Psilocybin Therapy for Advanced Cancer-related Psychiatric Distress

项目总结/摘要 据估计，30-40%的癌症患者经历临床显著的焦虑和抑郁。的负担 由精神痛苦引起的痛苦对生活质量（QOL），药物治疗 坚持，自杀率增加，甚至癌症存活率下降。约 25%的晚期或晚期癌症患者经历临床显著的生存痛苦 以士气低落、绝望、没有目的或意义、失去尊严和匆忙的 对死亡的渴望药物和心理社会治疗通常用于治疗抑郁症，焦虑症， 和存在的痛苦，但它们的有效性是有限的和混合的。裸盖菇素是一种 迷幻色胺在人体实验室和临床研究中具有良好的生理-心理安全性， 产生非常突出的有意义的体验，通常被描述为精神/神秘的精神状态， 与认知、情感、行为和灵性的持久（数月至数年）积极变化相关。 基于广泛的初步数据，裸盖菇素辅助治疗已经证明了安全性和有效性。 改善癌症相关抑郁和焦虑的初步疗效（效应量= 0.82-1.69）， 初步试验的参与者发现，这种体验既能改善生活质量， 可接受的，非常有意义的和精神上的。在初步工作的坚实基础上，我们 拟进行一项双中心、活性安慰剂对照、双盲、平行设计、随机对照 单次高剂量裸盖菇素辅助治疗与活性安慰剂（极低剂量裸盖菇素）200例的试验 患有晚期癌症和基线精神痛苦的参与者。所有参与者将获得预备， 活性剂量和作为裸盖菇素组和活性安慰剂组的一部分的综合治疗期。我们 建议进行以下目标：1）评估裸盖菇素对精神的短期和长期影响 健康（例如焦虑、抑郁、存在性痛苦）结果; 2）评估裸盖菇素对生活质量的影响; 和3）评估裸盖菇素诱导的心理变化机制（神秘的 经验，人格特质开放性，认知灵活性）对急性和长期心理健康结果的影响 （抑郁、焦虑、存在性痛苦）。我们将收集基线测量结果，并在1 天、1周、8周、12周和24周（6个月）。拟议的研究将影响以下患者的临床护理： 通过测试一种创新的、基于证据的干预措施来改善抑郁症， 焦虑、生存压力和生活质量。这项研究意义重大，因为它解决了重要的心理问题。 健康领域的痛苦与患者的生命限制癌症。这项研究具有创新性， 有效的治疗方法来缓解存在的痛苦。此外，这项研究将通过评估 心理变化机制，这种有前途的新的治疗干预。

Project Summary/ Abstract An estimated 30-40% of cancer patients experience clinically significant anxiety and depression. The burden of suffering caused by psychiatric distress has profound negative impacts on quality of life (QOL), medication adherence, increased rates of completed suicide, and even decreased cancer survival rates. Approximately 25% of cancer patients with advanced or terminal cancer experience clinically significant existential distress characterized by demoralization, hopelessness, absence of purpose or meaning, loss of dignity, and hastened desire for death. Pharmacologic and psychosocial treatments are commonly used to treat depression, anxiety and existential distress in cancer patients, but their effectiveness is limited and mixed. Psilocybin is a psychedelic tryptamine with a good physiologic-psychological safety profile in human lab and clinical research, producing highly salient meaningful experiences, often described as spiritual/mystical states of mind, associated with enduring (months to years) positive changes in cognition, affect, behavior, and spirituality. Based on extensive preliminary data, psilocybin-assisted therapy has demonstrated both safety and preliminary efficacy to improve cancer-related depression and anxiety (effect size = 0.82-1.69), and existential distress while improving quality of life, Participants in preliminary trials found the experience to be both acceptable and highly meaningful and spiritual. Building on this strong foundation of preliminary work, we propose to conduct a two-site, active placebo-controlled, double-blind, parallel design, randomized controlled trial of single high dose psilocybin-assisted therapy versus active placebo (very low dose psilocybin) for 200 participants with advanced cancer and baseline psychiatric distress. All participants will receive preparatory, active dosing, and integrative therapy sessions as part of the psilocybin and active placebo groups. We propose to conduct the following aims: 1) To assess the short- and long-term effects of psilocybin on mental health (e.g. anxiety, depression, existential distress) outcomes; 2) To assess the effects of psilocybin on QOL; and 3) To evaluate the contribution of psilocybin-induced psychological change mechanisms (mystical experience, personality trait openness, cognitive flexibility) on acute and long-term mental health outcomes (depression, anxiety, existential distress). We will collect baseline measures and follow up of outcomes at 1 day, 1 week, 8 weeks, 12 weeks, and 24 weeks (6 months). The proposed study will impact clinical care for persons with advanced cancer by testing an innovative, evidence-based intervention to improve depression, anxiety, existential distress, and quality of life. The study is significant because it addresses important mental health domains of suffering in patients with life-limiting cancer. The study is innovative as the potentially first effective therapy to impact existential distress. Furthermore, this study will further the science by evaluating the psychological change mechanisms for this promising new therapeutic intervention.