Study of Cannabidiol effects on neural cell behavior

Abstract

Cannabidiol (CBD) is a prominent chemical compound of the phytocannabinoids extracted from the Cannabis Sativa, which has been associated with various therapeutic effects on neurological disorders, such as neuroprotection, anti-inflammatory, antianxiety, antidepressant, and anticonvulsant actions. CBD is known to induce biochemical pathways in cells by interacting target molecules, including ion channels, receptors, transporters, and enzymes. This feature of CBD, having multiple target molecules, presents significant advantages as a therapeutic agent for multifactorial neurodegenerative diseases. However, current research on CBD is primarily focused on clinical trials or preclinical studies targeting animals, and the underlying biochemical mechanisms at the cellular and molecular levels remain largely unexplored. Therefore, it is crucial to conduct research on how CBD acts on cells through which pathways using in-vitro experiments that is easy to control variables. In this study, we aim to investigate the effects of CBD and related biochemical mechanisms on neural cells.

In this chapter, we summarize the effects of cannabidiol on neural cells, including neurons, glial cells (astrocytes, oligodendrocytes, and microglia), and neural stem cells. Previous studies have shown the neuroprotective effect of CBD against various toxic substances, the anti-inflammatory effect of CBD on active glial cells, and the supporting effect of CBD on survival and differentiation of neural stem cells. These findings suggest that CBD could be a promising treatment option for neurological disorders.

Oxidative stress, a pathological feature commonly observed in various neurodegenerative diseases, is known to induce damage to lipids, proteins, and DNA, leading to the death of neurons. In this study, we investigated the ability of cannabidiol to protect hippocampal neurons against oxidative stress. First, we investigated the neurotoxicity profiles of cannabidiol and hydrogen peroxide on cultured hippocampal neurons in vitro. Based on these results, we established concentration conditions and found that the co-treatment of cannabidiol and hydrogen peroxide decreased the neuronal death caused by hydrogen peroxide, supporting the neuroprotective effect of cannabidiol against oxidative stress on hippocampal neurons.

The central nervous system includes not only neurons but also glial cells that support and regulate neuronal function. Among them, astrocytes are the most abundant glial cells in the central nervous system, play a critical role in maintaining ion homeostasis, supplying nutrients, and regulating synaptic function. The aim of this chapter is to explore the impacts of cannabidiol on neural cells in a neuron-astrocyte sandwich co-culture model. In particular, we investigate the neurotoxicity of cannabidiol at high concentrations in order to understand its in-vivo stability for the therapeutic uses. In neuron-only culture, cannabidiol at concentrations of 15μM and 30μM decreased the neuronal viability, which was found to be caused by the activation of TRPV1, resulted in increase of intracellular calcium ion and depolarization of mitochondrial membrane potential. Surprisingly, in neuron-astrocyte co-cultured system, the neurotoxicity of cannabidiol was significantly reduced, with great reductions of the increase of intracellular calcium ions and dysfunction of mitochondrial membrane potential. In addition, it was found that cannabidiol promotes the early developmental process of neurons in the neuron-astrocyte co-culture. Cannabidiol at a concentration of 10μM increased the length of longest neurites, the number of primary neurites, and the number of branch points, and promoted the progression of neuron development. This is predicted to be due to the changes induced by cannabidiol in the cytokines secreted by astrocytes, which affect the development of neurons.

This dissertation thoroughly investigated the effects of cannabidiol on neural cells, including the neuroprotective effect of CBD, the neutralization of CBD neurotoxicity in neuron-astrocyte co-culture, and the accelerating effect of CBD on neural development. This research has facilitated the comprehension of the biochemical mechanisms triggered by cannabidiol through interactions with various biomolecules in the body. These findings offer fundamental and essential insights into the potential uses of CBD for the prevention and treatment of neurodegenerative disorders.