title: Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.
abstract: Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18-50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders.
authors.affiliation: Medical University of South Carolina College of Medicine, 67 President St., Charleston, SC 29425, United States. Electronic address: mccluree@musc.edu.
authors.forename: Erin A
authors.initials: EA
authors.lastname: McClure
authors.affiliation: Medical University of South Carolina College of Medicine, 67 President St., Charleston, SC 29425, United States.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Sonne
authors.affiliation: Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, United States.
authors.forename: Theresa
authors.initials: T
authors.lastname: Winhusen
authors.affiliation: Yale University School of Medicine, 950 Campbell Ave, West Haven, CT 06516, United States.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Carroll
authors.affiliation: Center for the Clinical Trials Network, National Institute on Drug Abuse, 6001 Executive Boulevard, MSC 9557, Bethesda, MD 20892, United States.
authors.forename: Udi E
authors.initials: UE
authors.lastname: Ghitza
authors.affiliation: Medical University of South Carolina College of Medicine, 67 President St., Charleston, SC 29425, United States.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: McRae-Clark
authors.affiliation: The EMMES Corporation, 401 N. Washington St., Rockville, MD 20850, United States.
authors.forename: Abigail G
authors.initials: AG
authors.lastname: Matthews
authors.affiliation: The EMMES Corporation, 401 N. Washington St., Rockville, MD 20850, United States.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Sharma
authors.affiliation: The EMMES Corporation, 401 N. Washington St., Rockville, MD 20850, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Veldhuisen
authors.affiliation: Johns Hopkins University, School of Medicine, 5510 Nathan Shock Dr., Baltimore, MD 21224, United States.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Vandrey
authors.affiliation: Columbia University/New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Levin
authors.affiliation: Division of Alcohol and Drug Abuse, McLean Hospital, 115 Mill St., Belmont, MA 02478, United States; Department of Psychiatry, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, United States.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Weiss
authors.affiliation: The EMMES Corporation, 401 N. Washington St., Rockville, MD 20850, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Lindblad
authors.affiliation: The EMMES Corporation, 401 N. Washington St., Rockville, MD 20850, United States.
authors.forename: Colleen
authors.initials: C
authors.lastname: Allen
authors.affiliation: University of California, Los Angeles, David Geffen School of Medicine, 1640 S. Sepulveda Blvd., Suite 120, Los Angeles, CA 90025, United States.
authors.forename: Larissa J
authors.initials: LJ
authors.lastname: Mooney
authors.affiliation: Medical University of South Carolina College of Medicine, 67 President St., Charleston, SC 29425, United States.
authors.forename: Louise
authors.initials: L
authors.lastname: Haynes
authors.affiliation: Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, United States.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Brigham
authors.affiliation: Center for the Clinical Trials Network, National Institute on Drug Abuse, 6001 Executive Boulevard, MSC 9557, Bethesda, MD 20892, United States.
authors.forename: Steve
authors.initials: S
authors.lastname: Sparenborg
authors.affiliation: University of California, Los Angeles, David Geffen School of Medicine, 1640 S. Sepulveda Blvd., Suite 120, Los Angeles, CA 90025, United States.
authors.forename: Albert L
authors.initials: AL
authors.lastname: Hasson
authors.affiliation: Medical University of South Carolina College of Medicine, 67 President St., Charleston, SC 29425, United States.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Gray
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D054577:National Institute on Drug Abuse (U.S.); D012107:Research Design; D012907:Smoking / Q000453:epidemiology; D014481:United States; D055815:Young Adult
chemical_list: D000111:Acetylcysteine
keywords: Cannabis; Clinical study design; Marijuana; N-acetylcysteine; Pharmacotherapy; Randomized trials