CBD and THC nanoemulsions showed anticonvulsant and antioxidant effects in mice
Nanoemulsion formulations of CBD, THC, and their combination all reduced seizures and brain oxidative stress in mice, with CBD and low-dose combinations delaying seizure kindling similarly to valproic acid.
Quick Facts
What This Study Found
In acute seizure tests, CBD and THC at 3-10 mg/kg and their 1:1 combinations increased latency to generalized seizures and improved survival. In the chronic kindling model, CBD 10 mg/kg and CBD/THC at 1.5 and 3 mg/kg delayed seizure progression, while reducing oxidative stress and brain inflammation markers.
Key Numbers
CBD and THC at 3-10 mg/kg significantly increased seizure latency and survival in acute tests. In chronic kindling, CBD 10 mg/kg and CBD/THC at 1.5 and 3 mg/kg delayed seizure progression. Treatments reduced GFAP expression (astrogliosis marker) and oxidative stress markers in hippocampal regions. CBD/THC at 6 mg/kg had no effect on kindling.
How They Did This
Mice received nanoemulsion formulations of CBD, THC, or 1:1 CBD/THC combinations orally one hour before pentylenetetrazole (PTZ) injection. In the acute model, a single high-dose PTZ induced seizures. In the chronic model, PTZ was given every other day for 21 days to model kindling. Behavioral, biochemical, and immunohistochemical analyses assessed seizure response, oxidative stress, and astroglia activation.
Why This Research Matters
While CBD is already approved for certain epilepsies, this study tests nanoemulsion delivery systems that may improve bioavailability and shows that lower-dose CBD/THC combinations can match the anticonvulsant effects of standard treatment. The finding about astrogliosis reduction adds mechanistic insight.
The Bigger Picture
The observation that the highest combination dose (6 mg/kg) failed to prevent kindling while lower doses succeeded suggests a non-linear dose-response, possibly related to THC's biphasic effects. The nanoemulsion vehicle itself improved cannabinoid delivery, which could be relevant for future formulation development.
What This Study Doesn't Tell Us
Mouse seizure models do not perfectly replicate human epilepsy. No cannabinoid treatment prevented cognitive impairment in memory tests. The study cannot determine whether nanoemulsion formulation offers advantages over standard CBD delivery in humans. Only male mice were used.
Questions This Raises
- ?Why did the highest CBD/THC combination dose fail to prevent kindling?
- ?Would nanoemulsion CBD be more effective than standard formulations in human epilepsy patients?
- ?Can the astrogliosis-reducing effects translate to neuroprotective benefits in other brain conditions?
Trust & Context
- Key Stat:
- Low-dose CBD/THC combinations matched valproic acid in delaying seizure kindling
- Evidence Grade:
- Animal study testing multiple cannabinoid formulations and doses in two seizure models with biochemical analysis, but only in male mice.
- Study Age:
- Published in 2025.
- Original Title:
- Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole.
- Published In:
- Pharmaceuticals (Basel, Switzerland), 18(6) (2025)
- Authors:
- de Aquino, Pedro Everson Alexandre, Júnior, Francisco Josimar Girão, de Souza Nascimento, Tyciane, Rosal Lustosa, Ítalo, de Andrade, Geanne Matos, Ricardo, Nágila Maria Pontes Silva, de Brito, Débora Hellen Almeida, de Almeida, Gabriel Érik Patrício, Silveira, Kamilla Barreto, Zampieri, Davila, de França Fonteles, Marta Maria, Silveira, Edilberto Rocha, Biagini, Giuseppe, de Barros Viana, Glauce Socorro
- Database ID:
- RTHC-06311
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Is the CBD/THC combination better than CBD alone?
In this mouse study, low-dose combinations performed similarly to higher-dose CBD alone, suggesting the combination may allow lower dosing. However, the highest combination dose did not work, indicating a complex dose relationship.
What are nanoemulsions?
Nanoemulsions are tiny droplets of oil-in-water that can improve absorption of poorly soluble compounds like cannabinoids. The researchers used this delivery method to enhance CBD and THC effectiveness.
Did the cannabinoids affect cognition?
None of the cannabinoid treatments prevented the memory impairment caused by repeated seizures in the novel object recognition and Y-maze tests.
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Cite This Study
https://rethinkthc.com/research/RTHC-06311APA
de Aquino, Pedro Everson Alexandre; Júnior, Francisco Josimar Girão; de Souza Nascimento, Tyciane; Rosal Lustosa, Ítalo; de Andrade, Geanne Matos; Ricardo, Nágila Maria Pontes Silva; de Brito, Débora Hellen Almeida; de Almeida, Gabriel Érik Patrício; Silveira, Kamilla Barreto; Zampieri, Davila; de França Fonteles, Marta Maria; Silveira, Edilberto Rocha; Biagini, Giuseppe; de Barros Viana, Glauce Socorro. (2025). Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole.. Pharmaceuticals (Basel, Switzerland), 18(6). https://doi.org/10.3390/ph18060782
MLA
de Aquino, Pedro Everson Alexandre, et al. "Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole.." Pharmaceuticals (Basel, 2025. https://doi.org/10.3390/ph18060782
RethinkTHC
RethinkTHC Research Database. "Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and T..." RTHC-06311. Retrieved from https://rethinkthc.com/research/de-2025-nanoemulsions-of-cannabidiol-9tetrahydrocannabinol
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.