People who use both cannabis and tobacco together have different brain chemistry when compared to people who only use cannabis, and the difference is linked to higher levels of anxiety, depression, and relapse into addiction, a new study claims.
The findings come from a study published in the journal Drug and Alcohol Dependence Reports, where researchers from McGill University at the Douglas Research Centre examined brain scans from 13 young adults and found significantly higher levels of fatty acid amide hydrolase (FAAH) in those who used both substances compared to cannabis-only users.
FAAH is an enzyme that breaks down the endocannabinoid anandamide, often called the brain’s “bliss molecule” due to its role in mood regulation.
Researchers used data taken from a previous study, which analysed the brains of 8 young adults who smoked cannabis only, and 5 who co-used cannabis and tobacco. The cannabis-only group smoked an average of 1.5 grams per day and had been using cannabis for an average of 4.5 years. The co-using group smoked an average of 1.3 grams of cannabis per day, and smoked an average of 6 cigarettes per day, with an average of 4.8 years of cannabis use.
Using a powerful Positron Emission Tomography (PET) imaging tool and a radiotracer called [11C]CURB, researchers examined areas of the brain that contained overlapping nicotine and cannabinoid receptors. They found an imbalance in those who co-use tobacco and cannabis, which could result in less natural mood regulation and greater vulnerability to stress and relapse.
Levels of FAAH were found to be significantly higher in those who co-used tobacco and cannabis, and higher levels of FAAH equal lower levels of anandamide.
Higher FAAH levels mean lower concentrations of anandamide, creating an imbalance that affects the brain’s natural reward and pleasure systems. This disruption may leave co-users more vulnerable to stress and increase their risk of relapse when attempting to quit.
This mechanism, the study says, could help identify the reason why co-users of tobacco and cannabis tend to have greater difficulty in giving up cannabis, and experience more instances of depression and anxiety than those who use 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,” said lead author Rachel Rabin, Associate Professor at McGill.
“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.”
One of the drawbacks of the study, a result of collating the data from a previous study, was the absence of a tobacco-smoking-only control group. Researchers acknowledged this and plan further research, which will involve one, as well as a cannabis-only group and a cannabis and tobacco co-use group.
The study claims to be the first to investigate differences in FAAH levels in the brain between people who use cannabis and people who co-use two substances that are commonly combined.
Co-author Romina Mizrahi, Professor of Psychiatry and director of the McGill Research Centre for Cannabis, noted the strength of the findings: “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.”
The researchers found significantly higher FAAH levels in people who used both cannabis and tobacco compared to cannabis-only users, particularly in two key brain regions: the substantia nigra and cerebellum. The differences were substantial, with what researchers described as ‘large’ effect sizes.
Importantly, the study showed that higher tobacco consumption was directly linked to higher FAAH levels in these brain areas – meaning the more cigarettes someone smoked, the higher their FAAH levels. However, cannabis use alone showed no such relationship with FAAH levels, suggesting that tobacco is the driving factor behind the elevated enzyme activity in co-users.
The results support previous research, which identified a correlation between tobacco and cannabis co-use and poor mental health outcomes. A 2023 analysis of data from over 50,000 US citizens found that the risk of anxiety and depression doubled when cannabis and tobacco were used together.
