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Acute effect of cannabidiol on the activity of various novel antiepileptic drugs in the maximal electroshock- and 6 Hz-induced seizures in mice: Pharmacodynamic and pharmacokinetic studies.
Neuropharmacology 2019; 158:107733N

Abstract

Cannabidiol and cannabidiol-enriched products have recently attracted much attention as an add-on therapy for epilepsy, especially drug-resistant seizures. It should be, however, remembered that concomitant use of cannabidiol and antiepileptic drugs may pose a risk of interactions between them. For this reason, the aim of our study was to assess the effect of cannabidiol on the activity of selected new antiepileptic drugs in the electrically-induced seizure models in mice. We studied the effect of cannabidiol on the anticonvulsant action of topiramate, oxcarbazepine, lamotrigine, and pregabalin in the maximal electroshock-induced seizure test as well as on the activity of levetiracetam, tiagabine, lacosamide, and gabapentin in the 6 Hz seizure test in mice. We showed that cannabidiol increased the activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin. It did not affect the anticonvulsant effect of lamotrigine and lacosamide. Interestingly, cannabidiol attenuated the anticonvulsant activity of levetiracetam. Co-administration of antiepileptic drugs with cannabidiol did not cause adverse effects such as impairment of motor coordination, changes in neuromuscular strength or potentiation of the cannabidiol-induced hypolocomotion. Serum and brain levels of antiepileptic drugs and cannabidiol were determined by using HPLC in order to ascertain any pharmacokinetic contribution to the observed behavioral effects. Only interaction with levetiracetam was purely pharmacodynamic in nature because no changes in serum and brain concentration of either levetiracetam or cannabidiol were observed. Increased anticonvulsant activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin could be, at least in part, related to pharmacokinetic interactions with cannabidiol because there were changes in serum and/or brain concentrations of antiepileptic drugs and/or cannabidiol. Pharmacokinetic interactions cannot be also excluded between lacosamide and cannabidiol because cannabidiol increased brain concentration of lacosamide and lacosamide increased brain concentration of cannabidiol. Further pharmacokinetic studies are required to evaluate the type of interactions between cannabidiol and novel antiepileptic drugs.

Authors+Show Affiliations

Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland. Electronic address: ksocala@op.pl.Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31377197

Citation

Socała, Katarzyna, et al. "Acute Effect of Cannabidiol On the Activity of Various Novel Antiepileptic Drugs in the Maximal Electroshock- and 6 Hz-induced Seizures in Mice: Pharmacodynamic and Pharmacokinetic Studies." Neuropharmacology, vol. 158, 2019, p. 107733.
Socała K, Wyska E, Szafarz M, et al. Acute effect of cannabidiol on the activity of various novel antiepileptic drugs in the maximal electroshock- and 6 Hz-induced seizures in mice: Pharmacodynamic and pharmacokinetic studies. Neuropharmacology. 2019;158:107733.
Socała, K., Wyska, E., Szafarz, M., Nieoczym, D., & Wlaź, P. (2019). Acute effect of cannabidiol on the activity of various novel antiepileptic drugs in the maximal electroshock- and 6 Hz-induced seizures in mice: Pharmacodynamic and pharmacokinetic studies. Neuropharmacology, 158, p. 107733. doi:10.1016/j.neuropharm.2019.107733.
Socała K, et al. Acute Effect of Cannabidiol On the Activity of Various Novel Antiepileptic Drugs in the Maximal Electroshock- and 6 Hz-induced Seizures in Mice: Pharmacodynamic and Pharmacokinetic Studies. Neuropharmacology. 2019 Nov 1;158:107733. PubMed PMID: 31377197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute effect of cannabidiol on the activity of various novel antiepileptic drugs in the maximal electroshock- and 6 Hz-induced seizures in mice: Pharmacodynamic and pharmacokinetic studies. AU - Socała,Katarzyna, AU - Wyska,Elżbieta, AU - Szafarz,Małgorzata, AU - Nieoczym,Dorota, AU - Wlaź,Piotr, Y1 - 2019/08/01/ PY - 2019/04/05/received PY - 2019/07/26/revised PY - 2019/07/31/accepted PY - 2019/8/5/pubmed PY - 2019/8/5/medline PY - 2019/8/5/entrez KW - Antiepileptic drugs KW - Cannabidiol KW - Drug-drug interactions KW - Seizures SP - 107733 EP - 107733 JF - Neuropharmacology JO - Neuropharmacology VL - 158 N2 - Cannabidiol and cannabidiol-enriched products have recently attracted much attention as an add-on therapy for epilepsy, especially drug-resistant seizures. It should be, however, remembered that concomitant use of cannabidiol and antiepileptic drugs may pose a risk of interactions between them. For this reason, the aim of our study was to assess the effect of cannabidiol on the activity of selected new antiepileptic drugs in the electrically-induced seizure models in mice. We studied the effect of cannabidiol on the anticonvulsant action of topiramate, oxcarbazepine, lamotrigine, and pregabalin in the maximal electroshock-induced seizure test as well as on the activity of levetiracetam, tiagabine, lacosamide, and gabapentin in the 6 Hz seizure test in mice. We showed that cannabidiol increased the activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin. It did not affect the anticonvulsant effect of lamotrigine and lacosamide. Interestingly, cannabidiol attenuated the anticonvulsant activity of levetiracetam. Co-administration of antiepileptic drugs with cannabidiol did not cause adverse effects such as impairment of motor coordination, changes in neuromuscular strength or potentiation of the cannabidiol-induced hypolocomotion. Serum and brain levels of antiepileptic drugs and cannabidiol were determined by using HPLC in order to ascertain any pharmacokinetic contribution to the observed behavioral effects. Only interaction with levetiracetam was purely pharmacodynamic in nature because no changes in serum and brain concentration of either levetiracetam or cannabidiol were observed. Increased anticonvulsant activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin could be, at least in part, related to pharmacokinetic interactions with cannabidiol because there were changes in serum and/or brain concentrations of antiepileptic drugs and/or cannabidiol. Pharmacokinetic interactions cannot be also excluded between lacosamide and cannabidiol because cannabidiol increased brain concentration of lacosamide and lacosamide increased brain concentration of cannabidiol. Further pharmacokinetic studies are required to evaluate the type of interactions between cannabidiol and novel antiepileptic drugs. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/31377197/Acute_effect_of_cannabidiol_on_the_activity_of_various_novel_antiepileptic_drugs_in_the_maximal_electroshock-_and_6_Hz-induced_seizures_in_mice:_Pharmacodynamic_and_pharmacokinetic_studies L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(19)30292-8 DB - PRIME DP - Unbound Medicine ER -