The Largest Study Yet on How Adolescent Cannabis Affects Brain Development Over Time
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.).
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Evidence Grade:
- Large longitudinal cohort with objective toxicology and extensive covariate adjustment—among the strongest observational evidence possible, though still a preprint.
- Study Age:
- Posted on bioRxiv in 2025, analyzing ABCD Study data from ages 9–17.
- Original Title:
- Longitudinal Neurocognitive Trajectories in a Large Cohort of Youth Who Use Cannabis: Combining Self-Report and Toxicology.
- Published In:
- bioRxiv : the preprint server for biology (2025) — bioRxiv is a preprint server for biology, known for sharing early research findings.
- Authors:
- Wade, Natasha E(18), Sullivan, Ryan M(9), Wallace, Alexander L(14), Visontay, Rachel, Szpak, Veronica, Lisdahl, Krista M, Huestis, Marilyn A, Gonçalves, Priscila Dib, Byrne, Hollie, Mewton, Louise, Jacobus, Joanna, Tapert, Susan F
- Database ID:
- RTHC-07890
Evidence Hierarchy
Follows a group of people over time to track how outcomes develop.
What do these levels mean? →Read More on RethinkTHC
- THC-amygdala-anxiety-brain
- anandamide-weed-withdrawal
- cannabinoid-receptors-recovery-time
- cannabis-developing-brain-teenagers
- cant-enjoy-anything-without-weed
- dopamine-recovery-after-quitting-weed
- endocannabinoid-system-explained-simply
- endocannabinoid-system-withdrawal
- nervous-system-weed-withdrawal-fight-flight
- teen-weed-use-under-18-effects-brain
- thc-brain-withdrawal
- thc-prefrontal-cortex-brain-effects
- weed-cortisol-stress-hormones
- weed-memory-loss-recovery
- weed-motivation-amotivational-syndrome
- weed-nervous-system-effects
- weed-reward-system-brain
- thc-and-productivity-help-or-hurt
- thc-and-studying-cannabis-learning-research
Cite This Study
https://rethinkthc.com/research/RTHC-07890APA
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
MLA
Wade, Natasha E, et al. "Longitudinal Neurocognitive Trajectories in a Large Cohort of Youth Who Use Cannabis: Combining Self-Report and Toxicology.." bioRxiv : the preprint server for biology, 2025. https://doi.org/10.64898/2025.12.20.695698
RethinkTHC
RethinkTHC Research Database. "Longitudinal Neurocognitive Trajectories in a Large Cohort o..." RTHC-07890. Retrieved from https://rethinkthc.com/research/wade-2025-longitudinal-neurocognitive-trajectories-in
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.