Phytocannabinoids are being discussed as neuroprotective agents. There is evidence that some phytocannabinoids can protect against excitotoxicity, oxidative stress and neuroinflammatinon. All these processes play a pivotal role in PD, Chorea Huntington and multiple sclerosis.
The objective of this study was to elucidate neuroprotective effects of the two cannabinoids THC (tetrahydrocannabinol) and CBD (cannabidiol) in two different cell culture models. These models include primary mesencephalic cell culture and a neuroblastoma cell line (N18TG2). In both models, rotenone, an inhibitor of complex I of the respiratory chain, was used to induce oxidative stress. Treatment with rotenone results in increased radical production and depletion of ATP. This substance is used as a toxin to mimic PD, as it is also capable of causing the formation of Lewy bodies, which are characteristic for PD.
In mesencephalic cell culture, we examined parameters of cell viability and oxidative stress after incubation with cannabinoids and/or rotenone for 48h. Both THC and CBD were able to reduce rotenone-induced dopaminergic cell loss significantly. THC and CBD were also capable of counteracting glutathione depletion by rotenone. Propidium iodide uptake was significantly increased by rotenone, but no significant difference was found for cannabinoid treated cells. Determination of SOD activity revealed no significant changes.
Neuroblastoma cells were used to quantify superoxide radical production by ESR. We found out that THC and CBD do not decrease superoxide radical production induced by rotenone. Propidiumiodide uptake was not increased after treatment with rotenone, suggesting that neuroblastoma cells are less sensitive to rotenone than mesencephalic cell culture.
It can be concluded that CBD and THC exhibit neuroprotective properties in mesencephalic cell culture treated with rotenone. THC and CBD do not exert these actions by directly reducing superoxide production. The alteration of glutathione levels may point to a mechanism of cannabinoids to alleviate rotenone toxicity. But it is also possible that cannabinoids scavenge other radicals than superoxide.