People who use both cannabis and tobacco show distinct brain changes compared to those who use cannabis alone, according to a new study led by McGill University researchers at the Douglas Research Centre.

The finding may help explain why people who use both cannabis and tobacco often report increased depression and anxiety, and why quitting cannabis is harder for them than for people only using cannabis

“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,” said lead author Rachel Rabin, Associate Professor in McGill’s Department of Psychiatry and researcher at the Douglas.

“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. Right now, the only available treatments are behavioural therapies such as counselling,” she said.

In Canada, about one in 20 people who used cannabis in the past year are considered at risk for cannabis use disorder. That figure rises to one in three among people who use it more frequently.

While tobacco-smoking rates are declining overall, most people who use cannabis also use tobacco, the researchers note. Most studies have looked at cannabis and tobacco in isolation, Rabin added, leaving a gap that this preliminary study begins to address.

Shifts in brain’s ‘bliss molecule’

PET brain scans revealed that people who used both tobacco and cannabis had higher levels of FAAH, relative to people who only used cannabis. FAAH is the enzyme that breaks down anandamide, a naturally occurring molecule sometimes called the “bliss molecule” for its role in mood and stress regulation. More FAAH means less anandamide, a pattern previously linked to anxiety, depression and relapse when trying to quit cannabis.

Researchers analyzed scans from 13 young adults. Eight smoked only cannabis, while five also smoked cigarettes daily. Cannabis users averaged just over one gram per day, while cigarette use ranged from one to 12 per day.

Because the data was originally collected for another study, the research did not include a tobacco-only group. So it’s possible tobacco alone caused the changes. However, the researchers say the results suggest something more is at play.

“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,” said co-author Romina Mizrahi, Professor of Psychiatry and director of the McGill Research Centre for Cannabis.

The researchers are now recruiting people who smoke cigarettes and people who vape nicotine in a new study to test whether the same brain changes occur without cannabis.

About the study

“A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use” by Rachel Rabin, Joseph Farrugia, Ranjini Garani and Romina Mizrahi was published in Drug and Alcohol Dependence Reports.

The study received funding form the National Institute of Mental Health.