title: Low Pretreatment Impulsivity and High Medication Adherence Increase the Odds of Abstinence in a Trial of N-Acetylcysteine in Adolescents with Cannabis Use Disorder.
abstract: BACKGROUND
  In light of recent progress toward pharmacologic interventions to treat adolescent cannabis use disorder, it is important to consider which adolescent characteristics may be associated with a favorable response to treatment. This study presents secondary analyses from a parent randomized controlled trial of N-acetylcysteine (NAC) in adolescents with cannabis use disorder. We hypothesized that high pretreatment impulsivity and medication non-adherence would be associated with reduced abstinence rates.
  
  
  METHODS
  Participants were treatment-seeking adolescents (N=115) who met criteria for cannabis use disorder and were assessed for pretreatment impulsivity. They received 1200 mg NAC or placebo orally twice daily for 8 weeks. An intent-to-treat analysis using a repeated-measures logistic regression model was used to relate pretreatment impulsivity (Barratt Impulsiveness Scale) and treatment group to abstinence rates, measured by urine cannabinoid tests. To explore mechanisms by which NAC may reduce cannabis use, relationships between impulsivity, adherence, and abstinence were assessed in a second statistical model using data from participants with recorded adherence and urine cannabinoid test results (n=54).
  
  
  RESULTS
  In the intent-to-treat analysis, low pretreatment impulsivity, NAC treatment, and negative baseline urine cannabinoid test results independently increased the odds of having negative urine cannabinoid tests during treatment (OR=2.1, 2.3, and 5.3 respectively). In the sample of participants with adherence data (n=54), adherence tripled the odds of abstinence. Notably, the effect of adherence on abstinence was only observed in the NAC treatment group. Lastly, although the highly impulsive participants had reduced rates of abstinence, highly impulsive individuals adherent to NAC treatment had increased abstinence rates compared to non-adherent individuals.
  
  
  CONCLUSIONS
  Low impulsivity, NAC treatment, medication adherence, and baseline negative cannabinoid testing were associated with increased rates of abstinence in adolescents seeking treatment for cannabis use disorder. Efforts to optimize pharmacotherapy adherence may be particularly crucial for highly impulsive individuals. Understanding and addressing factors, such as impulsivity and adherence, which may affect outcomes, may aid in the successful evaluation and development of potentially promising pharmacotherapies.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 125 Doughty Street, Suite 190, MSC861, Charleston, SC 29425, USA.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Bentzley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 125 Doughty Street, Suite 190, MSC861, Charleston, SC 29425, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Tomko
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 125 Doughty Street, Suite 190, MSC861, Charleston, SC 29425, USA. Electronic address: graykm@musc.edu.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Gray
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy*; D055118:Medication Adherence / Q000523:psychology*; D055815:Young Adult
chemical_list: D000111:Acetylcysteine
keywords: Abstinence; Adolescent; Cannabis; Impulsivity; Marijuana; N-acetylcysteine; Non-adherence; Pharmacotherapy; Youth
references.citation: J Subst Abuse Treat. 2008 Dec;35(4):362-8
references.pmid: 18342479
references.citation: Am J Addict. 2015 Jan;24(1):15-23
references.pmid: 25823631
references.citation: Front Psychol. 2010 Dec 14;1:225
references.pmid: 21833280
references.citation: Am J Drug Alcohol Abuse. 1999 Nov;25(4):573-91
references.pmid: 10548436
references.citation: Drug Alcohol Depend. 2007 Apr 17;88(1):79-82
references.pmid: 17049754
references.citation: Res Social Adm Pharm. 2014 Nov-Dec;10(6):e87-e98
references.pmid: 25088545
references.citation: Psychopharmacology (Berl). 2011 Aug;216(3):305-21
references.pmid: 21373791
references.citation: Front Pharmacol. 2013 Jul 25;4:91
references.pmid: 23898295
references.citation: J Stud Alcohol Drugs. 2011 Nov;72(6):1012-8
references.pmid: 22051215
references.citation: Alcohol Clin Exp Res. 2015 Feb;39(2):232-8
references.pmid: 25684046
references.citation: Addict Behav. 2012 Apr;37(4):420-6
references.pmid: 22189052
references.citation: Med Care. 2004 Mar;42(3):197-9
references.pmid: 15076818
references.citation: Exp Clin Psychopharmacol. 2007 Apr;15(2):165-75
references.pmid: 17469940
references.citation: Neuropsychopharmacology. 2003 Jul;28(7):1356-65
references.pmid: 12784123
references.citation: Clin Pharmacol Ther. 2014 Jun;95(6):617-26
references.pmid: 24739446
references.citation: Biol Psychiatry. 2011 Feb 1;69(3):260-5
references.pmid: 20965498
references.citation: Psychiatry Res. 2001 May 10;102(1):91-5
references.pmid: 11368844
references.citation: Pharmacol Biochem Behav. 2011 Apr;98(2):196-202
references.pmid: 21215769
references.citation: Exp Clin Psychopharmacol. 2012 Jun;20(3):205-12
references.pmid: 22182419
references.citation: Am J Med. 2013 Apr;126(4):357.e7-357.e27
references.pmid: 23507208
references.citation: J Clin Child Adolesc Psychol. 2008 Jan;37(1):238-61
references.pmid: 18444060
references.citation: Psychopharmacology (Berl). 2013 Aug;228(4):641-9
references.pmid: 23508556
references.citation: Exp Clin Psychopharmacol. 2010 Feb;18(1):99-107
references.pmid: 20158299
references.citation: Curr Pharm Des. 2014;20(13):2126-37
references.pmid: 23829358
references.citation: J Clin Exp Neuropsychol. 2007 May;29(4):357-64
references.pmid: 17497559
references.citation: Am J Psychiatry. 2012 Aug;169(8):805-12
references.pmid: 22706327
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):E2657-64
references.pmid: 22927402
references.citation: J Subst Abuse Treat. 2014 Jul;47(1):58-72
references.pmid: 24629886
references.citation: Neuropharmacology. 2014 Jan;76 Pt B:518-27
references.pmid: 23806805
references.citation: Psychopharmacology (Berl). 2013 Mar;226(2):307-19
references.pmid: 23138434
references.citation: J Clin Psychol. 1995 Nov;51(6):768-74
references.pmid: 8778124
references.citation: Psychopharmacology (Berl). 2007 Oct;194(2):279-88
references.pmid: 17594080
references.citation: Psychopharmacology (Berl). 2012 Jan;219(2):511-8
references.pmid: 21384105
references.citation: Drug Alcohol Depend. 2011 Apr 1;114(2-3):169-76
references.pmid: 21050679
references.citation: Neuropsychopharmacology. 2012 Aug;37(9):2143-52
references.pmid: 22549117
references.citation: Drug Alcohol Rev. 2015 Mar;34(2):119-34
references.pmid: 24684591
references.citation: Drug Alcohol Depend. 2009 Jun 1;102(1-3):35-40
references.pmid: 19217724
references.citation: J Correct Health Care. 2013 Oct;19(4):236-47
references.pmid: 23955055
references.citation: J Subst Abuse Treat. 2013 May-Jun;44(5):541-7
references.pmid: 23305820
references.citation: Addict Behav. 2008 Nov;33(11):1500-5
references.pmid: 18313860
references.citation: Braz J Psychiatry. 2010 May;32 Suppl 1:S46-55
references.pmid: 20512270