Acute impact of cannabidiol on the activity of numerous novel antiepileptic drugs in the maximal electroshock- and six Hz-induced seizures in mice: pharmacodynamic and pharmacokinetic research.


Cannabidiol and cannabidiol-enriched merchandise have not too long ago attracted considerably consideration as an add-on therapy for epilepsy, specifically drug-resistant seizures. It must be, nevertheless, remembered that concomitant use of cannabidiol and antiepileptic drugs might pose a danger of interactions in between them. For this explanation, the aim of our study was to assess the impact of cannabidiol on the activity of chosen new antiepileptic drugs in the electrically-induced seizure models in mice. We studied the impact of cannabidiol on the anticonvulsant action of topiramate, oxcarbazepine, lamotrigine, and pregabalin in the maximal electroshock-induced seizure test as nicely as on the activity of levetiracetam, tiagabine, lacosamide, and gabapentin in the six Hz seizure test in mice. We showed that cannabidiol improved the activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin. It did not have an effect on the anticonvulsant impact of lamotrigine and lacosamide. Interestingly, cannabidiol attenuated the anticonvulsant activity of levetiracetam. Co-administration of antiepileptic drugs with cannabidiol did not trigger adverse effects such as impairment of motor coordination, modifications in neuromuscular strength or potentiation of the cannabidiol-induced hypolocomotion. Serum and brain levels of antiepileptic drugs and cannabidiol had been determined by utilizing HPLC in order to ascertain any pharmacokinetic contribution to the observed behavioral effects. Only interaction with levetiracetam was purely pharmacodynamic in nature since no modifications in serum and brain concentration of either levetiracetam or cannabidiol had been observed. Enhanced anticonvulsant activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin could be, at least in element, associated to pharmacokinetic interactions with cannabidiol since there had been modifications in serum and/or brain concentrations of antiepileptic drugs and/or cannabidiol. Pharmacokinetic interactions can not be also excluded in between lacosamide and cannabidiol since cannabidiol improved brain concentration of lacosamide and lacosamide improved brain concentration of cannabidiol. Additional pharmacokinetic research are essential to evaluate the sort of interactions in between cannabidiol and novel antiepileptic drugs.


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