ACS Chem Neurosci. 2022 Apr 6. doi: 10.1021/acschemneuro.1c00667. Online ahead of print.
Cannabidiol is a nonpsychoactive phytocannabinoid produced by the Cannabis sativa plant and possesses a wide range of pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective activities. Cannabidiol functions in a neuroprotective manner, in part through the activation of cellular antioxidant pathways. The glyoxalase pathway detoxifies methylglyoxal, a highly reactive metabolic byproduct that can accumulate in the brain, and contributes to the severity of neurodegenerative diseases, including Alzheimer’s disease. While cannabidiol’s antioxidant properties have been investigated, it is currently unknown how it may modulate the glyoxalase pathway. In this research paper, we examine the effects of Cannabidiol on cerebellar neurons and in several Caenorhabditis elegans strains. We determined that a limited amount of Cannabidiol can prevent methylglyoxal-mediated cellular damage through enhancement of the neural glyoxalase pathway and extend the lifespan and survival of C. elegans, including a transgenic C. elegans strain modeling Alzheimer’s disease.