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ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task

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Abstract

Children diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for substance abuse. Response inhibition is a hallmark of ADHD, yet the combined effects of ADHD and regular substance use on neural networks associated with response inhibition are unknown. Task-based functional Magnetic Resonance Imaging (fMRI) data from young adults with childhood ADHD with (n = 25) and without (n = 25) cannabis use ≥ monthly in the past year were compared with a local normative comparison group (LNCG) with (n = 11) and without (n = 12) cannabis use. Go/NoGo behavioral and fMRI data were evaluated for main and interaction effects of ADHD diagnosis and cannabis use. ADHD participants made significantly more commission errors on NoGo trials than controls. ADHD participants also had less frontoparietal and frontostriatal activity, independent of cannabis use. No main effects of cannabis use on response inhibition or functional brain activation were observed. An interaction of ADHD diagnosis and cannabis use was found in the right hippocampus and cerebellar vermis, with increased recruitment of these regions in cannabis-using controls during correct response inhibition. ADHD participants had impaired response inhibition combined with less fronto-parietal/striatal activity, regardless of cannabis use history. Cannabis use did not impact behavioral response inhibition. Cannabis use was associated with hippocampal and cerebellar activation, areas rich in cannabinoid receptors, in LNCG but not ADHD participants. This may reflect recruitment of compensatory circuitry in cannabis using controls but not ADHD participants. Future studies targeting hippocampal and cerebellar-dependent function in these groups may provide further insight into how this circuitry is altered by ADHD and cannabis use.

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Abbreviations

LNCG:

Local Normative Comparison Group

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Acknowledgments

This project was funded by the National Institute on Drug Abuse (NIDA) Multimodal Treatment Study of Children with ADHD (MTA) Neuroimaging Study (NIDA Contract #: HHSN271200800009C).

We thank the participants of this study and the numerous staff involved with the coordination of visits, particularly Shichun Ling for her administrative support in the preparation of this manuscript.

Portions of this work were presented as a poster at the International Society for Magnetic Resonance Imaging in Medicine, Salt Lake City, USA 2013.

1The Multimodal Treatment Study of Children with ADHD (MTA) was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial, continued under an NIMH contract as a follow-up study and finally under a National Institute on Drug Abuse (NIDA) contract. Collaborators from NIMH: L. Eugene Arnold, M.D., M.Ed. (currently at Ohio State University). Principal investigators and co-investigators from the sites are: University of California, Berkeley/San Francisco: Stephen P. Hinshaw, Ph.D. (Berkeley), Glen R. Elliott, Ph.D., M.D. (San Francisco); Duke University: Karen C. Wells, Ph.D., Jeffery N. Epstein, Ph.D. (currently at Cincinnati Children’s Hospital Medical Center), Desiree W. Murray, Ph.D.; University of California, Irvine: James Swanson, Ph.D., Timothy Wigal, Ph.D.; New York University: Howard B. Abikoff, Ph.D.; New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center: Laurence L. Greenhill, M.D. (Columbia). University of Pittsburgh: Brooke Molina, Ph.D., Additional investigators for Neuroimaging Study: Leanne Tamm, Ph.D., PI (Cincinnati Children’s Hospital Medical Center), James Bjork, Ph.D. (Division of Clinical Neuroscience and Behavioral Research, NIDA), Daniel Mathalon, M.D., Ph.D. (UC San Francisco), Allen Song, Ph.D. (Duke), Bradley Peterson, M.D. (Columbia), Steven G. Potkin, M.D., Theo G.M. van Erp & Claudia Buss, Ph.D. (UC Irvine), Katerina Velanova, Ph.D. (Pittsburgh), Neuroimaging Consultants: Susan Tapert, Ph.D. & Joshua Kuperman, Ph.D. (UC San Diego), BJ Casey, Ph.D. (Sackler Institute, Weill Cornell Medical College), Leah Somerville, Ph.D.,(Department of Psychology, Harvard University), Krista Lisdahl, Ph.D. (University of Wisconsin-Milwaukee). Neuroimaging Analysis and Interpretation: Terry Jernigan, Ph.D. & Anders Dale, Ph.D. (UC San Diego), F. Xavier Castellanos, M.D. & Clare Kelly, Ph.D. (New York University).

Financial disclosures

Dr. Arnold has received research funding from CureMark, Fore- str, Lilly, and Shire, advisory board honoraria from Biomarin, Novartis, Noven, Roche, Seaside Therapeutics, and Shire, consulting fees from Tris Pharma, and travel support from Noven.

Dr. Swanson has received research support from Alza, Richwood, Shire, Celgene, Novartis, Celltech, Gliatech, Cephalon, Watson, CIBA, Janssen, and McNeil; has been on the advisory board for Alza, Rich- wood, Shire, Celgene, Novartis, Celltech, UCB, Gliatech, Cephalon, McNeil, and Lilly; has been on speaker’s bureau for Alza, Shire, Novartis, Celltech, UCB, Cephalon, CIBA, Janssen, and McNeil; and has consulted to Alza, Richwood, Shire, Celgene, Novartis, Celltech, UCB, Gliatech, Cephalon, Watson, CIBA, Janssen, McNeil, and Lilly.

Dr. van Erp has been a consultant for Roche Pharmaceuticals.

Dr. Mathalon is a consultant for Bristol-Myers Squibb and has consulted for Roche Pharmaceuticals.

Dr. Potkin’s work has been funded by the NIH. Dr. Potkin has received grant support, funding, honoraria, or has been a paid consultant to the following companies that conducted scientific or medical research and/or marketed medications related to psychiatric and neurodegenerative disorders: Alkermes, Eli Lilly, FORUM, Genentech, Janssen, Lundbeck, Merck, Novartis, Otsuka, Roche, Sunovion, Takeda, Toyama, and Vanda.

The remaining authors report no biomedical financial interests or potential conflicts of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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Rasmussen, J., Casey, B.J., van Erp, T.G.M. et al. ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task. Brain Imaging and Behavior 10, 761–771 (2016). https://doi.org/10.1007/s11682-015-9438-9

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