A new study from McGill University has found that people who use both cannabis and tobacco show unique changes in the brain that could help explain why they often experience more anxiety, depression, and difficulty quitting cannabis compared to those who use cannabis alone.
The research, led by Associate Professor Rachel Rabin at McGill’s Douglas Research Center, is the first to uncover a molecular mechanism in humans that may explain these effects.
“This is the first evidence in humans showing how combining cannabis and tobacco affects the brain differently,” said Rabin.
“It helps us understand why people who use both substances tend to have worse mental health outcomes and struggle more to stop using cannabis.”
The findings, published in Drug and Alcohol Dependence Reports, focus on a brain enzyme called FAAH (fatty acid amide hydrolase).
FAAH’s job is to break down anandamide, a naturally occurring brain chemical known as the “bliss molecule.” Anandamide helps regulate mood, stress, and emotion.
Using PET brain scans, the researchers discovered that people who used both tobacco and cannabis had higher levels of FAAH in the brain compared to those who only used cannabis.
Higher FAAH levels mean less anandamide activity—potentially leading to lower feelings of well-being and higher risk of anxiety and depression.
This same pattern has been linked in past research to increased relapse rates among people trying to quit cannabis.
The study involved 13 young adults—eight who smoked only cannabis and five who used both cannabis and cigarettes daily.
The cannabis users smoked just over one gram per day, while cigarette smokers averaged between one and twelve cigarettes daily.
Because the data came from an earlier study, there was no group of participants who smoked only tobacco.
This means researchers cannot yet rule out that tobacco alone might be responsible for the changes.
However, Rabin and her team believe that the combination of the two substances likely produces stronger effects than either alone.
“What surprised us was how big the difference was,” said co-author Professor Romina Mizrahi, director of the McGill Research Center for Cannabis.
“The brain scans of people using both substances looked clearly different from those who used only cannabis.”
The researchers are now expanding their work to study people who smoke or vape nicotine without using cannabis.
This will help determine whether nicotine alone causes similar brain changes or whether it’s the interaction between the two substances that disrupts the brain’s chemical balance.
Rabin said the results highlight the need for better treatments for people struggling with cannabis use, especially those who also use tobacco. “Right now, behavioral therapy is the only option,” she said. “Understanding these biological changes could lead to new medications that make quitting easier.”
