost its efficacy as expected.
Ahrens,
The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.
2009, Pubmed
Ahrens,
The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.
2009,
Pubmed
Amin,
Pharmacology of Medical Cannabis.
2019,
Pubmed
Bakas,
The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors.
2017,
Pubmed
,
Xenbase
Bisogno,
Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide.
2001,
Pubmed
Blauwblomme,
Gamma-aminobutyric acidergic transmission underlies interictal epileptogenicity in pediatric focal cortical dysplasia.
2019,
Pubmed
Blumcke,
Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.
2017,
Pubmed
Boluda,
Neuropathology of the temporal lobe.
2022,
Pubmed
Burman,
Why won't it stop? The dynamics of benzodiazepine resistance in status epilepticus.
2022,
Pubmed
Cepeda,
Pacemaker GABA synaptic activity may contribute to network synchronization in pediatric cortical dysplasia.
2014,
Pubmed
Cheng,
Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice.
2014,
Pubmed
Cifelli,
Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?
2020,
Pubmed
Cope,
Enhanced tonic GABAA inhibition in typical absence epilepsy.
2009,
Pubmed
Curatolo,
Advances in the genetics and neuropathology of tuberous sclerosis complex: edging closer to targeted therapy.
2022,
Pubmed
Czornyj,
Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?
2022,
Pubmed
Devinsky,
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.
2017,
Pubmed
Eusebi,
Microtransplantation of ligand-gated receptor-channels from fresh or frozen nervous tissue into Xenopus oocytes: a potent tool for expanding functional information.
2009,
Pubmed
,
Xenbase
Franco,
Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy.
2019,
Pubmed
Gambardella,
Pharmacological modulation in mesial temporal lobe epilepsy: Current status and future perspectives.
2016,
Pubmed
Hill,
Phytocannabinoids as novel therapeutic agents in CNS disorders.
2012,
Pubmed
Iannotti,
Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.
2014,
Pubmed
Ibeas Bih,
Molecular Targets of Cannabidiol in Neurological Disorders.
2015,
Pubmed
Iffland,
Focal Cortical Dysplasia: Gene Mutations, Cell Signaling, and Therapeutic Implications.
2017,
Pubmed
Kaplan,
Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.
2017,
Pubmed
Mahgoub,
Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors.
2013,
Pubmed
,
Xenbase
Matsuda,
Synapse organization and modulation via C1q family proteins and their receptors in the central nervous system.
2017,
Pubmed
Mazzuferi,
Enhancement of GABA(A)-current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy.
2010,
Pubmed
,
Xenbase
MECHOULAM,
A TOTAL SYNTHESIS OF DL-DELTA-1-TETRAHYDROCANNABINOL, THE ACTIVE CONSTITUENT OF HASHISH.
1965,
Pubmed
Miledi,
Microtransplantation of neurotransmitter receptors from cells to Xenopus oocyte membranes: new procedure for ion channel studies.
2006,
Pubmed
,
Xenbase
Miledi,
Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes.
2002,
Pubmed
,
Xenbase
Morano,
Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects.
2020,
Pubmed
Munro,
Molecular characterization of a peripheral receptor for cannabinoids.
1993,
Pubmed
Najm,
The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission.
2022,
Pubmed
Noebels,
Regulation of GABAA Receptor Gene Expression and Epilepsy
2012,
Pubmed
Palma,
The antiepileptic drug levetiracetam stabilizes the human epileptic GABAA receptors upon repetitive activation.
2007,
Pubmed
,
Xenbase
Palma,
Modulation of GABAA Receptors in the Treatment of Epilepsy.
2017,
Pubmed
Palma,
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
2004,
Pubmed
,
Xenbase
Palma,
Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy.
2002,
Pubmed
,
Xenbase
Palma,
GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) "phasic" receptors.
2007,
Pubmed
,
Xenbase
Pitkänen,
Mechanisms of epileptogenesis and potential treatment targets.
2011,
Pubmed
Poleg,
Cannabidiol as a suggested candidate for treatment of autism spectrum disorder.
2019,
Pubmed
Ragozzino,
Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.
2005,
Pubmed
,
Xenbase
Resstel,
5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats.
2009,
Pubmed
Roseti,
GABAA currents are decreased by IL-1β in epileptogenic tissue of patients with temporal lobe epilepsy: implications for ictogenesis.
2015,
Pubmed
,
Xenbase
Roseti,
Fractalkine/CX3CL1 modulates GABAA currents in human temporal lobe epilepsy.
2013,
Pubmed
,
Xenbase
Ross,
Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol.
2008,
Pubmed
Rudolph,
Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes.
2011,
Pubmed
Ruffolo,
A novel GABAergic dysfunction in human Dravet syndrome.
2018,
Pubmed
,
Xenbase
Ruffolo,
Functional aspects of early brain development are preserved in tuberous sclerosis complex (TSC) epileptogenic lesions.
2016,
Pubmed
,
Xenbase
Russo,
Agonistic properties of cannabidiol at 5-HT1a receptors.
2005,
Pubmed
Ryberg,
The orphan receptor GPR55 is a novel cannabinoid receptor.
2007,
Pubmed
Scheffer,
Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial.
2021,
Pubmed
Sieradzan,
Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study.
2001,
Pubmed
Stampanoni Bassi,
Cannabinoids in Parkinson's Disease.
2017,
Pubmed
Tang,
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.
2017,
Pubmed
Thiele,
Long-term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open-label extension trial.
2022,
Pubmed
Xiong,
Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors.
2012,
Pubmed
