{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:51:05Z","timestamp":1788184265646,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pes-soal de N\u00edvel Superior (CAPES)"},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)"},{"name":"Funda\u00e7\u00e3o Cearense de Apoio ao Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (FUNCAP)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: The main biologically active molecules of Cannabis sativa L. are cannabidiol (CBD) and \u03949-tetrahydrocannabinol (THC). Both exert anticonvulsant effects when evaluated as single drugs, but their possible interaction as components of C. sativa extracts has been scarcely studied. For this reason, we evaluated CBD and THC, combined or not, in two seizure models in mice, using an improved vehicle formula. Methods: Firstly, acute seizures were induced by intraperitoneal (i.p.) pentylenetetrazole (PTZ, 80 mg\/kg), and mice received CBD or THC at 1, 3, 6, and 10 mg\/kg, or a CBD\/THC 1:1 combination at 1.5, 3, and 6 mg\/kg, per os (p.o.), one hour before PTZ administration. Secondly, mice received p.o. CBD (10 mg\/kg), CBD\/THC (1.5, 3, and 6 mg\/kg), valproic acid (50 mg\/kg), or vehicle (nanoemulsions without CBD or THC), one hour before PTZ (30 mg\/kg, i.p.) every other day for 21 days. Behavioral, biochemical, and immunohistochemical analyses were performed to assess the response to PTZ, oxidative stress, and astroglial activation. Results: In the acute model, CBD and THC at 3\u201310 mg\/kg, and their combinations, significantly increased latency to generalized seizures and death, and improved survival rates. In the chronic model, similarly to valproic acid, CBD 10 mg\/kg and CBD\/THC at 1.5 and 3 mg\/kg delayed kindling acquisition, while CBD\/THC 6 mg\/kg had no effect. CBD and CBD\/THC treatments reduced oxidative and nitrosative stress and attenuated astrogliosis, as indicated by decreased glial fibrillary acidic protein and GABA transporter 1 expression and increased inwardly rectifying potassium channel 4.1 expression in hippocampal regions. However, no cannabinoid treatment prevented the impairment in novel object recognition and Y maze tests. Conclusions: These findings support the potential role of cannabinoids in counteracting seizures, possibly by reducing oxidative stress and astrogliosis. The study also highlights the importance of nanoemulsions as a delivery vehicle to enhance cannabinoid effectiveness while considering the risks associated with direct cannabinoid receptor activation.<\/jats:p>","DOI":"10.3390\/ph18060782","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T12:24:18Z","timestamp":1748003058000},"page":"782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nanoemulsions of Cannabidiol, \u03949-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole"],"prefix":"10.3390","volume":"18","author":[{"given":"Pedro","family":"de Aquino","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0407-1140","authenticated-orcid":false,"given":"Francisco","family":"J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyciane","family":"de Souza Nascimento","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4561-7955","authenticated-orcid":false,"given":"\u00cdtalo","family":"Rosal Lustosa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geanne","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-5403","authenticated-orcid":false,"given":"N\u00e1gila","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Material Innovation, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"de Brito","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Material Innovation, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Material Innovation, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamilla","family":"Silveira","sequence":"additional","affiliation":[{"name":"Federal Institute of Education, Science and Technology of Sert\u00e3o Pernambucano (IF-Sert\u00e3o PE), Petrolina 56302-100, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2702-7268","authenticated-orcid":false,"given":"Davila","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"de Fran\u00e7a Fonteles","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edilberto","family":"Silveira","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Federal University of Cear\u00e1, Fortaleza 60430-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2511","authenticated-orcid":false,"given":"Giuseppe","family":"Biagini","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glauce","family":"de Barros Viana","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-270, 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