Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.
JAMA Psychiatry. 2018 Nov 1;75(11):1107-1117. doi: 10.1001/jamapsychiatry.2018.2309.
Cannabidiol (CBD) has antipsychotic effects in humans, but how these are mediated in the brain remains unclear.
To investigate the neurocognitive mechanisms that underlie the therapeutic effects of CBD in psychosis.
DESIGN, SETTING, AND PARTICIPANTS: In this parallel-group, double-blind, placebo-controlled randomized clinical trial conducted at the South London and Maudsley NHS Foundation Trust in London, United Kingdom, 33 antipsychotic medication-naive participants at clinical high risk (CHR) of psychosis and 19 healthy control participants were studied. Data were collected from July 2013 to October 2016 and analyzed from November 2016 to October 2017.
A total of 16 participants at CHR of psychosis received a single oral dose of 600 mg of CBD, and 17 participants at CHR received a placebo. Control participants were not given any drug. All participants were then studied using functional magnetic resonance imaging (fMRI) while performing a verbal learning task.
Brain activation during verbal encoding and recall, indexed using the blood oxygen level-dependent hemodynamic response fMRI signal.
Of the 16 participants in the CBD group, 6 (38%) were female, and the mean (SD) age was 22.43 (4.95) years; of 17 in the placebo group, 10 (59%) were female, and the mean (SD) age was 25.35 (5.24) years; and of 19 in the control group, 8 (42%) were female, and the mean (SD) age was 23.89 (4.14) years. Brain activation (indexed using the median sum of squares ratio of the blood oxygen level-dependent hemodynamic response effects model component to the residual sum of squares) was analyzed in 15 participants in the CBD group, 16 in the placebo group, and 19 in the control group. Participants receiving placebo had reduced activation relative to controls in the right caudate during encoding (placebo: median, -0.027; interquartile range [IQR], -0.041 to -0.016; control: median, 0.020; IQR, -0.022 to 0.056; P < .001) and in the parahippocampal gyrus and midbrain during recall (placebo: median, 0.002; IQR, -0.016 to 0.010; control: median, 0.035; IQR, 0.015 to 0.039; P < .001). Within these 3 regions, activation in the CBD group was greater than in the placebo group but lower than in the control group (parahippocampal gyrus/midbrain: CBD: median, -0.013; IQR, -0.027 to 0.002; placebo: median, -0.007; IQR, -0.019 to 0.008; control: median, 0.034; IQR, 0.005 to 0.059); the level of activation in the CBD group was thus intermediate to that in the other 2 groups. There were no significant group differences in task performance.
Cannabidiol may partially normalize alterations in parahippocampal, striatal, and midbrain function associated with the CHR state. As these regions are critical to the pathophysiology of psychosis, the influence of CBD at these sites could underlie its therapeutic effects on psychotic symptoms.
isrctn.org Identifier: ISRCTN46322781.
重要性：大麻二酚（CBD）在人类中具有抗精神病作用，但在大脑中这些作用是如何介导的仍不清楚。
目的：研究 CBD 在精神病治疗中的作用的神经认知机制。
设计、地点和参与者：这是一项在英国伦敦南伦敦和莫兹利国民保健信托基金会进行的平行组、双盲、安慰剂对照随机临床试验，共有 33 名抗精神病药物初治的精神病高危（CHR）患者和 19 名健康对照参与者参与。数据收集于 2013 年 7 月至 2016 年 10 月进行，分析于 2016 年 11 月至 2017 年 10 月进行。
干预措施：16 名 CHR 精神分裂症患者接受了 600 毫克 CBD 的单次口服剂量，17 名 CHR 患者接受了安慰剂。对照组未给予任何药物。所有参与者在进行言语学习任务时都使用功能磁共振成像（fMRI）进行研究。
主要结果和测量：使用血氧水平依赖的血流动力学响应 fMRI 信号来表示言语编码和回忆期间的大脑激活。
结果：在 CBD 组的 16 名参与者中，有 6 名（38%）为女性，平均（SD）年龄为 22.43（4.95）岁；在安慰剂组的 17 名参与者中，有 10 名（59%）为女性，平均（SD）年龄为 25.35（5.24）岁；在对照组的 19 名参与者中，有 8 名（42%）为女性，平均（SD）年龄为 23.89（4.14）岁。在 CBD 组的 15 名参与者、安慰剂组的 16 名参与者和对照组的 19 名参与者中分析了大脑激活（使用血氧水平依赖的血流动力学响应效应模型成分与残差和的中位数平方比来表示）。与对照组相比，接受安慰剂的参与者在编码期间右侧尾状核的激活减少（安慰剂：中位数，-0.027；四分位距 [IQR]，-0.041 至-0.016；对照：中位数，0.020；IQR，-0.022 至 0.056；P<.001），在回忆期间在海马旁回和中脑的激活减少（安慰剂：中位数，0.002；IQR，-0.016 至 0.010；对照：中位数，0.035；IQR，0.015 至 0.039；P<.001）。在这 3 个区域内，CBD 组的激活高于安慰剂组，但低于对照组（海马旁回/中脑：CBD：中位数，-0.013；IQR，-0.027 至 0.002；安慰剂：中位数，-0.007；IQR，-0.019 至 0.008；对照：中位数，0.034；IQR，0.005 至 0.059）；CBD 组的激活水平因此介于其他 2 组之间。在任务表现方面，3 组之间没有显著的组间差异。
结论和相关性：大麻二酚可能部分纠正与 CHR 状态相关的海马旁回、纹状体和中脑功能的改变。由于这些区域对精神病的病理生理学至关重要，CBD 在这些部位的影响可能是其对精神病症状治疗作用的基础。
试验注册：isrctn.org 标识符：ISRCTN46322781。
