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Volume 18
Issue 6
10.3390/ph18060782
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Article

Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentyelenetetrazole

by
Pedro Everson Alexandre de Aquino
1,
Francisco Josimar Girão Júnior
1,
Tyciane de Souza Nascimento
1,
Ítalo Rosal Lustosa
1,
Geanne Matos de Andrade
1,
Nágila Maria Pontes Silva Ricardo
2,
Débora Hellen Almeida de Brito
2,
Gabriel Érik Patrício de Almeida
2,
Kamilla Barreto Silveira
3,
Davila Zampieri
4,
Marta Maria de França Fonteles
1,
Edilberto Rocha Silveira
4,
Giuseppe Biagini
5,* and
Glauce Socorro de Barros Viana
1
1
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, Brazil
2
Laboratory of Polymer and Material Innovation, Federal University of Ceará, Fortaleza 60430-270, Brazil
3
Federal Institute of Education, Science, and Technology of Sertão Pernambucano (IF-Sertão PE), Petrolina 56302-100, Brazil
4
Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza 60430-270, Brazil
5
Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(6), 782; https://doi.org/10.3390/ph18060782
Submission received: 3 April 2025 / Revised: 12 May 2025 / Accepted: 15 May 2025 / Published: 23 May 2025
(This article belongs to the Section Pharmacology)
Versions Notes

Abstract

Background/Objectives: The main biologically active molecules of Cannabis sativa L. are cannabidiol (CBD) and Δ9-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 3–10 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.
Keywords: cannabidiol; epilepsy; nanoemulsion; pentylenetetrazole; Δ9-tetrahydrocannabinol cannabidiol; epilepsy; nanoemulsion; pentylenetetrazole; Δ9-tetrahydrocannabinol

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MDPI and ACS Style

de Aquino, P.E.A.; Júnior, F.J.G.; de Souza Nascimento, T.; Rosal Lustosa, Í.; de Andrade, G.M.; Ricardo, N.M.P.S.; de Brito, D.H.A.; de Almeida, G.É.P.; Silveira, K.B.; Zampieri, D.; et al. Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentyelenetetrazole. Pharmaceuticals 2025, 18, 782. https://doi.org/10.3390/ph18060782

AMA Style

de Aquino PEA, Júnior FJG, de Souza Nascimento T, Rosal Lustosa Í, de Andrade GM, Ricardo NMPS, de Brito DHA, de Almeida GÉP, Silveira KB, Zampieri D, et al. Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentyelenetetrazole. Pharmaceuticals. 2025; 18(6):782. https://doi.org/10.3390/ph18060782

Chicago/Turabian Style

de Aquino, Pedro Everson Alexandre, Francisco Josimar Girão Júnior, Tyciane de Souza Nascimento, Ítalo Rosal Lustosa, Geanne Matos de Andrade, Nágila Maria Pontes Silva Ricardo, Débora Hellen Almeida de Brito, Gabriel Érik Patrício de Almeida, Kamilla Barreto Silveira, Davila Zampieri, and et al. 2025. "Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentyelenetetrazole" Pharmaceuticals 18, no. 6: 782. https://doi.org/10.3390/ph18060782

APA Style

de Aquino, P. E. A., Júnior, F. J. G., de Souza Nascimento, T., Rosal Lustosa, Í., de Andrade, G. M., Ricardo, N. M. P. S., de Brito, D. H. A., de Almeida, G. É. P., Silveira, K. B., Zampieri, D., de França Fonteles, M. M., Silveira, E. R., Biagini, G., & de Barros Viana, G. S. (2025). Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentyelenetetrazole. Pharmaceuticals, 18(6), 782. https://doi.org/10.3390/ph18060782

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