TY - JOUR
T1 - Association of Cannabis Use during Adolescence with Neurodevelopment
AU - Albaugh, Matthew D.
AU - Ottino-Gonzalez, Jonatan
AU - Sidwell, Amanda
AU - Lepage, Claude
AU - Juliano, Anthony
AU - Owens, Max M.
AU - Chaarani, Bader
AU - Spechler, Philip
AU - Fontaine, Nicholas
AU - Rioux, Pierre
AU - Lewis, Lindsay
AU - Jeon, Seun
AU - Evans, Alan
AU - D'Souza, Deepak
AU - Radhakrishnan, Rajiv
AU - Banaschewski, Tobias
AU - Bokde, Arun L.W.
AU - Quinlan, Erin Burke
AU - Conrod, Patricia
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Grigis, Antoine
AU - Gowland, Penny
AU - Heinz, Andreas
AU - Ittermann, Bernd
AU - Martinot, Jean Luc
AU - Paillère Martinot, Marie Laure
AU - Nees, Frauke
AU - Papadopoulos Orfanos, Dimitri
AU - Paus, Tomáš
AU - Poustka, Luise
AU - Millenet, Sabina
AU - Fröhner, Juliane H.
AU - Smolka, Michael N.
AU - Walter, Henrik
AU - Whelan, Robert
AU - Schumann, Gunter
AU - Potter, Alexandra
AU - Garavan, Hugh
N1 - Funding Information:
reported receiving grants from the National Institute of Mental Health (NIMH) during the conduct of the study. Dr Juliano reported receiving grants from the National Institutes of Health (NIH)/ National Institute on Drug Abuse (NIDA) during the conduct of the study. Dr D’Souza reported receiving grants from the NIDA, NIMH, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the Brain and Behavior Foundation during the conduct of the study; grants from the NIDA, Wallace Foundation, Cluster Headache-Trigeminal Autonomic Cephalalgia, Heffter Institute, NIMH, Brain and Behavior Foundation, Dana Foundation, NIAAA, and Takeda; and personal fees from Abide Therapeutics and Jazz Pharmaceuticals outside the submitted work. Dr Banaschewski reported receiving personal fees from Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Takeda, Infectopharm, and Eli Lilly outside the submitted work; serving as an advisor or consultant to Bristol Myers Squibb, Desitin Arzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma; receiving conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and UCB; being involved in clinical trials conducted by Eli Lilly, Novartis, and Shire; and receiving royalties from Hogrefe, Kohlhammer, CIP-Medien, and Oxford University Press. Dr Bokde reported receiving grants from the European Research Council during the conduct of the study; and grants from National Children’s Foundation–Tallaght and Health Research Board outside the submitted work. Dr Desrivières reported receiving grants from Medical Research Council, Medical Research Foundation, and NIH during the conduct of the study. Dr Ittermann reported receiving grants from the EU, King’s College London, and Charité Berlin during the conduct of the study. Dr Poustka reported receiving honoraria for public speaking by Shire, Takeda, and Infectopharm; and research funding from the EU, Deutsche Forschungsgemeinschaft, and Bundesministerium für Bildung und Forschung. Dr Föhner reported receiving personal fees from Bundesministerium für Bildung und Forschung during the conduct of the study. Dr Smolka reported receiving grants from Deutsche Forschungsgemeinschaft, the European Commission, and Bundesministerium für Bildung und Forschung during the conduct of the study. Dr Walter reported receiving grants from the EU Horizon 2020 ERC Advanced Grant “Stratify” (Brain network-based stratification of reinforcement-related disorders (694313) during the conduct of the study. No other disclosures were reported.
Funding Information:
from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT-2007-037286), the Horizon 2020-funded ERC Advanced Grant STRATIFY (brain network based stratification of reinforcement-related disorders) (695313), Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539), the Medical Research Council Grant “c-VEDA” (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the NIH (R01DA049238,
Funding Information:
A decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; Forschungsnetz AERIAL 01EE1406A, 01EE1406B; Forschungsnetz IMAC-Mind 01GL1745B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940, TRR 265, NE 1383/14-1), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), and the NIH-funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from the Agence Nationale de la Recherche (ANR-12-SAMA-0004, AAPG2019 – GeBra), the Eranet Neuron (AF12-NEUR0008-01– WM2NA; and ANR-18-NEUR00002-01–ADORe), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the Fondation de l’Avenir (grant AP-RM-17-013), the Fédération pour la Recherche sur le Cerveau, the NIH, Science Foundation Ireland (16/ERCD/3797), NIMH (Axon, Testosterone and Mental Health during Adolescence; R01 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. ImagenPathways “Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways” is a collaborative project supported by the European Research Area Network on Illicit Drugs (ERANID). This study is based on independent research commissioned and funded in England by the NIHR Policy Research Programme (project ref. PR-ST-0416-10001). Dr Albaugh is supported by grant K08 MH121654-01A1 from NIMH and a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - 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..
AB - 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..
UR - http://www.scopus.com/inward/record.url?scp=85108570817&partnerID=8YFLogxK
U2 - 10.1001/jamapsychiatry.2021.1258
DO - 10.1001/jamapsychiatry.2021.1258
M3 - Article
C2 - 34132750
AN - SCOPUS:85108570817
SN - 2168-622X
VL - 78
SP - 1031
EP - 1040
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 9
ER -