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• W3112635409 abstract "Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT 1A receptors. These receptors are coupled to G i/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT 1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT 1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery ( n = 11) and from a group of autopsies ( n = 11). The [ 3 H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT 1A receptors. The [ 35 S]-GTPγS assay was used to investigate the CBD-induced activation of G i/o proteins through its action on 5-HT 1A receptors.The CBD affinity (p K i ) for 5-HT 1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [ 35 S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue ( p &gt; 0.05) at low CBD concentrations (1 pM to 10 μM). In contrast, at high concentrations (100 μM), CBD reduced the constitutive activity of G i/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT 1A receptors, in the autopsy group (hippocampus, 59.8%, p &lt; 0.0001; temporal neocortex, 71.5%, p &lt; 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p &lt; 0.0001; temporal neocortex, 68.5%, p &lt; 0.001). Our results show that CBD interacts with human 5-HT 1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon G i/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT 1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE." @default.
• W3112635409 created "2020-12-21" @default.
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• W3112635409 date "2020-12-15" @default.
• W3112635409 modified "2023-09-23" @default.
• W3112635409 title "Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy" @default.
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• W3112635409 doi "https://doi.org/10.3389/fnbeh.2020.611278" @default.
• W3112635409 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7770178" @default.
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