Psilocybin and Affective Function in Chronic Lower Back Pain and Depression

裸盖菇素与慢性腰痛和抑郁症的情感功能

• 批准号: 10626449
• 负责人: Patrick Finan
• 金额: $ 47.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-25 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626449
• 关键词: Address; Affect; Affective; Aftercare; Amygdaloid structure; Attenuated; Chronic low back pain; Clinical; Clinical Trials; Cognitive; Data; Dose; Double-Blind Method; Ecological momentary assessment; Face; Future; Guidelines; Hallucinogens; Individual; Intervention; Laboratories; Lead; Life; Major Depressive Disorder; Malignant Neoplasms; Mediating; Medicine; Mental Depression; Modality; Monitor; Outcome; Pain; Pain intensity; Pain management; Patients; Placebos; Population; Positioning Attribute; Process; Psilocybin; Randomized, Controlled Trials; Reporting; Research; Risk; Ritalin; Safety; Sampling; Science; Sensory; Serotonin Receptor 5-HT2A; Stimulus; Supervision; Symptoms; Testing; Treatment Efficacy; United States National Institutes of Health; Work; active control; anxiety symptoms; cancer diagnosis; chronic pain; chronic pain patient; chronic painful condition; comorbid depression; comorbidity; coping; depressive symptoms; disability; efficacy trial; follow-up; functional improvement; improved; innovation; insight; negative affect; non-opioid analgesic; pain catastrophizing; pain inhibition; pain symptom; primary outcome; response; rumination; secondary analysis; treatment duration; treatment guidelines; trial comparing

PROJECT SUMMARY/ABSTRACT This R33 application proposes a mechanistic clinical trial testing the effects of psilocybin on affective mechanisms of chronic pain in patients with comorbid chronic low back pain and depression (CLBP+D). CLBP is the top cause of disability worldwide, and is highly comorbid with depression. Patients with CLBP+D face a fragmented and limited set of treatment options that insufficiently address their pain and depression symptoms. As such, CLBP treatment guidelines call for a shift away from a sole outcome focus on pain intensity and toward treatments that enhance affective function. Positive and negative affect, pain catastrophizing, and positive affective pain inhibition are well-characterized, modifiable, biologically-mediated mechanisms of chronic pain that we propose to target in this study of patients with CLBP+D. Psilocybin, a classic (5-HT2A receptor-mediated) psychedelic, is a promising non-opioid candidate for the treatment of CLBP+D that reliably and durably improves affective function in healthy individuals, patients with major depressive disorder, and patients with a life-threatening cancer diagnosis. We aim to test whether psilocybin will benefit patients with CLBP+D by durably improving positive affect, negative affect, and pain catastrophizing, and augmenting the ability of positive affect to inhibit pain. The proposed study addresses an important unmet need, as it will be the first, to our knowledge, to test the ability of psilocybin to target pain-related affective function in patients with chronic pain. We propose a double-blind, randomized, controlled trial comparing the administration of high- dose psilocybin (25mg absolute dose; n=20) to an active control (methylphenidate 40mg absolute dose; n=20) among patients with CLBP+D. Psilocybin or methylphenidate will be administered once in the laboratory under close supervision and supportive monitoring. Primary outcomes will be positive and negative affect (Aim 1), pain catastrophizing (Aim 2), and positive affective pain inhibition (Aim 3). Ecological momentary assessment will be used to evaluate the hypotheses that aggregated momentary reports of positive and negative affect and pain catastrophizing will improve from baseline to 1-week post-session to a greater extent in patients in the psilocybin versus the methylphenidate condition. Quantitative sensory testing will be used to evaluate the hypothesis that positive affective pain inhibition will increase from baseline to 1-week post-session to a greater extent in patients in the psilocybin versus the methylphenidate condition. The durability of outcomes will be tested at 1-month post-administration in secondary analyses. By testing the effects of psilocybin on affective function in CLBP+D, we will develop critical data that will provide mechanistic insight into the utility of psilocybin as a pain management medicine. These data will build off our extensive preliminary findings in support of psilocybin’s efficacy for major depressive disorder, and pave the way for future pivotal efficacy trials for psilocybin as a primary treatment for patients with CLBP+D.

项目摘要/摘要 该R33应用提出了一项机械临床试验，该试验测试psilocybin对情感的影响 合并症慢性下背部疼痛和抑郁症患者的慢性疼痛机制（CLBP+D）。 CLBP 是全世界残疾的主要原因，并且与抑郁症高度合并。 CLBP+D的患者面对A 分散且有限的治疗选择，这些选择不足以解决其疼痛和抑郁症状。 因此，CLBP治疗指南要求从唯一的结果转移到疼痛强度和 致力于增强情感功能的治疗。积极和负面影响，疼痛灾难性以及 受到正面影响的疼痛抑制作用是良好的，可修改的，生物学介导的机制 我们建议在这项CLBP+D患者的研究中靶向慢性疼痛。 psilocybin，经典（5-HT2A） 受体介导的）迷幻，是一种可靠的CLBP+D治疗的承诺的非阿片类药物候选者 并彻底改善健康个体的情感功能，重度抑郁症患者以及 患有生命的癌症诊断患者。我们旨在测试psilocybin是否将使患者受益 CLBP+D通过彻底改善积极影响，负面影响和疼痛灾难性，并增加 积极影响抑制疼痛的能力。拟议的研究解决了一个重要的未满足需求，因为这将是 首先，据我们所知，要测试psilocybin靶向与疼痛相关的情感功能的能力 慢性疼痛。我们提出了一项双盲，随机对照试验，比较了高级的给药 剂量psilocybin（25mg绝对剂量； n = 20）至有效对照（甲酯40mg绝对剂量； n = 20） 在CLBP+D的患者中。在实验室中，将在 密切监督和支持性监控。主要结果将是积极和负面影响（AIM 1）， 疼痛灾难性（AIM 2）和积极的情感疼痛抑制（AIM 3）。生态瞬间评估 将用于评估汇总瞬时报告积极和负面影响的假设 疼痛的灾难化将从基线从基线到1周的时间改善，在更大程度上 psilocybin与哌醋甲酯条件。定量感觉测试将用于评估 假设积极的情感抑制作用将从基线到1周后增加到更大 在甲氧甲吡啶与哌醋甲酯疾病的患者中的程度。结果的持久性将是 在二级分析中在管理后1个月测试。通过测试psilocybin对情感的影响 在CLBP+D中的功能，我们将开发关键数据，以提供机械洞察力 psilocybin作为疼痛管理医学。这些数据将在我们广泛的初步发现中建立 支持psilocybin对重度抑郁症的效率，并为将来的关键效率试验铺平道路 对于psilocybin作为CLBP+D患者的主要治疗方法。