Scientists Uncover the Genetic Connection Between Cannabis Use Disorder and Mental Health Illness

 Key Takeaways

• Cannabis use and cannabis use disorder (CanUD) are different entities and should not be treated as the same condition.
• Compared to cannabis use alone, CanUD had much higher genetic correlations with psychiatric disorders.
• This aligns with years of clinical studies that indicate that heavier and more problematic cannabis use is associated with mental health risks, compared to occasional use.
• The study revealed an overlap and interconnection of the genetic links between CanUD and a few mental disorders.
• Distinguishing cannabis use from CanUD could improve future research, risk assessment, and mental health care.

Mental health disorders are one of the most common causes of disability and loss of quality of life affecting hundreds of millions of people around the world. Many conditions including depression, anxiety, schizophrenia, bipolar disorder and post-traumatic stress disorder (PTSD) are caused by a combination of genetic, environmental and lifestyle factors. Among the many influences being investigated, cannabis has remained one of the most debated.

Over the past few decades, cannabis use has increased significantly, driven by changing public attitudes and expanding legalization for both medical and recreational purposes. Meanwhile, researchers have reported associations between cannabis and several psychiatric conditions. But these conclusions were often followed by more questions than answers. Did cannabis increase the risk of mental illness, or were people with a genetic predisposition to psychiatric disorders simply more likely to use cannabis? It was also important to determine whether occasional cannabis use and cannabis use disorder (CanUD) were equally associated with mental health risk.

Why Is Cannabis and Mental Health So Controversial?

 

1.               The Warning Signs Doctors Had Already Noticed About Self-Medicating with Cannabis

Long before scientists studied genes, there was this disturbing trend that came to light in the mind of the clinicians. The rate of cannabis use among people with mental illness is significantly higher than among the general population and their motivations are very similar. In multiple surveys, people reported using cannabis to manage pain, anxiety and depression, sometimes referring to it as their "medicine. About half of people who use cannabis because of anxiety, depression or sleeping difficulty actually use it to address those very issues.

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 The problem is that the clinical evidence was seldom to support the “medicine” label. Among schizophrenia patients, frequent cannabis use doubled the risk of psychosis, and excessive use quadrupled it. Most long-term studies have found that cannabis exacerbates the course of illness more than help in depression and bipolar disorder; and earlier onset of cannabis use has been associated with a reduced time latency for a diagnosis of depression. Even in PTSD, where cannabis is popularly seen as helpful for sleep, people who used it to cope with nightmares often reported worse sleep quality later on.

So, the real question is: why do so many people think that cannabis is working when it was not? Main idea: Cannabis provides short-term relief, a temporary distraction from distress (at the time), with the potential for increased withdrawal and craving over time. This is known as the self-medication trap: pain gets better for a short time, only to be diminished again by taking another dose or use of the medication.

2.               A Debate That Science Couldn't Settle: Genetics vs. Environment in Psychiatric Risk

Despite this pattern being well established in clinic, one fundamental question remained unanswered for years: Does cannabis contribute to mental illness, or are people with a genetic predisposition more likely to use cannabis in the first place?

Several factors made this question difficult to answer: 

• Conflicting evidence: There were some studies that reported cannabis use being associated with psychiatric disorders, but others indicated that there was a more complicated relationship. 
• Shared genetic risk: Mental illnesses and cannabis-related behaviors may share common genetic factors, making it difficult to determine cause and effect. 
• Association vs. causation: Observing a relationship between cannabis use and mental illness does not necessarily mean that one causes the other.
• Treating all cannabis users, the same: Previous studies did not differentiate between the two, although clinical observations suggested that they would pose very different risk.

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These unanswered questions laid the foundation for a new generation of genetic studies aimed at uncovering the true relationship between cannabis and mental health.

How Scientists Investigated the Genetic Link?

3.               Looking Beyond Cannabis Use Alone: Cannabis Use vs. Cannabis Use Disorder

As the scientific study of cannabis and mental health grew, researchers realized that simply asking about current or past cannabis use was not sufficient. Indeed, previous clinical research had suggested this: It appeared that occasional or casual use of cannabis was less consistently and strongly associated with mental illness, whereas long-term, high-dose use, which was more likely to qualify for a mental health diagnosis, was more strongly associated. 

This prompted researchers to look more closely at the pattern and severity of cannabis use, leading to an important distinction: 

• Cannabis use refers to whether a person has ever used cannabis. 
• Cannabis use disorder (CanUD): A diagnosis characterized by recurrent use of cannabis that results in dependence or major functional problems in life. 

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Emerging evidence suggested that these two traits might not have the same biological basis. This led to a very important question: is there a genetic difference between cannabis use and cannabis use disorder, and does that account for the difference in associations with mental illness?

    Cannabis Use vs. Cannabis Use Disorder (CanUD)

4.               A Breakthrough Unraveling the Genetic Link Through Genome-Wide Association Studies and Mendelian Randomization

A team of researchers from the United States conducted one of the most comprehensive genetic studies to date. To investigate the genetic relationship between cannabis-related behaviors and psychiatric disorders, the researchers separated out cannabis use and the diagnosis of cannabis use disorder (CanUD) to see if they shared the same relationship with psychiatric disorders.

 The researchers worked with a massive, genome-wide association study (GWAS) database representing hundreds of thousands of people. They used a variety of advanced genetic methods to examine both genetic correlation and potential causal associations between cannabis-related traits and major psychiatric conditions, such as genetic correlation analysis, local genetic correlation, Mendelian randomization, and genomic structural equation modeling (Genomic-SEM).

Implications for Future Mental Health Research

The researchers used more than one complementary measurement, so that they were able to come up with one of the most informative assessments to date on how different cannabis use and cannabis use disorder are related to mental illness, and shed new light on a debate that clinicians and scientists have long been debating.

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5.               The Genetic Evidence Revealed: Links to Schizophrenia, Depression, PTSD, Bipolar Disorder, and ADHD

The study uncovered several important discoveries that reshape our understanding of the relationship between cannabis and mental health: 

• Cannabis use disorder (CanUD) showed much stronger genetic links to psychiatric disorders than cannabis use alone. 
• Significant genetic similarity was found between CanUD and schizophrenia, bipolar disorder, major depression disorder, ADHD, and PTSD. 
• The analyses suggested bidirectional genetic relationships, meaning that genetic risk factors for some psychiatric diseases may make individuals more susceptible to CanUD, and genetic liability to CanUD may make individuals more susceptible to some psychiatric diseases. 
• One of the most significant findings was that cannabis use and cannabis use disorder are genetically distinct traits, rather than different stages of the same behavior. 
• The researchers isolated these two traits, and made a more clear and biological explanation for a pattern of problematic cannabis use that clinicians have been observing for years: the correlation between problematic cannabis use and mental illness is much stronger than the correlation between casual cannabis use and mental illness. 

 An exception to this is anorexia nervosa was not the typical case. It demonstrated a weak association to occasional cannabis use and none to CanUD at all, a reminder that this association is not universal in all conditions.

6.               Why Cannabis Use and Cannabis Use Disorder Aren't the Same: Understanding Problematic Cannabis Use and Dependence Genetics

There is a common misunderstanding in cannabis research that taking cannabis and having a cannabis use disorder are equivalent. The clinical picture, and now the genetic evidence, says they are not.

The difference is important because: 

• Cannabis use simply means a person has used cannabis, whether occasionally or regularly. 
• Cannabis use disorder (CanUD) is a medical condition that involves continued cannabis use despite negative consequences, frequently with dependence and a lack of control. 
• The genetic study found that dependency on a drug and not just exposure is what poses the most serious mental-health risks, and that the genetic links with psychiatric disorders were much stronger in the studies of CanUD than in those of cannabis alone, consistent with the clinical literature. 

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• This suggests that the impact of mental health risk is more associated with problematic cannabis use than cannabis exposure. 
• A distinction between these two attributes would facilitate future research, would provide identification of individuals at greater risk and would allow for more specific prevention and treatment strategies.

7. What This Means for Mental Health Research and the CanUD Genetic Study

This study will greatly contribute to the complex understanding between cannabis use and mental health. Importantly, it not only considers the difference between cannabis use and cannabis use disorder, but also provides examples of its importance for research and clinical practice.

These findings have implications for practice: 

• Better research design: Future research may examine use of cannabis and use of CanUD in isolation with the goal of more accurate and valid conclusions. 
• Identification at an earlier stage: Identifying patients who potentially have a genetic susceptibility to CanUD may enable mental health interventions to be implemented at an earlier stage. 
• Smarter public health approach: There is a focus on smarter public health approaches, prevention and education strategies can be targeted to problematic use and not to cannabis in general. 
• More specific treatments: Better understanding of common risk factors may enhance treatment of individuals who are at risk of psychiatric disorders and cannabis use disorders, thereby changing the way clinicians might react to patients stating that they use cannabis to "self-medicate.

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Although it is a piece of a larger puzzle, the study is important to the scientific understanding of the interrelatedness between cannabis use and mental illness, and offers exciting potential for future research.

8. Where Does Research Go from Here? Amid Bidirectional Genetic Risk and Cannabis Legalization

This study provides answers to a number of enduring questions, but also creates new spaces for inquiry.  Future research will aim to: 

• Identify stressors, trauma and early life events that influence genetic risk.  
• Discuss the biologic processes linking cannabis use disorder to psychiatric disorders. 
• Investigate whether these genetic connections are the same in various groups and ethnicities. 
• Be able to identify and talk about the potential for genetic research to aid in the identification, prevention and treatment of vulnerable people at an earlier age.  
• Long-term studies to gain a better understanding of the relationship between cannabis use disorder and mental health over time. 

Where Does Research Go from Here?

As technology in genetics continues to progress, researchers can gain a deeper insight into how cannabis-related behaviors relate to mental health, leading to better prevention and intervention strategies.

9. Limitations 

The study was predominantly genetic and environmental/lifestyle factors were not studied in all. 

• The genetic information was mainly from people with European ancestry, which may restrict the generalizability of the results to other groups. 
• The study found genetic connections, but these can't be used to fully account for the biological relationships between cannabis use disorder and psychiatric disorders. 
• Even the clinical studies used to provide background information on cannabis use have small sample sizes in some regions, and are based on self-reports of cannabis use, particularly in PTSD research.

10. Conclusion

The connection between cannabis and mental well-being has long been mysterious. The clinicians had long observed that heavy use of cannabis was associated with poorer psychiatric outcomes, while occasional use was quite a different story, with no clear biological basis to explain the relationship with poorer psychiatric outcomes. This ground-breaking genetic research is what we need to prove how different cannabis use is to cannabis use disorder and so should be treated. The findings provide a more solid basis for future investigations, public health approaches, and understanding of mental illness, as the genetic links to psychiatric disorders between the two distinct groups are uncovered. While scientists discover how complex it is for genes to interact with behavior and mental illness, can the future of prevention and treatment of psychiatric illnesses be influenced if we could understand the difference between genes and lifestyle?

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Frequently Asked Questions

• Is cannabis use disorder genetically linked to depression?

Yes. This study revealed that there was significant genetic overlap between cannabis use disorder (CanUD) and major depression, and that there was evidence of a bidirectional genetic risk between these two disorders.

• Does heavy cannabis use cause psychosis?

The study has found that clinical evidence indicates that frequent cannabis use doubles the risk of onset of psychosis among patients with schizophrenia, and excessive use quadruples the risk, which is consistent with the higher genetic correlation found for CanUD.

• What is the difference between cannabis use and cannabis use disorder?

Cannabis use is defined as use of cannabis at any point in one's life, and cannabis use disorder (CanUD) is defined as dependence and impairment of functioning. The genetic study validated the idea that these are genetically separate aspects of behavior, not separate phases of the same behavior.

• Can genetics predict cannabis use disorder risk?

The GWAS data indicated that genotypic liability is important for CanUD and its correlation with psychiatric disorders, but that environmental and lifestyle factors were not properly measured in this study.

• Why does cannabis make anxiety and depression worse over time?

Researchers say that cannabis addiction can be a self-medication trap, a situation in which people use drugs for short-term relief, but eventually find they feel more withdrawal and craving when they use the drug, making their condition worse.