Cannabidiol (CBD) Alters the Functionality of Neutrophils (PMN). Implications in the Refractory Epilepsy Treatment

GÓMEZ, CLAUDIA TABORDA; LAIRION, FABIANA; REPETTO, MARISA; ETTCHETO, MIREN; MERELLI, AMALIA; LAZAROWSKI, ALBERTO; AUZMENDI, JERÓNIMO

Pharmaceuticals

MDPI

Lugar: Basel; Año: 2021 vol. 14

Cannabidiol (CBD), a lipophilic cannabinoid compound without psychoactive effects, hasemerged 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 thatcould act throughout the canonical endocannabinoid receptors (CB1‐CB2) or multiple non‐canonicalpathways. Despite the fact that the CBD mechanism in RE is still unknown, experiments carried outin our laboratory showed that CBD has an inhibitory role on P‐glycoprotein excretory function,highly related to RE. Since CB2 is expressed mainly in the immune cells, we hypothesized that CBDtreatment could alter the activity of polymorphonuclear neutrophils (PMNs) in a similar way thatit does with microglia/macrophages and others circulating leukocytes. In vitro, CBD induced PMNcytoplasmatic vacuolization and proapoptotic nuclear condensation, associated with a significantlydecreased viability in a concentration‐dependent manner, while low CBD concentration decreasedPMN viability in a time‐dependent manner. At a functional level, CBD reduced the chemotaxis andoxygen consumption of PMNs related with superoxide anion production, while the singlet oxygenlevel was increased suggesting oxidative stress damage. These results are in line with the wellknownCBD anti‐inflammatory effect and support a potential immunosuppressor role on PMNsthat could promote an eventual defenseless state during chronic treatment with CBD in RE.