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

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 1200mg (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 1200mg 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.

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.

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.

Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis.

BACKGROUND: Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons. RESULTS: There was no pattern of vaccine-associated systemic reactions or clinically significant laboratory abnormalities. AIC did not alter the primary end point, the vascular permeability response (measured by the albumin level in nasal-lavage fluid) to nasal provocation. During the first ragweed season, the AIC group had better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak-season daily nasal symptom diary scores (P=0.02), and midseason overall quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1-specific IgE antibody. A reduction in the number of interleukin-4-positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the subsequent ragweed season, with improvements over placebo in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response was again suppressed, with no significant change in IgE antibody titer during the ragweed season (P=0.19). CONCLUSIONS: In this pilot study, a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .).