Cannabidiol (CBD) alters the funcionality of neutrophils (PMN) implicatins in the refractory epilepsy

TABORDA GOMEZ, C; LAIRION, F; REPETTO, MG; ETTCHETO, M; MERELLI, A; LAZAROWSKI, A; AUZMENDI, J

Pharmaceuticals

MDPI

Año: 2021 vol. 14

1424-8247

Cannabidiol (CBD), a lipophilic cannabinoid compound without psychoactive effects, has emerged as adjuvant of anti-epileptic drugs (AEDs) in the treatment of refractory epilepsy (RE), decreasing the severity and/or frequency of seizures. CBD is considered a multitarget drug that could act throughout the canonical endocannabinoid receptors (CB1-CB2) or multiples non-canonical pathway. Despite the CBD mechanism in RE is still unknow, we demonstrate that CBD have an inhibitory role on P-glycoprotein excretory function, highly related to RE. Since CB2 is expressed mainly in the immune cells, we hypothesized that CBD treatment could alter the activity of polymorphonuclear neutrophils (PMNs) in a similar way that it does with microglia/macrophages, and others circulating leukocytes. In vitro, CBD induced PMN cytoplasmatic vacuolization and proapoptotic nuclear condensation, associated with a significantly decreased viability in a concentration-dependent manner, while low CBD concentration decrease PMN viability in a time dependent manner. At functional level, CBD reduced the PMN´s chemotaxis and the oxygen consumes related with superoxide anion production while the singlet oxygen level was increased suggesting oxidative stress damage. These results are in line with the well-known CBD anti-inflammatory effect and support a potential immunosuppressor role on PMNs that could promote an eventual defenseless state during chronic treatment with CBD in RE.