Strong cannabis may leave a distinct mark on DNA and explain risk of psychosis

Cannabis is one of the most common drugs in the world. Literally hundreds of millions of people use it regularly around the world. But because it’s also illegal in countries including the US at the federal level, there’s a lot we don’t know about cannabis and how it affects the human brain.

Although cannabis is often considered relatively harmless, it is not without risks. Research has linked heavy and long-term cannabis use to memory deficits, cognitive decline and even increased vulnerability to mental disorders such as schizophrenia, especially in adolescents whose brains are still developing.

Now, researchers from King’s College London and the University of Exeter have made a surprising discovery: frequent use of highly potent cannabis, now readily available in pharmacies and on the streets, leaves a distinct mark on DNA.

The study offers new insight into how cannabis, especially stronger varieties with high levels of the psychoactive compound THC, can alter gene function, potentially increasing the risk of psychosis in some users.

“Our study is the first to show that high potency cannabis leaves a unique DNA signature associated with immune system and energy production mechanisms,” said senior author Martha Di Forti from King’s College.

Not your grandpa’s weed

Over the past few decades, the potency of cannabis has steadily increased. In states like Colorado, where it is legal, you can now buy products containing up to 90% tetrahydrocannabinol (THC), the compound responsible for the characteristic effects of cannabis. And while THC is just one of more than 100 chemicals found in the plant, it is what scientists use to measure a drug’s potency.

In 2022, the federal government reported that in samples seized by the Drug Enforcement Administration (DEA), the average level of THC had more than tripled from 25 years earlier, from 5 percent to 16 percent.

As cannabis becomes more potent, so too do concerns about its potential effects on mental health. Researchers have long known that daily use of potent cannabis increases the risk of psychosis – delusions, hallucinations and paranoia that can make people feel disconnected from reality. But the biological mechanisms behind this connection remain elusive. Di Forti and her colleagues decided to find out whether this high-quality marijuana could affect people at the molecular level, changing the very mechanism that controls gene function.

Their research focused on DNA methylation, a process that controls whether genes are turned on or off without changing the underlying DNA sequence. It’s like a dimmer switch for your genes, influenced by your lifestyle, diet and environment. In the case of cannabis, the researchers wanted to find out whether regular use leaves a molecular signature (an epigenetic fingerprint, if you will) that could help explain why some users are more vulnerable to psychosis than others.

Molecular signature

The team collected blood samples from 682 people from six countries, including 239 people experiencing a first episode of psychosis. They studied how cannabis use, especially high-potency varieties, affects DNA methylation in genes associated with the immune system and energy production. High potency cannabis was defined as containing more than 10% THC.

The results were amazing. Frequent users of potent cannabis showed distinct changes in DNA methylation patterns, particularly in genes that regulate how the body produces energy and responds to infections. One gene, called CAVIN1, stands out for its role in cellular energy management, which may provide insight into how cannabis affects brain function.

“Our findings provide important insight into how cannabis use can alter biological processes,” said Emma Dempster, first author of the study and senior lecturer at the University of Exeter.

Moreover, the researchers found that DNA changes in those who have experienced psychosis differed from DNA changes in people who had never had a psychotic episode, suggesting that cannabis may affect vulnerable people in unique ways. These changes were not explained by tobacco use—a common factor in cannabis research since many smokers put tobacco in their joints—meaning the effects were directly related to the cannabis itself.

The path to prevention?

The implications of the study are enormous. If cannabis use, especially high-potency varieties, leaves a molecular signature in users’ DNA, it may one day be possible to develop tests to determine who is at risk of developing psychosis. A simple blood test can reveal epigenetic markers in DNA, allowing doctors to predict which cannabis users may face the greatest mental health risks.

While this study opens new doors, it also raises critical questions. Can these molecular changes be reversed if someone stops using cannabis? Is the effect cumulative, increasing the longer and more often a person uses the drug? What about those who use cannabis for medical purposes? How will these results affect them?

As more places around the world move to legalize cannabis and its potency continues to increase, getting a full picture of what frequent marijuana use does to the human body and brain is becoming more important than ever. Marijuana has been hailed as a medicinal miracle and a recreational rite of passage, but it is becoming clear that there is more to the story.