If you smoke both cannabis and tobacco, your brain chemistry looks different in ways scientists are only now beginning to understand. And those differences might explain why quitting feels harder, why anxiety creeps in more often, and why the two substances together seem to amplify each other’s grip.
Researchers at McGill University used PET brain scans to peer inside the heads of young adults who use cannabis, some of whom also smoke cigarettes. What they found was a striking difference: people who used both substances showed elevated levels of an enzyme called FAAH, which breaks down anandamide, a naturally occurring brain chemical sometimes nicknamed the “bliss molecule” for its role in keeping mood stable and stress in check.
More FAAH means less anandamide floating around, and that shortage has been linked to anxiety, depression, and a higher likelihood of relapse when trying to quit cannabis. It is the first time researchers have documented this molecular shift in humans, and it may help explain why dual users often struggle more than people who stick to cannabis alone.
“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.”
Rachel Rabin, the study’s lead author and an associate professor in McGill’s Department of Psychiatry, said identifying this mechanism is a crucial step toward developing medications for cannabis use disorder, particularly for people who also use tobacco. Right now, the only treatments available are behavioral therapies like counseling.
A Gap in the Research
The study involved 13 young adults. Eight used only cannabis, averaging just over one gram per day. The other five also smoked cigarettes, ranging from one to 12 per day. The scans revealed a clear pattern: the dual users had higher FAAH levels than the cannabis-only group.
Most people who use cannabis also use tobacco, yet most studies have examined the two substances in isolation. That gap matters, especially in places like Canada, where roughly one in 20 people who used cannabis in the past year are considered at risk for cannabis use disorder. Among frequent users, that figure jumps to one in three.
Romina Mizrahi, a co-author and professor of psychiatry who directs the McGill Research Centre for Cannabis, said the strength of the effect caught the team off guard. The brain changes in dual users were markedly different from those in cannabis-only users, suggesting something beyond simple addition.
“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.”
What Comes Next
Because the data came from a study originally designed for another purpose, the research did not include a tobacco-only comparison group. That leaves open the possibility that tobacco alone drives the changes. However, the researchers suspect the interaction between the two substances plays a role.
They are now recruiting people who smoke cigarettes and people who vape nicotine for a new study to test whether the same brain changes occur without cannabis in the picture. If tobacco alone is responsible, that would be important to know. If not, it strengthens the case that the combination of cannabis and tobacco creates a unique neurochemical environment, one that makes quitting harder and mental health worse.
The findings could eventually pave the way for targeted medications that address the specific brain chemistry of dual users. For now, they offer a clearer picture of what is happening inside the brain when two widely used substances collide.
Drug and Alcohol Dependence Reports: 10.1016/j.dadr.2025.100369
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