Bornemann Julia, Close James B, Ahmad Kirran, Barba Tommaso, Godfrey Kate, Macdonald Lauren, Erritzoe David, Nutt David, Carhart-Harris Robin
Centre for Psychedelic Research, Department of Brain Science, Imperial College London, London, United Kingdom.
Psychedelics Division, Neurology, Psychiatry and Behavioural Sciences Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States.
Front Psychiatry. 2024 Jun 4;15:1320780. doi: 10.3389/fpsyt.2024.1320780. eCollection 2024.
Chronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI).
Twenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity - plus event-related potential functional plasticity markers, captured via EEG.
The results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT.
慢性疼痛是全球致残的主要原因。纤维肌痛是一种特别使人衰弱的广泛性慢性疼痛形式。人们对纤维肌痛的了解仍然很少，治疗选择有限，充其量也只是中等有效。在此，我们提出一项机制研究方案，调查迷幻辅助疗法对纤维肌痛患者群体的影响。该试验的主要重点是裸盖菇素疗法的核心机制，即在大脑中以及对相关心理模式的影响，主要通过急性迷幻状态的脑电图（EEG）记录以及磁共振成像（MRI）的前后对比来捕捉。
20名纤维肌痛患者将在8周内完成8次研究访视。这将包括两个给药阶段，在此期间参与者将至少接受一次裸盖菇素，剂量最高可达25毫克。我们的主要结果是：1）使用脑电图急性记录的莱普尔 - 齐夫复杂度（LZc），以及2）在基线和主要终点测量的（简要经验性回避问卷（BEAQ））。次要结果旨在通过神经影像学、自我报告测量、行为范式和定性访谈，全面了解疼痛体验及相关特征。疼痛症状将使用简明疼痛问卷干扰分量表（BPI - IS）进行测量，身心健康相关功能将使用36项简短健康调查（SF - 36）进行测量。进一步的神经生物学研究将包括功能磁共振成像（fMRI）和扩散张量成像（从基线到主要终点的变化），以及急性前后自发脑活动的急性变化 - 加上通过脑电图捕捉的事件相关电位功能可塑性标记。
本研究结果将为裸盖菇素疗法治疗纤维肌痛所涉及的脑机制提供有价值的见解，可能对更广泛的迷幻疗法的治疗作用产生影响。它还将提供重要数据，为后续潜在随机对照试验的设计提供参考。
