The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses antiepileptic, antipsychotic, anti-inflammatory and anxiolytic properties. Recent studies report that it also exerts antineoplastic effects in multiple types of cancers, including melanoma. In this in vitro study we tried to reveal the anticancer properties of CBD in malignant melanoma cell lines (SK-MEL 28, A375, FM55P and FM55M2) administered alone, as well as in combination with mitoxantrone (MTX) or cisplatin (CDDP). The effects of CBD on the viability of melanoma cells were measured by the MTT assay; cytotoxicity was determined in the LDH test and proliferation in the BrdU test. Moreover, the safety of CBD was tested in human keratinocytes (HaCaT) in LDH and MTT tests. Results indicate that CBD reduces the viability and proliferation of melanoma-malignant cells and exerts additive interactions with MTX. Unfortunately, CBD produced antagonistic interaction when combined with CDDP. CBD does not cause significant cytotoxicity in HaCaT cell line. In conclusion, CBD may be considered as a part of melanoma multi-drug therapy when combined with MTX. A special attention should be paid to the combination of CBD with CDDP due to the antagonistic interaction observed in the studied malignant melanoma cell lines.

Summary Introduction. Patients with pharmacoresistant epilepsy are usually treated with two or more antiepileptic drugs (AEDs). The search for therapeutically efficacious AED combinations is still a challenging issue for clinicians and epileptologists throughout the world. Aim. To determine the interaction profile for the combination of retigabine (RTG) and oxcarbazepine (OXC) in both, the model of tonic-clonic seizures, the maximal electroshock (MES)-induced seizure model and chimney test (motor performance) in adult male albino Swiss mice. Methods. Isobolographic analysis (type I) was applied to characterize interactions for the combination of RTG with OXC with respect to its anticonvulsant and acute side (neurotoxic) effects, as determined in the MES and chimney tests, respectively. Results. The combination of RTG with OXC at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in the MES test in mice. Similarly, the combination of RTG with OXC at the fixed-ratio of 1:1 produced additive interaction with a tendency towards sub-additivity in the chimney test in mice. Measurement of total brain concentrations of both AEDs revealed that RTG did not affect total brain concentrations of OXC and inversely, OXC had no impact on RTG’s total brain concentrations, confirming pharmacodynamic interaction between the drugs. Conclusions. The additive pharmacodynamic interactions in both the MES and chimney tests in mice were observed for the combination of RTG with OXC.

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Introduction. Assessment of interactions among antiepileptic drugs (AEDs) during polytherapy is still a challenging issue for physicians and epileptologists worldwide. In spite of 25 currently licensed AEDs, there are no algorithms allowing a proper choice of these drugs to create combinations which would offer epileptic patients an efficacious therapy in the case of seizures refractory to monotherapeutic use of the AEDs. To characterize a type of interaction for a three-drug mixture of oxcarbazepine (OXC), pregabalin (PGB) and topiramate (TPM) in an experimental model of tonic-clonic seizures, an isobolographic analysis of interaction was applied. Materials and Method. The anticonvulsant effects of the three-drug mixture of OXC, PGB and TPM with respect to suppression of tonic-clonic seizures in mice were assessed in the mouse maximal electroshock-induced seizure model. Type I isobolographic analysis was used to characterize the type of interactions among three AEDs. Potential acute adverse effects were evaluated in the chimney, passive avoidance and grip-strength tests. Results. The three-drug mixture of OXC, PGB and TPM exerted supra-additive (synergistic) interaction in the mouse maximal electroshock-induced seizure model. The combination of OXC, PGB and TPM did not produce any acute adverse effects in mice in the chimney, passive avoidance and grip-strength tests. Conclusions. The isobolographic synergy observed experimentally for the combination of OXC, PGB and TPM could be recommended to patients with drug-resistant epilepsy, if the results of this study were translated to clinical settings.