The role of subcortical brain tissue iron as an indicator of dopamine neurophysiology in adolescent cannabis use.
Sarah A Thomas, Meghan A Gonsalves, Gillian LeBlanc, Elizabeth Lorenc, Jane Metrik, Michael Frank, Sarah Ryan, Emily Olenik, Leslie Brick, Anthony Spirito, Jodi M Gilman
Neuropsychopharmacology June 2, 2026 DOI: 10.1038/s41386-026-02444-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional observational study Peer reviewed |
|---|---|
| Sample size | 81 |
| Population | Adolescents aged 14-17 with limited alcohol and nicotine use and no other illicit substance use, reporting either fewer than 5 or more than 11 lifetime cannabis episodes |
| Measures | 1/nT2* (inverse normalized T2*), substance use assessments |
| Topics | Cannabis |
| Key findings | Lower 1/nT2* signal, an MRI index of subcortical tissue iron, was associated with greater daily concentrate hits, cannabis hours high, cannabis use frequency, and cannabis use disorder severity, with the ventral tegmental area highlighted in post-hoc analyses. The authors interpret this as consistent with reduced dopamine-related neurophysiology linked to cannabis use. |
Abstract
Approximately 10-20% of U.S. adolescents report past-year cannabis use (CU). Although regular CU beginning in adolescence is expected to blunt dopamine-related neurophysiology, this hypothesis has not been tested in adolescents due to methodological limitations. However, neurophysiology contributing to dopamine can be noninvasively indexed via subcortical tissue iron measured with magnetic resonance imaging (MRI). We examined adolescent CU quantity, frequency, and problems in relation to tissue iron in regions with high dopamine activity, hypothesizing that greater CU would be linked to less tissue iron. Adolescents (n = 81; 64.2% female) aged 14-17 reporting either fewer than 5 lifetime cannabis episodes (n = 47) or more than 11 episodes (n = 34), with limited alcohol and nicotine use and no other illicit substance use, completed substance use assessments and an MRI. We calculated the inverse of the normalized T2* measurement (1/nT2*; lower values indicate less tissue iron) from resting-state functional scans by assessing relative T2* decay. 1/nT2* was estimated using subcortical masks for hypothesized regions. Lower 1/nT2* signal was associated with increased daily concentrate hits (b = -0.01, p < 0.001), cannabis hours high (b = -0.01, p = 0.016), CU frequency (b = -0.01, p = 0.01), and cannabis use disorder (CUD) severity (b = -0.01, p = 0.003). Post-hoc analyses highlighted the VTA as a key region. Results align with reduced dopamine-related neurophysiology associated with CU in adult and animal samples, and have implications for understanding adolescent CUD development. Measuring 1/nT2* offers an innovative, non-invasive method to index neurobiological alterations in adolescent CU.
Comparable studies
Other cross-sectional and survey studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... | 2011 | Observational cross-sectional study | n = 148 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |
| Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents | 2020 | Cross-sectional survey | |
| User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire | 2010 | Cross-sectional survey | n = 600 |
| Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... | 2012 | Cross-sectional survey | n = 337 |
Citations in the library
Cites 16
- Age-related differences in the impact of cannabis use on the brain and cognition: a systematic review European Archives of Psychiatry and Clinical Neuroscience January 24, 2019
- What are the psychological effects of using synthetic cannabinoids? A systematic review Journal of Psychopharmacology February 21, 2019
- Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions Neuropsychopharmacology August 22, 2022
- Convergence of Cannabis and Psychosis on the Dopamine System JAMA Psychiatry April 9, 2025
- Molecular brain differences and cannabis involvement: A systematic review of positron emission tomography studies. Journal of Psychiatric Research June 2023
and 11 more in the library