title: Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration.
abstract: Chronic cannabis use may interact with factors, such as age of onset of cannabis use, family history, and genetic factors, to elicit schizophrenia (SZ)-like symptoms, including sensory and cognitive deficits. However, evidence of a relationship between cannabis use and cognitive impairment is confounded by concomitant use of tobacco. The objective of this study was to compare tobacco-naïve cannabis users with individuals without a history of tobacco/cannabis use on the auditory mismatch negativity (MMN) event-related potential (ERP), a neural measure of auditory deviance detection which is diminished in SZ. An exploratory arm of the study, conducted within a randomized, double-blind, placebo controlled design, examined the acute effects of nicotine gum (6mg) on MMN in cannabis users. MMN was recorded in response to 5 deviant stimuli within an optimal MMN paradigm in 44 healthy, non-tobacco smoking volunteers aged 18-26. Cannabis users (n=21) started smoking cannabis prior to age 17, at least 1 joint per month. To examine the effects of chronicity, users were grouped into relatively heavy long-term (HLT; n=11) users and light short-term (LST; n=10) users. Impaired deviance detection was shown in cannabis users vs. nonusers as reflected by a smaller MMN to duration deviants. Chronicity of use was also associated with MMN alterations, as HLTs displayed a reduced duration and gap MMN vs. LSTs. Compared with placebo, nicotine treatment enhanced select MMN deviants in cannabis user subgroups. As deficits associated with early and persistent cannabis use are similar to those seen in SZ, these dose-dependant disturbances in early sensory processing with cannabis use may be one cognitive pathway which mediates an increased risk for SZ in vulnerable youth, and be influenced by concurrent cigarette smoking behavior.
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada; School of Psychology, University of Ottawa, Ottawa, ON, Canada. Electronic address: danielle.impey@theroyal.ca.
authors.forename: Danielle
authors.initials: D
authors.lastname: Impey
authors.affiliation: School of Psychology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: El-Marj
authors.affiliation: Department of Biomedical Science, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Parks
authors.affiliation: Department of Cellular and Molecular Medicine, Neuroscience Program, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Joelle
authors.initials: J
authors.lastname: Choueiry
authors.affiliation: Department of Psychology, Mount Saint Vincent University, Halifax, Nova Scotia, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Fisher
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada; School of Psychology, University of Ottawa, Ottawa, ON, Canada; Department of Biomedical Science, University of Ottawa, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Neuroscience Program, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Verner J
authors.initials: VJ
authors.lastname: Knott
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D001308:Auditory Perceptual Disorders / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D016022:Case-Control Studies; D004311:Double-Blind Method; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000150:complications / Q000503:physiopathology*; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D009538:Nicotine
keywords: Auditory deviance detection; Cannabis; Event-related potential; MMN; Mismatch negativity; Nicotine; Schizophrenia