Cannabis is one of the most common drugs in the world. Literally hundreds of millions of people use it regularly across the world. But since it is also illegal in some countries, including the U.S. at the federal levels, there is much we don’t know about cannabis and what it does to the human brain.

Although cannabis is often seen as relatively harmless, it is not without risks. Studies have linked heavy, long-term cannabis use to memory deficits, cognitive decline, and even an increased vulnerability to mental health disorders such as schizophrenia, particularly in adolescents whose brains are still developing.

Now, researchers at King’s College London and the University of Exeter have made a surprising discovery: frequent use of high-potency cannabis, the kind now readily available in dispensaries and on the streets, leaves a distinct signature on DNA.

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

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

Not your grandpa’s weed

The potency of cannabis has steadily increased over the past few decades. In states like Colorado, you can now buy products with up to 90% tetrahydrocannabinol (THC) — the compound responsible for cannabis’s characteristic high. And while THC is just one of over 100 chemicals found in the plant, it’s the primary one scientists use to measure the drug’s strength.

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

As cannabis became stronger, so too have concerns about its potential effects on mental health. Researchers have long known that daily use of high-potency cannabis increases the risk of developing psychosis — delusions, hallucinations, and paranoia that can leave people feeling disconnected from reality. But the biological mechanisms behind this connection have remained elusive. Di Forti and her colleagues set out to investigate whether this high-grade marijuana might be affecting people on a molecular level. It could be altering the very machinery that controls gene function.

So, their study focused on DNA methylation. This process controls how genes are turned on or off without changing the underlying DNA sequence. It’s a bit like a dimmer switch for your genes, influenced by your lifestyle, diet, and environment. When it comes to cannabis, the researchers wanted to see if regular use left a molecular trace — an epigenetic fingerprint, if you will — that could help explain why some users are more vulnerable to psychosis than others.

A Molecular Signature

The team collected blood samples from 682 people across six countries, including 239 individuals who had experienced their first episode of psychosis. They looked at how cannabis use, particularly high-potency strains, affected DNA methylation in genes related to the immune system and energy production. High-potency cannabis was defined as having more than 10% THC.

The findings were striking. Frequent users of high-potency cannabis showed distinct changes in their DNA methylation patterns, particularly in genes that regulate how the body produces energy and responds to infections. One gene, called CAVIN1, stood out for its role in managing cellular energy, which could provide clues about how cannabis affects brain function.

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

What’s more, the researchers found that the DNA changes in those who had experienced psychosis were different from those in people who had never had a psychotic episode. This suggests that cannabis may be impacting vulnerable individuals in a unique way. The changes weren’t explained by tobacco use — a common confounding factor in studies of cannabis, as many users mix tobacco into their joints — meaning the effects were directly tied to cannabis itself.

A Path to Prevention?

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

While this research opens new doors, it also raises critical questions. Could these molecular changes be reversed if someone stops using cannabis? Are the effects cumulative, growing stronger the longer or more frequently someone uses the drug? And what about those who use cannabis medicinally — how do these findings translate to them?

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