A preliminary investigation has found that those who use tobacco with cannabis show unique changes to their brain chemistry.

The findings could explain why those who use both often have worse addictions and mental health outcomes than those who use only one or the other.

In 2024, for instance, a study found that young people in the US who use tobacco and cannabis more commonly reported mental health problems than those who used cannabis on its own or only smoked tobacco.

Related: Study Reveals 2 Genes That Could Influence Your Interest in Cannabis

The current study is small and preliminary, but researchers were surprised by the results and want to conduct further trials on those who smoke and vape tobacco.

The team compared the brain scans of 8 participants who reported using only cannabis to 5 participants who reported using tobacco and cannabis.

The group that used both drugs had significantly higher levels of a key enzyme across multiple brain regions. This enzyme, called fatty acid amide hydrolase (FAAH), interacts with the endocannabinoid system, closely controlling levels of a neurotransmitter linked to feelings of bliss or joy.

Recent studies in animals suggest that FAAH could contribute to nicotine reward systems in the brain, but whether that is true in humans remains to be seen. Those with certain variants in the FAAH gene have higher risks of drug abuse and addiction. The gene also has links to anxiety.

“This is the first evidence in humans of a molecular mechanism that may underlie why people who use both cannabis and tobacco experience worse outcomes,” says lead author and psychology researcher Rachel Rabin from McGill University in Canada.

The study did not analyze those who smoke only cigarettes, so it’s possible that tobacco alone may be responsible for these brain changes. Further studies are needed to understand if this chemical profile is directly caused by tobacco, if cannabis exacerbates the profile, and if it puts a person’s mental health at greater risk. But the association is intriguing.

“What surprised us was how strong the effect was, and how different it was from those who only used cannabis, compared to those who used both tobacco and cannabis,” says co-author and psychiatrist Romina Mizrahi from McGill.

One of the current challenges surrounding cannabis research is disentangling those who smoke cannabis alone versus those who smoke cannabis and tobacco – a common pairing among recreational and medicinal users.

By some estimates, up to 80 percent of people who use cannabis also use tobacco products, and this overlap could be influencing cannabis research on lung diseases, mental health, the brain, and cognition.

Almost all current studies on the topic are observational, which means they can’t glean cause or effect. What’s more, they don’t often discriminate between how much someone uses tobacco or cannabis, which could influence the results.

For now, it seems plausible that tobacco and cannabis combined can have different impacts than cannabis on its own. But in time, more studies will tell.

“Identifying this mechanism is an important step toward finding targets for future medications to treat cannabis use disorder, especially among those that co-use tobacco,” says Rabin.

The study was published in Drug and Alcohol Dependence Reports.