5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use Disorder

我们建议对5-HT2A受体激动剂裸盖菇素进行多部位、双盲、随机临床试验。 戒烟。我们之前进行了裸盖菇素与认知药物配对的开放标签试点试验(N=15) 行为疗法(CBT)。数据显示，经过生物验证的7天点流行率戒断率为67% 12个月和60%(持续禁酒率分别为53%和47%)(Johnson等人， 2014年；Johnson等人，2017年)。我们现在正在进行一项开放标签的随机比较疗效试验 裸盖菇素与尼古丁贴片，两者均与CBT联合应用。中期结果(N=44；每组22)显示 生物验证的裸盖菇素在12个月的戒断率：7天点-流行率：59%对27%； 持续禁欲：36%对9%。尽管有这些令人振奋的发现，我们还没有进行双盲 裸盖菇素戒烟作用的研究。此外，以前的裸盖菇素研究样本在很大程度上 社会经济地位(SES)较高的白人，部分原因是缺乏参与者薪酬和适度 来自非营利组织的资金。目前的试验将通过以下三个站点解决这些问题 进行裸盖菇素研究的经验：约翰霍普金斯大学、阿拉巴马大学伯明翰分校(UAB)、 和纽约大学(NYU)。将招募一个关于民族身份和社会地位的不同样本。 在每个地点，并为考察访问提供补偿。拟议的双盲研究将治疗66名参与者(22名 每个部位)，随机接受：1)裸盖菇素；20 mg/70疗程1和30 mg/70 kg疗程2， 疗程间隔1周；或2)烟酸；疗程1 250 mg，疗程2 375 mg，疗程间隔1周。 之所以选择烟酸，是因为它在之前的两次随机治疗中被用作活性安慰剂 裸盖菇素的试验(Grob等人，2011年；Ross等人，2016年)，FDA已经通知我们烟酸是他们的首选 裸盖菇素活性安慰剂。CBT将对这两组人进行治疗，并允许我们测试裸盖菇素 疗效超过既定的治疗方法。生化.确认的7天点流行率 禁欲将在长达12个月的时间内进行评估。我们假设裸盖菇素(与烟酸相比) 将在12个月的随访中引起生物学证实的7天点戒断发生率的增加。基于 试点数据，我们将测试认知/心理调节治疗反应。我们假设裸盖菇素 将与认知控制的改善和戒烟缓解的预期降低有关 目标戒烟日期后1天，这将与12-12岁时更多的7天点戒烟有关- 一个月的随访。尽管迷幻疗法是一种新的方法，约翰霍普金斯大学的网站已经进行了 裸盖菇素在&gt；700会议上进行了16年的试验，并为人类的安全行为设定了标准 采用适当的风险缓解策略的迷幻研究(Johnson等人，2008年)。这项试验将提供一个 在不同的研究样本中进行严格的有效性测试，并测试相关机制，以实现创新吸烟 戒烟治疗显示出实质性疗效的潜力。

We propose a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. We previously conducted an open-label pilot trial (N = 15) of psilocybin paired with cognitive behavior therapy (CBT). Data showed a biologically-verified 7-day point-prevalence abstinence rate of 67% at 12 months and 60% at 2.5 years (continuous abstinence rates: 53% and 47%, respectively) (Johnson et al., 2014; Johnson et al., 2017). We are now conducting an open-label randomized comparative efficacy trial of psilocybin vs. nicotine patch, both in combination with CBT. Interim results (N = 44; 22 per group) show greater biologically-verified abstinence rates at 12 months for psilocybin: 7-day point-prevalence: 59% vs. 27%; continuous abstinence: 36% vs. 9%. Despite these promising findings, we have yet to conduct a double-blind study of psilocybin for smoking cessation. Furthermore, previous psilocybin study samples have been largely White with higher socioeconomic status (SES), partly due to lack of participant compensation and modest funding from non-profit organizations. The current trial will address these issues across three sites with experience in conducting psilocybin research: Johns Hopkins, the University of Alabama at Birmingham (UAB), and New York University (NYU). A diverse sample with regard to ethnoracial identity and SES will be recruited at each site with compensation for study visits. The proposed double-blind study will treat 66 participants (22 at each site), randomized to receive either: 1) psilocybin; 20 mg/70 in session 1 and 30 mg/70 kg in session 2, with sessions 1 week apart; or 2) niacin; 250 mg in session 1 and 375 mg in session 2, with sessions 1 week apart. Niacin was selected because it has been used as an active placebo in two previous randomized therapeutic trials of psilocybin (Grob et al., 2011; Ross et al., 2016), and the FDA has informed us that niacin is their preferred active placebo for psilocybin. CBT will be administered to both groups and will allow us to test psilocybin’s efficacy above and beyond an established treatment approach. Biochemically-confirmed 7-day point-prevalence abstinence will be assessed throughout for up to 12 months. We hypothesize that psilocybin (compared to niacin) will cause increased biologically-confirmed 7-day point-prevalence abstinence at 12-month follow-up. Based on pilot data, we will test cognitive/psychological mediators of treatment response. We hypothesize that psilocybin will be associated with improved cognitive control and decreased anticipation of withdrawal relief (from smoking) 1 day after the target quit date, which will be associated with greater 7-day point-prevalence abstinence at 12- month follow-up. Although psychedelic therapy is a novel approach, the Johns Hopkins site has conducted psilocybin trials with >700 sessions for >16 years, and has set the standard for the safe conduct of human psychedelic research with appropriate risk mitigation strategies (Johnson et al., 2008). This trial will provide a rigorous test of efficacy in a diverse study sample, and test relevant mechanisms, for an innovative smoking cessation treatment showing potential for substantial efficacy.