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 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, 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. Conclusion 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.

The neurobiology of impulsivity and substance use disorders: implications for treatment

“…One human study has examined pharmacological treatments for cannabis users with high impulsivity . The study was a clinical trial involving two treatment groups of contingency management (CM), but one including NAC administration .…”

“…One human study has examined pharmacological treatments for cannabis users with high impulsivity . The study was a clinical trial involving two treatment groups of contingency management (CM), but one including NAC administration . They found no differences between the treatment groups, indicating the lack of efficiency of NAC on impulsive cannabis users .…”

The structure of the UPPS-R-Child impulsivity scale and its relations with substance use outcomes among treatment-seeking adolescents

“…Studies of non-clinical, community samples often find that older adolescents high in impulsivity are at greater risk for problematic substance use (e.g., Cooper et al, 2003; von Diemen et al, 2008). Preliminary evidence also suggests that impulsivity may negatively impact substance use treatment outcome for adolescents and young adults (Feldstein Ewing et al, 2009; Stanger et al, 2012; Bentzley et al, in press). Therefore, early intervention efforts targeting adolescents with heightened impulsivity may be particularly useful.…”

Personalizing substance use treatment based on pre-treatment impulsivity and sensation seeking: A review

“…Over half of the studies (5 out of 9) did not find support for differential treatment efficacy based on pretreatment impulsivity/sensation seeking-treatment (Batra et al, 2010; Bentzley et al, 2016; Helmus et al, 2001; Kravitz et al, 1999; Schmitz et al, 2009). Of the few studies that examined interactions between pharmacological treatment and impulsivity and/or sensation seeking, no significant matching effects emerged.…”

“…Of the 9 reviewed studies examining impulsivity or sensation/novelty seeking (see Table 1), one study examined delay discounting (Washio et al, 2011), three studies used the BIS-11 (Bentzley et al, 2016; Morean et al, 2015; Schmitz et al, 2009), four studies used the Tridimensional Personality Questionnaire (TPQ)- Novelty-Seeking subscale and/or Zuckerman-Kuhlman Personality Questionnaire Impulsivity-Sensation Seeking subscale (Feldstein Ewing et al, 2009; Helmus et al, 2001; Helstrom et al, 2007; Kravitz et al, 1999), and one study used discriminant analysis of multiple impulsivity, hyperactivity, and novelty seeking measures to create a novelty seeking/hyperactivity profile (Batra et al, 2010) as a predictor of treatment outcome.…”