Summary: New brain imaging research finds that people who use both cannabis and tobacco have a distinctive biochemical profile linked to higher anxiety, depression and greater difficulty quitting cannabis. PET scans showed elevated levels of the enzyme FAAH, which breaks down the endocannabinoid anandamide—often called the brain’s “bliss molecule.” Higher FAAH levels imply lower anandamide availability, a pattern tied to poorer mood regulation, increased stress sensitivity and higher relapse risk.
These results point to a biological mechanism that may help explain worse clinical outcomes among individuals who co-use cannabis and tobacco and suggest a potential target for developing medications to treat cannabis use disorder, particularly for people who also use tobacco.
Key Facts:
- Distinct brain pattern: Co-use of cannabis and tobacco was associated with increased FAAH enzyme levels, which reduce anandamide.
- Mental health link: Reduced anandamide availability may contribute to higher rates of anxiety, depression and relapse among co-users.
- Treatment implications: Identifying FAAH-related changes highlights a biological target for future pharmacological interventions for cannabis use disorder in people who co-use tobacco.
Source: McGill University
Overview
Researchers at McGill University’s Douglas Research Centre report the first human evidence that tobacco co-use alters endocannabinoid system activity in people who use cannabis. Lead author Rachel Rabin, Associate Professor in McGill’s Department of Psychiatry, notes this molecular finding may help explain why co-users commonly experience worse mood symptoms and greater difficulty quitting cannabis compared with people who use cannabis only.
Shifts in the brain’s “bliss molecule”
Positron emission tomography (PET) scans revealed that individuals who smoked both cannabis and cigarettes had higher FAAH levels than those who used cannabis alone. FAAH (fatty acid amide hydrolase) breaks down anandamide, an endocannabinoid involved in mood and stress regulation. When FAAH activity is elevated, anandamide levels fall—an imbalance previously associated with anxiety, depressive symptoms and greater relapse risk during attempts to stop cannabis.
The study analyzed scans from 13 young adults: eight who used only cannabis and five who used cannabis and smoked cigarettes daily. On average, participants reported just over one gram of cannabis use per day; cigarette use among co-users ranged from one to 12 cigarettes per day.
Because these scans came from data originally collected for another study, there was no tobacco-only comparison group. That limitation means tobacco alone could partly explain the observed differences. Still, the researchers emphasize the magnitude and regional pattern of the FAAH increase in co-users suggest a specific effect of co-use that merits further investigation.
Co-author Romina Mizrahi, Professor of Psychiatry and director of the McGill Research Centre for Cannabis, said the magnitude of the effect and the contrast with cannabis-only users were notable. The team is now recruiting cigarette smokers and nicotine vapers to determine whether similar FAAH changes appear in people who use nicotine without cannabis.
About the study
Funding: The research received funding from the National Institute of Mental Health.
Key questions answered
A: People who use cannabis and tobacco together showed higher FAAH levels, which degrade anandamide, a molecule important for mood regulation and resilience to addiction-related stress.
A: The altered endocannabinoid profile may explain why co-users experience more anxiety and depression and have higher rates of relapse when trying to quit cannabis, highlighting a biological pathway for intervention.
A: The team is recruiting participants who smoke cigarettes or vape nicotine but do not use cannabis, to test whether nicotine alone produces similar brain changes and to isolate the mechanism behind the co-use effect.
About this neuroscience research news
Author: Keila DePape
Source: McGill University
Contact: Keila DePape – McGill University
Image: Image credited to Neuroscience News
Original research: Open access. “A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use” by Rachel Rabin et al., published in Drug and Alcohol Dependence Reports (DOI: 10.1016/j.dadr.2025.100369).
Abstract (summary)
Tobacco is frequently co-used with cannabis, and co-use appears to worsen some clinical outcomes related to cannabis. Prior evidence links low anandamide levels to poorer clinical trajectories. FAAH degrades anandamide, so higher FAAH could underlie worse outcomes in co-users compared with cannabis-only users. In this preliminary PET study, 13 cannabis users were divided into daily tobacco co-users (CT, n=5) and non-tobacco users (CAN, n=8). Researchers measured FAAH using [11C]CURB PET and controlled for sex and FAAH genotype across multiple brain regions. A significant group-by-region interaction emerged, with post-hoc tests showing higher FAAH in co-users versus cannabis-only users in the substantia nigra and cerebellum, and a trend in the sensorimotor striatum. These preliminary results suggest tobacco co-use is associated with elevated FAAH activity relative to cannabis-only use, a change that may contribute to poorer clinical outcomes among co-users.