Causality of the link between bipolar disorder and cannabis use

Diet and lifestyle 25. may 2021 3 min PhD student Oskar Hougaard Jefsen Written by Kristian Sjøgren

New research in Denmark shows that having bipolar disorder appears to increase the risk of using cannabis.

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People with a mental disorder are much more likely to use or misuse drugs – including cannabis.

For many years, researchers have investigated whether using cannabis increases people’s risk of developing a mental disorder or whether people with mental disorders are more likely to try smoking cannabis.

The results suggest that bipolar disorder increases the risk of trying cannabis, which may eventually lead to lifetime use. The researchers also investigated whether smoking cannabis increases the risk of developing bipolar disorder but found no evidence to suggest this.

“The results improve our understanding of why so many people with mental disorders use drugs with cannabis. This is a big problem in the mental health services, which often have to treat people not only for a mental disorder but also for a substance use disorder. Treating patients for these two disorders at the same time can be challenging, and our results also indicate that they may be inseparable, because their mental disorder is an important cause of their substance use,” explains a researcher behind the new study, Oskar Hougaard Jefsen, ph.d. student, Psychosis Research Unit, Aarhus University Hospital.

The research has been published in Addiction Biology.

Genetic link between mental disorders and substance use

Since clinical trials examining whether cannabis use causes mental disorders or vice versa are practically and ethically impossible, the researchers behind the new study used a statistical tool called Mendelian randomization.

Some people are more genetically predisposed to develop bipolar disorder (or use cannabis) than others, and this small difference in genetic predisposition is randomly distributed between people, resulting in a naturally randomized experiment.

Statistically comparing the different genetic effects for bipolar disorder and cannabis use then enables the researchers to infer causality: whether one seems to cause an increase in the risk of the other or vice versa.

Other researchers have used Mendelian randomization to determine that schizophrenia, depression and attention-deficit/hyperactivity disorder increase the risk of using cannabis.

“Several studies have used Mendelian randomization to determine that cannabis use increases the risk of developing schizophrenia and vice versa. However, there had been no Mendelian randomization studies on the link between bipolar disorder and cannabis use,” says Oskar Hougaard Jefsen.

Genetic variants associated with increased risk of mental disorders

Oskar Hougaard Jefsen says that this analysis requires determining which genetic variants are associated with an increased risk of bipolar disorder and cannabis use.

A genetic variant is a small genetic difference between people. Specific genetic variants are associated with increased risk of developing a specific disease, having specific personality traits, or exhibiting a specific type of behaviour. No single gene causes bipolar disorder or cannabis use, but the combination of many genetic variants with small effects can increase the risk.

If genetics can explain much of why someone develops bipolar disorder, for example, researchers characterize this as a powerful genetic instrument, but this does not apply to either bipolar disorder or cannabis use. In addition, some genetic variants may predispose to more than one thing.

“Genetic predisposition for bipolar disorder is similar to that for risk-taking behaviour and extroversion. We know that these personality traits are associated with an increased risk of using cannabis, and many people with bipolar disorder display the same personality traits,” explains Oskar Hougaard Jefsen.

Results not surprising

The researchers used publicly available data from previous genetic studies on mental disorders and cannabis use, such as the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) in Denmark and the UK Biobank, and Oskar Hougaard Jefsen found no evidence suggesting that cannabis use is associated with an increased risk of developing bipolar disorder.

Conversely, the researchers found a fairly robust signal suggesting that bipolar disorder increases the risk of using cannabis.

According to Oskar Hougaard Jefsen, the results are not surprising.

“People with bipolar disorder in the manic phase are often impulsive, sensation-seeking and prone to risk-taking. These traits may contribute to them using cannabis for the first time,” says Oskar Hougaard Jefsen.

The results are not totally clear-cut

Oskar Hougaard Jefsen also indicates that the genetic predisposition for both bipolar disorder and trying cannabis is so small that the results are not set in stone.

“The genetic instrument is especially very weak in relation to the genetic risk of trying cannabis. This is like comparing two groups of people with one only slightly more prone to try cannabis than the other,” explains Oskar Hougaard Jefsen.

Bipolar disorder is less strongly related to the use of cannabis than schizophrenia.

“Cannabis research has more strongly linked schizophrenia with cannabis use. Relatively good evidence indicates that long-term cannabis use can increase the risk of developing psychosis or schizophrenia,” says Oskar Hougaard Jefsen.

In addition, according to Oskar Hougaard Jefsen, smoking cannabis once and developing cannabis addiction differ vastly.

“Determining that bipolar disorder increases the risk of using cannabis does not necessarily mean that it also leads to cannabis dependence. Many people smoke cannabis once or twice and stop there,” he concludes.

Bipolar disorder and cannabis use: a bidirectional two-sample Mendelian randomization study” has been published in Addiction Biology. In 2020, the Novo Nordisk Foundation awarded a grant to Søren Dinesen Østergaard for the project Mental Health Consequences of the COVID-19 Pandemic.

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