Is Cannabis Use Disorder A Stepping Stone to Mental Health Disorders?

Summary: A new study sheds light on the strong link between cannabis use disorder and mental health conditions, indicating a much higher risk than previously thought.

The research, based on data from over six million Danes, reveals that individuals with cannabis use disorder have almost double the risk of developing depression and two to three times higher risk of bipolar disorder. This raises concerns as more countries are considering legalizing cannabis.

It is essential to remember that these results do not conclusively prove that cannabis use causes these disorders, as the study’s nature can’t exclude self-medication as a potential explanation.

Key Facts:

The study is one of the world’s largest of its kind, allowing for a comprehensive understanding of cannabis use disorder and its link to mental health disorders. The vast data size makes the conclusions more reliable than previous smaller studies.
According to the Danish Health Authority, a third of Danes under the age of 25 have smoked cannabis, indicating widespread usage among the youth. However, the study primarily focuses on those with a significant level of consumption to be registered with a substance use disorder.
One of the researchers, Oskar Hougaard Jefsen, emphasizes the need for more research into understanding whether cannabis has particularly harmful effects on certain individuals. This understanding could guide policies and prevention measures related to cannabis use and legalization.

Cannabis is one of the world’s most commonly used illegal drugs. New 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 legalizing 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 randomized 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.

Abstract

Cannabis Use Disorder and Subsequent Risk of Psychotic and Nonpsychotic Unipolar Depression and Bipolar Disorder

Importance

Cannabis use is increasing worldwide and is suspected to be associated with increased risk of psychiatric disorders; however, the association with affective disorders has been insufficiently studied.

Objective

To examine whether cannabis use disorder (CUD) is associated with an increased risk of psychotic and nonpsychotic unipolar depression and bipolar disorder and to compare associations of CUD with psychotic and nonpsychotic subtypes of these diagnoses.

Design, Setting, and Participants

This prospective, population-based cohort study using Danish nationwide registers included all individuals born in Denmark before December 31, 2005, who were alive, aged at least 16 years, and living in Denmark between January 1, 1995, and December 31, 2021.

Exposure

Main Outcome and Measures

The main outcome was register-based diagnosis of psychotic or nonpsychotic unipolar depression or bipolar disorder. Associations between CUD and subsequent affective disorders were estimated as hazard ratios (HRs) using Cox proportional hazards regression with time-varying information on CUD, adjusting for sex; alcohol use disorder; substance use disorder; having been born in Denmark; calendar year; parental educational level (highest attained); parental cannabis, alcohol, or substance use disorders; and parental affective disorders.

Results

A total of 6 651 765 individuals (50.3% female) were followed up for 119 526 786 person-years. Cannabis use disorder was associated with an increased risk of unipolar depression (HR, 1.84; 95% CI, 1.78-1.90), psychotic unipolar depression (HR, 1.97; 95% CI, 1.73-2.25), and nonpsychotic unipolar depression (HR, 1.83; 95% CI, 1.77-1.89). Cannabis use was associated with an increased risk of bipolar disorder in men (HR, 2.96; 95% CI, 2.73-3.21) and women (HR, 2.54; 95% CI, 2.31-2.80), psychotic bipolar disorder (HR, 4.05; 95% CI, 3.52-4.65), and nonpsychotic bipolar disorder in men (HR, 2.96; 95% CI, 2.73-3.21) and women (HR, 2.60; 95% CI, 2.36-2.85). Cannabis use disorder was associated with higher risk for psychotic than nonpsychotic subtypes of bipolar disorder (relative HR, 1.48; 95% CI, 1.21-1.81) but not unipolar depression (relative HR, 1.08; 95% CI, 0.92-1.27).

Conclusions and Relevance

This population-based cohort study found that CUD was associated with an increased risk of psychotic and nonpsychotic bipolar disorder and unipolar depression. These findings may inform policies regarding the legal status and control of cannabis use.