A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults

Abstract

Background Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Tobacco use during cannabis cessation: Use patterns and impact on abstinence in a National Drug Abuse Treatment Clinical Trials Network study

“…Participants meeting criteria for substance dependence (based on DSM-IV, not including tobacco and cannabis) were not eligible for study procedures and participants had to submit a negative urine drug screen at the randomization visit (for all drugs other than cannabis) to continue in the study. Primary cannabis abstinence outcomes can also be found elsewhere (Gray et al, 2017). Six geographically diverse study sites across the US participated in the ACCENT trial (Behavioral Health Services of Pickens County [Pickens, SC], The APT Foundation [New Haven, CT], University of Kentucky Medical Center [Lexington, KY], University of California, Los Angeles Integrated Substance Abuse Programs [Los Angeles, CA], The University of Texas Health Science Center at San Antonio [San Antonio, TX], and CODA, Inc. [Portland, OR]).…”

“…Demographic information was collected and measures are described elsewhere (Gray et al, 2017; McClure et al, 2014b). Cannabis use measures included; gram quantification at screening (Mariani et al, 2011), frequency of cannabis use (through time-line follow-back methods), quantitative urine cannabinoid tests (UCT; abstinence cut-point was set at <50 ng/ml), cannabis use history (age of first use, years to abuse and dependence), the Marijuana Craving Questionnaire (Heishman et al, 2001), the Cannabis Withdrawal Scale (Allsop et al, 2011), and the Marijuana Problems Scale (Stephens et al, 2000).…”

“…For example, tobacco use rates among adults in the US were 15.5% in 2016 (Jamal et al, 2018), but vary widely by state, ranging from 8.8% to 24.8% across the US (Centers for Disease Control and Prevention, 2016). Therefore, the current secondary analysis explored tobacco use within the context of a multi-site pharmacotherapy trial for cannabis dependence (parent trial) conducted within the National Drug Abuse Treatment (Jamal et al, 2018) Clinical Trials Network (NIDA CTN) (Gray et al, 2017; McClure et al, 2014b). The aims of this secondary analysis were to: 1) assess tobacco use changes during treatment for cannabis dependence based on treatment assignment (active medication or placebo; Aim 1a) and concurrent cannabis reduction/abstinence (Aim 1b); and 2) determine if tobacco users had more difficulty achieving cannabis cessation based on their nicotine dependence severity at baseline (Aim 2).…”

“…The aims of this secondary analysis were to: 1) assess tobacco use changes during treatment for cannabis dependence based on treatment assignment (active medication or placebo; Aim 1a) and concurrent cannabis reduction/abstinence (Aim 1b); and 2) determine if tobacco users had more difficulty achieving cannabis cessation based on their nicotine dependence severity at baseline (Aim 2). Since cigarette smoking status was found to be a moderator of cannabis treatment outcomes in the parent trial (Gray et al, 2017), it was of interest in this secondary analysis to determine if nicotine dependence was independently associated with cannabis abstinence during treatment.…”

Open-label pilot study of injectable naltrexone for cannabis dependence

“…Gray et al, however, showed lower odds of THC-positive urines over the same duration of treatment with N-acetylcysteine in a controlled study(27), though in that study of adolescents both groups received cessation counseling, participants with shorter use histories were shown to be more likely to test negative, and some participants had negative urines at the start of the trial (a subgroup who were much more likely to have negative urines throughout that study). A later trial of N-acetylcysteine in a larger adult sample showed no difference in cannabis abstinence(30). …”