Cannabis Use Disorder Linked to Depression and Bipolar Disorder in Observational Study

People with cannabis use disorder (CUD) are more likely to be diagnosed with depression and bipolar disorder than those without a cannabis dependence, according to a new observational study.

After analyzing the health data of six million Danish people – and adjusting the data to account for other substance use disorders – the researchers behind the study observed that individuals with CUD were 1.84 times more likely to be diagnosed with unipolar depression and almost three times as likely to be diagnosed with bipolar disorder. Males with CUD were 2.96 times more likely to be diagnosed with nonpsychotic bipolar disorder while women with CUD were 2.6 times more likely.

The researchers posit that THC’s effects on the brain’s CB1 receptors may, in some way, be contributing to these increased risks of psychiatric disorders.

The study, which was published in JAMA Psychiatry, follows on the heels of another paper, written by several of the same researchers, using the same Danish health survey, that found that men with CUD were more likely to develop schizophrenia than women with CUD.

Depression, bipolar disorder, and cannabis

Like their recent cannabis-schizophrenia study, the researchers – who were from Aarhus University Hospital–Psychiatry and Copenhagen University Hospital, Denmark – sifted through the country’s thorough health registers of 6,651,765 people to look for associations with CUD and other disorders. This time, they homed in on rates of depression and bipolar disorder.

Around 60,696 individuals in the health registers (0.9% of the total study population) had been diagnosed with CUD, while 260,746 (3.9%) had been diagnosed with an affective disorder (such bipolar disorder or unipolar depression).

The team found that, compared with Danes who didn’t have CUD, Danes with CUD were more likely to be diagnosed with both psychotic and nonpsychotic unipolar depression and bipolar disorder.

Around 10% of Danes without CUD are diagnosed with (any type of) unipolar depression at some point in their lives (up to the age of 75), according to the health survey. This figure jumps to around 40% for Danes already diagnosed with CUD.

Even after accounting for other substance disorders, such as alcohol use disorder (AUD), the researchers say that individuals with CUD are still more likely to be diagnosed with unipolar depression – 1.84 times more likely, to be precise.

“What we found was nearly two-fold increase in risk,” Carsten Hjorthøj, an associate professor at the University of Copenhagen and co-author of the study, said during a JAMA Psychiatry podcast.

“So people who had been diagnosed with cannabis use disorder and had not previously had a diagnosis of unipolar depression, they had about twice as high [a] risk of later developing unipolar depression compared to people who had not had cannabis use disorder,” he told the podcase.

“Even after five, ten years, we still saw increased risks of unipolar depression. We are talking about up to 40% of people with cannabis use disorder eventually coming into treatment for unipolar depression.”

This kind of diagnosis gulf only got starker when Hjorthøj and his team looked at the rates of CUD and bipolar disorder.

“The results for bipolar disorder were much the same but slightly stronger,” he said.

Around 1.5% of Danes without CUD are diagnosed with (any type of) bipolar disorder at some point in their lives, according to the health survey. This figure jumps to around 14% for Danes already diagnosed with CUD.

Hjorthøj and his colleagues also noticed a stronger gender divide when it came to bipolar diagnoses. After adjusting for other factors (AUD, etc.), they observed that males with CUD were 2.96 times more likely to be diagnosed with nonpsychotic bipolar disorder; women with CUD were 2.6 times more likely.

Knowing the risks

While their study may only have been observational, given just how many people they observed, Hjorthøj and his colleagues are confident that their findings evidence a strong association with cannabis dependence and affective disorders – an association that, up until the study’s publication – had never been documented as thoroughly.

With this association now established, the next task, says Hjorthøj, is to make it better known.

“Cannabis, at least when it comes into the realm of addition or cannabis use disorder, is not harmless,” he told the JAMA Psychiatry podcast. “There are links to – we’ve seen previously, schizophrenia, psychosis – we now see affective disorders, especially bipolar disorder.”

“So, if people want to use cannabis, that’s their own decision. But they should do so from an informed position where they’re not being told that cannabis I completely harmless, but they are aware of the potential harms.”

Some researchers, however, aren't quite convinced by Hjorthøj's conclusions. David Curtis, an honorary professor at the University College London Genetics Institute, for one, has questioned the reliability of using a CUD diagnosis as a proxy for regular cannabis use.

“I don’t think this study provides strong evidence that using cannabis increases one’s risk of depression or bipolar disorder," he said in a statement to the Science Media Centre.

“The study shows that people with depression or bipolar disorder are more likely to have been previously assigned a diagnosis of ‘cannabis use disorder’. But in order to have been registered as having ‘cannabis use disorder’ one needs to have had some kind of psychiatric or emotional problem with impaired functioning in addition to consuming significant quantities of cannabis. So it is entirely possible that the people who get assigned this diagnosis are those who have a susceptibility to depression and related disorders."

“Around 20% of young people in Denmark use cannabis but in this study fewer than 1% of the sample had been assigned a diagnosis of cannabis use disorder and these may well have been people who had a pre-existing susceptibility to depression and other psychiatric disorders," Curtis – who was not part of the Danish research group – continued. 

“I don’t think that this study provides us with much information to help decide the extent to which cannabis use is, or is not, harmful,” he added.

A previous JAMA Psychiatry paper, published in 2022, reported a link between a family history of bipolar disorder and CUD. The experimental study found that relatives of people with bipolar type-II disorder, but not bipolar type-I, had an increased risk of developing cannabis dependence.

Other studies have also documented a link between cannabis and depression, and even shown that reducing cannabis use can reduce depression, in some instances. A paper published last year in the American Journal on Addictions found that four weeks of abstinence from cannabis improved cognitive performance in people with major depressive disorder and comorbid CUD.

*This article was updated on May 30, 2023, to include quotes from David Curtis, as provided by the Science Media Centre.