Neuroprotective Effect of Cannabidiol Against Hydrogen Peroxide in Hippocampal Neuron Culture.

Reports on the neurotoxic and neuroprotective effects of cannabidiol (CBD) have not been in complete accord, showing different and somewhat contradictory results depending upon the brain cell types and experimental conditions employed. This work systematically examines the neuroprotective capability of CBD against oxidative stress (i.e., hydrogen peroxide [HO]) as well as its toxicity profile in the culture platform of primary hippocampal neurons. The low cell-density (100 neurons per mm) culture was used for analyzing the viability and morphology of neurons at a single-cell level with a confocal laser-scanning microscope (CLSM). Primary neurons were obtained from the hippocampal tissues of embryonic day-18 (E18) Sprague-Dawley rat pups and treated with CBD (0.1-100 μM) and/or HO (0.1-50 μM) at 1 DIV (days ). The lethal concentration 50 (LC) value (the concentration causing 50% cell death) of CBD was calculated to be 9.85 μM after 24 h of incubation, and that of HO was 2.46 μM under the same conditions. The neuroprotection ratio of CBD against HO ([HO]=10 μM) was 2.40 with 5 μM of CBD, increasing the cell viability to 57% from 24%. The CLSM analysis suggested that the cell-death mechanisms were different for CBD and HO, and CBD did not completely rescue the morphological alterations of primary hippocampal neurons caused by HO, such as neurite degeneration, at least in the neuron culture. Although CBD showed both neurotoxic and neuroprotective effects on hippocampal neurons in the setting, the use of low-concentrated (i.e., 5 μM) CBD, not causing toxic effects on the neurons, significantly rescued the neurons from the oxidative stress (HO), confirming its neuroprotection capability.