New research shows that a specific gene is associated with an increased risk of cannabis abuse. The gene is the source of a so-called nicotine receptor in the brain, and people with low amounts of this receptor have an increased risk of cannabis abuse.

Cannabis is the most commonly used illegal drug in both Denmark and internationally, and around one in ten users becomes addicted to the drug. Researchers from iPSYCH have discovered a gene that they associate with the abuse of cannabis.

"We discovered that the disorder was associated with a genetic variant. This variant affects how much of a certain nicotine receptor is formed in the brain," explains the senior author of the study.

The genetic variant discovered by the researchers affects how much of a specific nicotine receptor alpha 2 subunit (CHRNA2) is formed. People who have less of this receptor in the brain are at greater risk of becoming cannabis abusers.

Researchers used a nationwide Danish cohort to analyse the complete genome of more than 2,000 cannabis abusers and the genome of 50,000 control subjects. The researchers subsequently repeated these findings in an analysis of a further 5,500 cannabis abusers and more than 300,000 control subjects.

The researchers also included genetic data from studies in which researchers examined the underlying genetics for cognition such as e.g. the ability to complete an education.

Here, they found that people with a higher number of genetic variants associated with impaired cognition also have an increased risk of cannabis abuse. Analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with cannabis use disorder (CUD) in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.

"People who abuse cannabis often do worse in the education system, and our results show that this can be partly explained by genetics. That is to say that people with an abuse problem have more genetic variations in the genome which increase the risk of cannabis abuse, while at the same time negatively affecting their ability to get an education," explains the senior author.

The study is the first of its kind on this scale and represents a step towards understanding the particular biological mechanisms, which lie behind the abuse of cannabis.

"We need to undertake even more research into how the genetic differences in the genome contribute to the development of cannabis abuse, and we need to map out the precise biological mechanisms that lead to one person having a higher risk of becoming a substance abuser than another. Our hope is to be able to improve treatment and perhaps in the long-term even prevent this abuse," says the senior author.

https://www.nature.com/articles/s41593-019-0416-1