Teenagers already at clinical high risk for psychosis performed worse on standard cognitive tests when they used both cannabis and tobacco, compared with peers who used neither substance or only one. That finding comes from a study of 734 high-risk participants and 278 healthy controls drawn from the North American Prodrome Longitudinal Study (NAPLS2), a multisite prospective cohort tracking young people vulnerable to serious mental health conditions. The results land as clinicians and researchers search for clearer prevention targets among youth whose developing brains face compounding threats.
Why co-use in psychosis-prone youth demands attention now
Cannabis and tobacco are the two most commonly used substances among adolescents and young adults in the United States. Each carries its own cognitive risks. But the question of what happens when a young person already showing early warning signs of psychosis uses both at the same time has, until recently, lacked direct evidence from a large, well-characterized clinical sample.
The new analysis, published in a psychiatry journal, addresses that gap. Researchers compared neurocognitive performance across substance-use groups within the NAPLS2 cohort, which enrolled participants at eight sites across North America. Co-users, those reporting both cannabis and tobacco use, scored lower on a standardized cognitive battery than healthy controls. The pattern held after the team accounted for other variables, distinguishing co-use from the effects of either substance alone.
A separate but related line of research from the same NAPLS ecosystem examined whether co-use also predicted conversion to full psychosis. That study, available through a Nature platform, found that cannabis and tobacco co-use was associated with psychosis outcomes in clinical high-risk cohorts. Together, the two papers suggest that co-use is not just linked to lower test scores in the short term but may track with the progression of serious psychiatric illness.
One hypothesis running through the broader literature is that nicotine and cannabis interact in ways that are not simply additive. Nicotine has been shown in some populations to sharpen certain aspects of attention and processing speed, raising the possibility that it partially masks acute cannabis-related cognitive slowing. At the same time, structural brain research points in a different direction. A systematic review and meta-analysis published in a leading addiction journal found that co-use of cannabis and tobacco was associated with measurable differences in brain volume. If nicotine temporarily props up performance on timed tasks while both substances reshape brain architecture, clinicians face a deceptive signal: a young person who seems to function adequately on a given day may still be accumulating risk beneath the surface.
What the NAPLS2 data actually show
The NAPLS2 cohort is one of the largest prospective studies of individuals at clinical high risk for psychosis, often abbreviated CHR-P. Its methods and recruitment procedures were described in a foundational paper published in Schizophrenia Research, and the dataset is housed in the NIMH Data Archive, a federal repository maintained by the National Institutes of Health. The cohort was designed to identify predictors and mechanisms of conversion to psychosis, making it a natural platform for studying substance-use effects on cognition in this vulnerable group.
Within the 734 CHR-P participants and 278 controls, the researchers categorized individuals by substance-use patterns and administered a standardized cognitive battery. Co-users performed worse than non-users and single-substance users on these measures. The study materials that are publicly described do not enumerate exact subtest scores or effect sizes, but the direction and consistency of the finding across domains such as memory, processing speed, and executive functioning were emphasized as robust enough to support the paper’s central claim.
The nicotine-moderation question has also been explored outside the CHR-P population. A separate investigation indexed on PubMed examined cross-sectional and longitudinal associations between cannabis use and cognitive functioning in individuals with cannabis use disorder, with nicotine as a moderating variable. That work suggests the relationship between the two substances and cognition is interactive rather than simply cumulative, reinforcing the idea that co-use creates a distinct pharmacological environment in the brain instead of just adding one drug’s effects on top of the other.
A broader systematic review published in Neuroscience and Biobehavioral Reviews mapped the co-use literature across cognitive tests and neuroimaging outcomes. The review highlighted that the CHR-P teen and young adult sample studied through NAPLS2 fills a gap in the evidence base, because most prior co-use research focused on general populations or adults with established substance use disorders rather than on youth at elevated psychiatric risk. In this sense, the NAPLS2 cognitive analysis extends an emerging consensus: the timing and context of co-use matter as much as the substances themselves.
Gaps in the evidence and what to watch next
Several questions remain open. The NAPLS2 co-use analysis is cross-sectional in its cognitive findings, meaning it captures a snapshot rather than tracking the same individuals over time as their substance use changes. That design cannot prove that co-use caused the lower scores. It is possible that youth who were already experiencing greater cognitive difficulties were more likely to use both substances, reversing the assumed direction of the relationship. Confounding factors such as socioeconomic stress, co-occurring mental health problems, or exposure to other substances could also play a role.
The available materials also do not detail the frequency, potency, or duration of cannabis and tobacco use within the co-use group. A teenager who smokes cannabis weekly and occasionally vapes nicotine may have a different risk profile than one who uses high-potency cannabis concentrates daily and smokes multiple cigarettes. Without granular exposure data, clinicians must be cautious about translating group-level findings into precise individual risk estimates.
Another limitation is that standard cognitive batteries, while useful, capture only part of real-world functioning. Subtle difficulties in social cognition, motivation, or stress tolerance may not fully register on timed tests administered in a clinic. For CHR-P youth, who often juggle school, work, and family demands, even modest decrements in attention or working memory could translate into missed developmental milestones, compounding the challenges posed by emerging psychiatric symptoms.
Future research will likely push in two directions. Longitudinal analyses within NAPLS and similar cohorts could clarify whether changes in co-use patterns predict subsequent shifts in cognition or psychosis risk, strengthening the case for causality. At the same time, neuroimaging and biomarker studies may help disentangle how cannabis and nicotine interact at the level of brain circuits, potentially revealing targets for prevention or early intervention.
Implications for clinicians, families, and policy
For frontline clinicians working with CHR-P adolescents and young adults, the message is not that every instance of cannabis or tobacco use guarantees cognitive decline. Rather, the emerging evidence indicates that co-use should be treated as a meaningful risk marker, especially when layered onto an already vulnerable neurodevelopmental trajectory. Brief interventions that specifically address the appeal of combining substances, rather than discussing each in isolation, may be more resonant for youth who see co-use as part of their social identity.
Families and caregivers can also draw practical guidance from these findings. When a teenager at clinical high risk for psychosis reports using both cannabis and nicotine-whether through smoking, vaping, or other routes-that information should prompt a more detailed conversation about school performance, memory, and day-to-day functioning. Framing the discussion around protecting cognitive strengths, rather than moral judgments about drugs, may reduce defensiveness and open space for change.
On the policy front, the data arrive amid shifting landscapes for both substances. Legal cannabis markets and evolving nicotine delivery systems have altered how easily young people can access products and how those products are marketed. Prevention campaigns that continue to silo “tobacco” and “marijuana” into separate messages risk missing the combined patterns of use that appear most consequential for psychosis-prone youth. Integrating co-use explicitly into public health messaging, particularly in school and community settings that serve high-risk populations, could help close that gap.
Ultimately, the NAPLS2 findings do not offer simple answers, but they sharpen the questions that matter most. In adolescents already on a precarious psychiatric path, cannabis and tobacco co-use appears linked to measurable cognitive disadvantages and to the course of psychosis-related outcomes. As researchers refine the science, clinicians and families do not have to wait for perfect certainty to act. Reducing or eliminating co-use in this group is a plausible, actionable step toward preserving cognitive reserve at a critical stage of brain development-and may, for some, alter the trajectory of serious mental illness before it fully takes hold.
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*This article was researched with the help of AI, with human editors creating the final content.
