N-Acetylcysteine and Contingency Management for Youth Cannabis Use Disorder

摘要 青少年吸食大麻的情况特别普遍，数量也有问题。相比之下，每11人中只有1人 接触大麻的成年人中，每六名接触大麻的青年中就有一人患上大麻使用障碍。此外， 青少年比成年人更容易受到大麻使用的潜在持久不利影响，包括认知方面的不良影响。 损伤，大脑发育改变，教育结果差，生活成就感降低。尽管 这方面的工作相对较少，重点是开发最有效的大麻使用障碍治疗方法， 尤其是在年轻人中。目前的循证治疗一般传递小到中等的效果大小， 而且迫切需要新的方法。其中最有希望的方法是非处方药 抗氧化剂N-乙酰半胱氨酸(NAC)和行为治疗应急管理(CM)。 我们的团队之前在患有NAC的年轻人中展示了比安慰剂(PBO)更好的戒断结果 同时接收CM的CUD。现在需要进一步的工作来理清NAC和CM的影响。 它们可能是协同的，它们的结合对于最大限度地提高禁欲结果至关重要。 或者，NAC可能是有效的，独立于CM，但这还没有得到正式评估。为了 最佳地将NAC和CM的发现转化为现实世界的临床实践，以及它们对戒烟的相对贡献 必须对结果进行正式评估。我们建议对NAC和CM进行为期12周的2x2析因设计试验 青年组(N=336)。参与者将被随机分为双盲NAC或PBO组和CM组或非CM组， 产生四个平均分配的处理组：NAC+CM组、NAC+无CM组、PBO+CM组和PBO+无CM组。 所有参与者都将每周接受简短的大麻戒断咨询和药物治疗。这个 主要疗效结果将是在12周的活动期间尿大麻素试验阴性的比例 治疗，组间比较。我们还将连续评估认知任务的表现，检查 实现戒酒的参与者与没有实现禁欲的参与者之间的表现变化。这项建议 试验是评估NAC和CM作为极有希望的青年CUD治疗方案的明确“下一步” 医疗模式，并定位于告知研究人员、临床医生和普通公众，解决关键的 需要优化青少年CUD治疗。

Abstract Cannabis use is particularly prevalent and problematic amount youth. Compared with only one in eleven cannabis-exposed adults, one in six cannabis-exposed youth develops cannabis use disorder. Moreover, youth are more prone than adults to potentially lasting adverse effects of cannabis use, including cognitive impairment, altered brain development, poor educational outcome, and diminished life achievement. Despite this, relatively little work has focused on developing optimally efficacious cannabis use disorder treatments, particularly among youth. Current evidence-based treatments convey generally small to modest effect sizes, and novel approaches are critically needed. Among the most promising approaches are the over-the-counter antioxidant medication N-acetylcysteine (NAC) and the behavioral treatment contingency management (CM). Our team previously demonstrated superior NAC versus placebo (PBO) abstinence outcomes in youth with CUD who concurrently received CM. Further work is now needed to disentangle the effects of NAC and CM. It is possible that they are synergistic, with their combination being critical to maximizing abstinence outcomes. Alternatively, NAC may be efficacious independent of CM, but this has not been formally evaluated. In order to optimally translate NAC and CM findings to real-world clinical practice, their relative contributions to cessation outcomes must be formally evaluated. We propose a 12-week 2 x 2 factorial design trial of NAC and CM for CUD in youth (N=336). Participants will be randomized to double-blind NAC or PBO and to CM or no CM, yielding four equally-allocated treatment groups: NAC + CM, NAC + No CM, PBO + CM, and PBO + No CM. All participants will receive brief weekly cannabis cessation counseling and medication management. The primary efficacy outcome will be the proportion of negative urine cannabinoid tests during the 12-week active treatment, compared between groups. We will also serially assess cognitive task performance, examining changes in performance among participants who achieve abstinence versus those that do not. This proposed trial is the clear “next step” in the assessment of NAC and CM as extremely promising youth CUD treatment modalities, and is positioned to inform researchers, clinicians, and the general public, addressing a critical need for optimization of youth CUD treatments.