Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults
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BACKGROUND: The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms. METHODS: Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18-25). Multiple regressions examined the independent and interactive effects of variables on WM integrity. RESULTS: Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC. CONCLUSIONS: Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.
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Regular cannabis use is associated with lower FA.
“Two such studies found that regular cannabis to be associated with lower FA (Jakabek, Yücel, Lorenzetti, & Solowij, 2016; Shollenbarger, Price, Wieser, & Lisdahl, 2015).”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Shollenbarger, Price, Wieser, & Lisdahl, 2015
RD differences between cannabis users and controls are mixed, with studies reporting higher, lower, or nonsignificant differences.
“The relationship between RD and cannabis use is similarly mixed, with studies finding higher (Ashtari et al., 2009; Becker, Collins, Lim, Muetzel, & Luciana, 2015; Jakabek et al., 2016), lower (Filbey et al., 2014; Jakabek et al., 2016), or nonsignificant (Shollenbarger et al., 2015) differences in cannabis users relative to controls.”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Shollenbarger et al., 2015
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Flagged first, then by citations
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Cited by
Sorted by citations
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- Authors
- Shollenbarger, S. G., Price, J., Wieser, J., & Lisdahl, K.
- Affiliations
- University of Wisconsin–Milwaukee (US)
- Harvard University (US)
- Corresponding author
- Shollenbarger, Skyler G.
- Lisdahl, Krista
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2015
- Volume
- 8
- Pages
- 117-125
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC4473294
- OpenAlex
- W1986710580
- Cited by
- 64
- References
- 107
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 3 · 2021: 5 · 2020: 10 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 2
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Drug Abuse (R03 DA027457)
- University of Cincinnati Center for Environmental Genetics Pilot Program (P30 ES06096)
- NIDA (R01 DA030354)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- chronic cannabis use, white matter integrity, uncinate fasciculus, forceps minor, anterior thalamic radiation, depression, apathy, adolescents and young adults, white matter maturation, gene-environment interaction
- MeSH terms
- Fatty Acid Amide Hydrolases, Adolescent, Adult, Amidohydrolases, Cannabis, Depression, Female, Frontal Lobe, Genotype, Humans, Limbic System, Magnetic Resonance Imaging, Male, Young Adult, Apathy, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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