Bradley Ellen R, Sakai Kimberly, Fernandes-Osterhold Gisele, Szigeti Balázs, Ludwig Connie, Ostrem Jill L, Tanner Caroline M, Bock Meredith A, Llerena Katiah, Finley Patrick R, O'Donovan Aoife, Zuzuarregui Jose Rafael P, Busby Zachary, McKernan Amber, Penn Andrew D, Wang Aliss C C, Rosen Raymond C, Woolley Joshua D
Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Parkinson's Disease Research, Education, and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
Neuropsychopharmacology. 2025 Apr 9. doi: 10.1038/s41386-025-02097-0.
Mood dysfunction is highly prevalent in Parkinson's disease (PD), a main predictor of functional decline, and difficult to treat-novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot (NCT04932434), we examined the feasibility of psilocybin therapy among people with mild to moderate stage PD plus depression and/or anxiety. 12 participants (mean age 63.2 ± 8.2 years, 5 women) received psilocybin (one 10 mg followed by one 25 mg dose) with psychotherapy. There were no serious adverse events, no medical interventions required to manage effects of psilocybin, and no exacerbation of psychosis. Ten participants experienced treatment-emergent adverse events; the most frequent were anxiety, nausea, and increased blood pressure. We observed no worsening of PD symptomology measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). On the contrary, non-motor (MDS-UPDRS Part I: -13.8 ± 1.3, p < 0.001, Hedges' g = 3.0) and motor symptoms (Part II: -7.5 ± 0.9, p < 0.001, g = 1.2; Part III: -4.6 ± 1.3, p = 0.001; g = 0.3) as well as performance in select cognitive domains (Paired Associates Learning [-0.44 ± 0.14, p = .003, g = 0.4], Spatial Working Memory [-0.52 ± 0.17, p = 0.003, g = 0.7], and Probabilistic Reversal Learning [2.9 ± 0.9, p = 0.003, g = 1.3]) improved post-treatment, and improvements were sustained until the final safety assessment one month following drug exposure. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were 21.0 ± 8.7 and 17.0 ± 3.7, respectively. Both improved to a clinically meaningful degree post-treatment; these improvements persisted to the final assessment three months following drug exposure (MADRS: -9.3 ± 2.7, p = .001, g = 1.0; HAM-A: -3.8 ± 1.7; p = 0.031, g = 0.7). This study provides the first data on psilocybin's effects in any neurodegenerative disease. Results suggest that psilocybin therapy in PD warrants further investigation.
情绪功能障碍在帕金森病（PD）中极为普遍，是功能衰退的主要预测指标，且难以治疗，因此急需新的干预措施。裸盖菇素在治疗抑郁症和焦虑症方面显示出早期前景，但其在帕金森病中的潜力尚不清楚，因为安全问题使得神经退行性疾病患者被排除在以往试验之外。在这项开放标签试验（NCT04932434）中，我们研究了裸盖菇素疗法在轻度至中度帕金森病合并抑郁症和/或焦虑症患者中的可行性。12名参与者（平均年龄63.2±8.2岁，5名女性）接受了裸盖菇素（一次10毫克，随后一次25毫克剂量）联合心理治疗。未发生严重不良事件，无需进行医疗干预来处理裸盖菇素的影响，也没有精神病症状加重的情况。10名参与者出现了治疗中出现的不良事件；最常见的是焦虑、恶心和血压升高。我们观察到，根据运动障碍协会统一帕金森病评定量表（MDS-UPDRS）测量，帕金森病症状没有恶化。相反，非运动症状（MDS-UPDRS第一部分：-13.8±1.3，p<0.001，Hedges'g=3.0）和运动症状（第二部分：-7.5±0.9，p<0.001，g=1.2；第三部分：-4.6±1.3，p=0.001；g=0.3）以及特定认知领域的表现（配对联想学习[-0.44±0.14，p=0.003，g=0.4]、空间工作记忆[-0.52±0.17，p=0.003，g=0.7]和概率反转学习[2.9±0.9，p=0.003，g=1.3]）在治疗后有所改善，并且这些改善一直持续到药物暴露后一个月的最终安全性评估。蒙哥马利-阿斯伯格抑郁评定量表（MADRS）和汉密尔顿焦虑评定量表（HAM-A）的基线得分分别为21.0±8.7和17.0±3.7。两者在治疗后均有临床意义上的改善；这些改善持续到药物暴露后三个月的最终评估（MADRS：-9.3±2.7，p=0.001，g=1.0；HAM-A：-3.8±1.7；p=0.031，g=0.7）。本研究提供了关于裸盖菇素在任何神经退行性疾病中作用的首批数据。结果表明，帕金森病中的裸盖菇素疗法值得进一步研究。
