Longitudinal Neurocognitive Trajectories in a Large Cohort of Youth Who Use Cannabis: Combining Self-Report and Toxicology.
Natasha E Wade, Ryan M Sullivan, Alexander L. Wallace, Rachel Visontay, Veronica Szpak, Krista M. Lisdahl, Marilyn A. Huestis, Priscila Dib Goncalves, Hollie Byrne, Louise Mewton, Joanna Jacobus, Susan F Tapert
bioRxiv : the preprint server for biology March 6, 2026 preprint DOI: 10.64898/2025.12.20.695698 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Longitudinal cohort study |
|---|---|
| Sample size | 11,036 |
| Population | Adolescents aged 9-17 from the ABCD Study |
| Topics | Cannabis |
| Key findings | Cannabis use onset interacts with age to alter neurocognitive trajectories across multiple domains, with reduced improvement or flattened trajectories over time. THC exposure specifically predicted worse episodic memory compared to controls, while CBD exposure showed no difference. |
Abstract
Adolescents experience extensive neurocognitive development, with cannabis use potentially impacting developmental trajectories. Here, we comprehensively assess the influence of adolescent cannabis use onset on neurocognitive trajectories and consider how recent delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may influence neurocognition. We use the large, diverse longitudinal Adolescent Brain Cognitive Development (ABCD) Study dataset, combining self-reported substance use with objective toxicological tests (hair, urine, breath, oral fluid). Longitudinal mixed methods of the full cohort (n=11,036, ages 9-17; 47% Female/53% Male) investigate time-varying cannabis onset on neurocognitive performance. Primary model covariates include sociodemographics, family history of substance use disorder, prenatal substance exposure, early psychopathology, other substance use, and nesting for participant ID, study site, and family ID. Secondarily, in participants with repeat toxicological hair testing (n=645; 38% Female/62% Male) at ages 12-16, we consider the influence of THC v. CBD v. Controls. Primary models included false discovery rate corrections (FDR-p<.05) while secondary models were interpreted at p<.01. Cannabis group interacted with age to show altered neurocognitive trajectories across domains (immediate recall and delayed memory, processing speed, inhibitory control, visuospatial processing, language, and working memory; βs=-0.11- -0.52). Secondary models indicated hair-identified THC exposure*age predicted worse episodic memory than in Controls (β=-0.60, p=.007), with no difference between CBD exposed and Controls. Data suggest those who use cannabis show likely pre-existing better cognitive performance during late childhood, with reduced improvement or flattened trajectories over time. These neurocognitive trajectories in youth (ages 9-17) who initiate cannabis use were demonstrated after accounting for within-person change and numerous known confounds and improving accuracy in identifying cannabis use through incorporating toxicological measures. Continued monitoring of this cohort will clarify cannabinoid-cognition relationships into young adulthood, including the impact of timing of cannabis use initiation.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cites 9
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double‐blind, placebo‐controlled, crossover experiment Addiction February 8, 2023
- The Influence of Cannabis and Nicotine Co-Use on Neuromaturation – A Systematic Review of Adolescent and Young Adult Studies Biological Psychiatry September 29, 2020
- Association of Cannabis With Cognitive Functioning in Adolescents and Young Adults: A Systematic Review and Meta-analysis JAMA Psychiatry June 1, 2018
- Longitudinal Changes in Cognition in Young Adult Cannabis Users Journal of Clinical and Experimental Neuropsychology October 23, 2017
and 4 more in the library