Cannabis is one of the world's most commonly used illegal drugs. New Danish research suggests that cannabis use disorder is more strongly linked with the development of mental disorders than previously assumed.

The study includes register data from more than six million Danes and its findings indicate that cannabis use disorder increases the risk of both psychotic and non-psychotic depression and bipolar disorder.

"When we take differences in gender, age, socioeconomics and family history, and more into account, we see that cannabis use disorder is associated with almost twice the risk of developing depression and a two-to-three-times higher risk of developing bipolar disorder in both men and women," says Oskar Hougaard Jefsen, a PhD student from the Department of Clinical Medicine at Aarhus University. He is the lead author of the study, which has just been published in the scientific journal JAMA Psychiatry.

According to the Danish Health Authority, one in three Danes under the age of 25 has smoked cannabis. However, the new study only focuses on people with a significant consumption of cannabis such that they have been registered with a substance use disorder – e.g. because they have been in contact with the substance abuse treatment system or other parts of the healthcare system.

More countries are legalising cannabis

Several studies have supported the hypothesis that extensive cannabis use is not harmless to human mental health. For example, previous studies suggest that cannabis use disorder can increase the risk of developing schizophrenia. But until now, the risk of other mental disorders has been sparsely studied.

In this study, researchers from Aarhus University and the University of Copenhagen have analysed data from Danish nationwide registers such as the National Patient Register, the Danish Psychiatric Central Research Register and the Danish Register of Pharmaceutical Sales.

"The study is the largest of its kind in the world, and our findings suggests that cannabis use disorder is also associated with an increased risk of developing depression and bipolar disorder. The results recommend caution when it comes to using cannabis. This applies to people with an increased risk of developing mental illness, and to politicians and other decision-makers who are discussing the possibilities of legalising cannabis," says Oskar Hougaard Jefsen.

An increasing number of countries are legalising the production and sale of cannabis for medicinal and recreational use. Since 2018, general practitioners in Denmark have been able to write prescriptions for drugs based on cannabis for patients as part of a trial scheme that also gives companies and individuals the opportunity to produce cannabis for medicinal or industrial use.

Oskar Hougaard Jefsen believes that the results of the study should be considered when it comes to legalising and controlling cannabis use.

"We should conduct more research into whether there are people for whom cannabis is particularly harmful. This could strengthen preventative measures," he says, adding that there is a particular need for more knowledge about the dose-dependent effects of cannabis use on the brain, cognition and behaviour, and for identifying risk factors for the transition from cannabis use disorder to psychiatric disorders.

No conclusive evidence

Oskar Hougaard Jefsen points out that, despite the indications in the study, it does not provide conclusive evidence that cannabis causes these mental disorders.

For example, he cannot rule out that undiagnosed depression or bipolar disorder has led some of the people in the register-based study to develop cannabis use disorder – i.e. the disease resulted in the abuse and not the other way around.

"But when we see an increased disease risk – even ten years after the cannabis use disorder has been registered – I don't think that self-medication can be the only explanation. It seems unlikely that so many people would go undiagnosed for so long," he says.

"Danish register data really gives us a unique opportunity to take into account many of the crucial factors that could affect the results. However, conclusive evidence would require a randomised controlled trial in which a group of people would have to smoke large amounts of cannabis to see if this increased their risk of developing mental illness in the long term, and such a study would of course be unethical," he says.

The research results - more information

• The study is a register-based epidemiological cohort study of 6,651,765 people born in Denmark before 2006, and who lived in Denmark between 1995 and 2021. An equal number of men and women appear in the study.
• The partners are Associate Professor Carsten Hjorthøj, Senior Researcher Annette Erlangsen and Clinical Professor Merete Nordentoft – all three from the University of Copenhagen.
• Read more in the scientific article: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2804862

Contact

Oskar Hougaard Jefsen, PhD student
Aarhus University, Department of Clinical Medicine - Psychoses Research Unit
Email: oskar.jefsen@clin.au.dk

Ole Mors, professor and consultant
Aarhus University, Department of Clinical Medicine - Psychoses Research Unit
Telephone: +45 29 47 97 80
Email: ole.mors@clin.au.dk