Association of Cannabis Use During Adolescence With Neurodevelopment

JAMA psychiatry

JAMA Psychiatry. 2021 Jun 16;78(9):1-11. doi: 10.1001/jamapsychiatry.2021.1258. Online ahead of print.


IMPORTANCE: Animal studies have shown that the adolescent brain is sensitive to disruptions in endocannabinoid signaling, resulting in altered neurodevelopment and lasting behavioral effects. However, few studies have investigated ties between cannabis use and adolescent brain development in humans.

OBJECTIVE: To examine the degree to which magnetic resonance (MR) imaging-assessed cerebral cortical thickness development is associated with cannabis use in a longitudinal sample of adolescents.

DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the community-based IMAGEN cohort study, conducted across 8 European sites. Baseline data used in the present study were acquired from March 1, 2008, to December 31, 2011, and follow-up data were acquired from January 1, 2013, to December 31, 2016. A total of 799 IMAGEN participants were identified who reported being cannabis naive at study baseline and had behavioral and neuroimaging data available at baseline and 5-year follow-up. Statistical analysis was performed from October 1, 2019, to August 31, 2020.

MAIN OUTCOMES AND MEASURES: Cannabis use was assessed at baseline and 5-year follow-up with the European School Survey Project on Alcohol and Other Drugs. Anatomical MR images were acquired with a 3-dimensional T1-weighted magnetization prepared gradient echo sequence. Quality-controlled native MR images were processed through the CIVET pipeline, version 2.1.0.

RESULTS: The study evaluated 1598 MR images from 799 participants (450 female participants [56.3%]; mean [SD] age, 14.4 [0.4] years at baseline and 19.0 [0.7] years at follow-up). At 5-year follow-up, cannabis use (from 0 to >40 uses) was negatively associated with thickness in left prefrontal (peak: t785 = -4.87, cluster size = 1558 vertices; P = 1.10 × 10-6, random field theory cluster corrected) and right prefrontal (peak: t785 = -4.27, cluster size = 1551 vertices; P = 2.81 × 10-5, random field theory cluster corrected) cortices. There were no significant associations between lifetime cannabis use at 5-year follow-up and baseline cortical thickness, suggesting that the observed neuroanatomical differences did not precede initiation of cannabis use. Longitudinal analysis revealed that age-related cortical thinning was qualified by cannabis use in a dose-dependent fashion such that greater use, from baseline to follow-up, was associated with increased thinning in left prefrontal (peak: t815.27 = -4.24, cluster size = 3643 vertices; P = 2.28 × 10-8, random field theory cluster corrected) and right prefrontal (peak: t813.30 = -4.71, cluster size = 2675 vertices; P = 3.72 × 10-8, random field theory cluster corrected) cortices. The spatial pattern of cannabis-related thinning was associated with age-related thinning in this sample (r = 0.540; P < .001), and a positron emission tomography-assessed cannabinoid 1 receptor-binding map derived from a separate sample of participants (r = -0.189; P < .001). Analysis revealed that thinning in right prefrontal cortices, from baseline to follow-up, was associated with attentional impulsiveness at follow-up.

CONCLUSIONS AND RELEVANCE: Results suggest that cannabis use during adolescence is associated with altered neurodevelopment, particularly in cortices rich in cannabinoid 1 receptors and undergoing the greatest age-related thickness change in middle to late adolescence.

PMID:34132750 | PMC:PMC8209561 | DOI:10.1001/jamapsychiatry.2021.1258


Matthew D Albaugh
Jonatan Ottino-Gonzalez
Amanda Sidwell
Claude Lepage
Anthony Juliano
Max M Owens
Bader Chaarani
Philip Spechler
Nicholas Fontaine
Pierre Rioux
Lindsay Lewis
Seun Jeon
Alan Evans
Deepak D'Souza
Rajiv Radhakrishnan
Tobias Banaschewski
Arun L W Bokde
Erin Burke Quinlan
Patricia Conrod
Sylvane Desrivières
Herta Flor
Antoine Grigis
Penny Gowland
Andreas Heinz
Bernd Ittermann
Jean-Luc Martinot
Marie-Laure Paillère Martinot
Frauke Nees
Dimitri Papadopoulos Orfanos
Tomáš Paus
Luise Poustka
Sabina Millenet
Juliane H Fröhner
Michael N Smolka
Henrik Walter
Robert Whelan
Gunter Schumann
Alexandra Potter
Hugh Garavan
IMAGEN Consortium