For some people, trying cannabis once can develop into an addiction they have great difficulty escaping. Now researchers have shown which genetic variants are associated with cannabis use disorder. The research also shows the processes in the brain involved in developing it.
Some people occasionally use cannabis as an intoxicant, but others need a daily fix.
The risk of developing cannabis use disorder has long been known to have a genetic component, and researchers have now identified 22 genetic variants that appear to be correlated with this disorder.
The research indicates some areas of the brain that are likely sites for the mechanisms behind the development of cannabis use disorder and shows that it is genetically correlated with such mental disorders as schizophrenia and post-traumatic stress disorder.
“More and more countries are legalising cannabis, but we do not yet thoroughly understand how this affects people differently. This study found that some people are more predisposed to develop cannabis use disorder and that the disorder is associated with the development of some mental disorders,” explains a researcher behind the study, Daniel Levey, Assistant Professor of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
The research has been published in Nature Genetics.
Examined the genetics of more than 1 million people
The researchers obtained data from several large databases to investigate the genetic background for developing cannabis use disorder.
The sources for the data included the iPsych2015 cohort and a cohort from the Million Veteran Program of the United States Department of Veteran Affairs.
The researchers used data sets on 1,054,365 individuals to link genetic variants with the development of cannabis use disorder: 886,025 with European ancestry, 123,208 with African ancestry, 38,289 with mixed United States ancestry and 6,843 with eastern Asian ancestry.
In a meta-analysis, the researchers examined data for genetic variants associated with an increased risk of cannabis use disorder for each population group.
Both the Million Veterans Program and iPsych2015 data have information on cannabis dependence and mental disorders for each individual in the study populations.
22 genetic variants associated with increased risk among Europeans
The researchers found that specific genetic variants are associated with an increased risk of developing cannabis use disorder.
The researchers discovered associated genetic variants for each ancestry: 22 for European, two each for African and eastern Asian and one for mixed United States.
However, Daniel Levey notes that the smaller ancestry groups reduced the statistical power for identifying less strongly associated genetic variants.
Thus, individuals of European ancestry do not have more associated genetic variants than the other ancestries.
“Other studies have identified some of the same genetic variants we found, but others are new. The population groups also overlap,” says Daniel Levey.
Changes to receptors in the brain
The data on the genetic variants enabled the researchers to investigate the loci of the genes and thus to find relevant genes and biological functions.
For example, genetic variants in the genes for dopamine receptors, GABA receptors and cholinergic receptors are associated with the risk of developing cannabis use disorder.
However, Daniel Levey says that this is not surprising, since all these receptors are linked to the brain’s reward system.
The researchers also investigated whether cannabis use disorder is genetically associated with an increased risk of other diseases.
This showed that some of the same genetic variants are also statistically significantly associated with the development of lung cancer even after adjusting for smoking status.
A third part of the study showed that moderate cannabis use throughout life was associated with an increased incidence of schizophrenia but not post-traumatic stress disorder. However, cannabis use disorder was associated with an increased risk of both disorders.
According to Daniel Levey, the study does not have any immediate clinical implications, but it may in the future.
“We are still hoping that our characterisation of the genetics behind cannabis use disorder can be used in practice. Perhaps in the future we can develop a genetic risk score for cannabis use disorder and advise people with high risk that they should probably not use cannabis, since they may have difficulty quitting later. In addition, we should also learn more about the genetics that link cannabis use disorder with mental disorders and other diseases and disorders to determine how they arise and how to optimally treat the people who have them,” concludes Daniel Levey.
