Tobacco and Cannabis Together May Deplete the Brain’s “Bliss Molecule,” New Study Warns
A growing body of research is reshaping what scientists know about how cannabis affects the brain—but a new study suggests the real story may depend on what else people are smoking. Researchers from McGill University’s Douglas Research Centre in Canada have found the first evidence in humans that combining cannabis with tobacco profoundly alters brain chemistry, suppressing a natural compound linked to mood and stress regulation. The findings could help explain why people who use both substances often struggle more with depression, anxiety, and addiction recovery than those who use cannabis alone.
A New Look at the Brain’s Hidden Chemistry
For decades, scientists have known that the human brain relies on a network known as the endocannabinoid system to balance mood, sleep, motivation, and memory. The system’s primary messenger, anandamide, is sometimes called the “bliss molecule” for its ability to promote calm and emotional well-being. Now, a new imaging study is shedding light on how tightly this signaling system is intertwined with nicotine use.
Using positron emission tomography (PET) scans, researchers observed higher activity of the enzyme FAAH—short for fatty acid amide hydrolase—in the brains of individuals who regularly used both tobacco and cannabis. FAAH is responsible for breaking down anandamide. Elevated enzyme levels mean less anandamide remains available to stabilize mood, leaving individuals more susceptible to anxiety and depressive symptoms.
This biochemical fingerprint offers the first direct glimpse, through human neuroimaging, into why people who consume both substances may face steeper emotional and behavioral challenges. Lead author Rachel Rabin, Associate Professor of Psychiatry at McGill University, said the observations provide a missing molecular link between dual substance use and mental health outcomes. “Identifying this mechanism is an important step toward finding new treatment targets for cannabis use disorder, especially among those who also smoke tobacco,” she said in a press release accompanying the study.
The Study: How the Discovery Was Made
The McGill team analyzed PET brain scans from 13 young adults who reported either exclusive cannabis use or daily use of both cannabis and tobacco. Eight participants used only cannabis, consuming about one gram per day on average, while the other five smoked both cannabis and cigarettes, often between one and twelve cigarettes daily. Although the sample size was small and the dataset originally derived from another study, the results were clear: dual users exhibited consistently higher levels of FAAH activity across brain regions involved in emotion regulation and reward.
The researchers caution that since the study did not include a tobacco-only comparison group, tobacco use alone could influence FAAH levels. However, the pattern of differences between dual users and cannabis-only users suggests a more complex neurological interaction. Co-author Romina Mizrahi, Director of the McGill Research Centre for Cannabis, said the strength of the effect surprised her team. “We expected some modulation, but the distinction was unmistakable,” she noted.
The research, published in the journal Drug and Alcohol Dependence Reports in July 2025, provides a foundation for further investigation into how nicotine and cannabinoids interact at the biochemical level. The team is already recruiting new participants who smoke cigarettes or vape nicotine but do not use cannabis, to determine whether nicotine alone triggers the same molecular changes.
Why Anandamide Matters
Anandamide was first identified in the 1990s as part of the body’s innate endocannabinoid system, which mirrors some of the effects of plant-based cannabinoids like THC. When anandamide binds to cannabinoid receptors in the brain, it can induce a mild sense of pleasure, aid in stress relief, and modulate pain perception. The compound’s name comes from “ananda,” the Sanskrit word for “bliss.”
FAAH, the enzyme found at elevated levels in the recent study, works to degrade anandamide once it has carried out its signaling function. When FAAH activity becomes too high, anandamide availability declines, potentially leading to mood imbalance. A 2015 paper published in Nature Neuroscience found that individuals with genetically lower FAAH activity reported fewer symptoms of anxiety, illustrating how delicately tuned this system can be.
The McGill results suggest that dual exposure to nicotine and THC tilts this balance toward reduced endocannabinoid activity, potentially amplifying vulnerability to mental health disorders. That biochemical shift could explain the long-observed tendency of people who use both substances to report higher stress levels and difficulty quitting either habit.
The Public Health Context
The overlap between tobacco and cannabis use has long complicated addiction treatment and mental health interventions. Although tobacco smoking rates are declining across many developed nations, most cannabis users still report some use of tobacco or nicotine products. In Canada, government data indicate that roughly one in twenty individuals who used cannabis in the past year may meet the criteria for cannabis use disorder—a figure that triples among heavy users.
Health Canada defines cannabis use disorder as a problematic pattern of use that causes significant impairment or distress, affecting motivation, cognition, and emotional stability. Behavioral therapies, including cognitive-behavioral counseling and motivational interviewing, remain the only evidence-based treatments currently available. There are no approved pharmacological options, largely because the neurobiological underpinnings of cannabis dependence remain poorly understood.
That may soon change if research continues to connect molecular alterations, such as reduced anandamide signaling, to specific behavioral patterns. A senior clinical psychologist specializing in addiction medicine told The Globe Review that “the ability to visualize these neurochemical changes gives clinicians a bridge between subjective experience and biological mechanism.” The goal, she said, is not to stigmatize co-use but to understand and treat it more effectively.
Co-Use Compounds the Challenge of Quitting
Smoking cannabis and tobacco together poses unique challenges for those attempting to quit. Studies have shown that nicotine and THC can enhance each other’s reinforcing properties: nicotine makes cannabis more rewarding, while cannabis can reduce the discomfort associated with nicotine withdrawal. This bidirectional reinforcement can make abstinence particularly difficult.
A 2018 meta-analysis in Addiction estimated that dual users are nearly twice as likely to relapse when trying to quit cannabis compared with cannabis-only users. Dual exposure may also alter dopamine transmission in the brain’s reward circuitry, strengthening the habit formation process.
The FAAH findings from McGill lend biochemical weight to this clinical picture. Lower anandamide levels are associated with heightened stress reactivity—a known trigger for relapse. By identifying the enzyme responsible, scientists may eventually develop drugs that inhibit FAAH to restore endocannabinoid function and ease withdrawal symptoms. Several pharmaceutical companies have explored FAAH inhibitors for anxiety and depression, but human trials halted after a 2016 toxicity incident in France underscored the complexity of manipulating this system safely.
A Broader Look at Cannabis Research
The implications of this study resonate beyond dual-use populations. The scientific understanding of cannabis’s impact on the brain remains fluid. Over the past decade, PET and MRI imaging have revealed that chronic cannabis use can influence receptor density, blood flow, and neural connectivity across multiple brain regions. These effects tend to normalize with sustained abstinence, suggesting a reversible mechanism.
However, the addition of tobacco complicates those dynamics. Nicotine acts on cholinergic receptors, while THC targets the endocannabinoid system, yet both ultimately converge on dopamine pathways linked to reinforcement and pleasure. That convergence could magnify neurochemical changes and emotional outcomes beyond what either substance would cause alone.
Neuroscientist Anita Deshmukh, who was not involved in the McGill research, explains: “When two psychoactive substances act on complementary systems, we sometimes see non-linear effects. It’s not one plus one equals two—it can be one plus one equals five in terms of impact on mood regulation.”
The Next Phase: Testing Nicotine-Only Effects
To address the lingering question of causation, McGill researchers have begun a follow-up investigation comparing three groups: individuals who smoke only tobacco, those who vape nicotine products, and those who use both nicotine and cannabis. By expanding the sample size and including gender and age diversity, researchers hope to isolate nicotine’s role in altering FAAH activity and anandamide availability.
This second phase is particularly timely given the sharp rise in nicotine vaping among young adults. According to Health Canada, e-cigarette use among Canadians aged 20–24 increased by nearly 30 percent over the past five years, much of it among concurrent cannabis users. Understanding how vaporized nicotine affects endocannabinoid metabolism could influence both public health messaging and future regulation of multi-substance consumption.
Mental Health and the “Bliss Deficit”
While the neurochemical interplay is complex, the takeaway is straightforward: dual substance users may experience a measurable reduction in the brain’s capacity to sustain emotional equilibrium. Some clinicians are calling this emerging pattern a “bliss deficit,” reflecting an underactive endocannabinoid system.
In clinical settings, this deficit often manifests as irritability, restlessness, or diminished motivation—symptoms strikingly similar to those observed in mood disorders. Whether these effects result directly from reduced anandamide or downstream changes in other neurotransmitters remains an open question. Preliminary evidence from animal models indicates that nicotine exposure sensitizes certain FAAH gene pathways, exaggerating the degradation of endocannabinoids.
Importantly, researchers emphasize that these findings do not imply irreversible harm. Short-term cannabis use in isolation does not appear to permanently suppress endocannabinoid activity. However, simultaneous tobacco exposure may extend recovery time, especially in chronic users.
The Search for Therapeutic Solutions
With this new evidence, researchers hope to develop more targeted treatments for cannabis use disorder. Pharmacological efforts are underway to design FAAH inhibitors that safely increase anandamide levels without affecting other lipid signaling pathways. Behavioral interventions could also evolve to reflect the heightened biochemical vulnerability of dual users.
Cognitive-behavioral programs, for instance, might incorporate education about the physiological coupling of nicotine and THC. Training patients to recognize how one triggers craving for the other could improve quit rates. Digital therapeutic tools and mindfulness-based relapse prevention programs are already being adapted for this combined-use population in clinical pilot studies across Canada and Europe.
A public health policy analyst at the Canadian Centre for Substance Use and Addiction summarized the broader objective: “Effective prevention and treatment must address the real-world experience. Most consumers don’t separate cigarettes from cannabis joints; they mix them. Science is finally catching up to that reality.”
Policy and Education Implications
These findings arrive amid shifting policies on both substances. Canada legalized recreational cannabis in 2018, while continuing to regulate tobacco sales and advertising. Despite separate legal frameworks, dual consumption remains culturally entangled, influenced by social habits, perceived stress relief, and accessibility. Public education campaigns have historically treated the substances in isolation, an approach that the McGill researchers say needs reevaluation.
Health educators argue that prevention messaging should explicitly warn of the combined biochemical effects of dual use, not just the risks of each substance individually. Highlighting the neurochemical consequences—such as diminished anandamide function—could resonate with younger demographics who respond more strongly to neuroscience-based evidence than to moral appeals.
Public health initiatives could also use this research to inform tobacco cessation strategies tailored for cannabis users. Traditional smoke-free campaigns may need adaptation to reflect the intertwined nature of these substances in modern consumption patterns.
Limitations and the Road Ahead
As with all preliminary investigations, caution is warranted. The McGill study involved a small number of participants, lacked a tobacco-only group, and cannot yet determine whether FAAH increases are a cause or consequence of dual use. Longitudinal research, with repeated brain imaging before and after cessation, is necessary to establish directionality.
Still, experts see these findings as a crucial step toward closing a persistent knowledge gap. Few human studies have directly examined how tobacco modifies the neurobiological landscape of cannabis use, even though epidemiological data consistently show the two substances co-occur in most users.
Emerging brain imaging technologies, including ultra-high-resolution PET scanners and molecular tracers specific to endocannabinoid enzymes, may soon enable scientists to measure subtle biochemical shifts with unprecedented accuracy. Such tools could eventually allow doctors to personalize treatment for substance use disorders based on individual neurochemical profiles.
A Molecular Map for the Future
The story unfolding from this research is one of redefined boundaries: between legal and illegal substances, between emotional experience and molecular biology, and between traditional addiction models and those informed by neuroscience.
At its core, the McGill discovery illustrates that the brain’s systems of reward and regulation are delicately balanced. Interactions between nicotine and THC can disrupt that balance in ways that affect both mood stability and the ability to quit using either substance. The “bliss molecule,” once considered a metaphor for happiness, is revealing itself to be a pivot point of brain health—sensitive to the compounds people inhale and how often they do so.
The team behind the study hopes that understanding this mechanism will ultimately help clinicians design better treatments for those caught between two intertwined addictions. By tracing how these common substances drain the brain’s reservoir of contentment, researchers are offering more than just a biochemical insight. They are giving public health authorities a new path forward—one rooted in evidence, empathy, and the chemistry of the human mind.