Research Finds Combined Cannabis and Tobacco Use Impairs Brain Function in At-Risk Adolescents

New research published in the upcoming issue of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging casts new light on the cognitive risks associated with the co-use of cannabis and tobacco among individuals at clinical high risk for psychosis. The study addresses a significant gap in psychiatric and neurocognitive research by focusing on an adolescent and young adult population vulnerable to emerging psychotic symptoms. This investigation elucidates how combined substance use can detrimentally affect neurocognitive functioning during this critical developmental window, raising implications for early detection and intervention strategies.

The phenomenon of co-use—defined as the simultaneous or concurrent consumption of both cannabis and tobacco—has been gaining increasing prevalence, especially among young adults aged 18 to 25. Epidemiological data in the United States reveal that approximately 20% of daily cigarette smokers within this age group also consume cannabis on a daily basis. This duality in substance use carries complex implications, as prior research has linked co-use to a heightened risk of developing various mental health disorders, although few studies have parsed out its effects in populations already exhibiting signs of psychosis risk.

Prior investigations into substance use among individuals with psychotic disorders have yielded inconsistent findings concerning the cognitive repercussions of cannabis and tobacco use. Some studies suggested potential cognitive enhancement effects of tobacco in these individuals, while others reported cognitive impairments associated with cannabis use. However, none had directly explored the combined cognitive impact of co-use in the prodromal phase—the critical period before full-blown psychotic episodes emerge—making this present study pioneering in its approach and methodology.

Drawing from the extensive North American Prodrome Longitudinal Study 2 (NAPLS 2), this large-scale multisite research trial included a cohort of 734 clinically high-risk individuals and 278 healthy comparison subjects. Participants underwent rigorous neuropsychological assessments using the MATRICS Consensus Cognitive Battery (MCCB), which measures multiple cognitive domains relevant to psychosis, such as processing speed, working memory, attention, and verbal learning. Substance use history was self-reported, focusing on cannabis and tobacco consumption in the previous month to determine co-use status.

The analysis uncovered a compelling association between cannabis and tobacco co-use and diminished global neurocognitive performance in the at-risk group. Specifically, individuals who reported using both substances exhibited significantly poorer scores across a broad spectrum of cognitive functions compared to both healthy controls and at-risk individuals who used cannabis or tobacco alone. This finding is particularly significant given that impaired cognitive performance is one of the earliest measurable indicators predictive of psychosis onset.

Unexpectedly, the study also revealed that at-risk individuals abstaining from all substances demonstrated notably lower cognitive performance and social functioning compared to their substance-using counterparts. This suggests the presence of a distinct subset within the prodromal population characterized by social withdrawal and reduced engagement in substance use, potentially indicating a divergent pathophysiological or psychosocial trajectory. The relationship between social engagement and substance use behaviors underscores the complex interplay between environmental, behavioral, and neurodevelopmental factors in psychosis risk.

These results carry critical implications for clinical practice. They highlight the necessity for comprehensive substance use assessment, particularly focused on co-use patterns, when evaluating adolescents and young adults in early psychosis clinics. The cognitive impairments associated with co-use may augment the risk for conversion to full psychosis or exacerbate functional decline, thereby necessitating targeted interventions. Clinicians should integrate these findings into their screening and psychoeducational efforts to mitigate neurocognitive deterioration during this vulnerable period.

Despite the groundbreaking insights, the study acknowledges limitations related to causal inference due to its cross-sectional design. The directionality of the association between co-use and cognitive deficits remains to be fully elucidated—whether co-use precipitates cognitive decline or if inherent cognitive vulnerabilities predispose individuals to dual substance consumption. Longitudinal analyses tracking neurocognitive trajectories relative to changing substance use patterns will be essential to disentangle these complex relationships.

Neurobiological mechanisms potentially underlying the observed cognitive impairments may involve the interactions of cannabis and tobacco on brain systems implicated in psychosis risk. Cannabis primarily acts via the endocannabinoid system, modulating neurotransmission and neurodevelopmental processes related to cognition and psychosis. Tobacco, through nicotine and other constituents, affects cholinergic and dopaminergic pathways, which can temporarily enhance certain cognitive functions but may also induce neuroadaptations deleterious over time. The combined pharmacodynamic effects of these substances could synergize to disrupt cognitive networks in at-risk youth.

From a public health perspective, these findings resonate amid a shifting landscape of cannabis legalization and increased accessibility. The concurrent rise in tobacco and cannabis co-use in the general population underscores the urgency for informed policies and preventive strategies tailored to youth at risk for serious mental health conditions. Effective early intervention could attenuate or delay cognitive decline, optimize functional outcomes, and improve quality of life.

The involvement of key investigators such as Heather Burrell Ward, MD, from Vanderbilt University Medical Center, and co-investigator Ricardo E. Carrión, PhD, from Feinstein Institutes for Medical Research, strengthens the study’s credibility. Their multidisciplinary expertise bridges psychiatry, neuropsychology, and behavioral science, enabling a comprehensive approach to understanding the nuanced effects of co-use on cognition within this clinical population.

Moreover, Editor-in-Chief Cameron S. Carter, MD, of the University of California Irvine School of Medicine, emphasizes the novelty and clinical relevance of the research. His commentary draws attention to the early prodromal phase as a period ripe for preventive interventions that could alter the course of psychotic disorders. The study provides valuable evidence to inform how co-use practices are addressed therapeutically within this context.

In conclusion, this seminal study offers robust evidence linking cannabis and tobacco co-use to impaired cognitive performance in individuals at clinical high risk for psychosis, with significant ramifications for clinical assessment, intervention strategies, and public health policy. Further longitudinal and mechanistic investigations are warranted to elucidate causality and inform comprehensive risk reduction frameworks. As cannabis and tobacco co-use escalates globally, understanding its impact on vulnerable youth remains a priority for advancing mental health outcomes.

News Publication Date: June 2, 2026

Web References:
https://doi.org/10.1016/j.bpsc.2026.03.021
https://www.sobp.org/bpcnni