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Abstract：
BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin\'s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.
METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.
CONCLUSIONS: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin\'s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.
BACKGROUND: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.
METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.
CONCLUSIONS: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin\'s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.
BACKGROUND: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.
摘要：
背景：重度抑郁症（MDD）是全球范围内健康和认知领域的主要残疾原因，影响整体生活质量。大约三分之一的抑郁症患者对治疗没有完全反应(例如，常规抗抑郁药，心理治疗)和替代策略是必要的。最近的早期试验表明，psilocybin可能是具有快速作用的抗抑郁药特性的安全有效的干预措施。Psilocybin被认为通过改变大脑网络连接和诱导持续数周的神经可塑性变化来发挥治疗作用。尽管早期临床结果令人鼓舞，psilocybin对神经可塑性的急性神经生物学效应尚未得到充分研究。我们的目标是首次研究psilocybin急性（日内）和亚急性（周）如何改变与抑郁症有关的功能性大脑网络。
方法：将从三级情绪障碍诊所招募50名被诊断患有MDD或持续性抑郁障碍（PDD）的参与者，并将其1：1随机分为实验组或对照组。参与者将被给予25mgpsilocybin或25mg微晶纤维素（MCC）安慰剂作为第一次治疗。三周后,那些在控制臂将过渡到接受25毫克psilocybin。我们将研究治疗是否与急性和亚急性时间点的动脉自旋标记和血液氧合水平依赖性对比神经影像学评估的变化有关。主要结果包括：与安慰剂相比，psilocybin在与情绪调节和抑郁相关的网络中是否表现出（1）脑血流量和（2）功能性脑活动的急性变化。与安慰剂相比，MADRS评分随时间的变化。次要结果包括互补临床精神病学的变化，认知，以及从基线到最终随访的功能量表。将在基线和随访时收集血清周围神经营养和炎症生物标志物，以检查与临床反应的关系。和神经影像学测量。
结论：本研究将使用先进的系列神经成像方法，研究迷迭香素对抑郁症影响的脑网络的急性和亚急性神经可塑性作用。结果将提高我们对psilocybin抗抑郁机制与安慰剂反应的理解，以及脑功能的生物学指标是否可以提供治疗反应的早期预测因子。
背景：ClinicalTrials.gov标识符：NCT06072898。2023年10月6日注册。
方法：将从三级情绪障碍诊所招募50名被诊断患有MDD或持续性抑郁障碍（PDD）的参与者，并将其1：1随机分为实验组或对照组。参与者将被给予25mgpsilocybin或25mg微晶纤维素（MCC）安慰剂作为第一次治疗。三周后,那些在控制臂将过渡到接受25毫克psilocybin。我们将研究治疗是否与急性和亚急性时间点的动脉自旋标记和血液氧合水平依赖性对比神经影像学评估的变化有关。主要结果包括：与安慰剂相比，psilocybin在与情绪调节和抑郁相关的网络中是否表现出（1）脑血流量和（2）功能性脑活动的急性变化。与安慰剂相比，MADRS评分随时间的变化。次要结果包括互补临床精神病学的变化，认知，以及从基线到最终随访的功能量表。将在基线和随访时收集血清周围神经营养和炎症生物标志物，以检查与临床反应的关系。和神经影像学测量。
结论：本研究将使用先进的系列神经成像方法，研究迷迭香素对抑郁症影响的脑网络的急性和亚急性神经可塑性作用。结果将提高我们对psilocybin抗抑郁机制与安慰剂反应的理解，以及脑功能的生物学指标是否可以提供治疗反应的早期预测因子。
背景：ClinicalTrials.gov标识符：NCT06072898。2023年10月6日注册。
