Cannabis and tobacco co-use is a widespread phenomenon, yet the neurochemical consequences of this dual consumption have been poorly understood. Previous studies often considered cannabis and tobacco in isolation, ignoring the complex interactions between these substances. The McGill team’s novel investigation harnessed positron emission tomography (PET) brain imaging to explore variations in the enzyme fatty acid amide hydrolase (FAAH), which metabolizes anandamide—a lipid neurotransmitter often dubbed the “bliss molecule” for its involvement in regulating mood and stress responses.

FAAH plays a pivotal role in maintaining endocannabinoid system balance by breaking down anandamide. Elevated FAAH activity results in decreased anandamide levels, which has been linked to anxiety, depression, and increased risk of relapse in individuals attempting to quit cannabis. By analyzing PET scans of young adult participants who either smoked only cannabis or combined cannabis with daily cigarette use, the researchers identified a pronounced elevation of FAAH in the brains of those who used both substances. This enzyme elevation suggests diminished anandamide signaling in co-users, which may underlie their exacerbated mental health symptoms and challenges in cessation efforts.

The study involved a cohort of 13 young adults, with eight participants exclusively using cannabis and five engaging in both cigarette and cannabis use. Cannabis consumption averaged just over one gram per day, while cigarette intake ranged from one to twelve per day. Despite the relatively small sample size, the strength and clarity of the FAAH differences between groups were striking, signaling a robust biological effect linked to tobacco co-use. Notably, the absence of a tobacco-only control group limits definitive conclusions about tobacco’s sole contribution, but the evidence points toward a unique interaction when combined with cannabis.

Lead author Rachel Rabin, an Associate Professor at McGill’s Department of Psychiatry, emphasized the novelty of these findings: “This is the first evidence in humans of a molecular mechanism that may underpin why individuals who use both cannabis and tobacco experience worse clinical outcomes.” She highlighted the clinical implications, stressing that current treatments for cannabis use disorder rely largely on behavioral therapies. Identifying FAAH as a therapeutic target opens the possibility for pharmacological advances that could revolutionize treatment paradigms, especially for the significant subset of cannabis users who also smoke tobacco.

In Canada, the societal relevance of this research is underscored by epidemiological data showing that approximately one in twenty cannabis users is at risk for cannabis use disorder. This risk escalates substantially—up to one in three—among frequent users. Coupled with the fact that tobacco usage, though declining, remains prevalent among cannabis consumers, the interplay between these substances takes on added urgency from a public health perspective. Understanding the neurobiological factors involved in dual use can inform both prevention and treatment strategies.

The McGill researchers utilized sophisticated PET imaging to quantify FAAH concentrations in participants’ brains. This neuroimaging approach enabled them to non-invasively assess enzymatic activity within critical mood-regulating regions, adding a vital dimension to understanding substance co-use’s neural underpinnings. The elevation of FAAH in co-users aligns with existing preclinical data linking the enzyme’s upregulation to negative affective states and heightened propensity for substance dependence. These findings also dovetail with broader research on the endocannabinoid system’s crucial role in emotional regulation.

Co-author Romina Mizrahi, a Professor of Psychiatry and Director of the McGill Research Centre for Cannabis, expressed surprise at the pronounced FAAH differences observed. She noted, “The strikingly strong effect underscores that co-use of tobacco and cannabis engages neurobiological pathways distinct from cannabis use alone.” The team’s future research plans include expanding participant recruitment to include cigarette smokers and nicotine vapers who do not use cannabis. This will clarify whether tobacco alone can induce similar FAAH alterations or whether the combination with cannabis uniquely disrupts endocannabinoid signaling.

The preliminary nature of this investigation demands cautious interpretation, yet its implications resonate throughout the scientific and clinical communities. By delineating a concrete molecular pathway through which tobacco exacerbates cannabis-related harms, the study offers a compelling framework for re-evaluating treatment options. It also invites a broader dialogue about how polysubstance use reshapes neurochemical landscapes and influences addiction trajectories, a critical consideration as cannabis legalization spreads globally and consumption patterns evolve.

In addition to its clinical relevance, this research highlights the power of advanced neuroimaging techniques to unravel intricate biochemical processes in living human brains. FAAH’s modulation of anandamide presents a tangible pharmacological target, with potential for novel drug discoveries aiming to restore endocannabinoid balance. Such therapeutic strategies could dramatically improve outcomes for individuals struggling with the compounded effects of cannabis and tobacco dependence, addressing both mood disorders and substance use relapse risks.

Footing the intersection of psychiatry, neuropharmacology, and addiction science, this study marks a significant milestone in understanding complex substance use behaviors. It provides a mechanistic explanation for why tobacco co-use intensifies cannabis-related mental health challenges, particularly depression and anxiety, thereby legitimizing targeted pharmaceutical research. The findings also underscore the necessity of integrating assessments of tobacco involvement in clinical trials and treatment protocols for cannabis use disorder.

In conclusion, the McGill-led research illuminates a previously uncharted molecular dimension of co-use pathophysiology. By revealing elevated FAAH activity as a potential driver of diminished endocannabinoid function in cannabis and tobacco users, it paves the way for innovative interventions. The link between co-use and poorer mental health outcomes is substantiated at a biochemical level, highlighting the urgency of tailored therapies that address the dual substance burden. As public health landscapes continue to grapple with evolving patterns of cannabis and tobacco use, studies like this provide critical scientific guidance for future clinical and policy directions.

Subject of Research: People

Article Title: A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use

News Publication Date: 30-Jul-2025

Web References:
https://www.sciencedirect.com/science/article/pii/S2772724625000526
http://dx.doi.org/10.1016/j.dadr.2025.100369

References:
Rabin, R., Farrugia, J., Garani, R., & Mizrahi, R. (2025). A preliminary investigation of tobacco co-use on endocannabinoid activity in people with cannabis use. Drug and Alcohol Dependence Reports. https://doi.org/10.1016/j.dadr.2025.100369

Image Credits: The Neuro

Keywords

Cannabis, Tobacco, FAAH, Endocannabinoid, Mood Regulation, PET Brain Imaging, Cannabis Use Disorder, Neuropharmacology, Substance Co-use, Mental Health

The research team employed longitudinal data analytic techniques to identify distinct trajectories of eating behaviors beginning in early childhood. Approximately 60 percent of the sample exhibited no signs of overeating, while 14 percent initiated overeating behaviors early, between ages two and four, and 26 percent began such patterns slightly later, around age four. Strikingly, the emergence of these behaviors in girls was statistically associated with an increased likelihood of exhibiting symptoms related to anxiety, impulsivity, and hyperactivity during adolescence. Conversely, boys who displayed similar overeating patterns did not demonstrate the same risk, suggesting gender-specific environmental or biological moderators at play.

These observations provide critical insight into how early childhood behaviors, often dismissed as transient phases, may serve as early warning signs for future internalizing and externalizing psychopathologies. The study’s lead senior author, Dr. Linda Booij, a prominent figure in psychiatric research at McGill University, emphasizes that while overeating is not a deterministic cause of later mental health issues, its frequent occurrence warrants clinical attention. This finding challenges caregivers and health professionals to rethink early nutritional behaviors not merely as feeding issues but as potential markers of emotional distress.

Central to these findings is the socio-environmental context shaping eating behaviors, particularly around gender norms. Dr. Booij offers that parents might monitor and respond to girls’ eating habits more closely, potentially fostering restrictive eating environments. Such environments may paradoxically exacerbate the risk for disordered eating patterns and psychological difficulties later in life. This suggests that psychosocial stressors interacting with childhood overeating behaviors contribute significantly to the observed mental health outcomes among females, underscoring the complexity of the interplay between biology, behavior, and culture in child development.

The study also draws a clear distinction between overeating and picky eating patterns. While about one-third of children were characterized as picky eaters, this behavior showed no statistically significant association with later mental health challenges. Picky eating, often regarded by parents as a concern, appears to be a developmentally normative phase that does not inherently presage emotional or behavioral problems. However, the researchers caution that persistent picky eating behaviors that interfere with nutritional intake and growth metrics may signal more serious underlying issues, necessitating clinical evaluation.

Methodologically, the research utilized a meta-analytical framework, analyzing cohort data with repeated measures over time, allowing for the robust identification of behavior patterns and their psychological correlates. This approach strengthens the validity of the associations observed, while also highlighting the importance of longitudinal data in unraveling how early-life experiences shape adolescent outcomes. The integration of caregiver reports with standardized mental health assessments enhances the interpretability and clinical relevance of the findings.

Importantly, the study’s findings refute simplistic behavioral interventions such as imposing dietary restrictions on children who exhibit overeating tendencies. Dr. Booij cautions that restrictive feeding practices can increase the risk of disordered eating, advocating instead for holistic approaches that address emotional well-being alongside nutritional guidance. Early identification of maladaptive eating patterns provides an opportunity for intervening in the psychosocial domain, potentially mitigating adverse developmental trajectories.

From a clinical perspective, these results necessitate a paradigm shift in pediatric care and parental guidance. Pediatricians, psychologists, and other health care providers should consider integrating screening tools that assess eating behaviors within broader mental health evaluations from an early age. Moreover, public health messaging and caregiver education might benefit from emphasizing emotional support and the normalization of occasional overeating, while being vigilant for frequent patterns that may indicate distress.

The gender-specific nature of the findings also opens new avenues for research into the biological, psychological, and social determinants that differentiate how boys and girls experience and manifest mental health challenges in relation to early eating behaviors. Future studies might explore hormonal influences, differential stress responses, or socio-cultural parenting practices that contribute to these divergent outcomes. Understanding these mechanisms will be essential for designing targeted preventive strategies.

The ethical implications of these findings are equally significant. Recognizing overeating as a potential marker of emotional struggles calls for sensitive communication strategies that avoid stigmatizing children or parents. Interventions should focus on fostering supportive environments that promote healthy relationships with food and emotions. This nuanced understanding can inform policy development aimed at early childhood mental health promotion and eating disorder prevention.

In conclusion, the McGill-led study advances the field’s understanding of how early childhood eating behaviors, particularly overeating in girls, serve as significant predictors of adolescent mental health difficulties. By illuminating the gender-specific associations with anxiety, impulsivity, and hyperactivity, the research underscores the need for integrated, gender-sensitive approaches in clinical practice and public health. The findings advocate for an empathetic, evidence-based framework that prioritizes emotional well-being alongside nutritional status, reshaping how caregivers and professionals address childhood eating patterns and their broader psychosocial context.

Subject of Research: People
Article Title: Trajectories of childhood eating behaviors and their association with internalizing and externalizing symptoms in adolescence
News Publication Date: August 29, 2025
Web References: https://pubmed.ncbi.nlm.nih.gov/40883733/
References: Dufour, R., Booij, L., et al. (2025). Trajectories of childhood eating behaviors and their association with internalizing and externalizing symptoms in adolescence. BMC Pediatrics. DOI: 10.1186/s12887-025-06001-z
Keywords: Childhood eating behaviors, Overeating, Anxiety, Hyperactivity, Impulsivity, Adolescence, Gender differences, Mental health, Longitudinal study, Picky eating, Emotional well-being, Disordered eating