Article

A Double-Blind Randomized Controlled Trial of N-Acetylcysteine in Cannabis-Dependent Adolescents

Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States
American Journal of Psychiatry (Impact Factor: 13.56). 06/2012; 169(8):805-12. DOI: 10.1176/appi.ajp.2012.12010055
Source: PubMed

ABSTRACT Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine (NAC), via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy for substance dependence. The authors investigated NAC as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have shown limited efficacy.
In an 8-week double-blind randomized placebo-controlled trial, treatment-seeking cannabis-dependent adolescents (ages 15-21 years; N=116) received NAC (1200 mg) or placebo twice daily as well as a contingency management intervention and brief (<10 minutes) weekly cessation counseling. The primary efficacy measure was the odds of negative weekly urine cannabinoid test results during treatment among participants receiving NAC compared with those receiving placebo, in an intent-to-treat analysis. The primary tolerability measure was frequency of adverse events, compared by treatment group.
Participants receiving NAC had more than twice the odds, compared with those receiving placebo, of having negative urine cannabinoid test results during treatment (odds ratio=2.4, 95% CI=1.1-5.2). Exploratory secondary abstinence outcomes favored NAC but were not statistically significant. NAC was well tolerated, with minimal adverse events.
This is the first randomized controlled trial of pharmacotherapy for cannabis dependence in any age group to yield a positive primary cessation outcome in an intent-to-treat analysis. Findings support NAC as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents.

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Available from: Nathaniel L Baker, Jul 28, 2015
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    • "Chronic NAC reverses chronic cocaine-induced glutamate dysregulation, including normalizing drug-dependent decreases in extracellular glutamate levels, and protein expression levels of xCT (the catalytic subunit of the cystine-glutamate exchanger) and GLT-1 (a high affinity astroglial glutamate transporter) (Baker et al. 2003; Knackstedt, Melendez & Kalivas 2010). Extensive pre-clinical data supports the therapeutic potential for NAC in addiction and other psychiatric conditions (Dean, Giorlando & Berk 2011; Olive et al. 2012), and clinical data provides promising findings for treating cocaine and marijuana addiction (Kalivas & Volkow 2011; Schmaal et al. 2012; Gray et al. 2012). Hence, understanding the mechanism of action of NAC may aid in discovering therapeutic targets for treating addiction. "
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    • "Importantly, NAC was well tolerated, as has been the case in children with autism (Hardan et al. 2012), in adolescents with cannabis dependence (Gray et al. 2012), in adults with trichotillomania (Grant et al. 2009), and when used adjunctively with SSRIs, in adults with SSRI-resistant anxiety disorders (Lafleur et al. 2006). Additional, prospective trials are urgently needed to assess the potential role of glutamate modulators, such as NAC, in youth with anxiety disorders, including those who have had partial responses to ''first-line'' psychopharmacologic and psychotherapeutic interventions. "
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