Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

Abstract

Compounds present in Cannabis sativa L. preparations have recently attracted much attention in the treatment of drug-resistant epilepsy. Here, we screened two olive oil extracts from a non-psychoactive C. sativa variety, fully characterized by high-performance liquid chromatography and gas chromatography. Particularly, hemp oils with different concentrations of terpenes were administered at the same dose of cannabidiol (25 mg/kg/day orally), 1 h before the 6-Hz corneal stimulation test (44 mA). Mice were stimulated once a day for 5 days and evaluated by video-electrocorticographic recordings and behavioral analysis. Neuronal activation was assessed by FosB/ΔFosB immunoreactivity. Both oils significantly reduced the percentage of mice experiencing convulsive seizures in comparison to olive oil-treated mice (p < 0.050; Fisher’s exact test), but only the oil enriched with terpenes (K2) significantly accelerated full recovery from the seizure. These effects occurred in the presence of reduced power of delta rhythm, and, instead, increased power of theta rhythm, along with a lower FosB/ΔFosB expression in the subiculum (p < 0.050; Duncan’s method). The overall findings suggest that both cannabinoids and terpenes in oil extracts should be considered as potential therapeutic agents against epileptic seizures and epilepsy.

Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats

“…This agrees with recent data, which demonstrated that the administration of CBD at 25 mg/kg by gavage was ineffective at reducing seizures induced by the repeated 6-Hz corneal stimulation test in mice. However, a more complete whole-plant extract (i.e., oil enriched with terpenes) was more effective and reduced the therapeutic dose [ 22 ].…”

“…In preclinical studies, it was suggested that CBD attenuates seizures, improves survival, and behavioral comorbidities of Dravet syndrome in mice [ 19 , 20 ]. Similarly, CBD exerts anticonvulsant activities in a wide variety of acute seizure models, such as the audiogenic seizure, maximal electroshock, and 6 Hz-seizure models [ 21 , 22 ], or other models in which seizures are induced by isoniazid, cocaine, or gamma-aminobutyric acid type A (GABA A ) receptor antagonists [ 23 , 24 , 25 ]. Additionally, CBD seems to display anti-ictal activities in rodents when administered prior to the pilocarpine or penicillin-induced seizures [ 26 , 27 ].…”

Cannabidiol‐rich non‐psychotropic Cannabis sativa L. oils attenuate peripheral neuropathy symptoms by regulation of CB2‐mediated microglial neuroinflammation

“…For quantitative analysis, the selected ion monitoring (SIM) mode was applied to detect the most intense ion at 93 m/z for all the terpenes of interest and the ion at 74 m/z for methyl-octanoate used as the internal standard (I.S.) (Costa et al, 2021). Calibration curves for target compounds were constructed at five concentration levels in the range 1-50 μg/ml by plotting the peak areas of the analytes vs. their concentration.…”

Shared Etiology in Autism Spectrum Disorder and Epilepsy with Functional Disability

“…According to the findings, terpenic components have a role in increasing the antiepileptic action of cannabinoids in K2 hemp oil, compared to K1 and pure CBD, even if small chemicals in extracts might contribute to overall activity. The findings imply that both cannabinoids and terpenes found in oil extracts should be evaluated as potential therapeutic agents for epileptic seizures and epilepsy [ 126 ]. Conventional anticonvulsant drugs are ineffective in treating cognitive disorders characterized by an imbalance of E/I [ 127 ].…”