# Cannabinol’s Modulation of Genes Involved in Oxidative Stress Response and Neuronal Plasticity: A Transcriptomic Analysis

## TL;DR

This study explores how cannabinol affects genes related to stress and brain cell health, suggesting it could help treat neurodegenerative diseases.

## Contribution

The study identifies novel gene modulation by cannabinol in neuronal cells, particularly in stress response and axon guidance pathways.

## Key findings

- CBN pre-treatment did not harm cell viability but affected stress response and neuroplasticity genes.
- Transcriptomic analysis showed enrichment in cellular stress response and axon guidance pathways.
- CBN shows potential as an adjuvant for neurodegenerative diseases by supporting neuronal cell survival.

## Abstract

Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ9-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects. The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques. Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated. This analysis highlighted a significant enrichment in the Reactome pathway’s cellular response to stress, cellular response to stimuli, and axon guidance. Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance.