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.
People following cannabinoid research for epilepsy and seizure disorders.
Low-dose CBD/THC combinations matched valproic acid in delaying seizure kindling
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Animal study testing multiple cannabinoid formulations and doses in two seizure models with biochemical analysis, but only in male mice.
When this study was published
Published in 2025.
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.
Questions still open
- 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?
Common questions
Is the CBD/THC combination better than CBD alone?
What are nanoemulsions?
Did the cannabinoids affect cognition?
Read the original research
Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole.
Pharmaceuticals (Basel, Switzerland), 18(6)
Citation
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
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