The Relationship Between Using Cannabis, Consuming Isothiocyanate Rich Broccoli, and HDAC Expression in Schizophrenia: A Research Protocol

Abstract

Schizophrenia is a chronic brain disorder which affects the thoughts, feelings, and behaviour of people. According to current studies, there is a relationship between schizophrenia severity and amounts of the epigenetic marking histone acetylation in the brain. As histone acetylation increases, gene expression increases. Persons with schizophrenia show elevated histone deacetylase expression which leads to reduced amounts of acetyl markings and subsequent tightening of the chromatin structure. Additionally, Δ9-tetrahydrocannabinol, a psychoactive compound present in cannabis, has been found to also cause increased histone deacetylase levels, and several studies have shown a relationship between using cannabis and the development or worsening of schizophrenia, however, the exact molecular mechanisms are unknown. Isothiocyanates, a class of organic compounds found in vegetables like broccoli, have been found to be histone deacetylase inhibitors. This study will test the relationship between cannabis, isothiocyanates, and schizophrenia at the genetic level by using normal and Disrupted in Schizophrenia 1 mice, and Chromatin Immunoprecipitation, Sequencing, Reverse Transcription Quantitative Polymerase Chain Reaction, and Western Blot. These tests will be conducted in mice before they are conducted in humans in order to first confirm that the following relationship exists. It is hypothesized that if mice eat broccoli sprouts, their histone deacetylase will be inhibited, genes responsible for cognitive function will be euchromatin, and they will have improved cognition and functional outcomes. It is also hypothesized that if mice are exposed to ∆9-tetrahydrocannabinol, their histone deacetylase will be more active, genes responsible for cognitive function will be heterochromatin, and there may be a higher chance of the development or worsening of schizophrenia. Depending on which genes are affected and how much they are affected, understanding an epigenetic relationship between cannabis and schizophrenia may help determine why it can be harmful, and how molecules like isothiocyanates can potentially reduce the harm.