Summary: A large genetic study reveals that cannabis use disorder (CanUD) is strongly linked to increased risk for multiple psychiatric disorders, including depression, PTSD, ADHD, and schizophrenia. By analyzing global and local genetic correlations, colocalization, Mendelian randomization, and structural equation modeling, researchers showed CanUD has distinct genetic signatures compared to casual cannabis use.

The findings suggest bidirectional causal relationships between CanUD and many psychiatric conditions, raising concerns about the mental health risks of heavy and prolonged cannabis use. These results highlight the need for caution as cannabis becomes more widely used and legalized, particularly for individuals vulnerable to mental health disorders.

Key Facts

• CanUD Genetics: Cannabis use disorder (CanUD) shows strong genetic overlap with multiple psychiatric disorders, much more than occasional cannabis use.
• Bidirectional Risk: CanUD and many psychiatric disorders increase each other’s risk, creating a feedback loop of vulnerability.
• Shared Variants: Specific genetic regions, such as those near CHRNA2, are implicated in both CanUD and schizophrenia.

Source: Neuroscience News

As cannabis becomes more widely legalized and socially accepted, its use has skyrocketed — both recreationally and medically. Yet evidence is mounting that this seemingly benign plant may carry risks for mental health, particularly when use escalates into cannabis use disorder (CanUD).

A groundbreaking new genetic study now sheds light on how cannabis use, CanUD, and psychiatric disorders are intertwined — and the results may surprise both advocates and skeptics alike.

Researchers analyzed the genetic underpinnings of two distinct cannabis-related behaviors: occasional use and clinically diagnosed CanUD. They then compared these patterns to a range of psychiatric and personality traits, including schizophrenia, bipolar disorder, depression, anxiety, ADHD, and PTSD.

Their findings revealed striking differences between mere use and full-blown CanUD — differences that could help explain why some cannabis users develop serious mental health issues while others do not.

Cannabis Use vs. Cannabis Use Disorder

It’s well known that cannabis can have calming or even therapeutic effects for some people. But heavy, prolonged use can lead to CanUD, characterized by compulsive use despite harm. In the United States alone, over 16 million people meet criteria for CanUD each year — a staggering figure given the increasing perception of cannabis as harmless.

The researchers found that cannabis use and CanUD are genetically distinct, despite being moderately correlated. While both were associated with psychiatric risk to some degree, CanUD showed much stronger and broader genetic overlap with nearly every psychiatric disorder tested.

Specifically, CanUD had strong genetic correlations with ADHD, major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BPD), PTSD, and anxiety. Even personality traits such as neuroticism and low agreeableness were tied more to CanUD than to mere use. In contrast, cannabis use itself showed weaker associations, and in some cases none at all, with the same psychiatric traits.

One of the most notable findings was that while cannabis use was modestly correlated with anorexia nervosa (AN), CanUD was not — suggesting that the relationship between cannabis and body weight may involve different biological mechanisms than those driving CanUD.

The Case for Causality

Correlations alone can’t tell us which comes first — cannabis problems or psychiatric illness. To tackle this, the team used a technique called Mendelian randomization, which leverages genetic variants as natural experiments to infer causal relationships.

The results showed that CanUD has a bidirectional causal relationship with many psychiatric disorders. In other words, having CanUD increases the risk of developing disorders like schizophrenia, depression, ADHD, and PTSD — and having these disorders in turn raises the risk of developing CanUD. This two-way street underscores how vulnerable populations may spiral into cycles of worsening cannabis use and psychiatric symptoms.

Cannabis use itself, by contrast, showed almost no causal effects on psychiatric disorders, except for ADHD. Conversely, psychiatric disorders like schizophrenia and bipolar disorder increased the risk of cannabis use — suggesting that people with these conditions may be self-medicating with cannabis, even though it might worsen their underlying illness over time.

The Genetic Fingerprints

The study didn’t stop at correlations and causality. By zooming in on specific regions of the genome, the researchers identified shared genetic variants that may drive both CanUD and psychiatric disorders.

One such variant was strongly associated with both CanUD and schizophrenia, located near a gene that affects nicotinic receptors in the brain — which are also implicated in smoking and addiction.

This overlap highlights the biological commonalities between different forms of substance use and mental illness — and why treating one may require addressing the other.

Why This Matters

These findings carry significant public health implications. Cannabis is often promoted as a treatment for conditions like PTSD or depression — and in some U.S. states it’s even approved for such use despite limited evidence.

But if CanUD can actually worsen these very conditions in vulnerable individuals, as this genetic evidence suggests, then blanket claims of cannabis as harmless or therapeutic are misleading.

The authors caution that while cannabis use alone isn’t strongly linked to most psychiatric disorders, progression to CanUD appears to unleash a cascade of genetic risk factors that amplify mental illness. This dose–response relationship should inform both policy and clinical practice — encouraging prevention of heavy, compulsive use rather than demonizing casual users.

What’s Next?

The genetic insights from this study open avenues for more personalized approaches to cannabis regulation and treatment. Individuals at high genetic risk for CanUD and psychiatric disorders could be counseled about their susceptibility, just as we screen for genetic risk factors for heart disease or cancer.

Furthermore, understanding the shared genetic architecture could lead to therapies that target the common biological pathways underlying both CanUD and mental illness.

The Bottom Line

This study delivers a nuanced, data-driven message: Cannabis is not inherently dangerous for everyone, but the risk of harm rises sharply for those who develop CanUD — and this risk is deeply embedded in our biology.

As cannabis legalization spreads, public education campaigns should reflect these complexities, highlighting the risks of heavy, compulsive use while avoiding unnecessary stigma against responsible adult users.

Clinicians, too, should be aware of the bidirectional relationships uncovered here — screening for CanUD in patients with psychiatric disorders, and vice versa.

About this genetics, CUD, and mental health research news

Author: Neuroscience News Communications
Source: Neuroscience News
Contact: Neuroscience News Communications – Neuroscience News
Image: The image is credited to Neuroscience News

Source: Open access.
“The genetic relationship between cannabis use disorder, cannabis use and psychiatric disorders” by Marco Galimberti et al. Nature Mental Health

Abstract

The genetic relationship between cannabis use disorder, cannabis use and psychiatric disorders

Increasing prevalence of cannabis use and cannabis use disorder (CanUD) may increase risk for psychiatric disorders.

We evaluated the relationships between these cannabis traits and a range of psychiatric traits, running global and local genetic correlations, genomic structural equation modeling, colocalization analyses and Mendelian randomization analyses for causality.

Global genetic analyses identified significantly different correlations between CanUD and cannabis use.

A variant in strong linkage disequilibrium to one regulating CHRNA2 was significantly shared by CanUD and schizophrenia in colocalization analysis and included in a significant region in local genetic correlations between these traits.

A three-factor model from genomic structural equation modeling showed that CanUD and cannabis use partially map together onto a factor with major depressive disorder and ADHD.

In terms of causality, CanUD showed bidirectional causal relationships with most tested psychiatric disorders, differently from cannabis use.

Increasing use of cannabis can increase rates of psychiatric disorders over time, especially in individuals who progress from cannabis use to CanUD.