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Cannabis is the most widely used illicit drug worldwide (UNODC, 2023), and is likely to become more prevalent as the world sees an increase in legal cannabis markets. Meanwhile, the THC content of cannabis has increased dramatically over the past 50 years (Freeman et al., 2021), which may be associated with more serious health effects (Petrilli et al., 2021). As the US President, Joe Biden, once said, it’s like comparing the old days to modern-day marijuana “Comparing buckshot in a shotgun shell to a laser-guided missile” (Wice, 2019).
As we see greater access to more potent and more harmful cannabis products, understanding the health risks associated with use has never been more important.
But marijuana has been around for so long that we should already understand the harm, right? Unfortunately, our knowledge is…well, limited. We know that psychiatric conditions are common among cannabis users (Petrilli et al., 2021), but it is difficult to clarify whether a health condition contributes to cannabis use, cannabis use contributes to a health condition, or cannabis use and health. This situation is due to shared factors (eg low socioeconomic status). Chicken or egg type.
Several methods can be used to overcome this challenge, such as looking at genetics or following individuals long-term. Studies using these methods have found strong evidence of an association between cannabis use and psychiatric conditions including cannabis use disorder (CUD) (Petrilli et al., 2021). Unfortunately, very few of these high-quality studies have investigated the relationship between marijuana and affective disorders, some of the most common mental disorders worldwide.
In response, researchers from Denmark, Australia, and the US were able to use the most impressive data to understand whether cannabis use disorder is associated with a subsequent diagnosis of unipolar depression or bipolar disorder (Jeffsen et al., 2023).
The increased presence of THC content in marijuana underscores the need to understand the health risks associated with marijuana use.
methods
The study used nationwide Danish register data, which provides information from all permanent residents of Denmark since 1968. That’s right, Annie! Those aged at least 16 living in Denmark from 1995 to 2021 were included. Registry information captured by the study included recorded hospital diagnosis of cannabis use disorder (CUD), affective disorder, other substance use disorders (SUDs), demographics, and relevant parental information. This information was used to compare the risk of developing an affective disorder depending on whether residents had previously experienced a diagnosis for CUD.
Results
6,651,765 individuals (50.3% female; 49.7% male) were included in the analysis, followed for 119,526,786 person-years. Of these, 60,696 residents (0.9%) received a diagnosis of cannabis use disorder (CUD) and 260,746 (3.9%) developed an affective disorder.
40.7% of those with CUD had unipolar depression. After adjusting for the presence of other associated factors (eg, parental marijuana use disorder, other SUDs), individuals with CUD remained at increased risk for any type of unipolar depression (HR, 1.84; 95% CI, 1.78 to 1.90). No records of CUD. This association remained significant after adjusting for other psychiatric conditions that developed before CUD.
Another brilliance of these longitudinal data is the ability to look at the time taken between developing CUD and affective disorder. Relative to those without CUD, the risk of developing depression within the first 6-months of CUD diagnosis was higher. Despite the increased risk of depression up to 10 years after CUD.
When it comes to bipolar disorder, 14.1% received a diagnosis after CUD. As with depression, those diagnosed with CUD are more likely to develop any form of bipolar disorder. This was the case for both men (HR, 2.96; 95% CI, 2.73 to 3.21) and women (HR, 2.54; 95% CI, 2.31 to 2.80), even after adjustment for associated factors. This association remained significant after adjusting for other psychiatric conditions that developed before CUD.
Again, when looking at the time between CUD and bipolar disorder, the highest risk of diagnosis occurred within the first 6 months and remained significant beyond 10 years.
Relative to those without a cannabis use disorder, those diagnosed are significantly more likely to develop unipolar depression or bipolar disorder.
Conclusions
Two key implications are clear from these results:
- Individuals with cannabis use disorder (CUD) are at increased risk of later developing unipolar depression and bipolar disorder.
- The risk of this mutation is highest within the first 6 months of developing CUD, but remains elevated chronically.
A diagnosis of cannabis use disorder, especially within the first 6 months, increases the risk of developing an affective disorder.
Strengths and limitations
What makes this evidence compelling is the sheer size of the sample and the length of time they were monitored. Not only does this allow the authors to capture data from a broader population, but it also allows for dynamic changes in mental health and substance use that occur over the life course.
Sample size is also important when investigating the consequences of conditions with low prevalence (0.9% diagnosed with CUD). Given that the study included only 1,000 people, there were too few participants with exposure (CUD) to confidently identify an association with outcome (affective disorders).
The longitudinal nature of the study also helped with the chicken-or-egg situation. As the authors note, past studies often do not take into account the order in which these conditions occur, so they cannot draw conclusions about whether CUD increases the risk of affective disorders or vice versa. However, this study was able to focus on individuals with CUD first, providing greater certainty that CUD contributed to affective disorder and not the other way around.
On the other hand, it is worth pointing out two limitations of this study. First, participants were only identified as having CUD or other mental health diagnosis according to the psychiatric registry. While it captures people who start treatment, we know that people with these conditions often do not access treatment (Substance Abuse and Mental Health Services Administration, 2022). Therefore, the analysis could not account for these individuals, which may have altered the results.
Second, we must be cautious when interpreting these findings to international populations. Relative to other countries, treatment services are more affordable in Denmark, and the availability of cannabis products and their THC concentrations differ (Freeman et al., 2021). Therefore, these findings may be specific to individuals living in Denmark.
Although this study makes a significant contribution to the literature, caution should be exercised with its generalization to untreated populations and those outside of Denmark.
Implications for practice
Despite these limitations, these findings have major implications for clinical practice. As marijuana policies become more permissive, there is reasonable concern that this will increase rates of CUD and further contribute to the incidence of other mental health disorders. However, several strategies can be implemented to compensate for these losses.
The authors concluded that the greatest risk of transition from CUD to an affective disorder diagnosis is within the first 6 months, highlighting the importance of early treatment. Traditionally, the treatment of mental health and substance use disorders has been silenced (Nordentoft et al., 2022), where substance use disorders are often neglected in other mental health treatment and vice versa. Now that we know these conditions are often related, it is critical to devise treatment strategies that effectively address both conditions early in their development.
These conditions often emerge during adolescence, so youth must have the knowledge and skills to access treatment services. Governments must invest in prevention and information programs aimed at countering marijuana use and the harm it causes.
However, we have our heads buried in the sand to think that young people will stop using cannabis. Therefore, we need to effectively communicate harm-reduction strategies. The greatest risk of CUD and resulting harm occurs when young people use marijuana at a young age, so delaying use is key. We also know that frequent use of more potent products (higher concentrations of THC) is associated with a greater risk of harm. Although illegal marijuana markets make it difficult to gauge the potency of the product, users can titrate their use or use smaller amounts. For more details on these harm-reduction strategies and others, please see the Low-Risk Cannabis Use Guidelines (Fisher et al., 2017).
Finally, policymakers must craft marijuana legislation that focuses on health. Many countries have actually adopted legalized marijuana policies, but these policies vary dramatically in terms of what products can be obtained, from where, and how they can be consumed. Lawmakers should consider the health consequences of these factors and how they can be addressed before jumping into the marijuana pool.
Policymakers and clinicians should communicate the associated risks and effective harm-reduction strategies with individuals affected by cannabis use disorders.
Declaration of Interests
There are no conflicts of interest to declare.
Links
Primary paper
Jefsen OH, Erlangsen A, Nordentoft M, Hjorthøj C. (203) Cannabis use disorder and subsequent risk of psychotic and nonpsychotic unipolar depression and bipolar disorder. JAMA Psychiatry. 2023;80(8):803–810. doi:10.1001/jamapsychiatry.2023.1256
Other references
World Drug Report (2023). United Nations.
Freeman, TP, Croft, S., Wilson, J., Stylianou, S., ElSohly, M., Di Forti, M., & Lynskey, MT (2021). Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: a systematic review and meta-analysis. addiction, 116(5), 1000-1010.
Petrilli, K., Ofori, S., Hines, L., Taylor, G., Adams, S., & Freeman, TP (2022). Association of cannabis use with mental illness and addiction: a systematic review. Lancet Psychiatry, 9(9), 736-750.
VICE (2019). Weed is stronger than ever. That’s why it should be legal.
Administration of substance abuse and mental health services. (2022) Key Substance Use and Mental Health Indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration.
Nordentoft M, Krantz MF, Hageman I. Rights-based mental health care—the benefits of tax-financed universal mental health care: lessons from Denmark. JAMA Psychiatry.2022;79(1):7–8. doi:10.1001/jamapsychiatry.2021.3167
Victorovich, M., Abdulle, A., Di Pierdomenico, K., & Boma, SA (2019). Models of joint disorder service: approach, coordination and access to care. Frontiers in Psychiatry, 10430489.
Fisher, B., Russell, C., Sabioni, P., van den Brink, W., Le Fol, B., Hall, W., Rehm, J., & Room, R. (2017). Low-risk cannabis use guidelines: a comprehensive update of evidence and recommendations. American Journal of Public Health, 107(8), e1–e12.
