Study Links Cannabis and Tobacco Co-Use to Lower Brain Performance in At-Risk Adolescents

New research shows that among people at clinical high risk for psychosis, cannabis and tobacco co-use was associated with lower cognitive performance compared to healthy controls. The novel studyopens in new tab/window appearing in Biological Psychiatry: Cognitive Neuroscience and Neuroimagingopens in new tab/window, published by Elsevier, fills a critical gap in research, providing clinicians and scientists with vital new insights into the risks associated with cannabis and tobacco co-use and the potential impact on vulnerable adolescents.

Use of both cannabis and tobacco (known as “co-use”) has been on the rise in the general population for the past several decades. Of individuals aged 18-25 in the United States, one in five daily cigarette smokers is also a daily cannabis user. In the general population, co-use is associated with an increased risk for any mental health disorder. People with psychotic disorders have a very high prevalence of both tobacco and cannabis use, but information on co-use in this population is lacking.

This is the first study to investigate cannabis and tobacco co-use and neurocognitive performance in this population. Researchers analyzed data from 734 individuals at clinical high risk for psychosis and 278 healthy controls taking part in the multisite prospective North American Prodrome Longitudinal Study 2.

“Prior research investigating tobacco and cannabis use in people with psychotic disorders has been mixed, showing associations with better cognitive performance in some cases and worse in others,” notes Editor-in-Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Cameron S. Carter, MD, University of California Irvine School of Medicine. “Impaired cognitive performance is one of the earliest indicators of psychosis risk. Until now, there had been no studies examining the effects of co-use on cognitive performance in the psychosis population or in the prodrome—the critical early window when warning signs emerge before definitive illness-specific symptoms develop.”

Lead investigator Heather Burrell Ward, MD, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, says, “In this study individuals at clinical high risk for psychosis reported their substance use over the past month and completed a comprehensive battery of neuropsychological testing. Across a broad range of cognitive tests, we observed that at-risk individuals who used both cannabis and tobacco performed worse on cognitive testing compared to healthy controls.”

The researchers were surprised to find that individuals at risk for psychosis who reported that they did not use any substances also had lower cognitive performance and the lowest social function.

“We found that at-risk individuals who had not used any substances may represent a distinct, socially impaired subtype,” explains co-investigator Ricardo E Carrión, PhD, Institute for Behavioral Science, Feinstein Institutes for Medical Research, Northwell Health System, and Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. “Because these are adolescents and substance use is often linked to social interactions, those who are less social simply may not have as much opportunity to engage in substance use.”

While these findings offer important insights, causality remains unknown. Future studies should investigate associations over time between frequency of cannabis and tobacco use and neurocognitive performance to untangle the directionality of these links. Also, clinicians working with at-risk youth should regularly ask about co-use of tobacco and cannabis.

Dr. Ward concludes, “This research is especially important as the prevalence of cannabis and tobacco co-use in the general population is rising. It is crucial to understand the impact of this co-use in people at clinical high risk for psychosis—a period during adolescence when individuals may start to show attenuated psychotic symptoms and when substance use often begins. Our findings can inform early intervention and a more comprehensive approach to adolescent mental health.”

Notes for editors

The article is "Cannabis and Tobacco Co-Use Is Associated with Impaired Neurocognitive Performance in Individuals at Clinical High Risk for Psychosis," by Daniel Bello, BA, Jillian G. Connolly, BS, Jean Addington, PhD, Carrie E. Bearden, PhD, Kristin Cadenhead, MD, Tyrone D. Cannon, PhD, Barbara Cornblatt, PhD, MBA, Matcheri Keshavan, MD, Daniel H. Mathalon, PhD, MD, Diana O. Perkins, MD, MPH, Larry Seidman, PhD, William S. Stone, PhD, Ming T. Tsuang, MD, PhD, DSc, Elaine F. Walker, PhD, Scott Woods, MD, Roscoe O. Brady, Jr., MD, PhD, Ricardo E. Carrión, PhD, and Heather Burrell Ward, MD (https://doi.org/10.1016/j.bpsc.2026.03.021opens in new tab/window). It appears online in advance of volume 11, issue 8 (August 2026) of Biological Psychiatry: Cognitive Neuroscience and Neuroimagingopens in new tab/window, published by Elsevier.

The article is openly available at https://www.biologicalpsychiatrycnni.org/article/S2451-9022(26)00119-9/fulltextopens in new tab/window.

Copies of this paper are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected]opens in new tab/window. Journalists wishing to interview the study’s authors should contact Craig Boerner at [email protected]opens in new tab/window.

This work was supported by National Institutes of Health (NIH) grants U01 MH066134, P50 MH066286, U01 MH081944, U01 MH081902, U01 MH081857, R01 MH076989, U01 MH066069, U01 MH081928, U01 MH081988, U01 MH82022, R01 MH116170, and K23DA059690.

The authors’ affiliations and disclosures of financial relationships and conflicts of interest are available in the article.

Cameron S. Carter, MD, is Chair of the Department of Psychiatry & Human Behavior at the University of California Irvine School of Medicine. His disclosures of financial relationships and conflicts of interest are available hereopens in new tab/window.

About Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Biological Psychiatry: Cognitive Neuroscience and Neuroimagingopens in new tab/window is an official journal of the Society of Biological Psychiatryopens in new tab/window, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of noninvasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The 2024 Journal Impact Factor^TM score, from Clarivate, for Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is 4.8. www.sobp.org/bpcnniopens in new tab/window

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