Effects of Cannabidiol on 5-HT1A Receptors in Neocortex of Patients with Drug-Resistant Temporal Lobe Epilepsy
Abstract number :
2.255
Submission category :
7. Antiepileptic Drugs / 7E. Other
Year :
2019
Submission ID :
2421700
Source :
www.aesnet.org
Presentation date :
12/8/2019 4:04:48 PM
Published date :
Nov 25, 2019, 12:14 PM
Authors :
Luisa Rocha, Center of Research and Advanced Studies; Christopher Martinez, Center for Reserach and Advanced Studies; Manola Cuellar-Herrera, General Hospital of Mexico; Ana Luisa Velasco, General Hospital of Mexico; Francisco Velasco, General Hospital of
Rationale: Studies indicate that Cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT1A receptors. These receptors are coupled to Gi-proteins and induce inhibitory effects. At present, it is unknown if CBD interacts with 5-HT1A receptors in the human brain. The aim of this study focused to evaluate the interaction between CBD and 5-HT1A receptors in cell membranes obtained from the temporal neocortex of autopsies and patients with drug-resistant temporal lobe epilepsy (TLE). Methods: Cell membranes were isolated from temporal neocortex of patients with pharmacoresistant TLE who were surgically treated (n=11), and autopsies (n=11). [3H]-8-OH-DPAT binding assay was used to determine the affinity of CBD (RSHO-X™, HempMeds PX, LLC, USA) for 5-HT1A receptor. [35S]-GTP gammaS assay was used to evaluate the efficacy and potency of CBD to activate Gi proteins through its action on 5-HT1A receptors. Results: The CBD affinity for 5-HT1A receptors was similar for autopsies and patients with pharmacoresistant TLE (pKi 4.57 and 4.66, respectively). [35S]-GTP gammaS assay revealed a dual effect of CBD in the activation of Gi-proteins in autopsies: an activation at low concentrations (13.6%, p<0.05) and inhibition at high concentrations (36.7%, p<0.0001). These effects were less evident in patients with TLE. These changes were partially reverted in presence of WAY-100635, an antagonist of 5-HT1A receptors (71.5%, autopsies; 68.5%, patients). Conclusions: Our results revealed for the first time that CBD interacts with 5-HT1A receptor in human neocortex. At low concentrations, CBD may induce inhibitory effects mediated by activation of 5-HT1A receptors. However, at high concentrations, CBD may act as an inverse agonist of 5-HT1A receptors, a condition that could facilitate neuronal excitation and epileptic seizures in patients with epilepsy. Funding: Study supported by HempMeds, LLC, USA and Consejo Nacional de Ciencia y Tecnología (CONACyT; scholarship 858064 and grants CB-2012-01-177594 y 261481).
Antiepileptic Drugs