Effects of cannabidiol vehiculated in nanoemulsion in rats submitted to the chemical model of temporal lobe epilepsy

• Grant number: 19/02787-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2019
• Effective date (End): August 31, 2020
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Norberto Garcia Cairasco
• Grantee: Gabriel Servilha Menezes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/50891-1 - INCT 2014: Translational Medicine, AP.TEM

Abstract

The plants of Cannabis genus are constituted by a diversity of substances, among which the cannabinoids stand out, a group of active compounds which have been widely explored by the medical sciences due to their pharmacological properties. Cannabidiol (CBD) is a cannabinoid without psychotropic effects, besides having good tolerability and low toxicity, even when administered chronically. Among its multiple therapeutic effects, it is notable its anticonvulsant activity, demonstrated in pre-clinical and clinical tests. Epilepsies are severe disorders, leading to several damages to the health and quality of life of those affected. In this sense, antiepileptic drugs (AEDs) are essential to the improvement of the quality of life of these patients, either because they block the seizures or because they, at least, reduce their frequency and/or severity. However, a large proportion of patients with epilepsy are resistant or refractory to conventional AEDs, being, thus, necessary the development and application of new AEDs, as well as of new drug delivery systems that optimize the effects and pharmacokinetic parameters of existing AEDs. In this context, the main goal of this study is to investigate the efficacy of CBD vehiculated in a new nanoemulsion system (CBDne) in the treatment of rats submitted to a model of Status Epilepticus (SE) induced by intra-hippocampal pilocarpine microinjection (Pilo-IH). Therefore, male rats of the Sprague Dawley strain will be submitted to stereotaxic surgery to implant a chemitrode in the left hippocampus and a recording electrode in the contralateral hippocampus. Past the recovery time, these animals will be treated with a single intravenous dose of CBDne or with the empty nanoemulsion (neØ), followed by the microinjection of Pilo-IH, to induce seizures. Recordings of video-EEG will be used to determine the presence of SE, the latency of beginning and severity of seizures. The data will be processed and statistically analyzed, through comparison between the control and treated groups. At the end, we expect that the new delivery system presents advantages in relation to the control of the seizures and neuroprotection. The proposed delivery system might offer new possibilities for the use of CBD in the treatment of the epilepsies.

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GOMEZ-NIETO, RICARDO; LOPEZ, DOLORES E.; GARCIA-CAIRASCO, NORBERTO. Editorial: Challenges and Conundrums in Cannabinoid-Based Treatments for Epilepsy Syndromes and Associated Neurobehavioral Comorbidities. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 15, p. 4-pg., 2021-11-11. (19/05957-8, 19/16574-2, 14/50891-1, 19/00849-2, 19/02787-4)

LAZARINI-LOPES, WILLIAN; DA SILVA-JUNIOR, RUI M. P.; SERVILHA-MENEZES, GABRIEL; DO VAL-DA SILVA, RAQUEL A.; GARCIA-CAIRASCO, NORBERTO. Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 14, DEC 21 2020. (19/00849-2, 19/02787-4, 14/50891-1, 19/05957-8)

ALVES, SUELEN SANTOS; PATRICIO DA SILVA JUNIOR, RUI MILTON; DELFINO-PEREIRA, POLIANNA; ALVES GOULART PEREIRA, MARILIA GABRIELLA; VASCONCELOS, ISRAEL; SCHWAEMMLE, HANNA; MAZZEI, RODRIGO FOCOSI; CARLOS, MAIKO LUIZ; ESPREAFICO, ENILZA MARIA; TEDESCO, ANTONIO CLAUDIO; et al. A Genetic Model of Epilepsy with a Partial Alzheimer's Disease-Like Phenotype and Central Insulin Resistance. Molecular Neurobiology, v. 59, n. 6, p. 17-pg., 2022-04-04. (19/05957-8, 14/50891-1, 19/16574-2, 19/02787-4, 19/00849-2, 17/21155-3)

SERVILHA-MENEZES, GABRIEL; GARCIA-CAIRASCO, NORBERTO. A complex systems view on the current hypotheses of epilepsy pharmacoresistance. EPILEPSIA OPEN, v. N/A, p. 15-pg., 2022-03-11. (19/02787-4, 19/05957-8, 14/50891-1)

ALVES, SUELEN SANTOS; PATRICIO DA SILVA-JUNIOR, RUI MILTON; SERVILHA-MENEZES, GABRIEL; HOMOLAK, JAN; SALKOVIC-PETRISIC, MELITA; GARCIA-CAIRASCO, NORBERTO. Insulin Resistance as a Common Link Between Current Alzheimer's Disease Hypotheses. JOURNAL OF ALZHEIMER'S DISEASE, v. 82, n. 1, p. 71-105, 2021. (19/00849-2, 19/05957-8, 14/50891-1, 19/02787-4)

ALVES, SUELEN SANTOS; ANTONIO CORTES DE OLIVEIRA, JOSE; LAZARINI-LOPES, WILLIAN; SERVILHA-MENEZES, GABRIEL; GRIGORIO-DE-SANT'ANA, MARIANA; DEL VECCHIO, FLAVIO; FOCOSI MAZZEI, RODRIGO; SOUSA ALMEIDA, SEBASTIAO; MILTON PATRICIO DA SILVA JUNIOR, RUI; GARCIA-CAIRASCO, NORBERTO. Audiogenic Seizures in the Streptozotocin-Induced Rat Alzheimer's Disease Model. JOURNAL OF ALZHEIMER'S DISEASE, v. 94, n. 3, p. 18-pg., 2023-01-01. (21/13622-6, 14/50891-1, 17/21155-3, 19/02787-4, 19/00849-2, 19/05957-8)

ALVES, SUELEN SANTOS; SERVILHA-MENEZES, GABRIEL; ROSSI, LETICIA; DA SILVA JUNIOR, RUI MILTON PATRICIO; GARCIA-CAIRASCO, NORBERTO. Evidence of disturbed insulin signaling in animal models of Alzheimer's disease. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 152, p. 23-pg., 2023-09-01. (21/14907-4, 14/50891-1, 17/21155-3, 19/02787-4, 19/00849-2, 19/05957-8)