PET imaging has revealed the first evidence in humans of changes in brain chemistry among people who use both substances. This finding could help guide the development of new treatments for cannabis use disorder.
People who use both cannabis and tobacco show distinct brain differences compared to those who only use cannabis, according to a new study led by researchers from McGill University’s Douglas Research Centre.
The discovery could help explain why people who consume both substances often experience higher levels of depression and anxiety, and why quitting cannabis tends to be more difficult for them than for those who do not use tobacco.
“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 behavioral 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 number increases to one in three among those who use cannabis more frequently.
Although tobacco use is declining overall, most cannabis users also use tobacco, the researchers note. Rabin added that most previous studies examined each substance separately, leaving an important gap that this study begins to fill.
Shifts in brain’s ‘bliss molecule’
PET brain scans showed that participants who used both cannabis and tobacco had higher levels of FAAH compared to those who only used cannabis. FAAH is an enzyme that breaks down anandamide, a natural compound known as the “bliss molecule” because of its role in regulating mood and stress. Higher FAAH levels mean lower anandamide activity, a pattern previously linked to anxiety, depression, and relapse during attempts 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 that 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.
Reference: “A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use” by Rachel A. Rabin, Joseph Farrugia, Ranjini Garani, Romina Mizrahi and Pablo Rusjan, 30 July 2025, Drug and Alcohol Dependence Reports.
DOI: 10.1016/j.dadr.2025.100369
The study received funding form the National Institute of Mental Health.
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5 Comments
CBD inhibits FAAH
CBD helps keep anandamide active longer, improving mood and calming anxiety.
Anandamide (AEA)
Often called the “bliss molecule” (from ananda in Sanskrit), Binds primarily to the CB1 receptor in the brain.
The CB1 receptor plays a role in appetite, mood, memory, and pain sensation.
Both “Anandamide” and “THC” activates your CB1 receptors.
The resulting effects must have come from tobacco use because cannabis actually helps treat anxiety and depression. The Endocannabinoids & Phytocannabinoids system are mirror images of each other. All animals have an endocannabinoid system (ECS). This system predates the cannabis plant, but cannabis evolved to mimic and modulate this system almost perfectly.
That’s why cannabis “fits like a key” in our receptors.
What a really poor study. The N number is too small to account for anything and there are no control groups. Seems like someone did a study that didn’t show anything, so they repurposed the results to find a new conclusion. Most cannabis users also use tobacco? That was once true in Europe, where tobacco was added to extend the expensive illegal supply. In the USA and elsewhere, that has rarely been the practice and even in Europe, it’s becoming much less common as high quality cannabis becomes more easily available.
The kind of self-righteous social bullies trying to force everyone to comply with their anti-smoking aggressions makes me violently ill. The abuse they heap on me daily, with the very expensive taxation going into the pockets of the most despicable and corrupt your-money-or-your-life physicians, politicians, and healthcare scammers imaginable. I would be exposing myself to legal action if I told you what I really think about you people and your hysterical propaganda.
This is an incomplete study. The final results will never be released, because it wouldnt support their agenda..
Oh man, I truly pity the fool who reads this study/article/ self-righteous-propaganda-promotion, whatever you want to call it, and actually goes,” well ya don’t say!? Betty! Betty! Look right here, more proof that cigarettes r the devil!