Cannabis is the most widely used illegal drug in Denmark. Up to one in four Danes between the ages of 16 and 24 have taken the drug in the past year. At the same time, cannabis is also highly addictive. It is estimated that one in ten of those who use cannabis develop an addiction or a diagnosed cannabis use disorder.

A large genetic study with data from more than 380,000 people has identified two places in the genome, where genetic variation significantly increases the risk of cannabis use disorder.

The results are published in Lancet Psychiatry.

The researchers analysed DNA from 21,000 people with cannabis use disorder and 360,000 without this diagnosis. They could link genetic variation in the gene FOXP2 to cannabis use disorder – a gene that is also associated with language development and risk-taking behaviour. In addition to this, the researchers also confirmed a previous finding that links genetic variation in the gene CHRNA2 to cannabis use disorder, a gene which can also be linked to nicotine addiction, .

"We know that approximately fifty to seventy per cent of the risk of developing cannabis use disorder is due to genetics, but we know very little about where in the genome the genetic variants that increase the risk are located," says Ditte Demontis, who is associate professor at the Department of Biomedicine at Aarhus University and one of the leading researchers behind the study.

According to her, the genetic architecture of cannabis use disorder is complex and many risk genes still need to be identified. 

"The genetic risk of cannabis use disorder comprises many genetic variants, each of which only increases the risk slightly. So we can’t say anything about a person's risk of becoming addicted to cannabis by simply looking at the two variants we have identified so far," she says.

When researchers find more risk variants, it may be possible, based on the genetic profile, to advise people with many risk variants against using cannabis.

"We also hope that genetic studies will make it possible to identify which biological mechanisms are affected, and thus develop a treatment for cannabis use disorder," says Ditte Demontis.

With data from the Adolescent Brain Cognitive Development (ABCD) study, which has studied brain development in more than 4,500 children, the researchers also discovered that children who were more genetically predisposed to cannabis misuse had, on average, a slightly lower amount of nerve fibres in the brain than children who had a low genetic risk of developing cannabis use disorder – and this was the case before they began using the drug.

"This suggests that some people may be vulnerable to a possible misuse long before they smoke their first joint," says Ditte Demontis, and stresses that the study also shows that certain behavioural factors such as a willingness to take risks, schizophrenia and a lower educational level share genetics with cannabis use disorder. 

"Even though it is, of course, impossible to develop a problematic relationship with cannabis if you never use it, our data suggests that the genetic factors which may affect some people to use cannabis, differ from the genetics that form the basis of a diagnosed cannabis use disorder," she says.

The correlation between education, use of cannabis and cannabis use disorder is particularly interesting because the genetic disposition for using cannabis overlaps with the genetics associated with a higher level of education, while the genetics underlying a misuse are linked to a lower level of education. 

"The positive genetic correlation between the use of cannabis and more years in the educational system may possibly be due to other factors that we’re not yet completely aware of. One possibility is that the genetic variants that are shared also affect social skills. If you are very social and out-going, you may have a higher probability of using cannabis occasionally, without becoming addicted. If a person also functions well socially, this will also have a positive effect on their opportunities for taking an education," says Ditte Demontis.

Background for the results

• Type of study:iPSYCH has collected genetic information on 21.000 people diagnosed with cannabis use disorder and 360.000 control subjects.
• Partners:The Psychiatric Genomics Consortium
• Professor Arpana Agrawal, Washington University School of Medicine, Saint Louis, USA, deCODE Genetics from Island
• The study is financed by the Lundbeck Foundation and international foundations such as NIH.
• The scientific article is available in Lancet Psychiatry

Contact 

Associate Professor Ditte Demontis 
Aarhus University, Department of Biomedicine 
Email: ditte@biomed.au.dk
Mobile: (+45) 2853 9746