In over 11,000 adolescents from the ABCD Study, cannabis use onset altered neurocognitive trajectories across multiple domains—and hair testing revealed that THC and CBD had different associations with cognition.
Developmental neuroscientists, pediatricians counseling families, policymakers weighing age-of-access laws, and parents of teenagers.
What the researchers found
This is the most comprehensive longitudinal study to date on adolescent cannabis use and cognitive development, drawing from the ABCD Study—a landmark NIH-funded project tracking brain development in American children.
The primary analysis followed 11,036 participants from ages 9 to 17, combining self-reported substance use with objective toxicological testing (hair, urine, breath, oral fluid). Cannabis use onset interacted with age to alter neurocognitive trajectories across multiple domains: immediate recall, delayed memory, processing speed, and other measures.
The secondary analysis was particularly innovative. In 645 participants with repeat hair toxicology at ages 12–16, the researchers distinguished between THC exposure and CBD exposure. The two cannabinoids showed different cognitive associations—consistent with RTHC-00193's finding that THC and CBD may push psychosis risk in opposite directions, and suggesting the composition of cannabis products matters for developmental outcomes.
The study controlled for an unusually comprehensive set of confounders: sociodemographics, family history of substance use disorder, prenatal substance exposure, early psychopathology, other substance use, and statistical nesting for participant ID, study site, and family. This extensive covariate adjustment strengthens confidence that the cannabis-cognition associations aren't driven by pre-existing differences.
Why it matters
The ABCD Study is the gold standard for adolescent brain development research—large, diverse, longitudinal, and multi-modal. This analysis leverages those strengths to provide the most definitive evidence yet that cannabis onset during adolescence alters cognitive development trajectories. The THC vs. CBD distinction using objective hair testing pushes beyond the simplistic question of whether 'cannabis' affects the brain to ask which components matter most.
The numbers in context
N = 11,036 (full cohort, ages 9–17). N = 645 (hair toxicology subsample, ages 12–16). Cannabis onset altered trajectories in: immediate recall, delayed memory, processing speed, and additional domains. THC and CBD showed different cognitive associations.
How the study worked
Longitudinal mixed-methods analysis of the ABCD Study. Primary: n=11,036, ages 9–17, time-varying cannabis onset on neurocognitive trajectories. Secondary: n=645 with repeat hair toxicology at ages 12–16, comparing THC vs. CBD vs. Controls. Covariates: sociodemographics, family SUD history, prenatal exposure, early psychopathology, other substance use. Nested by participant, site, and family.
Who was studied
N=11,036 youth aged 9-17, diverse US cohort from the Adolescent Brain Cognitive Development Study.
What this study cannot tell us
Preprint (bioRxiv)—not yet peer reviewed. Even with extensive covariates, observational data can't prove causation. Hair toxicology captures recent weeks of exposure, not lifetime use patterns. The secondary analysis (n=645) is much smaller than the full cohort. Self-reported cannabis use may undercount, while toxicology may miss intermittent use. Cannot control for all possible confounders (genetic liability, peer effects, etc.).
How to read the evidence
Large longitudinal cohort with objective toxicology and extensive covariate adjustment—among the strongest observational evidence possible, though still a preprint.
When this study was published
Posted on bioRxiv in 2025, analyzing ABCD Study data from ages 9–17.
The bigger picture
This is the human longitudinal evidence that animal studies like RTHC-00197 (adolescent cannabinoid exposure disrupting hippocampal theta rhythms) and RTHC-00210 (CB1-GABA memory mechanism) have predicted. RTHC-00014 (teen brain effects) and RTHC-00162 (adolescent cannabis review) raised the concern; this study quantifies it with the largest, most methodologically rigorous dataset available. The THC/CBD distinction connects to RTHC-00187's finding that CBD didn't protect memory from THC in adults.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Are the altered cognitive trajectories reversible with cessation? Does the age of onset within adolescence matter (early teens vs. late teens)? Could the different THC/CBD associations inform harm reduction product design for young adults?
Read the original research
Longitudinal Neurocognitive Trajectories in a Large Cohort of Youth Who Use Cannabis: Combining Self-Report and Toxicology.
bioRxiv : the preprint server for biology
bioRxiv is a preprint server for biology, known for sharing early research findings.
Citation
Wade, Natasha E; Sullivan, Ryan M; Wallace, Alexander L; Visontay, Rachel; Szpak, Veronica; Lisdahl, Krista M; Huestis, Marilyn A; Gonçalves, Priscila Dib; Byrne, Hollie; Mewton, Louise; Jacobus, Joanna; Tapert, Susan F. (2025). Longitudinal Neurocognitive Trajectories in a Large Cohort of Youth Who Use Cannabis: Combining Self-Report and Toxicology.. bioRxiv : the preprint server for biology. https://doi.org/10.64898/2025.12.20.695698
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