Cannabis Use Disorder Linked to High Bipolar Disorder, Depression Risk

Cannabis use disorder may increase risk of both psychotic and nonpsychotic bipolar disorder, as well as unipolar depression.¹

New data from a prospective, population-based cohort analysis of Danish individuals show persons with an addiction to cannabis are at a nearly two-fold increased risk of depression, and nearly three-fold increased risk of bipolar disorder. The Denmark investigators believe the findings should implicate the standards for cannabis legalization and regulation, as well as efforts to increase public knowledge regarding cannabis’ impact on mental health and cognition.

A team led by Oskar Hougaard Jefsen, MD, of the psychosis research unit at Aarhus University Hospital – Psychiatry, sought to assess the potential link between cannabis use disorder and increased prevalence of unipolar depression and bipolar disorder—both psychotic and nonpsychotic subtypes—among the Denmark population.

Though many countries and territories including Denmark that have legalized cannabis for medicinal and/or recreational use are supported by a positive benefit-risk profile across numerous chronic conditions,² Jefsen and colleagues noted that the use and average potency of cannabis has increased over time.

“Cannabis use disorder is frequent among individuals with affective disorders and, in this group, is associated with increased symptom severity, suicidality, and mortality,” investigators wrote. “Although disputed, evidence suggests that use of cannabis may be associated with increased risk of developing psychiatric disorders; however, the association could also be reversed or attributable to confounding (ie, common genetic liability for cannabis use and psychiatric disorders).”

They conducted their longitudinal cohort analysis using national registrant data for all individuals born in Denmark before 2006 who were ≥16 years old and living in the country between 1995 – 2021.

The analysis included 6.65 million individuals followed up for more than 119.53 million person-years. Overall, just 60,696 individuals (0.9%) had received a cannabis use disorder diagnosis during the follow-up period; another 260,746 (3.9%) had developed an affective disorder relevant to the analysis.

Jefsen and colleagues observed a nearly two-fold increased risk of each of the following affective disorders among persons with cannabis use disorder:

• Unipolar depression (hazard ratio [HR], 1.84; 95% CI, 1.78 – 1.90)
• Psychotic unipolar depression (HR, 1.97; 95% CI, 1.73 – 2.25)
• Nonpsychotic unipolar depression (HR, 1.83; 95% CI, 1.77 – 1.89)

Overall cannabis use was associated with an increased risk of bipolar disorder—however, the risk was more pronounced in men (HR, 2.96; 95% CI, 2.73 – 3.21) than women (HR, 2.54; 95% CI, 2.31 – 2.80). Persons who used cannabis had a more than four-fold increased risk of psychotic bipolar disorder (HR, 4.05; 95% CI, 2.73 – 3.21).

Among persons with cannabis use disorder, associated risk was greater for psychotic bipolar disorder versus nonpsychotic subtypes (relative HR, 1.48; 95% CI, 1.21 – 1.81), but not unipolar depression (HR, 1.08; 95% CI, 0.92 – 1.27).

Despite limitations including an uncertainty of classified cannabis use disorder diagnoses and affective disorders, as well as the risk of detection bias, investigators stressed the findings are possibly the largest investigation to date into associations between cannabis use disorder and affective disorders.

“The results of this cohort study suggest that cannabis use is associated with an increased risk of psychotic and nonpsychotic bipolar disorder and unipolar depression,” they wrote.

The team suggested their data implicate the legalization and control strategies surrounding cannabis.

“Importantly, there appears to be a need for improved knowledge on the dose-dependent effects of cannabis use on brain, cognition, and behavior; identification of risk factors for transition from cannabis use (disorder) to psychiatric disorders; and the effects of cannabis cessation on long-term psychiatric risk,” Jefson and colleagues concluded.

References

1. ^{Jefsen OH, Erlangsen A, Nordentoft M, Hjorthøj C. Cannabis Use Disorder and Subsequent Risk of Psychotic and Nonpsychotic Unipolar Depression and Bipolar Disorder. JAMA Psychiatry. Published online May 24, 2023. doi:10.1001/jamapsychiatry.2023.1256}
2. ^{Walter K. Cannabis Use Higher in Patients With Rheumatic Diseases. HCPLive. Published June 26, 2023. Accessed May 29, 2023. https://www.hcplive.com/view/cannabis-use-higher-patients-rheumatic-diseases}